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    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 0,
    "text": "REVIEW\nOpen Access\nNutrient timing revisited: is there a post-exercise\nanabolic window?\nAlan Albert Aragon1 and Brad Jon Schoenfeld2*\nAbstract\nNutrient timing is a popular nutritional strategy that involves the consumption of combinations of\nnutrients–primarily protein and carbohydrate–in and around an exercise session. Some have claimed that this\napproach can produce dramatic improvements in body composition. It has even been postulated that the\ntiming of nutritional consumption may be more important than the absolute daily intake of nutrients. The\npost-exercise period is widely considered the most critical part of nutrient timing."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
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    "text": "Theoretically, consuming the\nproper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and\nrestoration of energy reserves, but it does so in a supercompensated fashion that enhances both body\ncomposition and exercise performance.Several researchers have made reference to an anabolic “window of\nopportunity” whereby a limited time exists after training to optimize training-related muscular adaptations.\nHowever, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a\nnumber of factors. Not only is nutrient timing research open to question in terms of applicability, but recent\nevidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with\nrespect to anabolism."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 2,
    "text": "Therefore, the purpose of this paper will be twofold: 1) to review the existing literature\non the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant\nconclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the\nanabolic response to exercise.\nIntroduction\nOver the past two decades, nutrient timing has been the\nsubject of numerous research studies and reviews.The\nbasis of nutrient timing involves the consumption of combi-\nnations of nutrients--primarily protein and carbohydrate--in\nand around an exercise session. The strategy is designed to\nmaximize exercise-induced muscular adaptations and facili-\ntate repair of damaged tissue [1]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 3,
    "text": "Some have claimed that\nsuch timing strategies can produce dramatic improvements\nin body composition, particularly with respect to increases\nin fat-free mass [2].It has even been postulated that the tim-\ning of nutritional consumption may be more important than\nthe absolute daily intake of nutrients [3].\nThe post-exercise period is often considered the most\ncritical part of nutrient timing. An intense resistance train-\ning workout results in the depletion of a significant propor-\ntion of stored fuels (including glycogen and amino acids) as\nwell as causing damage to muscle fibers."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 4,
    "text": "Theoretically, con-\nsuming the proper ratio of nutrients during this time not\nonly initiates the rebuilding of damaged tissue and restor-\nation of energy reserves, but it does so in a supercompen-\nsated fashion that enhances both body composition and\nexercise performance.Several researchers have made refer-\nence to an “anabolic window of opportunity” whereby a\nlimited time exists after training to optimize training-\nrelated muscular adaptations [3-5].\nHowever, the importance – and even the existence –\nof a post-exercise ‘window’ can vary according to a num-\nber of factors. Not only is nutrient timing research open\nto question in terms of applicability, but recent evidence\nhas directly challenged the classical view of the relevance\nof post-exercise nutritional intake on anabolism."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 5,
    "text": "There-\nfore, the purpose of this paper will be twofold: 1) to re-\nview the existing literature on the effects of nutrient\ntiming with respect to post-exercise muscular adapta-\ntions, and; 2) to draw relevant conclusions that allow\nevidence-based nutritional recommendations to be made\nfor maximizing the anabolic response to exercise.\n* Correspondence: brad@workout911.com\n2Department of Health Science, Lehman College, Bronx, NY, USA\nFull list of author information is available at the end of the article\n© 2013 Aragon and Schoenfeld; licensee BioMed Central Ltd."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 6,
    "text": "This is an Open Access article distributed under the terms of the\nCreative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,\ndistribution, and reproduction in any medium, provided the original work is properly cited.\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nhttp://www.jissn.com/content/10/1/5\nGlycogen repletion\nA primary goal of traditional post-workout nutrient timing\nrecommendations is to replenish glycogen stores.Glycogen\nis considered essential to optimal resistance training per-\nformance, with as much as 80% of ATP production during\nsuch training derived from glycolysis [6]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 7,
    "text": "MacDougall et al.\n[7] demonstrated that a single set of elbow flexion at 80%\nof 1 repetition maximum (RM) performed to muscular fail-\nure caused a 12% reduction in mixed-muscle glycogen con-\ncentration, while three sets at this intensity resulted in a\n24% decrease.Similarly, Robergs et al. [8] reported that 3\nsets of 12 RM performed to muscular failure resulted in a\n26.1% reduction of glycogen stores in the vastus lateralis\nwhile six sets at this intensity led to a 38% decrease, primar-\nily resulting from glycogen depletion in type II fibers com-\npared to type I fibers."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 8,
    "text": "It therefore stands to reason that\ntypical high volume bodybuilding-style workouts involving\nmultiple exercises and sets for the same muscle group\nwould deplete the majority of local glycogen stores.\nIn addition, there is evidence that glycogen serves to me-\ndiate intracellular signaling.This appears to be due, at least\nin part, to its negative regulatory effects on AMP-activated\nprotein kinase (AMPK)."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 9,
    "text": "Muscle anabolism and catabolism\nare regulated by a complex cascade of signaling pathways.\nSeveral pathways that have been identified as particularly\nimportant to muscle anabolism include mammalian target\nof rapamycin (mTOR), mitogen-activated protein kinase\n(MAPK), and various calcium- (Ca2+) dependent pathways.\nAMPK, on the other hand, is a cellular energy sensor that\nserves to enhance energy availability.As such, it blunts\nenergy-consuming processes including the activation of\nmTORC1 mediated by insulin and mechanical tension, as\nwell as heightening catabolic processes such as glycolysis,\nbeta-oxidation, and protein degradation [9]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 10,
    "text": "mTOR is con-\nsidered a master network in the regulation of skeletal\nmuscle growth [10,11], and its inhibition has a decidedly\nnegative effect on anabolic processes [12].Glycogen has\nbeen shown to inhibit purified AMPK in cell-free assays\n[13], and low glycogen levels are associated with an\nenhanced AMPK activity in humans in vivo [14].\nCreer et al. [15] demonstrated that changes in the phos-\nphorylation of protein kinase B (Akt) are dependent on\npre-exercise muscle glycogen content. After performing 3\nsets of 10 repetitions of knee extensions with a load equat-\ning to 70% of 1 repetition maximum, early phase post-\nexercise Akt phosphorylation was increased only in the\nglycogen-loaded muscle, with no effect seen in the\nglycogen-depleted contralateral muscle."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 11,
    "text": "Glycogen inhib-\nition also has been shown to blunt S6K activation, impair\ntranslation, and reduce the amount of mRNA of genes re-\nsponsible for regulating muscle hypertrophy [16,17].In\ncontrast to these findings, a recent study by Camera et al.\n[18] found that high-intensity resistance training with low\nmuscle glycogen levels did not impair anabolic signaling\nor muscle protein synthesis (MPS) during the early (4 h)\npostexercise recovery period. The discrepancy between\nstudies is not clear at this time.\nGlycogen availability also has been shown to mediate\nmuscle protein breakdown. Lemon and Mullin [19] found\nthat nitrogen losses more than doubled following a bout\nof exercise in a glycogen-depleted versus glycogen-loaded\nstate."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 12,
    "text": "Other researchers have displayed a similar inverse\nrelationship between glycogen levels and proteolysis [20].\nConsidering the totality of evidence, maintaining a high\nintramuscular glycogen content at the onset of training\nappears beneficial to desired resistance training outcomes.\nStudies show a supercompensation of glycogen stores\nwhen carbohydrate is consumed immediately post-exercise,\nand delaying consumption by just 2 hours attenuates the\nrate of muscle glycogen re-synthesis by as much as 50%\n[21].Exercise enhances insulin-stimulated glucose uptake\nfollowing a workout with a strong correlation noted be-\ntween the amount of uptake and the magnitude of glyco-\ngen utilization [22]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 13,
    "text": "This is in part due to an increase in\nthe translocation of GLUT4 during glycogen depletion\n[23,24] thereby facilitating entry of glucose into the cell.In\naddition, there is an exercise-induced increase in the activ-\nity of glycogen synthase—the principle enzyme involved in\npromoting glycogen storage [25]. The combination of these\nfactors facilitates the rapid uptake of glucose following an\nexercise bout, allowing glycogen to be replenished at an\naccelerated rate.\nThere is evidence that adding protein to a post-workout\ncarbohydrate meal can enhance glycogen re-synthesis.\nBerardi et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 14,
    "text": "[26] demonstrated that consuming a protein-\ncarbohydrate supplement in the 2-hour period following a\n60-minute cycling bout resulted in significantly greater\nglycogen resynthesis compared to ingesting a calorie-\nequated carbohydrate solution alone.Similarly, Ivy et al.\n[27] found that consumption of a combination of protein\nand carbohydrate after a 2+ hour bout of cycling and\nsprinting increased muscle glycogen content significantly\nmore than either a carbohydrate-only supplement of\nequal carbohydrate or caloric equivalency. The synergis-\ntic effects of protein-carbohydrate have been attributed\nto a more pronounced insulin response [28], although it\nshould be noted that not all studies support these find-\nings [29]. Jentjens et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 15,
    "text": "[30] found that given ample\ncarbohydrate dosing (1.2 g/kg/hr), the addition of a pro-\ntein and amino acid mixture (0.4 g/kg/hr) did not in-\ncrease glycogen synthesis during a 3-hour post-depletion\nrecovery period.\nDespite a sound theoretical basis, the practical signifi-\ncance of expeditiously repleting glycogen stores remains\ndubious.Without question, expediting glycogen resynth-\nesis is important for a narrow subset of endurance sports\nwhere the duration between glycogen-depleting events is\nlimited to less than approximately 8 hours [31]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 16,
    "text": "Similar\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 2 of 11\nhttp://www.jissn.com/content/10/1/5\nbenefits could potentially be obtained by those who per-\nform two-a-day split resistance training bouts (i.e.morn-\ning and evening) provided the same muscles will be\nworked during the respective sessions. However, for\ngoals that are not specifically focused on the perform-\nance of multiple exercise bouts in the same day, the ur-\ngency of glycogen resynthesis is greatly diminished.\nHigh-intensity resistance training with moderate volume\n(6-9 sets per muscle group) has only been shown to re-\nduce glycogen stores by 36-39% [8,32]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 17,
    "text": "Certain athletes\nare prone to performing significantly more volume than\nthis (i.e., competitive bodybuilders), but increased vol-\nume typically accompanies decreased frequency.For ex-\nample, training a muscle group with 16-20 sets in a\nsingle session is done roughly once per week, whereas\nroutines with 8-10 sets are done twice per week. In sce-\nnarios of higher volume and frequency of resistance\ntraining, incomplete resynthesis of pre-training glycogen\nlevels would not be a concern aside from the far-fetched\nscenario where exhaustive training bouts of the same\nmuscles occur after recovery intervals shorter than 24\nhours."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 18,
    "text": "However, even in the event of complete glycogen\ndepletion, replenishment to pre-training levels occurs\nwell-within this timeframe, regardless of a significantly\ndelayed post-exercise carbohydrate intake.For example,\nParkin et al [33] compared the immediate post-exercise\ningestion of 5 high-glycemic carbohydrate meals with a\n2-hour wait before beginning the recovery feedings. No\nsignificant\nbetween-group\ndifferences\nwere\nseen\nin\nglycogen levels at 8 hours and 24 hours post-exercise. In\nfurther support of this point, Fox et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 19,
    "text": "[34] saw no sig-\nnificant reduction in glycogen content 24 hours after de-\npletion despite adding 165 g fat collectively to the post-\nexercise recovery meals and thus removing any potential\nadvantage of high-glycemic conditions.\nProtein breakdown\nAnother purported benefit of post-workout nutrient tim-\ning is an attenuation of muscle protein breakdown.This\nis\nprimarily\nachieved\nby\nspiking\ninsulin\nlevels,\nas\nopposed to increasing amino acid availability [35,36].\nStudies show that muscle protein breakdown is only\nslightly elevated immediately post-exercise and then\nrapidly rises thereafter [36]. In the fasted state, muscle\nprotein breakdown is significantly heightened at 195\nminutes following resistance exercise, resulting in a net\nnegative protein balance [37]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 20,
    "text": "These values are increased\nas much as 50% at the 3 hour mark, and elevated prote-\nolysis can persist for up to 24 hours of the post-workout\nperiod [36].\nAlthough\ninsulin\nhas\nknown\nanabolic\nproperties\n[38,39], its primary impact post-exercise is believed to\nbe anti-catabolic [40-43].The mechanisms by which in-\nsulin reduces proteolysis are not well understood at this\ntime. It has been theorized that insulin-mediated phos-\nphorylation of PI3K/Akt inhibits transcriptional activity\nof the proteolytic Forkhead family of transcription fac-\ntors, resulting in their sequestration in the sarcoplasm\naway from their target genes [44]. Down-regulation of\nother aspects of the ubiquitin-proteasome pathway are\nalso believed to play a role in the process [45]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 21,
    "text": "Given\nthat muscle hypertrophy represents the difference be-\ntween myofibrillar protein synthesis and proteolysis, a\ndecrease in protein breakdown would conceivably en-\nhance accretion of contractile proteins and thus facilitate\ngreater hypertrophy."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 22,
    "text": "Accordingly, it seems logical to\nconclude that consuming a protein-carbohydrate supple-\nment following exercise would promote the greatest re-\nduction in proteolysis since the combination of the two\nnutrients has been shown to elevate insulin levels to a\ngreater extent than carbohydrate alone [28].\nHowever, while the theoretical basis behind spiking in-\nsulin post-workout is inherently sound, it remains ques-\ntionable as to whether benefits extend into practice.\nFirst and foremost, research has consistently shown that,\nin the presence of elevated plasma amino acids, the ef-\nfect of insulin elevation on net muscle protein balance\nplateaus within a range of 15–30 mU/L [45,46]; roughly\n3–4 times normal fasting levels."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 23,
    "text": "This insulinogenic effect\nis easily accomplished with typical mixed meals, consid-\nering that it takes approximately 1–2 hours for circulat-\ning substrate levels to peak, and 3–6 hours (or more) for\na complete return to basal levels depending on the size\nof a meal.For example, Capaldo et al. [47] examined\nvarious metabolic effects during a 5-hour period after\ningesting a solid meal comprised of 75 g carbohydrate\n37 g protein, and 17 g fat. This meal was able to raise\ninsulin 3 times above fasting levels within 30 minutes of\nconsumption. At the 1-hour mark, insulin was 5 times\ngreater than fasting. At the 5-hour mark, insulin was still\ndouble the fasting levels. In another example, Power\net al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 24,
    "text": "[48] showed that a 45g dose of whey protein isolate\ntakes approximately 50 minutes to cause blood amino\nacid levels to peak.Insulin concentrations peaked 40\nminutes after ingestion, and remained at elevations seen\nto maximize net muscle protein balance (15-30 mU/L,\nor 104-208 pmol/L) for approximately 2 hours. The in-\nclusion of carbohydrate to this protein dose would cause\ninsulin levels to peak higher and stay elevated even\nlonger. Therefore, the recommendation for lifters to\nspike insulin post-exercise is somewhat trivial."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 25,
    "text": "The clas-\nsical post-exercise objective to quickly reverse catabolic\nprocesses to promote recovery and growth may only be\napplicable in the absence of a properly constructed pre-\nexercise meal.\nMoreover, there is evidence that the effect of protein\nbreakdown on muscle protein accretion may be over-\nstated.Glynn et al. [49] found that the post-exercise\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 3 of 11\nhttp://www.jissn.com/content/10/1/5\nanabolic response associated with combined protein and\ncarbohydrate consumption was largely due to an eleva-\ntion in muscle protein synthesis with only a minor influ-\nence from reduced muscle protein breakdown. These\nresults were seen regardless of the extent of circulating\ninsulin levels."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 26,
    "text": "Thus, it remains questionable as to what,\nif any, positive effects are realized with respect to muscle\ngrowth from spiking insulin after resistance training.\nProtein synthesis\nPerhaps the most touted benefit of post-workout nutri-\nent timing is that it potentiates increases in MPS.Resist-\nance training alone has been shown to promote a\ntwofold increase in protein synthesis following exercise,\nwhich is counterbalanced by the accelerated rate of pro-\nteolysis [36]. It appears that the stimulatory effects of\nhyperaminoacidemia on muscle protein synthesis, espe-\ncially from essential amino acids, are potentiated by pre-\nvious exercise [35,50]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 27,
    "text": "There is some evidence that\ncarbohydrate has an additive effect on enhancing post-\nexercise muscle protein synthesis when combined with\namino acid ingestion [51], but others have failed to find\nsuch a benefit [52,53].\nSeveral studies have investigated whether an “anabolic\nwindow” exists in the immediate post-exercise period\nwith respect to protein synthesis.For maximizing MPS,\nthe evidence supports the superiority of post-exercise\nfree amino acids and/or protein (in various permutations\nwith or without carbohydrate) compared to solely carbo-\nhydrate or non-caloric placebo [50,51,54-59]. However,\ndespite the common recommendation to consume pro-\ntein as soon as possible post-exercise [60,61], evidence-\nbased support for this practice is currently lacking.\nLevenhagen et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 28,
    "text": "[62] demonstrated a clear benefit to\nconsuming nutrients as soon as possible after exercise as\nopposed to delaying consumption.Employing a within-\nsubject design,10 volunteers (5 men, 5 women) con-\nsumed an oral supplement containing 10 g protein, 8 g\ncarbohydrate and 3 g fat either immediately following or\nthree hours post-exercise. Protein synthesis of the legs\nand whole body was increased threefold when the sup-\nplement was ingested immediately after exercise, as\ncompared to just 12% when consumption was delayed.\nA limitation of the study was that training involved\nmoderate intensity, long duration aerobic exercise."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 29,
    "text": "Thus,\nthe increased fractional synthetic rate was likely due to\ngreater mitochondrial and/or sarcoplasmic protein frac-\ntions, as opposed to synthesis of contractile elements\n[36].In contrast to the timing effects shown by Levenha-\ngen et al. [62], previous work by Rasmussen et al. [56]\nshowed no significant difference in leg net amino acid\nbalance between 6 g essential amino acids (EAA) co-\ningested with 35 g carbohydrate taken 1 hour versus 3\nhours post-exercise."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 30,
    "text": "Compounding the unreliability of\nthe post-exercise ‘window’ is the finding by Tipton et al.\n[63] that immediate pre-exercise ingestion of the same\nEAA-carbohydrate solution resulted in a significantly\ngreater and more sustained MPS response compared to\nthe immediate post-exercise ingestion, although the val-\nidity of these findings have been disputed based on\nflawed methodology [36].Notably, Fujita et al [64] saw\nopposite results using a similar design, except the EAA-\ncarbohydrate was ingested 1 hour prior to exercise com-\npared to ingestion immediately pre-exercise in Tipton\net al. [63]. Adding yet more incongruity to the evidence,\nTipton et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 31,
    "text": "[65] found no significant difference in net\nMPS between the ingestion of 20 g whey immediately\npre- versus the same solution consumed 1 hour post-\nexercise.Collectively, the available data lack any consist-\nent indication of an ideal post-exercise timing scheme\nfor maximizing MPS.\nIt also should be noted that measures of MPS assessed\nfollowing an acute bout of resistance exercise do not al-\nways occur in parallel with chronic upregulation of\ncausative myogenic signals [66] and are not necessarily\npredictive\nof\nlong-term\nhypertrophic\nresponses\nto\nregimented resistance training [67]. Moreover, the post-\nexercise rise in MPS in untrained subjects is not recapi-\ntulated in the trained state [68], further confounding\npractical relevance."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 32,
    "text": "Thus, the utility of acute studies is\nlimited to providing clues and generating hypotheses\nregarding hypertrophic adaptations; any attempt to ex-\ntrapolate findings from such data to changes in lean\nbody mass is speculative, at best.\nMuscle hypertrophy\nA number of studies have directly investigated the long-\nterm hypertrophic effects of post-exercise protein con-\nsumption.The results of these trials are curiously\nconflicting, seemingly because of varied study design\nand methodology. Moreover, a majority of studies\nemployed both pre- and post-workout supplementation,\nmaking it impossible to tease out the impact of consum-\ning nutrients after exercise."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 33,
    "text": "These confounding issues\nhighlight the difficulty in attempting to draw relevant\nconclusions as to the validity of an “anabolic window.”\nWhat follows is an overview of the current research on\nthe topic.Only those studies that specifically evaluated\nimmediate (≤1 hour) post-workout nutrient provision\nare discussed (see Table 1 for a summary of data).\nEsmarck et al. [69] provided the first experimental evi-\ndence that consuming protein immediately after training\nenhanced muscular growth compared to delayed protein\nintake. Thirteen untrained elderly male volunteers were\nmatched in pairs based on body composition and daily\nprotein intake and divided into two groups: P0 or P2.\nSubjects performed a progressive resistance training pro-\ngram of multiple sets for the upper and lower body."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 34,
    "text": "P0\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 4 of 11\nhttp://www.jissn.com/content/10/1/5\nTable 1 Post-exercise nutrition and muscle hypertrophy\nStudy\nSubjects\nSupplementation\nProtein matched\nwith Control?\nMeasurement\ninstrument\nTraining protocol\nResults\nEsmarck\net al.[69]\n13 untrained\nelderly males\n10 g milk/soy protein combo consumed\neither immediately or 2 hours after exercise\nYes\nMRI and muscle\nbiopsy\nProgressive resistance training\nconsisting of multiple sets of lat\npulldown, leg press and knee\nextension performed 3 days/wk\nfor 12 wk\nSignificant increase in muscle CSA\nwith immediate vs."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 35,
    "text": "delayed\nsupplementation\nCribb and\nHayes [70]\n23 young\nrecreational male\nbodybuilders\n1 g/kg of a supplement containing 40 g\nwhey isolate, 43 g glucose, and 7 g creatine\nmonohydrate consumed either immediately\nbefore and after exercise or in the early\nmorning and late evening\nYes\nDXA and muscle\nbiopsy\nProgressive resistance training\nconsisting of exercises for the\nmajor muscle groups performed\n3 days/wk for 10 wks\nSignificant increases in lean body\nmass and muscle CSA of type II\nfibers in immediate vs.delayed\nsupplementation\nWilloughby\net al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 36,
    "text": "[71]\n19 untrained\nyoung males\n20 g protein or 20 g dextrose consumed\n1 hour before and after exercise\nNo\nHydrostatic\nweighing, muscle\nbiopsy, surface\nmeasurements\nProgressive resistance training\nconsisting of 3 sets of 6–8 repetitions\nfor all the major muscles performed\n4 days/wk for 10 wks\nSignificant increase in total body\nmass, fat-free mass, and thigh\nmass with protein vs.carb\nsupplementation\nHulmi\net al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 37,
    "text": "[72]\n31 untrained\nyoung males\n15 g whey isolate or placebo consumed\nimmediately before and after exercise\nNo\nMRI, muscle\nbiopsy\nProgressive, periodized total body\nresistance training consisting of 2–5\nsets of 5–20 repetitions performed\n2 days/wk for 21 wks.\nSignificant increase in CSA of the\nvastus lateralis but not of the\nother quadriceps muscles in\nsupplemented group versus\nplacebo.\nVerdijk\net al.[73]\n28 untrained\nelderly males\n10 g casein hydrolysate or placebo\nconsumed immediately before and after\nexercise\nNo\nDXA, CT, and\nmuscle biopsy\nProgressive resistance training consisting\nof multiple sets of leg press and knee\nextension performed 3 days/wk for\n12 wks\nNo significant differences in\nmuscle CSA between groups\nHoffman\net al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 38,
    "text": "[74]\n33 well-trained\nyoung males\nSupplement containing 42 g protein (milk/\ncollagen blend) and 2 g carbohydrate\nconsumed either immediately before and\nafter exercise or in the early morning and\nlate evening\nYes\nDXA\nProgressive resistance training consisting\nof 3–4 sets of 6–10 repetitions of multiple\nexercises for the entire body peformed 4\ndays/wk for 10 weeks.\nNo significant differences in total\nbody mass or lean body mass\nbetween groups.\nErskine\net al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 39,
    "text": "[75]\n33 untrained\nyoung males\n20 g high quality protein or placebo\nconsumed immediately before and after\nexercise\nNo\nMRI\n4-6 sets of elbow flexion performed\n3 days/wk for 12 weeks\nNo significant differences in\nmuscle CSA between groups\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 5 of 11\nhttp://www.jissn.com/content/10/1/5\nreceived an oral protein/carbohydrate supplement im-\nmediately post-exercise while P2 received the same sup-\nplement 2 hours following the exercise bout.Training\nwas carried out 3 days a week for 12 weeks. At the end\nof the study period, cross-sectional area (CSA) of the\nquadriceps femoris and mean fiber area were signifi-\ncantly increased in the P0 group while no significant\nincrease was seen in P2."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 40,
    "text": "These results support the pres-\nence of a post-exercise window and suggest that delaying\npost-workout nutrient intake may impede muscular\ngains.\nIn contrast to these findings, Verdijk et al.[73] failed to\ndetect any increases in skeletal muscle mass from con-\nsuming a post-exercise protein supplement in a similar\npopulation of elderly men. Twenty-eight untrained sub-\njects were randomly assigned to receive either a protein or\nplacebo supplement consumed immediately before and\nimmediately following the exercise session."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 41,
    "text": "Subjects per-\nformed multiple sets of leg press and knee extension 3\ndays per week, with the intensity of exercise progressively\nincreased over the course of the 12 week training period.\nNo significant differences in muscle strength or hyper-\ntrophy were noted between groups at the end of the study\nperiod indicating that post exercise nutrient timing strat-\negies do not enhance training-related adaptation."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 42,
    "text": "It should\nbe noted that, as opposed to the study by Esmark et al.\n[69] this study only investigated adaptive responses of sup-\nplementation on the thigh musculature; it therefore is not\nclear based on these results whether the upper body might\nrespond differently to post-exercise supplementation than\nthe lower body.\nIn an elegant single-blinded design, Cribb and Hayes\n[70] found a significant benefit to post-exercise protein\nconsumption in 23 recreational male bodybuilders.Sub-\njects were randomly divided into either a PRE-POST\ngroup that consumed a supplement containing protein,\ncarbohydrate and creatine immediately before and after\ntraining or a MOR-EVE group that consumed the same\nsupplement in the morning and evening at least 5 hours\noutside the workout."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 43,
    "text": "Both groups performed regimented\nresistance training that progressively increased intensity\nfrom 70% 1RM to 95% 1RM over the course of 10 weeks.\nResults showed that the PRE-POST group achieved a sig-\nnificantly greater increase in lean body mass and increased\ntype II fiber area compared to MOR-EVE.Findings sup-\nport the benefits of nutrient timing on training-induced\nmuscular adaptations. The study was limited by the\naddition of creatine monohydrate to the supplement,\nwhich may have facilitated increased uptake following\ntraining. Moreover, the fact that the supplement was taken\nboth pre- and post-workout confounds whether an ana-\nbolic window mediated results.\nWilloughby et al. [71] also found that nutrient timing\nresulted in positive muscular adaptations."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 44,
    "text": "Nineteen\nuntrained male subjects were randomly assigned to\neither receive 20 g of protein or 20 grams dextrose\nadministered 1 hour before and after resistance exercise.\nTraining consisted of 3 sets of 6–8 repetitions at 85%–\n90% intensity.Training was performed 4 times a week\nover the course of 10 weeks. At the end of the study\nperiod, total body mass, fat-free mass, and thigh mass\nwas significantly greater in the protein-supplemented\ngroup compared to the group that received dextrose.\nGiven that the group receiving the protein supplement\nconsumed an additional 40 grams of protein on training\ndays, it is difficult to discern whether results were due\nto the increased protein intake or the timing of the\nsupplement.\nIn a comprehensive study of well-trained subjects,\nHoffman et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 45,
    "text": "[74] randomly assigned 33 well-trained\nmales to receive a protein supplement either in the\nmorning and evening (n = 13) or immediately before and\nimmediately after resistance exercise (n = 13).Seven par-\nticipants served as unsupplemented controls. Workouts\nconsisted of 3–4 sets of 6–10 repetitions of multiple\nexercises for the entire body.\nTraining was carried out\non 4 day-a-week split routine with intensity progres-\nsively increased over the course of the study period.\nAfter 10 weeks, no significant differences were noted be-\ntween groups with respect to body mass and lean body\nmass."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 46,
    "text": "The study was limited by its use of DXA to assess\nbody composition, which lacks the sensitivity to detect\nsmall changes in muscle mass compared to other im-\naging modalities such as MRI and CT [76].\nHulmi et al.[72] randomized 31 young untrained male\nsubjects into 1 of 3 groups: protein supplement (n = 11),\nnon-caloric placebo (n = 10) or control (n = 10). High-\nintensity resistance training was carried out over 21\nweeks. Supplementation was provided before and after\nexercise. At the end of the study period, muscle CSA\nwas significantly greater in the protein-supplemented\ngroup compared to placebo or control. A strength of the\nstudy was its long-term training period, providing sup-\nport for the beneficial effects of nutrient timing on\nchronic hypertrophic gains."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 47,
    "text": "Again, however, it is unclear\nwhether enhanced results associated with protein sup-\nplementation were due to timing or increased protein\nconsumption.\nMost recently, Erskine et al.[75]\nfailed to show a\nhypertrophic benefit from post-workout nutrient timing.\nSubjects were 33 untrained young males, pair-matched\nfor habitual protein intake and strength response to a 3-\nweek pre-study resistance training program. After a 6-\nweek washout period where no training was performed,\nsubjects were then randomly assigned to receive either a\nprotein supplement or a placebo immediately before and\nafter resistance exercise."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 48,
    "text": "Training consisted of 6– 8 sets\nof elbow flexion carried out 3 days a week for 12 weeks.\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 6 of 11\nhttp://www.jissn.com/content/10/1/5\nNo significant differences were found in muscle volume\nor anatomical cross-sectional area between groups.\nDiscussion\nDespite claims that immediate post-exercise nutritional\nintake\nis\nessential\nto\nmaximize\nhypertrophic\ngains,\nevidence-based support for such an “anabolic window of\nopportunity” is far from definitive.The hypothesis is based\nlargely on the pre-supposition that training is carried out\nin a fasted state."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 49,
    "text": "During fasted exercise, a concomitant in-\ncrease in muscle protein breakdown causes the pre-\nexercise net negative amino acid balance to persist in the\npost-exercise period despite training-induced increases in\nmuscle protein synthesis [36].Thus, in the case of resist-\nance training after an overnight fast, it would make sense\nto provide immediate nutritional intervention--ideally in\nthe form of a combination of protein and carbohydrate--\nfor the purposes of promoting muscle protein synthesis\nand reducing proteolysis, thereby switching a net catabolic\nstate into an anabolic one."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 50,
    "text": "Over a chronic period, this tac-\ntic could conceivably lead cumulatively to an increased\nrate of gains in muscle mass.\nThis inevitably begs the question of how pre-exercise\nnutrition might influence the urgency or effectiveness of\npost-exercise nutrition, since not everyone engages in\nfasted training.In practice, it is common for those with\nthe primary goal of increasing muscular size and/or\nstrength to make a concerted effort to consume a pre-\nexercise meal within 1-2 hours prior to the bout in at-\ntempt to maximize training performance. Depending on\nits size and composition, this meal can conceivably func-\ntion as both a pre- and an immediate post-exercise meal,\nsince the time course of its digestion/absorption can per-\nsist well into the recovery period. Tipton et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 51,
    "text": "[63]\nobserved that a relatively small dose of EAA (6 g) taken\nimmediately pre-exercise was able to elevate blood and\nmuscle amino acid levels by roughly 130%, and these\nlevels remained elevated\nfor 2 hours after the exercise\nbout.Although this finding was subsequently challenged\nby Fujita et al. [64], other research by Tipton et al. [65]\nshowed that the ingestion of 20 g whey taken immedi-\nately pre-exercise elevated muscular uptake of amino\nacids to 4.4 times pre-exercise resting levels during exer-\ncise, and did not return to baseline levels until 3 hours\npost-exercise. These data indicate that even minimal-to-\nmoderate pre-exercise\nEAA or high-quality protein\ntaken immediately before resistance training is capable\nof sustaining amino acid delivery into the post-exercise\nperiod."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 52,
    "text": "Given this scenario, immediate post-exercise\nprotein dosing for the aim of mitigating catabolism\nseems redundant.The next scheduled protein-rich\nmeal (whether it occurs immediately or 1–2 hours\npost-exercise) is likely sufficient for maximizing recov-\nery and anabolism.\nOn the other hand, there are others who might train\nbefore lunch or after work, where the previous meal was\nfinished 4–6 hours prior to commencing exercise. This\nlag in nutrient consumption can be considered signifi-\ncant enough to warrant post-exercise intervention if\nmuscle retention or growth is the primary goal. Layman\n[77] estimated that the anabolic effect of a meal lasts 5-6\nhours based on the rate of postprandial amino acid me-\ntabolism."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 53,
    "text": "However, infusion-based studies in rats [78,79]\nand humans [80,81]\nindicate that the postprandial rise\nin MPS from ingesting amino acids or a protein-rich\nmeal is more transient, returning to baseline within 3\nhours despite sustained elevations in amino acid avail-\nability.It thus has been hypothesized that a “muscle full”\nstatus can be reached where MPS becomes refractory,\nand circulating amino acids are shunted toward oxida-\ntion or fates other than MPS."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 54,
    "text": "In light of these findings,\nwhen training is initiated more than ~3–4 hours after\nthe preceding meal, the classical recommendation to\nconsume protein (at least 25 g) as soon as possible\nseems warranted in order to reverse the catabolic state,\nwhich in turn could expedite muscular recovery and\ngrowth.\nHowever, as illustrated previously, minor pre-\nexercise nutritional interventions can be undertaken if a\nsignificant delay in the post-exercise meal is anticipated.\nAn interesting area of speculation is the generalizability\nof these recommendations across training statuses and\nage groups.Burd et al."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 55,
    "text": "[82] reported that an acute bout of\nresistance training in untrained subjects stimulates both\nmitochondrial and myofibrillar protein synthesis, whereas\nin trained subjects, protein synthesis becomes more pre-\nferential toward the myofibrillar component.This suggests\na less global response in advanced trainees that potentially\nwarrants closer attention to protein timing and type (e.g.,\nhigh-leucine sources such as dairy proteins) in order to\noptimize rates of muscular adaptation. In addition to\ntraining status, age can influence training adaptations. Eld-\nerly subjects exhibit what has been termed “anabolic re-\nsistance,” characterized by a lower receptivity to amino\nacids and resistance training [83]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 56,
    "text": "The mechanisms under-\nlying this phenomenon are not clear, but there is evidence\nthat in younger adults, the acute anabolic response to pro-\ntein feeding appears to plateau at a lower dose than in eld-\nerly subjects.Illustrating this point, Moore et al. [84]\nfound that 20 g whole egg protein maximally stimulated\npost-exercise MPS, while 40 g increased leucine oxidation\nwithout any further increase in MPS in young men. In\ncontrast, Yang et al. [85] found that elderly subjects dis-\nplayed greater increases in MPS when consuming a post-\nexercise dose of 40 g whey protein compared to 20 g.\nThese findings suggest that older subjects require higher\nindividual protein doses for the purpose of optimizing the\nanabolic response to training."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 57,
    "text": "Further research is needed\nto better assess post-workout nutrient timing response\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 7 of 11\nhttp://www.jissn.com/content/10/1/5\nacross various populations, particularly with respect to\ntrained/untrained and young/elderly subjects.\nThe body of research in this area has several limita-\ntions.First, while there is an abundance of acute data,\ncontrolled, long-term trials that systematically compare\nthe effects of various post-exercise timing schemes are\nlacking. The majority of chronic studies have examined\npre- and post-exercise supplementation simultaneously,\nas opposed to comparing the two treatments against\neach other. This prevents the possibility of isolating the\neffects of either treatment."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 58,
    "text": "That is, we cannot know\nwhether pre- or post-exercise supplementation was the\ncritical contributor to the outcomes (or lack thereof).\nAnother important limitation is that the majority of\nchronic studies neglect to match total protein intake be-\ntween the conditions compared.As such, it’s not pos-\nsible\nto\nascertain\nwhether\npositive\noutcomes\nwere\ninfluenced by timing relative to the training bout, or\nsimply by a greater protein intake overall. Further, dos-\ning strategies employed in the preponderance of chronic\nnutrient timing studies have been overly conservative,\nproviding only 10–20 g protein near the exercise bout.\nMore research is needed using protein doses known to\nmaximize acute anabolic response, which has been\nshown to be approximately 20–40 g, depending on age\n[84,85]."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 59,
    "text": "There is also a lack of chronic studies examining\nthe co-ingestion of protein and carbohydrate near train-\ning.Thus far, chronic studies have yielded equivocal\nresults. On the whole, they have not corroborated the\nconsistency of positive outcomes seen in acute studies\nexamining post-exercise nutrition.\nAnother limitation is that the majority of studies on\nthe topic have been carried out in untrained individuals.\nMuscular adaptations in those without resistance train-\ning experience tend to be robust, and do not necessarily\nreflect gains experienced in trained subjects."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 60,
    "text": "It therefore\nremains to be determined whether training status influ-\nences the hypertrophic response to post-exercise nutri-\ntional supplementation.\nA final limitation of the available research is that current\nmethods used to assess muscle hypertrophy are widely\ndisparate, and the accuracy of the measures obtained are\ninexact [68].As such, it is questionable whether these\ntools are sensitive enough to detect small differences in\nmuscular hypertrophy. Although minor\nvariances in\nmuscle mass would be of little relevance to the general\npopulation, they could be very meaningful for elite ath-\nletes and bodybuilders. Thus, despite conflicting evidence,\nthe potential benefits of post-exercise supplementation\ncannot be readily dismissed for those seeking to optimize\na hypertrophic response."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 61,
    "text": "By the same token, widely vary-\ning feeding patterns among individuals challenge the com-\nmon assumption that the post-exercise “anabolic window\nof opportunity” is universally narrow and urgent.\nPractical applications\nDistilling the data into firm, specific recommendations is\ndifficult due to the inconsistency of findings and scarcity\nof systematic investigations seeking to optimize pre-\nand/or post-exercise protein dosage and timing.Practical\nnutrient timing applications for the goal of muscle\nhypertrophy inevitably must be tempered with field\nobservations and experience in order to bridge gaps in\nthe scientific literature."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 62,
    "text": "With that said, high-quality pro-\ntein dosed at 0.4–0.5 g/kg of LBM at both pre- and\npost-exercise is a simple, relatively fail-safe general\nguideline that reflects the current evidence showing a\nmaximal acute anabolic effect of 20–40 g [53,84,85].For\nexample, someone with 70 kg of LBM would consume\nroughly 28–35 g protein in both the pre- and post exer-\ncise meal. Exceeding this would be have minimal detri-\nment if any, whereas significantly under-shooting or\nneglecting it altogether would not maximize the anabolic\nresponse.\nDue to the transient anabolic impact of a protein-rich\nmeal and its potential synergy with the trained state,\npre- and post-exercise meals should not be separated by\nmore than approximately 3–4 hours, given a typical re-\nsistance training bout lasting 45–90 minutes."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 63,
    "text": "If protein\nis delivered within particularly large mixed-meals (which\nare inherently more anticatabolic), a case can be made\nfor lengthening the interval to 5–6 hours.This strategy\ncovers the hypothetical timing benefits while allowing\nsignificant flexibility in the length of the feeding win-\ndows before and after training. Specific timing within\nthis general framework would vary depending on indi-\nvidual preference and tolerance, as well as exercise\nduration. One of many possible examples involving a 60-\nminute resistance training bout could have up to 90-\nminute feeding windows on both sides of the bout, given\ncentral placement between the meals."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 64,
    "text": "In contrast, bouts\nexceeding typical duration would default to shorter feed-\ning windows if the 3–4 hour pre- to post-exercise meal\ninterval is maintained.Shifting the training session\ncloser to the pre- or post-exercise meal should be dic-\ntated by personal preference, tolerance, and lifestyle/\nscheduling constraints.\nEven more so than with protein, carbohydrate dosage\nand timing relative to resistance training is a gray area\nlacking cohesive data to form concrete recommenda-\ntions. It is tempting to recommend pre- and post-\nexercise carbohydrate doses that at least match or\nexceed the amounts of protein consumed in these meals.\nHowever, carbohydrate availability during and after exer-\ncise is of greater concern for endurance as opposed to\nstrength or hypertrophy goals."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 65,
    "text": "Furthermore, the import-\nance of co-ingesting post-exercise protein and carbohy-\ndrate has recently been challenged by studies examining\nthe early recovery period, particularly when sufficient\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 8 of 11\nhttp://www.jissn.com/content/10/1/5\nprotein is provided.Koopman et al [52] found that after\nfull-body resistance training, adding carbohydrate (0.15,\nor 0.6 g/kg/hr) to amply dosed casein hydrolysate (0.3 g/\nkg/hr) did not increase whole body protein balance dur-\ning a 6-hour post-exercise recovery period compared to\nthe protein-only treatment."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 66,
    "text": "Subsequently, Staples et al\n[53] reported that after lower-body resistance exercise\n(leg extensions), the increase in post-exercise muscle\nprotein balance from ingesting 25 g whey isolate was not\nimproved by an additional 50 g maltodextrin during a 3-\nhour recovery period.For the goal of maximizing rates\nof muscle gain, these findings support the broader ob-\njective of meeting total daily carbohydrate need instead\nof specifically timing its constituent doses. Collectively,\nthese data indicate an increased potential for dietary\nflexibility while maintaining the pursuit of optimal\ntiming.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthors’ contribution\nAAA and BJS each contributed equally to the formulation and writing of the\nmanuscript."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 67,
    "text": "Both authors read and approved the final manuscript.\nAuthor details\n1California State University, Northridge, CA, USA.2Department of Health\nScience, Lehman College, Bronx, NY, USA.\nReceived: 20 December 2012 Accepted: 25 January 2013\nPublished: 29 January 2013\nReferences\n1.\nKerksick C, Harvey T, Stout J, Campbell B, Wilborn C, Kreider R, Kalman D,\nZiegenfuss T, Lopez H, Landis J, Ivy JL, Antonio J: International Society of\nSports Nutrition position stand: nutrient timing. J Int Soc Sports Nutr.\n2008, 5:17.\n2.\nIvy J, Portman R: Nutrient Timing: The Future of Sports Nutrition. North\nBergen, NJ: Basic Health Publications; 2004.\n3.\nCandow DG, Chilibeck PD: Timing of creatine or protein supplementation\nand resistance training in the elderly."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 68,
    "text": "Appl Physiol Nutr Metab 2008, 33\n(1):184–90.\n4.\nHulmi JJ, Lockwood CM, Stout JR: Effect of protein/essential amino acids\nand resistance training on skeletal muscle hypertrophy: A case for whey\nprotein.Nutr Metab (Lond). 2010, 7:51.\n5.\nKukuljan S, Nowson CA, Sanders K, Daly RM: Effects of resistance exercise\nand fortified milk on skeletal muscle mass, muscle size, and functional\nperformance in middle-aged and older men: an 18-mo randomized\ncontrolled trial. J Appl Physiol 2009, 107(6):1864–73.\n6.\nLambert CP, Flynn MG: Fatigue during high-intensity intermittent\nexercise: application to bodybuilding. Sports Med. 2002, 32(8):511–22.\n7.\nMacDougall JD, Ray S, Sale DG, McCartney N, Lee P, Garner S: Muscle\nsubstrate utilization and lactate production."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 69,
    "text": "Can J Appl Physiol 1999,\n24(3):209–15.\n8.\nRobergs RA, Pearson DR, Costill DL, Fink WJ, Pascoe DD, Benedict MA,\nLambert CP, Zachweija JJ: Muscle glycogenolysis during differing\nintensities of weight-resistance exercise.J Appl Physiol 1991, 70(4):1700–6.\n9.\nGoodman CA, Mayhew DL, Hornberger TA: Recent progress toward\nunderstanding the molecular mechanisms that regulate skeletal muscle\nmass. Cell Signal 2011, 23(12):1896–906.\n10.\nBodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R,\nZlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD: Akt/\nmTOR pathway is a crucial regulator of skeletal muscle hypertrophy and\ncan prevent muscle atrophy in vivo. Nat Cell Biol. 2001, 3(11):1014–9.\n11.\nJacinto E, Hall MN: Tor signalling in bugs, brain and brawn."
  },
  {
    "filename": "1550-2783-10-5.pdf",
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    "text": "J Am Coll Nutr 2004, 23(6 Suppl):631S–6S.\n78.\nNorton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ: The\nleucine content of a complete meal directs peak activation but not\nduration of skeletal muscle protein synthesis and mammalian target of\nrapamycin signaling in rats.J Nutr 2009, 139(6):1103–9.\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 10 of 11\nhttp://www.jissn.com/content/10/1/5\n79.\nWilson GJ, Layman DK, Moulton CJ, Norton LE, Anthony TG, Proud CG,\nRupassara SI, Garlick PJ: Leucine or carbohydrate supplementation\nreduces AMPK and eEF2 phosphorylation and extends postprandial\nmuscle protein synthesis in rats."
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    "text": "Am J Physiol Endocrinol Metab 2011,\n301(6):E1236–42.\n80.\nAtherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K,\nRennie MJ: Muscle full effect after oral protein: time-dependent\nconcordance and discordance between human muscle protein synthesis\nand mTORC1 signaling.Am J Clin Nutr 2010, 92(5):1080–8.\n81.\nBohe J, Low JF, Wolfe RR, Rennie MJ: Latency and duration of stimulation\nof human muscle protein synthesis during continuous infusion of amino\nacids. J Physiol 2001, 532(Pt 2):575–9.\n82.\nBurd NA, Tang JE, Moore DR, Phillips SM: Exercise training and protein\nmetabolism: influences of contraction, protein intake, and sex-based\ndifferences."
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    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
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    "text": "J Appl Physiol 2009, 106(5):1692–701.\n83.\nBreen L, Phillips SM: Interactions between exercise and nutrition to\nprevent muscle waste during aging.Br J Clin Pharmacol 2012."
  },
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    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 92,
    "text": "doi:10.1111/\nj.1365-2125.2012.04456.x [Epub ahead of print].\n84.\nMoore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T,\nTarnopolsky MA, Phillips SM: Ingested protein dose response of muscle\nand albumin protein synthesis after resistance exercise in young men.\nAm J Clin Nutr 2009, 89(1):161–8.\n85.\nYang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR,\nTarnopolsky MA, Phillips SM: Resistance exercise enhances myofibrillar\nprotein synthesis with graded intakes of whey protein in older men.\nBr J Nutr 2012, 108(10):1780–8.\ndoi:10.1186/1550-2783-10-5\nCite this article as: Aragon and Schoenfeld: Nutrient timing revisited: is\nthere a post-exercise anabolic window?."
  },
  {
    "filename": "1550-2783-10-5.pdf",
    "pdf_title": "Nutrient timing revisited: is there a post-exercise anabolic window?",
    "chunk_id": 93,
    "text": "Journal of the International\nSociety of Sports Nutrition 2013 10:5.\nSubmit your next manuscript to BioMed Central\nand take full advantage of: \n• Convenient online submission\n• Thorough peer review\n• No space constraints or color figure charges\n• Immediate publication on acceptance\n• Inclusion in PubMed, CAS, Scopus and Google Scholar\n• Research which is freely available for redistribution\nSubmit your manuscript at \nwww.biomedcentral.com/submit\nAragon and Schoenfeld Journal of the International Society of Sports Nutrition 2013, 10:5\nPage 11 of 11\nhttp://www.jissn.com/content/10/1/5"
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 0,
    "text": "Vol.:(0123456789)\nSports Medicine (2022) 52:25–36 \nhttps://doi.org/10.1007/s40279-021-01572-0\nREVIEW ARTICLE\nIs there Evidence for the Suggestion that Fatigue Accumulates \nFollowing Resistance Exercise?\nRyo Kataoka1 · Ecaterina Vasenina1 · William B. Hammert1 · Adam H. Ibrahim1 · Scott J. Dankel2 · \nSamuel L. Buckner1 \nAccepted: 18 September 2021 / Published online: 6 October 2021 \n© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021\nAbstract\nIt has been suggested that improper post-exercise recovery or improper sequence of training may result in an ‘accumulation’ of \nfatigue. Despite this suggestion, there is a lack of clarity regarding which physiological mechanisms may be proposed to con-\ntribute to fatigue accumulation."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 1,
    "text": "The present paper explores the time course of the changes in various fatigue-related measures \nin order to understand how they may accumulate or lessen over time following an exercise bout or in the context of an exercise \nprogram.Regarding peripheral fatigue, the depletion of energy substrates and accumulation of metabolic byproducts has been \ndemonstrated to occur following an acute bout of resistance training; however, peripheral accumulation and depletion appear \nunlikely candidates to accumulate over time. A number of mechanisms may contribute to the development of central fatigue, \npostulating the need for prolonged periods of recovery; however, a time course is difficult to determine and is dependent on \nwhich measurement is examined."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 2,
    "text": "In addition, it has not been demonstrated that central fatigue measures accumulate over time.\nA potential candidate that may be interpreted as accumulated fatigue is muscle damage, which shares  similar characteristics \n(i.e., prolonged strength loss). Due to the delayed appearance of muscle damage, it may be interpreted as accumulated fatigue. \nOverall, evidence for the presence of fatigue accumulation with resistance training is equivocal, making it difficult to draw \nthe conclusion that fatigue accumulates. Considerable work remains as to whether fatigue can accumulate over time. Future \nstudies are warranted to elucidate potential mechanisms underlying the concept of fatigue accumulation.\n *\t Samuel L."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 3,
    "text": "Buckner \n\t\nslbuckner@usf.edu\n1\t\nUSF Muscle Lab, Exercise Science Program, University \nof South Florida, 4202 E.Fowler Ave."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 4,
    "text": "PED 214, Tampa, \nFL 33620‑8600, USA\n2\t\nExercise Physiology Laboratory, Department of Health \nand Exercise Science, Rowan University, Glassboro, NJ, \nUSA\nKey Points \nThe concept of long-term fatigue accumulation has \nappeared repeatedly in the literature without clear \nelucidation of what is accumulating and how/why this is \noccurring.\nDue to the delayed appearance of muscle damage, it may \nbe interpreted as accumulated fatigue.\nInsufficient evidence exists on the presence of fatigue \naccumulation following resistance training, and future \nstudies are warranted to elucidate potential mechanisms \nunderlying the concept of fatigue accumulation.\n1  Introduction\nFatigue is a complex and multifactorial phenomenon and \nmuch is still unknown about why an individual becomes \nfatigued under various exercise conditions [1]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 5,
    "text": "Research on \nresistance training is no exception, as mechanisms underly-\ning fatigue following resistance exercise have not been fully \ndelineated [2].While a number of definitions of fatigue \nhave been proposed [1, 3–5], a common tenet indicates that \nfatigue is the failure to maintain the required or expected \nforce-generating capacity in response to voluntary effort. \nDuring resistance exercise, the extent of fatigue may be \ndependent on the level of effort [6], type of exercise selec-\ntion [7], degree of active muscle mass [8], or volume of \ntraining [9]. Taking into consideration other variables such \nas sleep [10] and stress [11], the rate of recovery may dic-\ntate the readiness for the subsequent workout."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 6,
    "text": "Although \nless recovery time between each resistance training ses-\nsion (i.e., < 24 h between sessions vs. < 48–72 h between \nsessions) may not necessarily cause negative outcomes in \nmuscle growth and strength within a short period of time \n(i.e., 12 weeks) [12], it has been suggested that improper \n26\n\t\nR. Kataoka et al.\npost-exercise recovery or sequence of training may result \nin an increase in accumulated fatigue [13, 14].\nThe concept of long-term fatigue accumulation has \nappeared repeatedly in the literature without clear eluci-\ndation of what is accumulating and how/why this is occur-\nring [13–19].Fatigue accumulation refers to the fatigue \nthat summates over repeated bouts of training that is \nbelieved to be additive to pre-existing fatigue."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 7,
    "text": "Regardless \nof the lack of clarity on physiological aspects, the idea \nhas been explained conceptually using the fitness-fatigue \nmodel originally proposed by Banister et al.[20]. This \nmodel is postulated as a way of explaining the interac-\ntion between two after-effects—fitness and fatigue—that \nmay result from training. Fitness after-effect causes a posi-\ntive physiological response that increases performance, \nwhereas fatigue after-effect causes a negative physiologi-\ncal response that adversely influences performance. The \nfitness gain resulting from training is suggested to be \nmoderate in magnitude but long-lasting (i.e., increases \nin muscle strength), while the fatigue effect is large in \nmagnitude with a brief duration (i.e., reduction in force-\ngenerating capacity) [14, 21]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 8,
    "text": "Consequently, the differ-\nence between these two antagonist effects is believed to \ndescribe performance and state of preparedness (prepar-\nedness = fitness − fatigue).Based on the assumption that \nfatigue would accumulate over the course of training [22], \nthe concept is often reflected in the training structure (i.e., \nmesocycle) by creating a discrete period of deload (i.e., \nreduction in training volume and/or load). In addition, a \ntapering strategy is often structured in training to create \na period of reduced training volume and/or load prior to \na competition to express an athlete’s current level of fit-\nness by dissipating fatigue [18, 23, 24]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 9,
    "text": "Mujika and Padilla \nhave proposed that athletes who undergo tapering should \nachieve the expected improved performance level once \naccumulated fatigue fades away [23].Of note, an increase \nin the testosterone/cortisol ratio during the taper has been \nsuggested as one of the indices of enhanced recovery and \nelimination of accumulated fatigue [23, 25]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 10,
    "text": "However, the \nendocrine responses to resistance training remain unclear \ndue to the variability of the measurement results [26, 27].\nWhile several mathematical models have been proposed \nto quantify the training and performance relationship [28, \n29], the commonly used fitness-fatigue equation presents \nthat (Eq. 1) [30, 31]:\nwhere p(t) is the performance at time t; p (0) is the ini-\ntial performance level; k1 and k2 are the fitness and fatigue \nmagnitude factors, respectively (i.e., how the training load \nimpacts the fitness and fatigue effect on performance); τ1 and \n(1)\nP(t) = p(0) + k1\nt−1\n∑\ns=0\ne\n−t−s\nτ1 ⋅w(s) −k2\nt−1\n∑\ns=0\ne\n−t−s\nτ2 ⋅w(s),\nτ2 are the fitness and fatigue decay time constant, respec-\ntively; and w is the known training load per week (or day) \nfrom the first week of training to the week (or day) preceding \nthe performance."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 11,
    "text": "These parameters are interpreted as indi-\nvidual response profiles, and the mathematical model may \npredict the effects of training on physical capability [30, 32].\nFurthermore, the model suggests that fatigue has a \ncumulative effect, and when fatigue accumulates to the \npoint where fatigue after-effects significantly exceed fit-\nness after-effects (i.e., depletion of the individual’s adap-\ntive abilities), overtraining occurs [14].Although the \nmodel may conceptually give some insights, the criticism \nhas been made in regard to the discrepancies between the \npredicted and measured time course of physiological adap-\ntations [32]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 12,
    "text": "Thus, it seems that there is a gap between \nthe model and the underlying physiology, certainly with \nregard to the physiological aspects of fatigue accumulation \n(i.e., what is accumulating and how/why is this occurring).\nCurrently, the majority of investigations on fatigue or over-\ntraining have been conducted in aerobic-oriented activi-\nties [33–36]. Furthermore, the mechanisms that underlie \novertraining in resistance exercise largely remain uncertain \n[17], and further investigation on this mode of training is \nwarranted."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 13,
    "text": "Therefore, the purpose of this review was to \nevaluate the time course of the changes in various fatigue \nmeasures in response to resistance exercise with an aim \nto elucidate some of the potential mechanisms that may \ncontribute to accumulating fatigue in resistance training.\n2  \u0007Types of Fatigue\nOne of the most well-accepted models for explaining the \ncauses of neuromuscular fatigue involves the concept of \ntask dependency.The task dependency model of muscle \nfatigue implies that the cause of the fatigue is dependent \non characteristics of the exercise that is being performed, \nmeaning that dominant fatigue-inducing mechanisms \ninvolved in limiting performance may differ in various \nconditions [37]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 14,
    "text": "Although the specificity of the impair-\nments that contribute to the development of muscle fatigue \n(i.e., contraction mode, muscles involved, type of exer-\ncise) [38] and the approaches to study fatigue (i.e., muscle \nin vivo, isolated muscle, isolated single fiber) [39] would \nmake a causal mechanism of muscle fatigue difficult to \ndecipher, it has been suggested that the mechanisms under-\nlying fatigue can be of central or peripheral origin [40].\nIn essence, central fatigue occurs proximal to the neuro-\nmuscular junction (i.e., within the motor neurons and cen-\ntral nervous system), whereas peripheral fatigue includes \nthe neuromuscular junction and muscle fibers themselves \n[39, 41, 42]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 15,
    "text": "As proposed in the task dependency model, \nthe cause of fatigue is dictated by the characteristics of \n27\nFatigue Accumulation with Training\nthe exercise task that is being performed.For example, \nperipheral fatigue contributes relatively more to maximum \nvoluntary contraction (MVC) reduction during short, high-\nintensity exercise, and central fatigue contributes relatively \nmore during longer duration, moderate-intensity exercise \n[40]. In resistance training, a different acute neuromus-\ncular fatigue profile was observed between a maximal \nstrength loading protocol (15 sets of 1 repetition maxi-\nmum) and a hypertrophic loading protocol (5 sets of 10 \nrepetition maximum) [43]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 16,
    "text": "The results indicated that the \nhypertrophic loading protocol resulted in greater losses in \npost-loading maximum isometric force accompanied by \nreduced neuromuscular efficiency (force/electromyography \n[EMG] amplitude), reduced median frequency, and main-\ntained EMG amplitude, which was related to the greater \ndegree of peripheral fatigue [43].On the other hand, a \nmaximal strength loading protocol led to decreased con-\ncentric and isometric force in conjunction with reduced \nEMG amplitude and maintained median frequency [43]. \nBased on the lack of change in median frequency, the \nauthors speculated that the same motor units were active \nthroughout the exercise protocol."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 17,
    "text": "Furthermore, when con-\nsidering the decrease in concentric and eccentric EMG \namplitudes, the authors suggested that a reduction in fir-\ning frequency may occur as a consequence of maximal \nstrength loading.The difference in the degree of peripheral \nfatigue during these loadings may imply that there were \ndifferent neuromuscular responses between conditions \n[44]. Within the scope of complexities that cause fatigue, \nsubsequent sections will discuss the potential mechanisms \nof neuromuscular fatigue to present knowledge of the \nperipheral and central factors of muscle fatigue that are \nrelated to resistance exercise."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 18,
    "text": "In addition, the time course \nof the changes in fatigue phenomenon will be evaluated to \nhelp determine whether fatigue ‘accumulates’ over time.\n3  \u0007Peripheral Fatigue\nPotential sites of peripheral fatigue occur in the peripheral \nnerve, neuromuscular junction, muscle cell membrane, \ncalcium release machinery, and sliding filaments [41, 42].\nWithin these structures, perturbations of neuromuscular \ntransmission, propagation of the muscle action potential, \nexcitation–contraction coupling, and contractile mecha-\nnisms correspond to the decline in tension development [39, \n41, 45]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 19,
    "text": "In regard to the mechanisms underlying peripheral \nfatigue, it has been proposed that fatigue could be due to \nthe depletion of energy substrates or to the accumulation of \nmetabolites [42].\n3.1  \u0007Depletion Hypothesis\nThe depletion or exhaustion hypothesis largely involves \nthe depletion of energy substrates: phosphagens (adeno-\nsine triphosphate [ATP] and phosphocreatine) and skeletal \nmuscle glycogen [42].In the broad sense, fatigue can be \nviewed as the net balance between the ATP utilization of \nmuscle cells and their ATP-resynthesizing capacity. Since \nthere is a limited supply of readily available intramuscular \nATP stores, a sustained contractile activity is hindered for an \nextended period of time [46]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 20,
    "text": "Thus, to prevent muscle fibers \nfrom exhausting their ATP stores, other metabolic pathways, \nsubstrate-level phosphorylation (or anaerobic) and oxida-\ntive phosphorylation (aerobic), must be activated to produce \nATP.ATP resynthesis that is predominantly involved in \nintense anaerobic exercise includes the breakdown of phos-\nphocreatine and glycogen. These ATP-generating pathways \nhave a greater rate of ATP production with a smaller capac-\nity (total ATP produced) compared with aerobic pathways \n[46]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 21,
    "text": "Although it is less studied relative to aerobic and other \nanaerobic activities, it has been demonstrated that deple-\ntion of muscle phosphocreatine and glycogen plays a role, \nin some part, in inducing fatigue during resistance exercise \n[47, 48].\nPhosphocreatine is the high-energy phosphagen that pro-\nvides the immediate energy in the initial stages of intense \nexercise by donating its phosphate molecule to adenosine \ndiphosphate to resynthesize ATP [49].During resistance \nexercise, it has been reported that the concentration of \nphosphocreatine is significantly depleted at the point of \nfatigue [48]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 22,
    "text": "For instance, when resistance-trained individu-\nals performed either one or three sets of a biceps exercise \nto failure at 80% of one-repetition maximum (1RM), the \nphosphocreatine concentration was lower by a mean value \nof 62% in the 1-set group and 50% in 3-sets group [48].The \nfact that performing 3 sets did not lead to greater deple-\ntion of phosphocreatine indicated that the 3 min rest period \nbetween sets was long enough to restore phosphocreatine. \nIn line with this finding, sustaining isometric contraction \nat 66% of MVC until force declined to approximately 50% \nof MVC resulted in a rapid recovery of phosphocreatine \nresynthesis [50]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 23,
    "text": "It was reported that approximately 67% of \nphosphocreatine was restored following 2 min of recovery \nand approximately 84% of phosphocreatine was recovered \nafter 4 min of recovery, demonstrating that the majority of \nresynthesis completed immediately after the exercise [50].\nSimultaneously, as the stores of available phospho-\ncreatine deplete, the rate of ATP regeneration from the \nbreakdown of glycogen will be augmented.Skeletal mus-\ncle glycogen is the major readily available energy source \nthat plays a role in muscular contractile activity, demon-\nstrated by the inability to sustain a high-intensity exercise \nwhen glycogen stores are depleted [51]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 24,
    "text": "Glycogen is also \n28\n\t\nR. Kataoka et al.\ndifferently distributed within a muscle and is located in the \nsubsarcolemmal region, intermyofibril, and intramyofibril, \nwith possible distinct functions [52].It has been suggested \nthat glycogen located between the myofibrils close to the \nlongitudinal sarcoplasmic reticulum (intermyofibrillar gly-\ncogen) powers the release of sarcoplasmic stored calcium \n­(Ca2+) and activates tropomyosin binding sites, whereas \nthe glycogen located inside the myofibrils (intramyofibril-\nlar glycogen) is preferably depleted during high-intensity \nexercise and plays a role in excitability and/or sarcoplasmic \nreticulum ­Ca2+ release properties [53, 54]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 25,
    "text": "It is generally \naccepted that impaired sarcoplasmic reticulum ­Ca2+ release \nis a major factor in fatigue after performing exercise due to \ndisruptions of the excitation–contraction coupling process \n[39].Furthermore, one of the relevant potential mechanisms \ninvolving a glycogenolytic complex is associated with the \nsarcoplasmic reticulum. This was portrayed in the work of \nØrtenblad et al., who reported that the depletion of glyco-\ngen during exhausting exercise was associated with impaired \nmuscle ability to release sarcoplasmic reticulum ­Ca2+ [55]. \nWhile the reduction in muscle glycogen may be dictated by \nthe duration, intensity, and volume of performed exercise, \na typical resistance exercise bout has been shown to reduce \nglycogen levels by approximately 25–40% [47, 48, 56–58]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 26,
    "text": "For instance, Hokken et al.reported that muscle glycogen \ndecreased by 38% when 10 male weightlifters performed \nresistance exercises consisting of four sets of five repetitions \n(4 × 5) at 75% of 1RM back squats, 4 × 5 at 75% of 1RM \ndeadlifts, and 4 × 12 at 65% of 1RM rear foot elevated squats \n[57]. Although skeletal muscle glycogen can be resynthe-\nsized with no calorie/carbohydrate (CHO) intake during the \npost-workout period [59], immediate provision of CHO to \nthe muscle cell is recommended to initiate effective refueling \nas glycogen depletion provides a strong drive for its own \nenhanced resynthesis rates during the early phase (0–4 h) \nafter exercise [60]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 27,
    "text": "When 1.5 g CHO/kg body weight was \ningested immediately after and 1 h after the resistance exer-\ncise, the muscle glycogen content was restored to 91% of the \npre-exercise level following 6 h of training bout [56].Similar \nresults were reported by Roy and Tarnopolsky in which the \nrate of muscle glycogen synthesis was significantly higher \nat a dose of 1 g CHO/kg body weight over the first 4 h of \nthe recovery period compared with a placebo group [58]. \nThe glycogen resynthesis and degradation rates following \nresistance exercise may range from 1.9 to 11.1 mmol/kg/h \nand 40.6 to 46.9 mmol/kg wet weight, respectively [56, 59]. \nA complete glycogen restoration might occur within 4–5 h \nif glycogen depletion is only around 40 mmol/kg wet weight \nand sufficient CHO is provided [61]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 28,
    "text": "If glycogen depletion \nis 150 mmol/kg wet weight following resistance training \n[57], a complete glycogen restoration might take up to 24 h, \nwith the maximal glycogen resynthesis rates occurring after \nexercise (10 mmol/kg/h) for 4 h and a mean glycogen storage \nrate of 4–6 mmol/kg/h [60, 61].Taken together, the con-\nsideration of the time course of glycogen resynthesis may \nbe particularly important for an individual who undertakes \nmultiple training sessions within the same day (i.e., < 12 h \nrecovery from the first session). To summarize, resistance \nexercise predominantly involves the breakdown of muscle \nphosphocreatine and glycogen to sustain ATP resynthesis."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 29,
    "text": "The depletion of phosphocreatine and glycogen plays a role \nin inducing fatigue during resistance exercise, yet the time \ncourse of depletion appears to be short-lived.For muscle \nphosphocreatine, the majority of resynthesis occurs immedi-\nately after the completion of exercise. Similarly, the greater \npart of the recovery of glycogen storage takes place within \na 24-h period.\n3.2  \u0007Accumulation Hypothesis\nThe accumulation hypothesis relates to the build-up of a \nnumber of metabolites within muscle fibers [42]. Although \nnot exhaustive, two end products of anaerobic metabo-\nlism, hydrogen ion ­(H+) and inorganic phosphate ­(Pi), have \nreceived the most attention in this regard [62–65]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 30,
    "text": "In the \ncontext of the accumulation hypothesis, if fatigue accumu-\nlates in response to resistance exercise, potential scenarios \nwould be that either the exercise-induced metabolic byprod-\nucts accumulate acutely but dissipate shortly after training, \nor the exercise-induced metabolic byproducts accumulate \nacutely and also exacerbate over time (prolonged accumu-\nlation of metabolic byproducts).Indeed, if the latter case \nis supported, it may serve as a partial explanation for the \npurported fatigue accumulation that may cause prolonged \nimpairments in muscular function. Intense muscular contrac-\ntion creates an increased intramuscular pressure condition \nthat causes a partial occlusion of the blood flow [66, 67]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 31,
    "text": "Accordingly, impairment of oxygen availability may result \nin a more rapid accumulation of metabolites and interference \nin contractile function (i.e., cross-bridge cycling) [68, 69].\nWhen considering the major potential sites of peripheral \nfatigue, including sarcolemma excitability, excitation–con-\ntraction coupling, contractile mechanisms, metabolic energy \nsupply, and metabolic accumulation, a diminished contrac-\ntile function corresponding to the decline in tension develop-\nment may occur if any of these sites are disrupted by intense \nmuscular contractions [70]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 32,
    "text": "Muscle contractions depend on \nelectrical excitation of the muscle fibers in such a way that \nneuromuscular transmission initiates an action potential \nand propagates along the sarcolemma, leading each action \npotential to an efflux of potassium ­(K+) (i.e., an increase in \nextracellular ­K+) [39, 71].As such, alternation in excitabil-\nity at the sarcolemma might be the site of fatigue due to the \ninability to maintain electrical gradients (sodium ­[Na+] and \n­K+) during repeated stimulation [39]. When ­K+ channels \nopen up due to a drop in ATP concentration, ­K+ floods out \n29\nFatigue Accumulation with Training\nand causes an extracellular ­K+ accumulation and depolarizes \nthe cell membrane, which in turn inactivates the ­Na+ chan-\nnel and reduces membrane excitability [72, 73]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 33,
    "text": "This may \nreduce the action potential of the T-tubules and limit ­Ca2+ \nrelease from the sarcoplasmic reticulum [39, 45].However, \nunder normoxic conditions, the ­K+ channels do not seem \nto contribute significantly to the decrease in force during \nfatigue [73].\nOther potential sites of peripheral fatigue include the \ncross-bridge’s ability to ‘cycle’. The cross-bridge cycle is \ninitiated with a sequence of events leading to the release of \n­Ca2+ from the sarcoplasmic reticulum [74]. Thus, at the cel-\nlular level, force production may depend on (1) the concen-\ntration of ­Ca2+ surrounding the myofilaments; (2) the ­Ca2+ \nsensitivity of the myofilaments; and (3) the maximum ­Ca2+ \nactivated force (force produced by the cross-bridge) [4]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 34,
    "text": "In \nthe case of fatigue associated with ­H+, accumulation of ­H+ \nresulting from ATP catabolism and glycolysis has shown a \ncorrelation between the extent of acidosis (increase in ­H+) \nand impairment in contractility [63].Specifically, acidosis \ncaused by elevated ­H+ (reduced intracellular pH) has been \nproposed to induce fatigue by suppressing myofibrillar ­Ca2+ \nsensitivity [75]. Furthermore, the elevated ­H+ reduces the \naffinity of the binding sites on troponin C [76], and indirectly \nimpairs contractile function by inhibiting the key glycogeno-\nlytic enzyme activities such as phosphorylase [51]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 35,
    "text": "However, \nthe role of ­H+ in fatigue is the current topic of debate as to \nwhether ­H+ plays a central role in skeletal muscle fatigue \n[77, 78] since the effect of acidosis on reduced maximum \nshortening velocity of mammalian muscle has been shown \nto be small at physiological temperature (i.e., 30 °C) [79].\nThe time course of changes in the accumulation of ­H+ is also \nacute in nature, as Degroot et al. reported that the clearance \nof ­H+ was mostly completed in the first 15 min following a \nmaximal isometric foot plantar flexion sustained for 4 min \n[64]. The authors further noted the dissociation between \nchanges in pH and MVC at the onset of both exercise and \nrecovery, suggesting that ­H+ might not be a primary regula-\ntor of muscle fatigue [64]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 36,
    "text": "In addition, resistance training \nappears to improve muscle ­H+ regulatory capacity over time.\nIt was found that bodybuilders who performed static hand-\ngrip exercise at 30% of MVC had significantly less ­H+ accu-\nmulation (attenuated pH response) compared with untrained \nindividuals [80]. Taken together, these findings suggest that \nintracellular accumulation of ­H+ per se may not be a major \ncontributor to muscle fatigue.\nBy the same token, during high-intensity exercise, the \nconcentration of ­Pi increases due to the breakdown of phos-\nphocreatine [63]. This can occur rapidly with maximum acti-\nvation, and ­Pi accumulation contributes to the changes in \ncross-bridge behavior."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 37,
    "text": "According to the current cross-bridge \naction model, ­Pi is released in the transition from a weakly \nbound (low-force) state to a strongly attached (high-force) \nstate at the actin-myosin binding sites.This indicates that the \ntransition to the high-force cross-bridge states is hindered \nby increased ­Pi, and force production would decrease as a \nconsequence of fewer cross-bridges in high-force states [74, \n81]. Furthermore, the rise in ­Pi induces fatigue by acting \non sarcoplasmic reticulum ­Ca2+ handling. The amount of \n­Ca2+ released from the sarcoplasmic reticulum is reduced \nwhen ­Pi diffuses from the myoplasm into the sarcoplas-\nmic reticulum through a ­Pi permeable channel and binds \nto ­Ca2+ to form calcium phosphate ­(CaPi) [4, 69]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 38,
    "text": "Similar \nto the discussion on ­H+, the time course of recovery from \naccumulated ­Pi completes quickly.To illustrate, Baker et al. \ncompared two exercise protocols that produced similar lev-\nels of moderate fatigue, to examine the role of metabolic \nand non-metabolic factors [65]. The short-duration exer-\ncise (SDE) group consisted of 2 min of sustained MVC of \nthe ankle dorsiflexor muscles with blood flow restriction \n(anaerobic exercise), and the long-duration exercise (LDE) \ngroup performed 15–20 min of intermittent ankle dorsiflex-\nion exercise without applying blood flow restriction (aerobic \nexercise)."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 39,
    "text": "The major finding of the study was that for SDE, \nfatigue correlated with increased inorganic phosphate, and, \nimportantly, both force and inorganic phosphate recovered \nwithin 5 min following exercise.For LDE, recovery of \nforce took over 15 min following exercise, but the recovery \nof inorganic phosphate was not slowed (recovered within \n5 min). Thus, the results of the study indicated that fatigue \ncaused by short-duration anaerobic exercise might be more \ndue to a metabolic inhibition of the contraction, whereas \nthe fatigue caused from long-duration aerobic exercise may \ninvolve a contribution from non-metabolic factors, such as \nan impaired excitation–contraction coupling [65]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 40,
    "text": "In closing, \nthe data on the accumulation hypotheses suggest that the \nbuild-up of two end products of anaerobic metabolism, ­H+ \nand ­Pi, may only last a short period of time (i.e., < 1 h), cor-\nresponding to acute fatigue within a single training session.\n4  \u0007Central Mechanisms of Fatigue\nExercise-induced reductions in maximal voluntary force \ncannot be solely explained by the mechanisms related to \nperipheral fatigue.This is illustrated by the coexistence of \ncentral and peripheral fatigue during resistance exercise [82, \n83]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 41,
    "text": "For example, when the magnitude of both central and \nperipheral fatigue was measured following 10 sets of 5 rep-\netitions of the high bar back squat at 80% of 1RM, the reduc-\ntion in voluntary activation (indicative of central fatigue) \nand twitch force (indicative of peripheral fatigue) persisted, \nwith a faster recovery of central compared with peripheral \nfatigue [83].Thus, part of exercise-induced fatigue is related \nto modifications within the central aspects. Any breakdown \nin muscular activation within the motor neurons and central \n30\n\t\nR. Kataoka et al.\nnervous system is generally considered central, and central \nfatigue is the degradation of the muscle voluntary activation \nattributed to a decline in motoneuronal output [84]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 42,
    "text": "A num-\nber of mechanisms may contribute to the development of \ncentral fatigue, such as inhibition of motoneuron excitability \nby afferent feedback from the muscle (i.e., groups III and IV \nmuscle afferents), a decline in motor neuron firing rate, and \na reduction in the number of motor units recruitment [85, \n86].Notably, peripheral factors are also implicated in central \nfatigue. During muscle contraction, the group III and IV \nafferent nerve fibers contribute to motor command and sense \nboth mechanical and metabolic stimuli, respectively [87]. \nAccordingly, information about contractile events at the \nperiphery is delivered to the central nervous system, lead-\ning to altered efferent output."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 43,
    "text": "Of note, release of cytokines, \nespecially interleukin (IL)-6, has been suggested to initiate \nafferent signals to the brain during exercise, and may con-\ntribute to feelings of fatigue and decreased efferent drive to \nthe muscles [88].Ultimately, a feedback loop from group III \nand IV nerve fibers to the central nervous system potentially \nleads to (1) a decrease in the firing frequency of the motor \nneuron; (2) an inhibition or facilitation of the motor neuron; \nand/or (3) an inhibition of the motor cortex neuron [41]. \nThe extent of central fatigue that appears after resistance \nexercise may be dictated by factors such as the type of exer-\ncise [7] and intensity of the load [89]. For instance, Yoon \net al."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 44,
    "text": "demonstrated that a low-force contraction using 20% of \nMVC induced greater central fatigue than a high-force con-\ntraction using 80% of MVC for both men and women when \nexercising to task failure [89].The authors suggested that \nthe difference in voluntary activation likely resulted from \na reduced descending drive and excitability of the motor \nneuron pool at spinal sources for the low-force contraction. \nThe finding that low-load training elicited greater central \nfatigue than a high-load condition was also illustrated by \nFarrow et al., who compared the fatigue responses to low- \nand high-load dynamic knee extension exercise (40% and \n80% MVC, respectively) to momentary failure in both an \nexercised and non-exercised limb [90]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 45,
    "text": "It was demonstrated \nthat low-load exercise induced greater fatigue in both exer-\ncised and non-exercised limbs compared with the high-load \ngroup.A presence of greater fatigue found in the non-exer-\ncised leg indicates that central mechanisms predominately \nmediated the exercise-induced fatigue produced by low-load \nexercise. The authors suggested that performing low-load \ntraining accompanied with a longer time under load likely \nresulted in greater acto-myosin cross-bridge cycling and a \ngreater accumulation of metabolites, leading to a greater \ninfluence of group III/IV afferent motor unit firing rates and \nthe need for greater central motor command [90].\nCentral fatigue can be quantified as voluntary activation, \nas estimated using twitch interpolation during an MVC [91]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 46,
    "text": "In essence, the additional force elicited by supramaximal \nelectrical stimulation is delivered to a nerve or muscle during \na voluntary contraction, and, correspondingly, an increase in \nthe amplitude of the interpolated twitch during maximal efforts \nis established as evidence of decreasing voluntary drive that is \ndemonstrative of central fatigue [92].Transcranial magnetic \nstimulation (TMS) can also investigate the human motor cor-\ntex by measuring corticospinal excitability with motor evoked \npotentials (MEPs), which are used to evaluate the existence of \ncentral fatigue [82]. Here, an important consideration is the \ndiscrepancy in the time course of central fatigue with different \ntypes of measurement. For example, Latella et al."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 47,
    "text": "conducted \nan acute training study where participants completed a single \nsession of heavy strength training of the biceps curl (5 sets \nof 3 repetitions maximum).Acute changes in corticospinal \nexcitability were measured, and MEP response from TMS \nshowed an immediate reduction in corticospinal excitability, \nwhich returned to baseline in 30 min [93]. While studies have \ndemonstrated that the changes in cortical excitability may \nnot necessarily be the direct cause of central fatigue [94], the \ndevelopment of central fatigue is accompanied by changes in \nthe excitability of the motor cortex [84]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 48,
    "text": "Conversely, unlike the \nreduction in corticospinal excitability which returned to base-\nline within 1 h, a reduction in voluntary activation persisted \nfor 48 h when a heavy resistance exercise session of the back \nsquat (10 sets of 5 repetitions at 80% of 1RM) was performed \n[83].Prasartwuth et al. also noted that voluntary activation \nwas impaired for more than 24 h after eccentric exercise when \nmeasured with motor nerve stimulation, but when assessed \nwith TMS, there was only a trend toward a decline in vol-\nuntary activation immediately after eccentric exercise [95]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 49,
    "text": "The authors posited that reduced voluntary activation seemed \nto contribute to the force loss in the first 24 h after eccentric \nexercise, and this may be attributed to inhibition in the motor \ncortex and/or the motor neurons.Besides the limitations of \nmeasurement [92], these results illustrate that the discrepan-\ncies of time course changes of central fatigue may in part be \nexplained by the methodologies employed to measure central \nfatigue. As such, different types of measurements provide var-\nied information about the limits of voluntary drive to mus-\ncles, and the postulate that central fatigue requires prolonged \nrecovery may be an oversimplification. Furthermore, the time \ncourse in the recovery of central fatigue may be positively \nmodified in the long-term."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 50,
    "text": "When examined with an isoki-\nnetic dynamometer, it has been demonstrated that a repeated \nbout of eccentric training elicited a faster recovery period of \nreduced voluntary activation compared with the initial bout of \neccentric exercise [96].The authors noted a modification in \nneural drive (i.e., motor corticospinal drive) and an attenuated \ndegree of supraspinal fatigue following the repeated bout of \nexercise, suggesting that a protective mechanism following a \nrepeated bout of damaging exercise (repeated bout effect) may \nbe partly explained by a modification in the central nervous \nsystem [96]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 51,
    "text": "Nonetheless, the common assessment of central \n31\nFatigue Accumulation with Training\nfatigue only involves a single bout of exercise [82, 83, 89, 97] \nand the question remains as to whether long-term repeated \nexposures of resistance exercise (i.e., in the form of dynamic \nor isotonic exercise) accumulate or exacerbate central fatigue \nover time.Even when individuals experience central fatigue, \na smaller relative contribution of central-mediated fatigue \ncompared with peripheral-mediated fatigue during voluntary \ncontractions also raises concerns regarding the relevance of \ncentral factors in fatigue accumulation."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 52,
    "text": "Acutely, a larger part \nof the force reduction seems to be attributed to peripheral fac-\ntors (i.e., 89%) [97], and the reduction in voluntary drive is \ntypically low (i.e., 20%) [98], suggesting a minor influence on \nmuscle fatigue.Furthermore, a model simulating motor unit \nfiring behavior and muscle force during MVC that involves \nonly peripheral factors of muscle fatigue was able to explain \nthe modifications in force behavior commonly attributed to \ncentral fatigue [92]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 53,
    "text": "This is not to refute the concept of central \nfatigue but presents data that raise important concerns about \nthe discrepancy in the time course of central fatigue with dif-\nferent types of measurement, and interpretation of central \nfatigue in relation to the contribution of accumulated fatigue.\n5  \u0007Complexity of Interpreting Prolonged \nImpairments of Muscle Function\nThe different states of preparedness within training have \nbeen described as overreaching or overtraining."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 54,
    "text": "The former \nis defined as an accumulation of training and/or non-training \nstress resulting in a short-term decrement in performance \ncapacity with or without related symptoms of maladaptation, \nwhereas the latter is defined as an accumulation of training \nand/or non-training stress resulting in a long-term decrement \nin performance capacity with or without related symptoms \nof maladaptation [35].The process of recurrent training \nleading to overreaching and/or overtraining is often viewed \nas a continuum where overreaching is believed to precede \novertraining if high levels of training persist and/or recovery \nis inadequate [99], yet the overtraining continuum may be an \noversimplification [17, 100]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 55,
    "text": "Indeed, a substantial amount of \nwork is required to elicit overtraining in a controlled scien-\ntific setting for resistance exercise (i.e., 10 sets of 1 repeti-\ntion at 100% 1RM, every day for 2 weeks) [101–103], and \nmany studies have not followed up the length of recovery \nand time course of changes in physical performance, which \nmakes it challenging to investigate the manifestation of over-\ntraining [27, 104, 105].These findings can also be difficult \nto interpret due to the lack of clear guidelines or established \ndiagnostic tools other than a sustained decrease in perfor-\nmance (i.e., 1RM strength) for overreaching and overtraining \nin resistance exercise [17]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 56,
    "text": "In particular, the magnitude of \nthe performance decline required to diagnose overreaching \nor overtraining varies depending on the specific performance \nassessment.Currently, the development of overtraining is \ndetermined when long-term decrements in measured perfor-\nmance (i.e., 1RM strength) are detected relative to nothing \n[103] or a control group with a substantially lower workload \ncompared with the overtraining group (i.e., 10 × 1 at 100% \n1RM, every day for 2 weeks vs. 3 × 5 at 50% 1RM, twice \nweekly for 2 weeks) [101, 102]. Within such studies, it is \nuncertain if the proclaimed state of ‘accumulated’ fatigue \nis a reflection of a single bout of training or repeated expo-\nsures of training over time."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 57,
    "text": "The feelings of weakness and \nexhaustion or the decline in performance that individuals \nexperience following the series of training bouts may be per-\nceived as accumulated fatigue, but, without establishing an \nappropriate assessment means, it is also reasonable to claim \nthat a single bout of training is enough to induce fatigue \naccumulation as long as individuals experience prolonged \nimpairments of muscle function.\nOne of the potential candidates that has been interpreted \ninterchangeably as ‘accumulated fatigue’ might be mus-\ncle damage, which also induces prolonged impairments in \nmuscle function (i.e., prolonged strength loss [106])."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 58,
    "text": "Mus-\ncle damage is typically caused by predominantly eccentric \nactivity, and prolonged loss of maximal voluntary force \nafter exercise is considered to be one of the most reliable \nindirect measures of muscle damage [107].Damage may \nbe manifested in the sarcolemma, T-tubules, myofibrils, \nand cytoskeletal system [108]. Potential mechanisms that \ncause prolonged reductions in force production include \nionic changes and disruption of calcium homeostasis and \nmechanical stress to the cells [109]. For example, length-\nening contractions causes disruption in the sarcomeres and \nZ-disk streaming [110]. The most prevalent intermediate \nfilament protein in skeletal muscle, desmin, attaches to the \nZ-disk and eccentric contraction involves disruptions to the \nintermediate filament system [111]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 59,
    "text": "Desmin is also a target \nof calpain, which is involved in muscle damage following \neccentric contractions, causing an elevation of cytosolic \n­Ca2+concentrations [112].Consequently, an unregulated \ninflux of ­Ca2+ leads to a disruption of normal homeostasis \nwithin a muscle cell. Elevations of cytosolic ­Ca2+ concen-\ntrations seem to be a key event for activation of calpain pro-\nteolytic activity, and calpain promotes muscle damage regu-\nlated by calpastatin [113]. Furthermore, increased activity \nof calpain promotes the activation of neutrophils and mac-\nrophages, leading to reactive oxygen species (ROS) produc-\ntion [111]. Notably, the interaction between neutrophils and \nmacrophages promotes an inflammatory response of mus-\ncle damage."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 60,
    "text": "In addition, mechanical stress may damage the \nexcitation–contraction coupling complex by deforming the \nconnection between the T-tubules and the ryanodine recep-\ntors of the sarcoplasmic reticulum (known as junctophilin).\nIt has been demonstrated that the level of junctophilin was \nsignificantly reduced after 50 eccentric contractions, and the \n32\n\t\nR. Kataoka et al.\ndamage to junctophilin was associated with the decline in \nforce [114]. A sustained increase in ­Ca2+ levels also acti-\nvates phospholipase, particularly phospholipase A2, which \nis the mechanism independent of calpain-mediated prote-\nolysis [112]. Phospholipase produces arachidonic acid and \nlysophospholipids, both of which are known to cause mem-\nbrane structural damage [112]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 61,
    "text": "Importantly, these biochemi-\ncal changes of the cell indicate that much of the damage is \ncaused by factors that are secondary to mechanical load-\ning.If mechanical loading predominantly causes membrane \ndamage (i.e., rupture of the membrane) to a greater extent, \nthe increased level of extracellular markers in damaged \nmuscle would appear immediately after exercise. However, \nan indirect marker of muscle damage (i.e., creatine kinase) \ngradually increases over days and may peak a few days (i.e., \n4 days) after resistance exercise is performed [115]. This \ndelayed nature of the appearance of muscle damage may \ntherefore be interpreted as fatigue accumulation.\nNonetheless, the muscle damage also does not seem to \naccumulate following a resistance training program per se \n[116]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 62,
    "text": "Twenty untrained women performed two bouts of \neccentric exercise consisting of 70 maximum eccentric con-\ntractions where one 2–3 s action was performed every 15 s.\nSubjects were randomly divided into group A or group B, in \nwhich the second bout was performed on days 5 and 14 follow-\ning the first bout, respectively. The purpose of the study was to \nexamine whether the second bout of exercise in an unrecovered \nstate would exacerbate performance decrements and elevation \nof the muscle damage marker in the blood [116]. Perceived \nsoreness, elbow joint angles, isometric strength, and creatine \nkinase were measured. No measure had returned to initial val-\nues by day 5 post-exercise."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 63,
    "text": "Thus, when group A performed \nthe second bout of exercise, the subjects did not fully restore \nmuscle function from the first bout of training.On the con-\ntrary, group B restored measured values to the baseline level \nafter 14 days. The isometric strength of both groups A and \nB significantly decreased following the first bout of training \nand produced only 45% and 40% of initial strength, respec-\ntively. When the second bout was performed, group A had \nregained 66% of initial strength, whereas group B regained \n87% of baseline strength. The peak activity of serum creatine \nkinase was observed on days 4 and 5 but did not become sig-\nnificant until day 3."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 64,
    "text": "After performing the second bout, creatine \nkinase activity steadily decreased in group A and reached the \nbaseline level by day 3 post-exercise.Creatine kinase activity \nlevel in group B remained stable following the second bout \nand there was no significant difference between values. The \nresults of the study demonstrated that recovery time following \nthe repeated bout was faster compared with following the ini-\ntial bout whether or not muscle functions were fully restored. \nSimilar results were reported in a follow-up study where a \nbout of eccentric exercise was repeated 3 and 6 days after the \ninitial bout, and no indication of increased muscle damage or \nslowed recovery were documented [117]."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 65,
    "text": "Granted, isometric \nstrength measured before eccentric exercise at days 3 and 6 \nwas still lower than the baseline measures but repeated bouts \ndid not exacerbate the strength loss; rather, strength gradually \nrecovered over the 9 days.Although the question remains as \nto whether a repeated bout of exercise with a shorter recov-\nery (i.e., 24 h) would change this relationship, these instances \nindicated that the repeated bout effect was powerful enough to \ncause adaptations in the absence of complete muscle function \nrestoration and further mitigate muscle damage. Overall, what \nis perceived as accumulated fatigue may be more accurately \ninterpreted as muscle damage per se."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 66,
    "text": "Whether it is caused by \na single bout or series of training, the overlap area of muscle \ndamage and fatigue causes difficulty when interpreting what \nmay ‘accumulate’ following resistance training."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 67,
    "text": "An exhaustive \ncoverage of what is currently known about the physiological \nprocesses of fatigue following resistance exercise is beyond \nthe scope of this paper, but other potential mechanisms that \nmay accumulate or induce prolonged force reduction after \nexercise include psychological changes [11, 102], inflamma-\ntory responses (i.e., leukocytes) [118], neuromodulators (i.e., \ncytokines) [119], and neurotransmitters (i.e., epinephrine) \n[101].\n6  \u0007Conclusion\nDespite the substantial advancement in fatigue research, a \nsignificant gap still remains in understanding the mecha-\nnisms that mediate long-term fatigue symptoms."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 68,
    "text": "Regard-\nless of the lack of clarity on physiological mechanisms, it \nhas been suggested that improper post-exercise recovery \nor sequence of training may result in greater accumulated \nfatigue.This idea has been explained conceptually using \nthe fitness-fatigue model. Within the current model, it is \nbelieved that fatigue has a cumulative effect, and when \nfatigue accumulates to the point where fatigue after-effects \nsignificantly exceed fitness after-effects, overtraining \noccurs."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 69,
    "text": "However, due to the lack of evidence regarding \nthe exact role of biochemical, physiological, and psy-\nchological markers in overtraining in resistance training, \nquestions remain whether a change in any aspect of acute \nfatigue reflects the contribution to fatigue accumulation \nin the long-term, which is proposed to precede overtrain-\ning.In the current paper, the time course of fatigue was \nevaluated to help determine whether fatigue accumulates \nover time.\nFor peripheral fatigue, both depletion and accumulation \nhypotheses suggest that potential mechanisms of fatigue may \nbe acute (i.e., < 24 h), by which the depletion of these energy \nsubstrates and accumulation of metabolic byproducts cor-\nrespond to fatigue within a single session."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 70,
    "text": "A discrepancy in \nthe time course of central fatigue among different types of \n33\nFatigue Accumulation with Training\nmeasurements and a smaller relative contribution of central-\nmediated fatigue compared with peripheral-mediated fatigue \nduring voluntary contractions also raises concerns regarding \nthe role of central factors in fatigue accumulation.A poten-\ntial candidate that may be interpreted as accumulated fatigue \nis muscle damage, which shares similar characteristics with \nfatigue. Overall, considerable work remains to determine \nwhether fatigue accumulates over time."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 71,
    "text": "Insufficient evi-\ndence exists on the presence of fatigue accumulation fol-\nlowing resistance training and future studies are warranted \nto elucidate potential mechanisms underlying the concept of \nfatigue accumulation.\nDeclarations \nFunding  No external sources of funding were used in the preparation \nof this article.\nConflict of interest  Ryo Kataoka, Ecaterina Vasenina, William B.\nHammert, Adam H. Ibrahim, Scott J. Dankel, and Samuel L. Buckner \ndeclare they have no conflicts of interest that are relevant to the con-\ntents of this article.\nAuthorship contributions  The first draft of this manuscript was written \nby RK and SLB. All authors commented and modified previous ver-\nsions of the manuscript, and read and approved the final manuscript.\nReferences\n\t 1.\t Enoka RM, Duchateau J."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 72,
    "text": "Muscle fatigue: what, why and how \nit influences muscle function.J Physiol. 2008;586(1):11–23.\n\t 2.\t Zając A, Chalimoniuk M, Maszczyk A, Gołaś A, Lngfort J. \nCentral and peripheral fatigue during resistance exercise—a \ncritical review. J Hum Kinet. 2015;49:159–69.\n\t 3.\t Edwards RH. Biochemical bases of fatigue in exercise per-\nformance: catastrophe theory of muscular fatigue. Biochem \nExerc. 1983;13(13):3–28.\n\t 4.\t Allen DG, Westerblad H. Role of phosphate and calcium stores \nin muscle fatigue. J Physiol. 2001;536(Pt 3):657–65.\n\t 5.\t Søgaard K, Gandevia SC, Todd G, Petersen NT, Taylor JL. The \neffect of sustained low-intensity contractions on supraspinal \nfatigue in human elbow flexor muscles. J Physiol."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 73,
    "text": "2006;573(Pt \n2):511–23.\n\t 6.\t Morán-Navarro R, Pérez CE, Mora-Rodríguez R, de la Cruz-\nSánchez E, González-Badillo JJ, Sánchez-Medina L, et al.\nTime course of recovery following resistance training leading \nor not to failure. Eur J Appl Physiol. 2017;117(12):2387–99.\n\t 7.\t Barnes MJ, Miller A, Reeve D, Stewart RJC. Acute neuro-\nmuscular and endocrine responses to two different com-\npound exercises: squat vs deadlift. J Strength Cond Res. \n2019;33(9):2381–7.\n\t 8.\t Rossman MJ, Garten RS, Venturelli M, Amann M, Richardson \nRS. The role of active muscle mass in determining the magni-\ntude of peripheral fatigue during dynamic exercise. Am J Physiol \nRegul Integr Comp Physiol. 2014;306(12):R934–40.\n\t 9.\t Bartolomei S, Sadres E, Church DD, Arroyo E, Gordon JA III, \nVaranoske AN, et al."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 74,
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    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 98,
    "text": "Junctophilin damage contributes to early strength deficits and EC \ncoupling failure after eccentric contractions.Am J Physiol Cell \nPhysiol. 2010;298(2):C365–76.\n\t115.\t Clarkson PM, Nosaka K, Braun B. Muscle function after exer-\ncise-induced muscle damage and rapid adaptation. Med Sci \nSports Exerc. 1992;24(5):512–20.\n\t116.\t Ebbeling CB, Clarkson PM. Muscle adaptation prior to recovery \nfollowing eccentric exercise. Eur J Appl Physiol Occup Physiol. \n1990;60(1):26–31.\n\t117.\t Nosaka K, Clarkson P. Muscle damage following repeated \nbouts of high force eccentric exercise. Med Sci Sports Exerc. \n1995;27(9):1263–9.\n\t118.\t Paulsen G, Crameri R, Benestad HB, Fjeld JG, Mørkrid \nL, Hallén J, et al. Time course of leukocyte accumulation in \nhuman muscle after eccentric exercise."
  },
  {
    "filename": "s40279-021-01572-0.pdf",
    "pdf_title": "Is there Evidence for the Suggestion that Fatigue Accumulates Following Resistance Exercise?",
    "chunk_id": 99,
    "text": "Med Sci Sports Exerc.\n2010;42(1):75–85.\n\t119.\t Izquierdo M, Ibañez J, Calbet JAL, Navarro-Amezqueta \nI, González-Izal M, Idoate F, et  al. Cytokine and hor-\nmone responses to resistance training. Eur J Appl Physiol. \n2009;107(4):397."
  },
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "THE MECHANISMS OF MUSCLE HYPERTROPHY AND\nTHEIR APPLICATION TO RESISTANCE TRAINING\nBRAD J. SCHOENFELD\nGlobal Fitness Services, Scarsdale, New York\nABSTRACT\nSchoenfeld, BJ. The mechanisms of muscle hypertrophy and\ntheir application to resistance training. J Strength Cond Res\n24(10): 2857–2872, 2010—The quest to increase lean body\nmass is widely pursued by those who lift weights. Research is\nlacking, however, as to the best approach for maximizing\nexercise-induced muscle growth. Bodybuilders generally train\nwith moderate loads and fairly short rest intervals that induce\nhigh amounts of metabolic stress. Powerlifters, on the other\nhand, routinely train with high-intensity loads and lengthy rest\nperiods between sets."
  },
  {
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    "text": "Although both groups are known to\ndisplay impressive muscularity, it is not clear which method is\nsuperior for hypertrophic gains.It has been shown that many\nfactors mediate the hypertrophic process and that mechanical\ntension, muscle damage, and metabolic stress all can play a role\nin exercise-induced muscle growth."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Therefore, the purpose of\nthis paper is twofold: (a) to extensively review the literature as to\nthe mechanisms of muscle hypertrophy and their application to\nexercise training and (b) to draw conclusions from the research\nas to the optimal protocol for maximizing muscle growth.\nKEY WORDS muscle development, hypertrophic response,\nmuscle growth, muscle tension, muscle damage, metabolic stress\nINTRODUCTION\nT\nhe quest to increase lean body mass is widely\npursued by those who lift weights."
  },
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    "text": "Given the strong\ncorrelation between muscle cross-sectional area\nand muscular strength (111), increased muscle\nmass is a primary goal of athletes involved in strength and\npower sports such as football, rugby, and powerlifting.\nMuscle mass also is vital to the sport of bodybuilding, where\ncompetitors are judged on both the quantity and quality of\ntheir muscle development."
  },
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    "text": "On a more general level, muscle\nhypertrophy is also pursued by the many recreational lifters\nwho aspire to develop their physiques to the fullest.\nTherefore, the maximization of muscle mass has far reaching\nimplications to a variety of populations associated with sports\nand health.\nIn untrained subjects, muscle hypertrophy is virtually\nnonexistent during the initial stages of resistance training,\nwith the majority of strength gains resulting from neural\nadaptations (124).Within a couple of months of training,\nhowever, hypertrophy begins to become the dominant\nfactor, with the upper extremities shown to hypertrophy\nbefore the lower extremities (124,177)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Genetic background,\nage, gender, and other factors have been shown to mediate\nthe hypertrophic response to a training protocol, affecting\nboth the rate and the total amount of gains in lean muscle\nmass (93).Further, it becomes progressively more difficult to\nincrease lean muscle mass as one gains training experience,\nheightening the importance of proper routine design.\nAlthough muscle hypertrophy can be attained through\na wide range of resistance training programs, the principle of\nspecificity dictates that some routines will promote greater\nhypertrophy than others (16). Research is lacking, however,\nas to the best approach for achieving this goal."
  },
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Bodybuilders\ngenerally train with moderate loads and fairly short rest\nintervals that induce high amounts of metabolic stress.\nPowerlifters, on the other hand, routinely train with high-\nintensity loads and lengthy rest periods between sets.\nAlthough both groups are known to display impressive mus-\ncularity, it is not clear which method is best for maximizing\nhypertrophic gains (149) or whether other training methods\nmay perhaps be superior."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 7,
    "text": "Therefore, the purpose of this\npaper is twofold: (a) to extensively review the literature as to\nthe mechanisms of muscle hypertrophy and their application\nto resistance training variables and (b) to draw conclusions\nfrom the research and develop a hypertrophy-specific routine\nfor maximizing muscle growth.\nTYPES OF MUSCLE HYPERTROPHY\nMuscle hypertrophy can be considered distinct and separate\nfrom muscle hyperplasia.During hypertrophy, contractile\nelements enlarge and the extracellular matrix expands to\nsupport growth (187). This is in contrast to hyperplasia,\nwhich results in an increase in the number of fibers within\na muscle."
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Contractile hypertrophy can occur either by adding\nsarcomeres in series or in parallel.\nThe majority of exercise-induced hypertrophy subsequent\nto traditional resistance training programs results from an\nBRIEF REVIEW\nAddress correspondence to Brad Schoenfeld, brad@workout911.com.\n24(10)/2857–2872\nJournal of Strength and Conditioning Research\n\u0001 2010 National Strength and Conditioning Association\nVOLUME 24 | NUMBER 10 | OCTOBER 2010 | 2857\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nincrease of sarcomeres and myofibrils added in parallel\n(135,179).When skeletal muscle is subjected to an overload\nstimulus, it causes perturbations in myofibers and the related\nextracellular matrix."
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    "text": "This sets off a chain of myogenic events\nthat ultimately leads to an increase in the size and amounts\nof the myofibrillar contractile proteins actin and myosin,\nand the total number of sarcomeres in parallel.This, in turn,\naugments the diameter of individual fibers and thereby results\nin an increase in muscle cross-sectional area (182).\nA serial increase in sarcomeres results in a given muscle\nlength corresponding to a shorter sarcomere length (182). In-\nseries hypertrophy has been shown to occur when muscle is\nforced to adapt to a new functional length. This is seen with\nlimbs that are placed in a cast, where immobilization of\na joint at long muscle lengths results in an increased number\nof sarcomeres in series, whereas immobilization at shorter\nlengths causes a reduction (182)."
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    "text": "There is some evidence that\ncertain types of exercise can affect the number of sarcomeres\nin series.Lynn and Morgan (107) showed that when rats\nclimbed on a treadmill (i.e., incline), they had a lower\nsarcomere count in series than those who descended (i.e.,\ndecline). This suggests that repeated eccentric-only actions\nlead to a greater number of sarcomeres in series, whereas\nexercise consisting solely of concentric contractions results in\na serial decrease in sarcomere length.\nIt is hypothesized that hypertrophy may be augmented\nby an increase in various noncontractile elements and fluid\n(108,205)."
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    "text": "This has been termed ‘‘sarcoplasmic hypertro-\nphy,’’ and may result in greater muscle bulk without\nconcomitant\nincreases\nin\nstrength\n(154).\nIncreases\nin\nsarcoplasmic hypertrophy are thought to be training specific,\na belief\nperpetuated by studies showing that muscle\nhypertrophy is different in bodybuilders than in powerlifters\n(179).Specifically, bodybuilders tend to display a greater\nproliferation of fibrous endomysial connective tissue and\na\ngreater\nglycogen\ncontent\ncompared\nto\npowerlifters\n(109,177), presumably because of differences in training\nmethodology."
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    "text": "Although sarcoplasmic hypertrophy is often\ndescribed as nonfunctional, it is plausible that chronic\nadaptations associated with its effects on cell swelling may\nmediate subsequent increases in protein synthesis that lead\nto greater contractile growth.\nSome researchers have put forth the possibility that\nincreases in cross-sectional area may be at least partly\nbecause of an increase in fiber number (8).A meta-analysis by\nKelley (84) found that hyperplasia occurs in certain animal\nspecies\nunder\nexperimental\nconditions\nas\na\nresult\nof\nmechanical overload. Increases in muscle fiber number were\ngreatest among those groups that used an avian vs.\na mammalian model, and stretch overload yielded larger\nincreases in fiber count than exercise."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "chunk_id": 13,
    "text": "However, subsequent\nresearch suggests that such observations may be erroneous,\nwith results attributed to a miscounting of the intricate\narrangements of elongating fibers as a greater fiber number\n(135).Evidence that hyperplasia occurs in human subjects is\nlacking and, if it does occur at all, the overall effects on muscle\ncross-sectional area would appear to be minimal (1,108).\nSATELLITE CELLS AND MUSCLE HYPERTROPHY\nMuscle is a postmitotic tissue, meaning that it does not\nundergo significant cell replacement throughout life. An\nefficient method for cell repair is therefore required to avoid\napoptosis and maintain skeletal mass. This is carried out\nthrough the dynamic balance between muscle protein\nsynthesis and degradation (69,182)."
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    "text": "Muscle hypertrophy\noccurs when protein synthesis exceeds protein breakdown.\nHypertrophy is thought to be mediated by the activity\nof satellite cells, which reside between the basal lamina\nand sarcolemma (66,146).These ‘‘myogenic stem cells’’ are\nnormally quiescent but become active when a sufficient\nmechanical stimulus is imposed on skeletal muscle (187).\nOnce aroused, satellite cells proliferate and ultimately fuse to\nexisting cells or among themselves to create new myofibers,\nproviding the precursors needed for repair and subsequent\ngrowth of new muscle tissue (182).\nSatellite cells are thought to facilitate muscle hypertrophy\nin several ways. For one, they donate extra nuclei to muscle\nfibers, increasing the capacity to synthesize new contractile\nproteins (123)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "chunk_id": 15,
    "text": "Because a muscle’s nuclear-content-to-fiber-\nmass ratio remains constant during hypertrophy, changes\nrequire an external source of mitotically active cells.Satellite\ncells retain mitotic capability and thus serve as the pool of\na myonuclei to support muscle growth (15). This is consistent\nwith the concept of myonuclear domain, which proposes\nthat the myonucleus regulates mRNA production for a finite\nsarcoplasmic volume and any increases in fiber size must be\naccompanied by a proportional increase in myonuclei. Given\nthat muscles are comprised of multiple myonuclear domains,\nhypertrophy could conceivably occur as a result of either\nan increase in the number of domains (via an increase in\nmyonuclear number) or an increase in the size of existing\ndomains."
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    "text": "Both are thought to occur in hypertrophy, with\na significant contribution from satellite cells (182).\nMoreover, satellite cells coexpress various myogenic\nregulatory factors (including Myf5, MyoD, myogenin, and\nMRF4) that aid in muscle repair, regeneration, and growth\n(27).These regulatory factors bind to sequence specific DNA\nelements present in the muscle gene promoter, with each\nplaying distinct roles in myogenesis (148,155).\nMYOGENIC PATHWAYS\nExercise-induced\nmuscle\nhypertrophy\nis\nfacilitated\nby\na number of signaling pathways, whereby the effects of\nmechano-stimulation are molecularly transduced to down-\nstream targets that shift muscle protein balance to favor\nsynthesis over degradation."
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    "text": "Several primary anabolic signal-\ning pathways have been identified including Akt/mammalian\ntarget of rapamycin (mTOR), mitogen-activated protein\nkinase (MAPK), and calcium-(Ca2+) dependent pathways.\nThe following is an overview of each of these pathways.\n2858\nJournal of Strength and Conditioning Research\nthe\nTM\nMechanisms of Muscle Hypertrophy\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nAkt/Mammalian Target of Rapamycin Pathway\nThe Akt/mTOR pathway is believed to act as a master\nnetwork regulating skeletal muscle growth (18,77,181).\nAlthough the specific molecular mechanisms have not been\nfully elucidated, Akt is considered a molecular upstream\nnodal point that is both an effector of anabolic signaling and\na dominant inhibitor of catabolic signals (126,182)."
  },
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    "text": "When\nactivated, Akt signals mTOR, which then exerts effects on\nvarious downstream targets that promote hypertrophy in\nmuscle tissue.\nMitogen-Activated Protein-Kinase Pathway\nMitogen-activated protein kinase is considered a master\nregulator of gene expression, redox status, and metabolism\n(88).Specific to exercise-induced skeletal muscle hypertro-\nphy, MAPK has been shown to link cellular stress with an\nadaptive response in myocytes, modulating growth and\ndifferentiation (147). Three distinct MAPK signaling modules\nare associated with exercise-induced muscle hypertrophy:\nextracellular signal-regulated kinases (ERK 1/2), p38 MAPK,\nand c-Jun NH2–terminal kinase (JNK)."
  },
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    "text": "Of these modules,\nJNK has shown to be the most responsive to mechanical\ntension and muscle damage, and it is particularly sensitive to\neccentric exercise.Exercise-induced activation of JNK has\nbeen linked to a rapid rise in mRNA of transcription factors\nthat modulate cell proliferation and DNA repair (9,10).\nCalcium-Dependent Pathways\nVarious Ca2+-dependent pathways have been implicated in\nthe regulation of muscle hypertrophy. Calcineurin (Cn), a\nCa2+-regulated phosphatase, is believed to be a particularly\ncritical regulator in the Ca2+ signaling cascade. Cn acts down-\nstream in the Ca2+ pathway and mediates various hypertro-\nphic effectors such as myocyte enhancing factor 2, GATA\ntranscription factors, and nuclear factor of activated T cells\n(118)."
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    "text": "Cn-dependent signaling is linked to hypertrophy of all\nfiber types, and its inhibition has been shown to prevent\nmuscle growth even in the presence of muscular overload\n(35,36).\nHORMONES AND CYTOKINES\nHormones and cytokines play an integral role in the hyper-\ntrophic response, serving as upstream regulators of anabolic\nprocesses.Elevated anabolic hormone concentrations in-\ncrease the likelihood of receptor interactions, facilitating\nprotein metabolism and subsequent muscle growth (31).\nMany are also involved in satellite cell proliferation and\ndifferentiation and perhaps facilitate the binding of satellite\ncells to damaged fibers to aid in muscular repair (182,187).\nThe hormonal regulation of hypertrophy is complex, with\nmany hormones and cytokines believed to contribute to the\nresponse."
  },
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    "text": "Hepato growth factor, Interleukin-5 (IL-5), In-\nterleukin-6 (IL-6), fibroblast growth factor, and leukemia\ninhibitory factor, all have been shown to promote anabolism\n(162,182,187).Insulin also has been shown to possess\nanabolic properties, with greater effects on attenuating\nproteolysis rather than heightening protein synthesis. Insulin\nalso is believed to induce mitosis and differentiation of\nsatellite cells (187). Given that insulin levels are suppressed\nduring exercise, however, it is not a modifiable aspect of an\nexercise regimen and thus will not be addressed further here.\nVarious types of exercise have been shown to cause acute,\nand in some cases chronic, hormonal alterations that appear\nto play a role in mediating hypertrophic signaling systems\n(119)."
  },
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "chunk_id": 22,
    "text": "The 3 most widely studied of these hormones are\ninsulin-like growth factor (IGF-1), testosterone, and growth\nhormone (GH).Whether the acute hormonal response to\nexercise provides a significant anabolic stimulus has been\nquestioned by some researchers (191,194), however with\nthe inherent experimental limitations in these studies and a\nlarger body of\nprevailing basic and applied evidence to\nthe contrary, such an overt dismissal of the importance of\nhormonal signaling in the physiological adaptations resulting\nfrom resistance exercise over a training period is without\ncontext and premature.\nInsulin-Like Growth Factor\nInsulin-like growth factor is often referred to as the most\nimportant mammalian anabolic hormone."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "It is thought to\nprovide the main anabolic response for the body as a whole\nand shows enhanced effects in response to mechanical\nloading (19,63).Structurally, IGF-1 is a peptide hormone, so\nnamed because of its structural similarities to insulin. Insulin-\nlike growth factor receptors are found in activated satellite\ncells, adult myofibers, and Schwann cells (15). During\nexercise, muscles not only produce more systemic IGF-1\nthan the liver but also use more circulating IGF-1 (49).\nAvailability of IGF-1 for muscle is controlled by IGF-1\nbinding proteins (IGFBPs), which either stimulate or inhibit\nthe effects of IGF-1 after binding to a specific IGFBP (182).\nThree distinct IGF-1 isoforms have been identified: the\nsystemic forms IGF-1Ea and IGF-1Eb, and a splice variant, IGF-\n1Ec."
  },
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    "text": "Although all 3 isoforms are expressed in muscle tissue, only\nIGF-1Ec appears to be activated by mechanical signals (63,199).\nBecause of its response to mechanical stimulation, IGF-1Ec is\nfamiliarly called mechano growth factor (MGF).\nAlthough the exact mechanisms of IGF-1’s mode of action\nhave not been fully elucidated, it is believed that mechano-\nstimulation causes the IGF-1 gene to be spliced toward MGF,\nwhich in turn ‘‘kick starts’’ muscle hypertrophy.Within a day\nor so, MGF then completely splices toward the systemic\nIGF-1 isoforms (IGF-1Ea and IGF-1Eb) (54,69). Levels of\nIGF-1 then remain elevated in muscle tissue for some time\nthereafter, with myogenic effects seen up to 72 hours\npostexercise (117)."
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    "text": "Although MGF has been shown to be\nparticularly sensitive to muscle damage, it is not clear\nwhether the isoform is upregulated by membrane damage or\nif membrane damage initiates MGF production (48).\nInsulin-like growth factor has been shown to induce\nhypertrophy in both an autocrine and paracrine manner (34)\nand exerts its effects in multiple ways.For one, IGF-1 directly\nVOLUME 24 | NUMBER 10 | OCTOBER 2010 | 2859\nJournal of Strength and Conditioning Research\nthe\nTM\n| www.nsca-jscr.org\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\npromotes anabolism by increasing the rate of protein\nsynthesis in differentiated myofibers (15,63)."
  },
  {
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    "text": "Moreover,\nlocally expressed MGF has been shown to activate satellite\ncells and mediate their proliferation and differentiation\n(69,200).IGF-IEa, on the other hand, is thought to enhance\nfusion of satellite cells with muscle fibers, facilitating the\ndonation of myonuclei and helping to maintain optimal DNA\nto protein ratios in muscle tissue (182).\nInsulin-like growth factor also activates L-type calcium\nchannel gene expression, resulting in an increased intracel-\nlular Ca2+ concentration (125). This leads to the activation\nof multiple anabolic Ca2+-dependent pathways, including\ncalcineurin and its numerous downstream signaling targets.\nTestosterone\nTestosterone is a cholesterol-derived hormone that has a\nconsiderable anabolic effect on muscle tissue (33,105)."
  },
  {
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    "text": "In\naddition to its effects on muscle, testosterone also can interact\nwith receptors on neurons and thereby increase the amount\nof neurotransmitters released, regenerate nerves, and increase\ncell body size.\nThe majority of testosterone is synthesized and secreted by\nthe Leydig cells of the testes via the hypothalamic–pituitary–\ngonadal axis, with small amounts derived from the ovaries and\nadrenals (22).In the blood, the great majority of testosterone\nis bound to either albumin (38%) or steroid hormone binding\nglobulin (60%), with the remaining 2% circulating in an\nunbound state. Although only the unbound form is bi-\nologically active and available for use by tissues, weakly\nbound testosterone can become active by rapidly disassoci-\nating from albumin (105)."
  },
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Unbound testosterone binds to\nandrogen receptors of target tissues, which are located in the\ncell’s cytoplasm.This causes a conformational change that\ntransports the testosterone to the cell nucleus where it\ninteracts directly with chromosomal DNA.\nAlthoughthe effects of testosterone on muscleare seen inthe\nabsence of exercise, its actions are magnified by mechanical\nloading, promoting anabolism both by increasing the protein\nsynthetic rate and inhibiting protein breakdown (22). Testos-\nterone may also contribute to protein accretion indirectly by\nstimulating the release of other anabolic hormones such as\nGH (31)."
  },
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    "text": "Moreover, it has been shown to promote satellite cell\nreplication and activation, resulting in an increase in the\nnumber of myogenically committed satellite cells (155).\nSuppression of testosterone has been shown to seriously\ncompromise the response to resistance exercise (100).\nResistance training also has been shown to upregulate\nandrogen receptor content in humans (13,80).In rodents,\nmodulation of androgen receptor content appears to take\nplace in a fiber-type specific manner, with increases specific\nto fast-twitch muscles (20). This would seem to enhance the\npotential for testosterone binding at the cellular level, and\nthus facilitate its uptake into target tissues.\nResistance exercise can have a substantial acute effect\non testosterone secretion. Ahtiainen et al."
  },
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "(2) found significant\ncorrelations between training-induced elevations in testosterone\nand muscle cross-sectional area, suggesting that acute, exercise-\ninduced elevations in testosterone may play an important role\nin muscle hypertrophy.However, acute responses are limited in\nwomen and the elderly, mitigating the hypertrophic potential in\nthese populations (61,90,130).\nThe chronic effects of resistance training on bodily\ntestosterone concentrations are not clear at this time.\nAlthough some studies show sustained increases as a result\nof regimented resistance exercise (60,93,163), others show\nlittle to no change (3,142)."
  },
  {
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    "chunk_id": 31,
    "text": "Further research is needed to\nenhance understanding on this topic.\nGrowth Hormone\nGrowth hormone is a polypeptide hormone considered to\nhave both anabolic and catabolic properties.Specifically, GH\nacts as a repartitioning agent to induce fat metabolism toward\nmobilization of triglycerides, and stimulating cellular uptake\nand incorporation of amino acids into various proteins,\nincluding muscle (187). In the absence of mechanical loading,\nGH preferentially upregulates the mRNA of systemic IGF-1,\nand mediating nonhepatic IGF-1 gene expression in an\nautocrine/paracrine manner (63).\nGrowth hormone is secreted by the anterior pituitary gland\nand released in a pulsatile fashion, with the greatest\nnonexercise secretions occurring during sleep."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "More than\n100 molecular isoforms of GH have been identified; however,\nmost resistance training studies have focused solely on the\n22-kDa\nisoform,\nlimiting\nconclusions.\nRecent\nresearch\nsuggests a preferential release of multiple GH isoforms with\nextended half-lives during exercise, allowing for sustained\naction on target tissues (131).\nIn addition to exerting effects on muscle tissue, GH also is\ninvolved in the regulation of immune function, bone model-\ning, and extracellular fluid volume.In total, GH is implicated\nas promoting over 450 actions in 84 cell types (190).\nGrowth hormone levels spike after the performance of\nvarious types of exercise (96). An exercise-induced increase in\nGH has been highly correlated with the magnitude of type I\nand type II muscle fiber hypertrophy (113)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "It is postulated\nthat a transient GH increase may lead to an enhanced\ninteraction with muscle cell receptors, facilitating fiber\nrecovery and stimulating a hypertrophic response (134).\nGrowth hormone is also thought to be involved in the\ntraining-induced increase of locally expressed IGF-1 (75).\nWhen combined with intense exercise, GH release is\nassociated with marked upregulation of the IGF-1 gene in\nmuscle so that more is spliced toward the MGF isoform (63).\nSome researchers have questioned whether GH does, in\nfact, have a significant hypertrophic effect on muscle tissue\n(143).This view is based on the results of several studies that\nhave failed to find significant increases in muscle mass when\nGH was administered as part of a resistance training protocol\n(101,201–203)."
  },
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    "pdf_title": "",
    "chunk_id": 34,
    "text": "However, these protocols did not replicate\nthe large spikes in GH seen postexercise, nor did they take\n2860\nJournal of Strength and Conditioning Research\nthe\nTM\nMechanisms of Muscle Hypertrophy\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\ninto account the time course of GH elevation in conjunction\nwith myotrauma.Thus, it is impossible to draw conclusions\nfrom these studies as to whether an exercise-induced GH\nresponse is associated with skeletal muscle anabolism. Much\nis still unclear about the anabolic actions of GH, and further\nresearch is needed to fully elucidate its role in muscular\ndevelopment.\nCELL SWELLING\nCellular hydration (i.e., cell swelling) serves as a physiological\nregulator of cell function (65)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 35,
    "text": "It is known to simulate anabolic\nprocesses, both through increases in protein synthesis and\ndecreases in proteolysis (53,120,165).Although a physiological\nbasis linking cell swelling with an anabolic drive is yet to be\ndetermined, it is conceivable that increased pressure against\nthe membrane is perceived as a threat to cellular integrity,\nwhich in turn causes the cell to initiate a signaling response\nthat ultimately leads to reinforcement of its ultrastructure.\nA hydrated cell has been shown to initiate a process that\ninvolves activation of protein-kinase signaling pathways in\nmuscle, and possibly mediating autocrine effects of growth\nfactors in signaling the anabolic response to membrane stretch\n(106)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 36,
    "text": "Cell swelling induced membrane stretch may also have\na direct effect on the amino acid transport systems mediated\nthrough an integrin-associated volume sensor.Phosphatidyli-\nnositol 3-kinase appears to be an important signaling component\nin modulating glutamine and alpha-(methyl)aminoisobutyric\nacid transport in muscle because of cell swelling (106).\nResistance exercise has been shown to induce alterations of\nintra- and extracellular water balance (156), the extent of\nwhich is dependent upon the type of exercise and intensity\nof training. Cell swelling is maximized by exercise that relies\nheavily on glycolysis, with the resultant lactate accumulation\nacting as the primary contributor to osmotic changes in\nskeletal muscle (41,157)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 37,
    "text": "Fast-twitch fibers are particularly\nsensitive to osmotic changes, presumably related to a high\nconcentration of water transport channels called aquaporin-4.\nAquaporin-4 has been shown to be strongly expressed in the\nsarcolemma of mammalian fast-twitch glycolytic and fast-\ntwitch oxidative-glycolytic fibers, facilitating the influx\nof fluid into the cell."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 38,
    "text": "Given that fast-twitch fibers are most\nresponsive to hypertrophy, it is conceivable that cellular\nhydration augments the hypertrophic response during\nresistance training that relies heavily on anaerobic glycolysis.\nExercise regimens that cause an increased glycogen storage\ncapacity also have the potential to augment cell swelling.\nGiven that glycogen attracts three grams of water for every\ngram of glycogen (25), this may reflect an increased capacity\nfor protein synthesis in those who possess greater in-\ntramuscular glycogen stores.\nHYPOXIA\nHypoxia has been shown to contribute to increases in muscle\nhypertrophy, with effects seen even in the absence of exercise.\nTakarada et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 39,
    "text": "(172) found that 2 daily sessions of vascular\nocclusion\nsignificantly\nattenuated muscular\natrophy in\na group of patients confined to bed rest.Similar findings\nwere observed by Kubota et al. (62,98), with occlusion\nconferring a protective effect on muscle strength and cross-\nsectional area during a 2-week period of leg immobilization.\nWhen combined with exercise, hypoxia seems to have an\nadditive effect on hypertrophy. This was demonstrated by\nTakarada et al. (173), who divided 24 older women into\n3 subgroups: low-intensity elbow flexion exercise (;50%\n1 repetition maimum [1RM]) with vascular occlusion, low-\nintensity elbow flexion exercise (;50% 1RM) without occlu-\nsion, and high- to medium-intensity elbow flexion exercise\nwithout occlusion (;80% 1RM)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 40,
    "text": "After 16 weeks, the group\nthat performed low-intensity training with occlusion showed\na significantly greater cross-sectional area of the elbow flexor\nmuscles as compared to low-intensity exercise without occlu-\nsion.Moreover, the hypertrophic gains realized were similar\nto those experienced by the moderate- to high-intensity group.\nThere are several theories as to the potential hypertrophic\nbenefits of muscle hypoxia. For one, hypoxia has been shown\nto cause an increased lactate accumulation and reduced acute\nlactate clearance rate (173). This may mediate increased cell\nswelling, which has been shown to upregulate protein syn-\nthesis. Moreover, the rise in lactate may mediate elevations in\nanabolic hormones and cytokines. Takarada et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 41,
    "text": "(172) noted\na 290% increase in GH levels after low-intensity hypoxic\ntraining and an increase in the concentration of the myogenic\ncytokine IL-6, which was sustained for 24 hours postexercise.\nAnother potential mechanism of hypoxic-induced hyper-\ntrophy is its effect on the activity of reactive oxygen species\n(ROS).Reactive oxygen species production has been shown\nto promote growth in both smooth muscle and cardiac\nmuscle (170), and it is theorized to have similar hypertrophic\neffects on skeletal muscle (171). Nitric oxide, an ROS pro-\nduced during exercise, has been shown to mediate the pro-\nliferation of satellite cells, which would presumably lead to\ngreater skeletal muscle growth (81,174)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 42,
    "text": "Reactive oxygen\nspecies generated during resistance training also has been\nshown to activate MAPK signaling in skeletal myoblasts (83),\npotentially modulating a hypertrophic response.\nHypoxia also may promote hypertrophic effects from\nreactive hyperemia (i.e., increased blood flow) after ischemic\nexercise (173).Hyperemia within damaged muscle would\nconceivably allow for the delivery of anabolic endocrine\nagents and growth factors to satellite cells, thereby regulating\ntheir proliferation and subsequent fusion into myotubes (187).\nINITIATION OF EXERCISE-INDUCED MUSCLE\nHYPERTROPHY\nIt is hypothesized that 3 primary factors are responsible for\ninitiating the hypertrophic response to resistance exercise:\nmechanical tension, muscle damage, and metabolic stress\n(38,79,153,185)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 43,
    "text": "The following is an overview of each of these\nfactors.\nVOLUME 24 | NUMBER 10 | OCTOBER 2010 | 2861\nJournal of Strength and Conditioning Research\nthe\nTM\n| www.nsca-jscr.org\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nMechanical Tension\nMechanically induced tension produced both by force genera-\ntion and stretch is considered essential to muscle growth, and\nthe combination of these stimuli appears to have a pro-\nnounced additive effect (48,72,185).More specifically, mech-\nanical overload increases muscle mass while unloading results\nin atrophy (47)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 44,
    "text": "This process appears largely controlled by\nprotein synthetic rate during the initiation of translation (11,87).\nIt is believed that tension associated with resistance training\ndisturbs the integrity of skeletal muscle, causing mechano-\nchemically transduced molecular and cellular responses\nin myofibers and satellite cells (182).Upstream signaling is\nthought to occur through a cascade of events that involve\ngrowth factors, cytokines, stretch-activated channels, and\nfocal adhesion complexes (23,48,162). Evidence suggests that\nthe downstream process is regulated via the AKT/mTOR\npathway, either through direct interaction or by modulating\nproduction of phosphatidic acid (72,73)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 45,
    "text": "At this point,\nhowever, research has not provided a clear understanding of\nhow these processes are carried out.\nDuring eccentric contractions, passive muscular tension\ndevelops because of lengthening of extramyofibrillar ele-\nments, especially collagen content in extracellular matrix and\ntitin (182)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 46,
    "text": "This augments the active tension developed by the\ncontractile elements, enhancing the hypertrophic response.\nBoth the amplitude and duration of excitation coupling is\ndetermined by motor unit (MU) firing frequency, the extent\nof\nwhich\nare\nbelieved\nto\nencode\nsignals\nto\nvarious\ndownstream pathways including Ca2+ calmodulin phospha-\ntase calcineurin, CaMKII, and CAMKIV, and PKC (26).\nThese pathways help to determine gene expression, coupling\nmuscle excitation with transcription (182).\nPassive tension produces a hypertrophic response that\nis fiber-type specific, with an effect seen in fast-twitch but\nnot slow-twitch fibers."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 47,
    "text": "This was demonstrated by Prado et al.\n(139), who found that slow-twitch fibers in rabbits exhibited\nlow passive tension in titin, but the tension was highly\nvariable in fast-twitch fibers.\nAlthough mechanical tension alone can produce muscle\nhypertrophy, it is unlikely to be solely responsible for\nhypertrophic gains associated with exercise (79).In fact,\ncertain resistance training routines employing high degrees of\nmuscle tension have been shown to largely induce neural\nadaptations without resultant hypertrophy (28,188).\nMuscle Damage\nExercise training can result in localized damage to muscle\ntissue which, under certain conditions, is theorized to\ngenerate a hypertrophic response (38,69)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 48,
    "text": "Damage can be\nspecific to just a few macromolecules of tissue or result in\nlarge tears in the sarcolemma, basal lamina, and supportive\nconnective tissue, and induces injury to contractile elements\nand the cytoskeleton (187).Because the weakest sarcomeres\nare located at different regions of each myofibril, the\nnonuniform lengthening causes a shearing of myofibrils.\nThis deforms membranes, particularly T-tubules, leading to\na disruption of calcium homeostasis and consequently\ndamage because of tearing of membranes and/or opening\nof stretch-activated channels (4).\nThe response to myotrauma has been likened to the acute\ninflammatory response to infection."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 49,
    "text": "Once damage is perceived\nby the body, neutrophils migrate to the area of microtrauma\nand agents are then released by damaged fibers that attract\nmacrophages and lymphocytes.Macrophages remove cellular\ndebris to help maintain the fiber’s ultrastructure and produce\ncytokines that activate myoblasts, macrophages and lympho-\ncytes. This is believed to lead to the release of various growth\nfactors that regulate satellite cell proliferation and differenti-\nation (182,187).\nFurthermore, the area under the myoneural junction\ncontains a high concentration of satellite cells, which have\nbeen shown to mediate muscle growth (69,155)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 50,
    "text": "This gives\ncredence to the possibility that nerves impinging on damaged\nfibers might stimulate satellite cell activity, thereby pro-\nmoting hypertrophy (187).\nMetabolic Stress\nNumerous studies support an anabolic role of exercise-\ninduced metabolic stress (145,149,161) and some have\nspeculated that metabolite accumulation may be more\nimportant than high force development in optimizing the\nhypertrophic response to training (153).Although metabolic\nstress does not seem to be an essential component of mus-\ncular growth (40), a large body of evidence shows that it can\nhave a significant hypertrophic effect, either in a primary or\nsecondary manner."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 51,
    "text": "This can be noted empirically by exam-\nining the moderate intensity training regimes adopted by\nmany bodybuilders, which are intended to heighten metab-\nolic stress while maintaining significant muscular tension.\nMetabolic stress manifests as a result of exercise that relies\non anaerobic glycolysis for ATP production, which results in\nthe subsequent buildup of metabolites such as lactate,\nhydrogen ion, inorganic phosphate, creatine, and others\n(169,178).Muscle ischemia also has been shown to produce\nsubstantial metabolic stress, and potentially produces an\nadditive hypertrophic effect when combined with glycolytic\ntraining (136,182)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 52,
    "text": "The stress-induced mechanisms theorized\nto mediate the hypertophic response include alterations in\nhormonal milieu, cell swelling, free-radical production, and\nincreased activity of growth-oriented transcription factors\n(50,51,171).It also has been hypothesized that a greater acidic\nenvironment promoted by glycolytic training may lead\nto increased fiber degradation and greater stimulation of\nsympathetic nerve activity, thereby mediating an increased\nadaptive hypertrophic response (22).\nTRAINING VARIABLES AND MUSCLE HYPERTROPHY\nConsistent with the principle of specificity, proper manipu-\nlation of training variables is essential for maximizing\nexercise-induced muscle hypertrophy."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 53,
    "text": "The following is\n2862\nJournal of Strength and Conditioning Research\nthe\nTM\nMechanisms of Muscle Hypertrophy\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\na review as to how each training variable impacts the\nhypertrophic response with respect to the physiological\nvariables previously discussed.\nIntensity\nIntensity (i.e., load) has been shown to have a significant\nimpact on muscle hypertrophy and is arguably the most\nimportant exercise variable for stimulating muscle growth\n(42).Intensity is customarily expressed as a percentage of\n1RM and equates to the number of repetitions that can be\nperformed with a given weight. Repetitions can be classified\ninto 3 basic ranges: low (1–5), moderate (6–12), and high\n(15+)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 54,
    "text": "Each of these repetition ranges will involve the use of\ndifferent energy systems and tax the neuromuscular system in\ndifferent ways, impacting the extent of the hypertrophic\nresponse.\nThe use of high repetitions has generally proven to be\ninferior to moderate and lower repetition ranges in eliciting\nincreases in muscle hypertrophy (24,71).In the absence of\nartificially induced ischemia (i.e., occlusion training), a load\nless than approximately 65% of 1RM is not considered suffi-\ncient to promote substantial hypertrophy (115)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 55,
    "text": "Although\nsuch high rep training can bring about significant metabolic\nstress, the load is inadequate to recruit and fatigue the highest\nthreshold MUs.\nWhether low reps or moderate reps evoke a greater\nhypertrophic response has been a matter of debate, and both\nproduce significant gains in muscle growth (24).However,\nthere is a prevailing belief that a moderate range of approx-\nimately 6–12 reps optimizes the hypertrophic response\n(86,89,205).\nThe anabolic superiority of moderate repetitions has been\nattributed to factors associated with metabolic stress. Although\nlow repetition sets are carried out almost exclusively by the\nphosphocreatine system, moderate repetition schemes rely\nheavily on anaerobic glycolysis\n(144).\nThis\nresults\nin\na significant buildup of metabolites."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 56,
    "text": "Studies of bodybuilding-\nstyle exercise routines performed with multiple sets of 6–12\nreps show significant postexercise declines in ATP, creatine\nphosphate, and glycogen, along with marked increases in\nblood lactate, intramuscular lactate, glucose and glucose-\n6-phosphate (37,178).Buildup of these metabolites has been\nshown to have a significant impact on anabolic processes (96).\nIt is therefore conceivable that there is a maximum threshold\nfor tension-induced hypertrophy, above which metabolic\nfactors become more important than additional increases\nin load.\nResultant to metabolic buildup, moderate repetition range\ntraining has been shown to maximize the acute anabolic\nhormonal response of exercise."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 57,
    "text": "Both testosterone and GH are\nacutely elevated to a greater degree from routines employing\nmoderate rep sets as compared to those using lower\nrepetitions (57,90,92,94,114), thereby increasing the potential\nfor downstream cellular interactions that facilitate remodel-\ning of muscle tissue.\nTraining in a moderate repetition range also maximizes\nacute cellular hydration.During moderate rep training, the\nveins taking blood out of working muscles are compressed\nwhile arteries continue to deliver blood into the working\nmuscles, thereby creating an increased concentration of\nintramuscular blood plasma. This causes plasma to seep out of\nthe capillaries and into the interstitial spaces."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 58,
    "text": "The buildup\nof fluid in the interstitial spaces causes an extracellular\npressure gradient, which causes a flow of plasma back into the\nmuscle causing the phenomenon commonly referred to as\na ‘‘pump.’’ This is augmented by the accumulation of\nmetabolic byproducts, which function as osmolytes, drawing\nfluid into the cell (157).Whether acute exercise-induced cell\nswelling mediates muscle hypertrophy is not known, but it\nseems plausible given the known role of hydration in\nregulating cell function.\nMoreover, the extra time under tension associated with\na moderate repetition scheme as compared to a lower rep\nscheme would theoretically enhance the potential for\nmicrotrauma and fatigueability across the full spectrum of\nmuscle fibers."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 59,
    "text": "This would seem to have greatest applicability\nfor hypertrophy of slow-twitch fibers, which have greater\nendurance capacity than fast-twitch fibers and thus would\nbenefit by increased time under tension.Although slow-\ntwitch fibers are not as responsive to growth as fast-twitch\nfibers, they nevertheless do display hypertrophy when sub-\njected to an overload stimulus. Given that the majority of\nwhole muscles exhibit significant slow-twitch profiles (55,102),\nthis can potentially help to maximize whole muscle girth.\nSome researchers have postulated that muscles containing\na greater percentage of slow-twitch fibers might have the\ngreatest hypertrophic response to a higher repetition range,\nwhereas fast-twitch muscles would respond best to lower\nrepetitions (138,192)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 60,
    "text": "Although this concept is intriguing,\na fiber-type prescription with respect to repetition range\nhas not been borne out by research.Moreover, given the\nvariability of fiber-type composition between individuals, it\nwould be difficult to impossible to determine fiber-type ratios\nwithout muscle biopsy, thus making application impractical\nfor the vast majority of people.\nVolume\nA set can be defined as the number of repetitions performed\nconsecutively without rest, whereas exercise volume can be\ndefined as the product of total repetitions, sets, and load\nperformed in a training session."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 61,
    "text": "Higher-volume, multiple-set\nprotocols have consistently proven superior over single set\nprotocols with respect to increased muscle hypertrophy\n(97,197).\nIt is not clear whether the hypertrophic superiority of\nhigher-volume workloads is the product of greater total\nmuscle tension, muscle damage, metabolic stress, or some\ncombination of these factors."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 62,
    "text": "Higher-volume, body-building-\nstyle programs that generate significant glycolytic activity\nhave been consistently proven to elevate acute testosterone\nVOLUME 24 | NUMBER 10 | OCTOBER 2010 | 2863\nJournal of Strength and Conditioning Research\nthe\nTM\n| www.nsca-jscr.org\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nlevels to a greater extent than low-volume routines (92,94).\nSchwab et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 63,
    "text": "(150) showed that testosterone did not significantly\nincrease during squat performance until after completion of\nthe fourth set, indicating a clear benefit of multiple-set routines in\nthis regard.\nHigher-volume programs also have been shown to mediate\nthe acute release of GH, particularly in routines designed\nto heighten metabolic stress (70).A large body of research\nshows multiple-set protocols elicit greater GH responses\nthan single set protocols (29,124). Smilios et al. (158)\ncompared the GH response of a maximum strength (MS)\nroutine consisting of 5 reps at 88% of 1RM, 3 minutes rest\nwith a maximal hypertrophy (MH) routine consisting of 10\nreps at 75% of 1RM, 2 minutes rest in young men. Post-\nexercise GH was measured after 2, 4, and 6 sets."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 64,
    "text": "GH levels\nwere significantly greater after the 4-set compared to the\n2-set sessions in MH but not in MS, indicating a superiority\nof higher-volume routines that generate metabolite buildup.\nA split body routine where multiple exercises are per-\nformed for a specific muscle group in a session may help to\nmaximize the hypertrophic response (86).Compared to full\nbody routines, a split routine allows total weekly training\nvolume to be maintained with fewer sets performed per\ntraining session and greater recovery afforded between ses-\nsions (85). This may enable the use of heavier daily training\nloads and thus generate greater muscular tension."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 65,
    "text": "Moreover,\nsplit routines can serve to increase muscular metabolic stress\nby prolonging the training stimulus within a given muscle\ngroup, potentially heightening acute anabolic hormonal\nsecretions, cell swelling, and muscle ischemia.\nTo maximize hypertrophy, evidence exists that volume\nshould be progressively increased over a given periodized\ncycle, culminating in a brief period of overreaching.Over-\nreaching can be defined as a planned, short-term increase in\nvolume and/or intensity intended to improve performance.\nImprovements are thought to be obtained by initiating\na ‘‘rebound effect’’ where an initial decrease in anabolic drive\ncauses the body to supercompensate by significantly in-\ncreasing accretion of body proteins (42,189)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 66,
    "text": "Training status\nhas been shown to affect the overreaching response, with\nreduced detrimental effects to the endocrine system seen in\nthose with 1-plus years of experience (44).To ensure optimal\nsupercompensation, the period of overreaching should be\nfollowed by a brief taper or cessation from training (99).\nProlonged periods of overreaching, however, can rapidly\nlead to an overtrained state (62). Overtraining has catabolic\neffects on muscle tissue, and is characterized by chronically\ndecreased concentrations of testosterone and luteinizing\nhormone, and increased cortisol levels (43,58,140)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 67,
    "text": "The\ncytokine hypothesis of overtraining states that primary cause\nof overtraining syndrome is repetitive trauma to the\nmusculoskeletal system resulting from high-intensity and\nhigh-volume training (159,160).However, studies seem to\nshow that overtraining is more a result of excessive volume\nthan intensity (43,59). Given that recuperative abilities are\nhighly variable between individuals, it is essential to be\ncognizant of an athlete’s training status and adjust volume\naccordingly to avoid a negative effect on protein accretion.\nFurthermore, the quest to train with a high volume must be\nbalanced with performance decrements arising from lengthy\nexercise sessions."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 68,
    "text": "Long workouts tend to be associated with\nreduced intensity of effort, decreased motivation, and alter-\nations in immune response (92)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 69,
    "text": "Accordingly, it has been\nproposed that intense workouts should not last longer than\none hour to ensure maximal training capacity throughout the\nsession (205).\nExercise Selection\nIt is a well-accepted fitness tenet that varying exercise\nparameters (i.e., angle of pull, position of extremities, etc.) can\ncause different activation patterns within muscle compart-\nments, and making synergists more active or less active (17).\nThis is particularly important in a hypertrophy-oriented\nprotocol, where promoting uniform growth of muscle tissue\nis essential for maximizing overall muscle girth.\nMuscles can have different attachment sites that provide\ngreater leverage for varying actions."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 70,
    "text": "The trapezius, for\nexample, is subdivided so that the upper aspect elevates the\nscapula, the middle aspect abducts the scapula and the lower\nportion depresses the scapula (103).With respect to the\npectoralis major, the sternal head is significantly more active\nthan the clavicular head in the decline bench press (46).\nFurther, the clavicular head of the pectoralis major and long\nhead of the triceps have been shown to be more active in the\nnarrow grip bench press vs. the wide grip variation, with\nanterior deltoid activity increasing in conjunction with\nincreases in the degree of trunk inclination (14).\nRegional differences within various muscles can impact\ntheir response to exercise choice."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 71,
    "text": "For example, slow and fast\nMUs are often scattered across muscle, so that a slow-twitch\nfiber can be activated while an adjacent fast-twitch fiber is\ninactive and vice versa (7).Moreover, muscles are sometimes\ndivided into neuromuscular components—distinct regions\nof muscle each of which is innervated by its own nerve\nbranch—suggesting that portions of a muscle can be called\ninto play depending on the activity (7). For example, the\nsartorius, gracilis, biceps femoris, and semitendinosus are all\nsubdivided by one or more fibrous bands or inscriptions, with\neach compartment innervated by separate nerve branches\n(193,198)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 72,
    "text": "Further, the gracilis and sartorius are composed of\nrelatively short, in series fibers that terminate intrafascicu-\nlarly, refuting the supposition that muscle fibers always span\nthe entire origin to insertion (67).\nThe effects of muscle partitioning on mechanical activity\nare seen in the biceps brachii, where both the long and short\nheads have architectural compartments that are innervated\nby private branches of the primary neurons (151)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 73,
    "text": "Studies\ninvestigating muscle activity of the long head of the biceps\nbrachii show that MUs in the lateral aspect are recruited for\nelbow flexion, MUs in the medial aspect are recruited for\n2864\nJournal of Strength and Conditioning Research\nthe\nTM\nMechanisms of Muscle Hypertrophy\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nsupination, and centrally located MUs are recruited for non-\nlinear combinations of flexion and supination (175,176,184).\nFurther, the short head appears to be more active in the latter\npart of an arm curl (i.e., greater elbow flexion), whereas the\nlong head is more active in the early phase (21).\nThese architectural variances of muscle give support for\nthe need to adopt a multiplanar, multiangled approach to\nhypertrophy training using a variety of different exercises.\nMoreover, given the need to fully stimulate all fibers within\na muscle, it would seem that a frequent exercise rotation is\nwarranted to maximize the hypertrophic response.\nThere is evidence to support the inclusion of both\nmultijoint and single-joint exercises in a hypertrophy-specific\nroutine."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 74,
    "text": "Multijoint exercises recruit large amounts of muscle\nmass to carry out work.This has an impact on the anabolic\nhormonal response to training. Specifically, the magnitude\nof postexercise hormonal elevations has been shown to be\nrelated to the extent of muscle mass involved, with multijoint\nmovements producing larger increases in both testosterone\nand GH levels compared to single-joint exercises (64,91).\nMoreover, multijoint movements tend to require significant\nstabilization of the entire body, thereby involving numerous\nmuscles that otherwise might not be stimulated in the per-\nformance of single-joint movements."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "chunk_id": 75,
    "text": "The squat, for example,\ndynamically recruits not only the quadriceps femoris and hip\nextensors but also most of the other lower body muscles\nincluding the hip adductors, hip abductors, and triceps surae\n(132).In addition, significant isometric activity is required by\na wide range of supporting muscles (including the abdomi-\nnals, erector spinae, trapezius, rhomboids, and many others)\nto facilitate postural stabilization of the trunk. In all, it is\nestimated that over 200 muscles are activated during squat\nperformance (167)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 76,
    "text": "To achieve a comparable degree of mus-\ncular coverage would necessitate the performance of dozens\nof single-joint movements—a strategy that is both inefficient\nand impractical.\nOn the other hand, single-joint exercises allow for a greater\nfocus on individual muscles compared to multijoint move-\nments.During performance of multijoint movements, certain\nprime movers may take precedence over others, creating\na hypertrophic imbalance between muscles. The use of single-\njoint exercises can selectively target underdeveloped muscles,\nimproving muscular symmetry."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 77,
    "text": "Moreover, the unique archi-\ntecture of individual muscles suggests employing single-joint\nmovements can elicit differing neuromuscular activation\npatterns that heighten overall muscular development (7).\nThe use of unstable surfaces in a hypertrophy-oriented\nroutine is generally not supported by research.Resistance\nexercise on an unstable surface requires extensive activation of\nthe core musculature to carry out performance (6,110). This,\nin turn, results in significant decreases in force output to the\nprime muscle movers. Anderson and Behm (5) found that\nforce output was 59.6% lower when performing a chest press\non an unstable surface compared to a stable surface. Similarly,\nMcBride et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 78,
    "text": "(112) demonstrated significant reductions in\npeak force and rate of force development (by 45.6 and 40.5%,\nrespectively) when performing a squat on an unstable vs.\nstable surface.Such large reductions in force output diminish\ndynamic tension to the target muscles, mitigating the\nhypertrophic response.\nAn exception to the use of unstable surfaces in a hypertro-\nphy-oriented routine involves exercises for the core muscu-\nlature. Sternlicht et al. (164) found that crunches performed\non a stability ball elicited significantly greater muscle activity\nin both the upper and lower rectus abdominus than crunches\nperformed under stable conditions. Similar results were\nshown by Vera-Garcia et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 79,
    "text": "(186), who displayed significantly\nincreased activity of both the rectus abdominis and the exter-\nnal obliques when performing curl ups on an unstable surface\ncompared to a stable surface.These results suggest a role for\nunstable surface training in developing the abdominals.\nRest Interval\nThe time taken between sets is referred to as the rest interval.\nRest intervals can be classified into 3 broad categories: short\n(30 seconds or less), moderate (60–90 seconds), and long (3\nminutes or more). The use of each of these categories has\ndistinct effects on strength capacity and metabolite buildup,\nthereby impacting the hypertrophic response (195).\nShort rest intervals tend to generate significant metabolic\nstress, thereby heightening anabolic processes associated with\nmetabolite buildup (52)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 80,
    "text": "However, limiting rest to 30 seconds\nor less does not allow sufficient time for an athlete to regain\nmuscular strength, significantly impairing muscular perfor-\nmance in subsequent sets (137,141).Thus, the hypertrophic\nbenefits associated with greater metabolic stress are seem-\ningly counterbalanced by a decreased strength capacity,\nmaking short rest intervals suboptimal for maximizing\nhypertrophic gains.\nLong rest intervals afford full recovery of strength between\nsets, facilitating the ability to train with maximum force\ncapacity (121). de Salles et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 81,
    "text": "(32) displayed that rest intervals\nof 3–5 minutes allowed for greater repetitions over multiple\nsets when training with loads between 50 and 90% of 1RM.\nHowever, although mechanical tension is maximized by long\nrest periods, metabolic stress is compromised (92,94).This\nmay blunt anabolic drive, attenuating a maximal hypertro-\nphic response.\nModerate rest intervals appear to provide a satisfactory\ncompromise between long and short rest periods for\nmaximizing the muscle hypertrophy. Research indicates that\na majority of an athlete’s strength capacity is recovered within\nthe first minute after cessation of a set (168)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 82,
    "text": "Moreover,\nconsistently training with shorter rest intervals leads to\nadaptations that ultimately allow a lifter to sustain a signif-\nicantly higher mean percentage of 1RM during training (95).\nThese adaptations include increased capillary and mito-\nchondrial density and an improved capacity to buffer H+ and\nshuttle it out of muscle, thereby minimizing performance\ndecrements.\nVOLUME 24 | NUMBER 10 | OCTOBER 2010 | 2865\nJournal of Strength and Conditioning Research\nthe\nTM\n| www.nsca-jscr.org\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\nModerate rest intervals also help to enhance the body’s\nanabolic environment to a greater extent than longer rest\nintervals."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 83,
    "text": "For one, moderate rest induces greater hypoxia,\nheightening the potential for increased muscular growth\n(182).Moderate rest also is associated with a greater metab-\nolic buildup, mediating a large spike in anabolic hormonal\nconcentrations after exercise (94). However, there is some\nevidence that this hormonal advantage is not sustained over\ntime. Buresh et al. (22) compared the anabolic hormonal\nresponse to routines with rest intervals of 1 vs. 2.5 minutes.\nAlthough the shorter rest intervals had a significantly greater\nimpact on elevating GH levels in the early stages of the\nprotocol, the difference in hormonal response was not\nsignificant between routines by end of the fifth week and\nwas nonexistent by week 10."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 84,
    "text": "This suggests a postadaptive\nresponse by the muscles to reduced rest intervals, lending\nsupport to the need for periodization in a hypertrophy-\noriented resistance training program.\nMuscular Failure\nMuscular failure can be defined as the point during a set when\nmuscles can no longer produce necessary force to concen-\ntrically lift a given load.Although the merits of training\nto failure are still a matter of debate, it is commonly believed\nthat training to muscular failure is necessary to maximize\nthe hypertrophic response (196). Several theories have been\nproposed in support of this contention.\nFor one, training to failure is hypothesized to activate\na greater number of MUs (196)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 85,
    "text": "When a lifter becomes\nfatigued, a progressively greater number of MUs are recruited\nto continue activity, providing an additional stimulus for\nhypertrophy (145).In this way, failure may provide increased\nstimulation to the highest threshold MUs when moderate\nrepetition ranges are employed.\nTraining to failure also may enhance exercise-induced\nmetabolic stress, thereby potentiating a hypertrophic re-\nsponse. Continuing to train under conditions of anaerobic\nglycolysis heightens the buildup of metabolites, which in turn\nenhances the anabolic hormonal milieu. Linnamo et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 86,
    "text": "(104)\ndisplayed that performing sets at 10RM to failure caused\na significantly greater postexercise elevation in GH secretion\ncompared to the same load not performed to failure.\nAlthough training to failure does appear to confer hyper-\ntrophic benefits, there is evidence that it also increases the\npotential for overtraining and psychological burnout (43).\nIzquierdo et al.(76) found that training to failure caused\nreductions in resting IGF-1 concentrations and a blunting of\nresting testosterone levels over a 16-week protocol, suggest-\ning that subjects may have been overtrained."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 87,
    "text": "Thus, although\nit seems prudent to include sets performed to failure in\na hypertrophy-oriented program, its use should be perio-\ndized and/or limited to avoid an overtrained state.\nRepetition Speed\nThe speed with which a lifter performs repetitions can impact\nthe hypertrophic response.Despite limitations both in the\nquantity of research and aspects of study design, some\nconclusions can be drawn on the topic.\nWith respect to concentric repetitions, there is some\nevidence that faster repetitions are beneficial for hypertrophy.\nNogueira et al. (133) found that performing concentric\nactions at 1-second cadence instead of three seconds had\ngreater impact on both upper and lower limb muscle thick-\nness in elderly men."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 88,
    "text": "This may be attributed to an increased\nrecruitment and corresponding fatigue of high-threshold\nMUs.Other studies, however, suggest that training at moder-\nate speeds has greater effects on hypertrophy (56), perhaps\nthrough a heightened metabolic demand (12). Maintaining\ncontinuous muscle tension at moderate repetition speeds also\nhas been shown to enhance muscle ischemia and hypoxia,\nthereby augmenting the hypertrophic response (174)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 89,
    "text": "Train-\ning at very slow velocities (i.e., superslow training) has\ngenerally been shown to be suboptimal for the development\nof strength and hypertrophy (82,129), and therefore should\nnot be employed when the goal is to maximize muscle growth.\nFrom a hypertrophy standpoint, speed of movement may\nhave greater importance on the eccentric component of a\nrepetition.Although concentric and isometric contractions\nhave been shown to produce a hypertrophic response, a\nmajority of studies seem to show that eccentric actions have\nthe greatest effect on muscle development. Specifically,\nlengthening exercise is associated with a more rapid rise in\nprotein synthesis (122) and greater increases in IGF-1 mRNA\nexpression (152) compared to shortening exercise."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 90,
    "text": "Moreover,\nisotonic and isokinetic training that does not include\neccentric contractions result in less hypertrophy than those\nthat include lengthening contractions (39,68,74).\nThe hypertrophic superiority of eccentric exercise is largely\nattributed to a greater muscular tension under load.It is\ntheorized that this is because of a reversal of the size principle\nof recruitment, which results in fast-twitch fibers being\nselectively recruited (152,173). This was demonstrated by\nNardone and Schieppati (128), who showed derecruitment of\nthe slow-twitch soleus muscle and a corresponding increase\nin activity of the gastroc during eccentric plantar flexion\ncontractions."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 91,
    "text": "There is also evidence that eccentric contrac-\ntions result in additional recruitment of previously inactive\nMUs (116,127).\nAs a result of the excessive stress on a small number of\nactive fibers, eccentric exercise also is associated with greater\nmuscle damage when compared to concentric and isometric\ncontractions (116).This manifests as Z-line streaming, which\ncurrent\nresearch\nsuggests\nis\nindicative\nof\nmyofibrillar\nremodeling\n(30,204).\nIt\nhas\nbeen\nshown\nthat MyoD\nmRNA expression is specifically upregulated by eccentric\ncontractions (78).\nShepstone et al."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 92,
    "text": "(152) found that fast (3.66 rads\u0001s21) eccen-\ntric repetitions resulted in significantly greater hypertrophy\nof type II fibers compared to slow (0.35 rad\u0001s21) repetitions.\nThis is consistent with the lengthening portion of the force–\nvelocity curve, which shows greater muscle forces are\n2866\nJournal of Strength and Conditioning Research\nthe\nTM\nMechanisms of Muscle Hypertrophy\nCopyright © National Strength and Conditioning Association Unauthorized reproduction of this article is prohibited.\ngenerated at higher velocities.However, findings of this study\nare limited because subjects trained on an isokinetic\ndynamometer, which provides a resistive force against the\nagonist muscle and is not gravity dependent."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 93,
    "text": "Traditional\ndynamic constant resistance exercise (i.e., free weights, cable\npulleys, etc.) does not confer such an advantage.Rather,\neccentric contractions are aided by the pull of gravitational\nforce, requiring the lifter to resist gravity to sustain muscular\ntension. Thus, a slower speed of movement is necessary to\nmaximize the training response (45).\nPRACTICAL APPLICATIONS\nCurrent research suggests that maximum gains in muscle\nhypertrophy are achieved by training regimens that produce\nsignificant metabolic stress while maintaining a moderate\ndegree of muscle tension. A hypertrophy-oriented program\nshould employ a repetition range of 6–12 reps per set with rest\nintervals of 60–90 seconds between sets."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 94,
    "text": "Exercises should\nbe varied in a multiplanar, multiangled fashion to ensure\nmaximal stimulation of all muscle fibers.Multiple sets should\nbe employed in the context of a split training routine to\nheighten the anabolic milieu. At least some of the sets should\nbe carried out to the point of concentric muscular failure,\nperhaps alternating microcycles of sets to failure with those\nnot performed to failure to minimize the potential for\novertraining. Concentric repetitions should be performed at\nfast to moderate speeds (1–3 seconds) while eccentric\nrepetitions should be performed at slightly slower speeds\n(2–4 seconds)."
  },
  {
    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
    "pdf_title": "",
    "chunk_id": 95,
    "text": "Training should be periodized so that the\nhypertrophy phase culminates in a brief period of higher-\nvolume overreaching followed by a taper to allow for optimal\nsupercompensation of muscle tissue.\nACKNOWLEDGMENT\nThe author would like to thank Dr.William Kraemer, Dr.\nJames Eldridge, and Dr. Sue Mottinger for their assistance and\nguidance in this research review.\nREFERENCES\n1. Abernethy, PJ, Ju¨rima¨e, J, Logan, PA, Taylor, AW, and Thayer, RE.\nAcute and chronic response of skeletal muscle to resistance\nexercise. Sports Med 17: 22–38, 1994.\n2. Ahtiainen, JP, Pakarinen, A, Alen, M, Kraemer, WJ, and\nHa¨kkinen, K. Muscle hypertrophy, hormonal adaptations and\nstrength development during strength training in strength-trained\nand untrained men. Eur J Appl Physiol 89: 555–563, 2003.\n3."
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    "text": "Ale´n, M, Pakarinen, A, Ha¨kkinen, K, and Komi, PV.Responses of\nserum androgenic-anabolic and catabolic hormones to prolonged\nstrength training. Int J Sport Med 9: 229–233, 1988.\n4. Allen, DG, Whitehead, NP, and Yeung, EW. Mechanisms of\nstretch-induced muscle damage in normal and dystrophic muscle:\nRole of ionic changes. J Physiol 567: 723–735, 2005.\n5. Anderson, KG and Behm, DG. Maintenance of EMG activity and\nloss of force output with instability. J Strength Cond Res 18: 637–640,\n2004.\n6. Anderson, KG and Behm, DG. Trunk muscle activity increases\nwith unstable squat movements. Can J Appl Physiol 30: 33–45, 2005.\n7. Antonio, J. Nonuniform response of skeletal muscle to heavy\nresistance training: can bodybuilders induce regional muscle\nhypertrophy?"
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    "filename": "the_mechanisms_of_muscle_hypertrophy_and_their.40.pdf",
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    "text": "Claims for the anabolic effects of growth hormone:\nA case of the emperor’s new clothes?Br J Sport Med 37: 100–105,\n2003.\n144. Robergs, RA, Ghiasvand, F, and Parker, D. Biochemistry of exercise\ninduced metabolic acidosis. Am J Physiol. Reg Int Comp Physiol\n287: R502–R516, 2003.\n145. Rooney, KJ, Herbert, RD, and Balnave, RJF. Fatigue contributes to\nthe strength training stimulus. Med Sci Sport Exerc 26: 1160–1164,\n1994.\n146. Rosenblatt, JD, Yong, D, and Parry, DJ. Satellite cell activity is\nrequired for hypertrophy of overloaded adult rat muscle. Mus Nerve\n17: 608–613, 1994.\n147. Roux, PP and Blenis, J. ERK and p38 MAPK-activated protein\nkinases: A family of protein kinases with diverse biological\nfunctions. Microbiol Mol Biol Rev 68: 320–344, 2004.\n148. Sabourin, LA and Rudnicki, MA."
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  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 0,
    "text": "n engl j med 360;9  nejm.org  february 26, 2009\n859\nThe new england  \njournal of medicine\nestablished in 1812\t\nfebruary 26, 2009\t\nvol. 360 \nno. 9\nComparison of Weight-Loss Diets with Different Compositions \nof Fat, Protein, and Carbohydrates \nFrank M. Sacks, M.D., George A. Bray, M.D., Vincent J. Carey, Ph.D., Steven R. Smith, M.D., Donna H. Ryan, M.D., \nStephen D. Anton, Ph.D., Katherine McManus, M.S., R.D., Catherine M. Champagne, Ph.D., Louise M. Bishop, M.S., R.D., \nNancy Laranjo, B.A., Meryl S. Leboff, M.D., Jennifer C. Rood, Ph.D., Lilian de Jonge, Ph.D., Frank L. Greenway, M.D., \nCatherine M. Loria, Ph.D., Eva Obarzanek, Ph.D., and Donald A."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 1,
    "text": "Williamson, Ph.D.\nAbstr act\nFrom the Department of Nutrition, Har-\nvard School of Public Health (F.M.S., \nL.M.B.); \nthe \nChanning \nLaboratory \n(F.M.S., V.J.C., N.L.) and the Endocrine \nDivision (M.S.L.), Department of Medi-\ncine, Brigham and Women’s Hospital \nand Harvard Medical School; and the De-\npartment of Nutrition, Brigham and \nWomen’s Hospital (K.M.) — all in Bos-\nton; Pennington Biomedical Research \nCenter of the Louisiana State University \nSystem, Baton Rouge (G.A.B., S.R.S., \nD.H.R., S.D.A., C.M.C., J.C.R., L.J., F.L.G., \nD.A.W.); and the National Heart, Lung, \nand Blood Institute, Bethesda, MD \n(C.M.L., E.O.)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 2,
    "text": "N Engl J Med 2009;360:859-73.\nCopyright © 2009 Massachusetts Medical Society.\nBackground\nThe possible advantage for weight loss of a diet that emphasizes protein, fat, or car-\nbohydrates has not been established, and there are few studies that extend beyond \n1 year.\nMethods\nWe randomly assigned 811 overweight adults to one of four diets; the targeted per-\ncentages of energy derived from fat, protein, and carbohydrates in the four diets were \n20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%.The diets \nconsisted of similar foods and met guidelines for cardiovascular health. The partici-\npants were offered group and individual instructional sessions for 2 years."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 3,
    "text": "The pri-\nmary outcome was the change in body weight after 2 years in two-by-two factorial \ncomparisons of low fat versus high fat and average protein versus high protein and \nin the comparison of highest and lowest carbohydrate content.\nResults\nAt 6 months, participants assigned to each diet had lost an average of 6 kg, which \nrepresented 7% of their initial weight; they began to regain weight after 12 months."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 4,
    "text": "By 2 years, weight loss remained similar in those who were assigned to a diet with \n15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respec-\ntively); in those assigned to a diet with 20% fat and those assigned to a diet with \n40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbo-\nhydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, re-\nspectively) (P>0.20 for all comparisons).Among the 80% of participants who com-\npleted the trial, the average weight loss was 4 kg; 14 to 15% of the participants had \na reduction of at least 10% of their initial body weight."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 5,
    "text": "Satiety, hunger, satisfaction \nwith the diet, and attendance at group sessions were similar for all diets; atten-\ndance was strongly associated with weight loss (0.2 kg per session attended).The \ndiets improved lipid-related risk factors and fasting insulin levels.\nConclusions\nReduced-calorie diets result in clinically meaningful weight loss regardless of which \nmacronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.)\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025. For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 6,
    "text": "All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n860\nT\nhere is intense debate about what \ntypes of diet are most effective for treating \noverweight — those that emphasize protein, \nthose that emphasize carbohydrates, or those that \nemphasize fat.1-3 Several trials showed that low-\ncarbohydrate, high-protein diets resulted in more \nweight loss over the course of 3 to 6 months than \nconventional high-carbohydrate, low-fat diets,4-12 \nbut other studies did not show this effect.13-17 \nA smaller group of studies that extended the fol-\nlow-up to 1 year did not show that low-carbohy-\ndrate, high-protein diets were superior to high-\ncarbohydrate, low-fat diets.6,10,16,18-21 In contrast, \nother researchers found that a very-high-carbohy-\ndrate, very-low-fat vegetarian diet was superior to \na conventional high-carbohydrate, low-fat diet.22‑24 \nAmong the few studies that extended beyond  \n1 year, one showed that a very-low-fat vegetarian \ndiet was superior to a conventional low-fat diet,24 \none showed that a low-fat diet was superior to a \nmoderate-fat diet,25 two showed that a moderate-\nfat, Mediterranean-style diet was superior to a low-\nfat diet,12,26 one showed that a low-carbohydrate \ndiet was superior to a low-fat diet,12 and another \nshowed no difference between high-protein and \nlow-protein diets.10 Small samples, underrepresen-\ntation of men, limited generalizability, a lack of \nblinded ascertainment of the outcome, a lack of \ndata on adherence to assigned diets, and a large \nloss to follow-up limit the interpretation of many \nweight-loss trials.27 The novelty of the diet, media \nattention, and the enthusiasm of the researchers \ncould affect the adherence of participants to any \ntype of diet."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 7,
    "text": "The crucial question is whether over-\nweight people have a better response in the long \nterm to diets that emphasize a specific macronu-\ntrient composition.Thus, we recognized the need \nfor a large trial that would be designed to over-\ncome the limitations of previous trials and that \nwould compare the effects of three principal di-\netary macronutrients."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 8,
    "text": "We studied weight change \nover the course of 2 years, since weight loss typi-\ncally is greatest 6 to 12 months after initiation \nof the diet, with steady regain of weight subse-\nquently.28\nMethods\nStudy Design and Sites\nWe designed a randomized clinical trial to com-\npare the effects on body weight of energy-reduced \ndiets that differed in their targets for intake of \nmacronutrients — low or high in fat, average or \nhigh in protein, or low or high in carbohydrates \n— and otherwise followed recommendations for \ncardiovascular health.29 The trial was conducted \nfrom October 2004 through December 2007.An \nexpanded description of the methods is available \nin the Supplementary Appendix, available with the \nfull text of this article at NEJM.org."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 9,
    "text": "The trial was \nconducted at two sites: the Harvard School of Pub-\nlic Health and Brigham and Women’s Hospital, \nBoston; and the Pennington Biomedical Research \nCenter of the Louisiana State University System, \nBaton Rouge.The data coordinating center was at \nBrigham and Women’s Hospital. The project staff \nof the National Heart, Lung, and Blood Institute \nalso participated in the development of the proto-\ncol, monitoring of progress, interpretation of re-\nsults, and critical review of the manuscript.\nParticipants\nOur goal was to recruit 800 overweight and obese \nsubjects (400 at each site), of whom about 40% \nwould be men. Participants had to be 30 to 70 years \nof age and have a body-mass index (the weight in \nkilograms divided by the square of the height in \nmeters) of 25 to 40."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 10,
    "text": "Major criteria for exclusion \nwere the presence of diabetes or unstable cardio-\nvascular disease, the use of medications that affect \nbody weight, and insufficient motivation as as-\nsessed by interview and questionnaire.The study \nwas approved by the human subjects committee at \neach institution and by a data and safety monitor-\ning board appointed by the National Heart, Lung, \nand Blood Institute. All participants gave written \ninformed consent. They were informed that the \nstudy would be comparing diets with different fat, \nprotein, and carbohydrate contents and that they \nwould be assigned a diet at random. Mass mailings \nwere the primary means of recruitment; names were \nidentified with the use of lists of registered voters \nor drivers."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 11,
    "text": "Random assignments to one of four diet \ngroups were generated by the data manager at the \ncoordinating center on request of a study dietitian, \nafter eligibility of a participant was confirmed.\nWeight-Loss Intervention\nThe nutrient goals for the four diet groups were: \n20% fat, 15% protein, and 65% carbohydrates (low-\nfat, average-protein); 20% fat, 25% protein, and \n55% carbohydrates (low-fat, high-protein); 40% fat, \n15% protein, and 45% carbohydrates (high-fat, av-\nerage-protein); and 40% fat, 25% protein, and 35% \ncarbohydrates (high-fat, high-protein).Thus, two \ndiets were low-fat and two were high-fat, and two \nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 12,
    "text": "For personal use only.\n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n861\nwere average-protein and two were high-protein, \nconstituting a two-by-two factorial design. The four \ndiets also allowed for a dose–response test of car-\nbohydrate intake that ranged from 35 to 65% of \nenergy. Other goals for all groups were that the \ndiets should include 8% or less of saturated fat, \nat least 20 g of dietary fiber per day, and 150 mg \nor less of cholesterol per 1000 kcal. Carbohydrate-\nrich foods with a low glycemic index were recom-\nmended in each diet."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 13,
    "text": "Each participant’s caloric pre-\nscription represented a deficit of 750 kcal per day \nfrom baseline, as calculated from the person’s rest-\ning energy expenditure and activity level.\nBlinding was maintained by the use of similar \nfoods for each diet.Staff and participants were \ntaught that each diet adhered to principles of a \nhealthful diet29 and that each had been recom-\nmended for long-term weight loss, thereby estab-\nlishing equipoise.1,2,26 Investigators and staff who \nmeasured outcomes were unaware of the diet as-\nsignment of the participants.\nGroup sessions were held once a week, 3 of \nevery 4 weeks during the first 6 months and 2 of \nevery 4 weeks from 6 months to 2 years; individu-\nal sessions were held every 8 weeks for the entire \n2 years."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 14,
    "text": "Daily meal plans in 2-week blocks were \nprovided (see the Supplementary Appendix).Par-\nticipants were instructed to record their food and \nbeverage intake in a daily food diary and in a Web-\nbased self-monitoring tool that provided informa-\ntion on how closely their daily food intake met the \ngoals for macronutrients and energy. Behavioral \ncounseling was integrated into the group and \nindividual sessions to promote adherence to the \nassigned diets. Contact among the groups was \navoided.\nThe goal for physical activity was 90 minutes \nof moderate exercise per week."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 15,
    "text": "Participation in \nexercise was monitored by questionnaire30 and by \nthe online self-monitoring tool.\nMeasurements\nBody weight and waist circumference were mea-\nsured in the morning before breakfast on 2 days \nat baseline, 6 months, and 2 years, and on a single \nday at 12 and 18 months.Dietary intake was as-\nsessed in a random sample of 50% of the par-\nticipants, by a review of the 5-day diet record at \nbaseline and by 24-hour recall during a telephone \ninterview on 3 nonconsecutive days at 6 months \nand at 2 years.31 Questionnaires that asked for in-\nformation on satiety, food craving, eating behav-\nior, and satisfaction with the diet32,33 were admin-\nistered at baseline (except for diet satisfaction) and \nat 6 months and 2 years."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 16,
    "text": "Fasting blood samples, \n24-hour urine samples, and measurement of rest-\ning metabolic rate were obtained on 1 day, and \nblood-pressure measurement on 2 days, at base-\nline, 6 months, and 2 years.Levels of serum lip-\nids, glucose, insulin, and glycated hemoglobin were \nmeasured at the clinical laboratory at the Penning-\nton Biomedical Research Center. Blood pressure \nwas measured with the use of an automated de-\nvice (HEM-907XL, Omron)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 17,
    "text": "The participants were \nevaluated for the presence of the metabolic syn-\ndrome, which was defined by the presence of at \nleast three of the following five criteria: waist cir-\ncumference of more than 102 cm in men or more \nthan 88 cm in women, a triglyceride level of 150 mg \nper deciliter (1.69 mmol per liter) or more, a high-\ndensity lipoprotein (HDL) cholesterol level of less \nthan 40 mg per deciliter (1.03 mmol per liter) in \nmen or less than 50 mg per deciliter (1.29 mmol per \nliter) in women, a blood pressure of 130/85 mm Hg \nor more, and a fasting glucose level of 110 mg per \ndeciliter (6.1 mmol per liter) or more.\nStatistical Analysis\nThe primary outcome of the study was the change \nin body weight over a period of 2 years, and the \nsecondary outcome was the change in waist cir-\ncumference."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 18,
    "text": "Data were pooled from the diets for \nthe two factorial comparisons: low fat versus high \nfat and average protein versus high protein.The \nanalysis also included a comparison of two of the \nfour diets, the diet with the lowest carbohydrate \ncontent and the diet with the highest carbohydrate \ncontent, and included a test for trend across the \nfour levels of carbohydrates. The effects of protein, \nfat, and carbohydrate levels were evaluated inde-\npendently with the use of two-sample t-tests at a \ntwo-sided significance level of 0.05. Exploratory \npost hoc analyses were performed with threshold \namounts of weight loss as outcomes, with Bonfer-\nroni’s adjustment for multiple comparisons."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 19,
    "text": "As-\nsociations between adherence to the fat and pro-\ntein goals and weight loss were also explored in \npost hoc analyses (see Methods in the Supplemen-\ntary Appendix).\nWe performed an intention-to-treat analysis in \nwhich long-term weight loss for persons who with-\ndrew from the study early (after at least 6 months \nof participation) was imputed on the basis of a rate \nof 0.3 kg per month of regained weight34 and a \nrate of 0.3 cm per month of regained waist circum-\nference after withdrawal (see Methods in the Sup-\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 20,
    "text": "All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n862\nplementary Appendix).Risk factors for cardiovas-\ncular disease and diabetes were also analyzed \naccording to the intention-to-treat principle, with \nzero change from baseline imputed for missing \ndata. The study was powered to detect a 1.67-kg \nweight loss as an effect of the level of protein or \nfat in the diet over the 2-year period, assuming \na withdrawal rate of 40%.\nTable 1."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 21,
    "text": "Baseline Characteristics of the Study Participants.*\nCharacteristic\nLow-Fat, \nAverage- \nProtein Group\n(N = 204)\nLow-Fat, \nHigh-Protein \nGroup\n(N = 202)\nHigh-Fat, \nAverage- \nProtein Group\n(N = 204)\nHigh-Fat, \nHigh-Protein \nGroup\n(N = 201)\nAll \nParticipants\n(N = 811)\nParticipants \nWho \nCompleted \nthe Study\n(N = 645)\nAge — yr\n51±9\n50±10\n52±9\n51±9\n51±9\n52±9\nSex — no.(%)\nFemale\n126 (62)\n135 (67)\n125 (61)\n129 (64)\n515 (64)\n397 (62)\nMale\n78 (38)\n67 (33)\n79 (39)\n72 (36)\n296 (36)\n248 (38)\nRace or ethnic group — no."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 22,
    "text": "(%)†\nWhite\n159 (78)\n158 (78)\n165 (81)\n161 (80)\n643 (79)\n525 (81)\nBlack \n33 (16)\n33 (16)\n28 (14)\n33 (16)\n127 (16)\n88 (14)\nAsian\n1 (<1)\n1 (<1)\n1 (<1)\n2 (1)\n5 (1)\n3 (<1)\nHispanic\n8 (4)\n7 (3)\n9 (4)\n5 (2)\n29 (4)\n23 (4)\nOther\n3 (1)\n3 (1)\n1 (<1)\n0\n7 (1)\n6 (1)\nHeight — m \n1.69±0.09\n1.67±0.08\n1.68±0.09\n1.68±0.09\n1.68±0.09\n1.68±0.09\nWeight — kg \n94±16\n92±13\n92±17\n94±16\n93±16\n93±16\nBody-mass index‡\nMean\n33±4\n33±4\n32±4\n33±4\n33±4\n33±4\n25.0–29.9 — no.(%)\n51 (25)\n54 (27)\n60 (29)\n58 (29)\n223 (27)\n183 (28)\n≥30.0 — no. (%)\n153 (75)\n148 (73)\n144 (71)\n143 (71)\n588 (73)\n462 (72)\nWaist circumference — cm\n104±13\n102±12\n103±14\n104±13\n103±13\n104±13\nHypertension — no. (%)\n70 (34)\n70 (35)\n67 (33)\n80 (40)\n287 (35)\n233 (36)\nUse of medication — no."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 23,
    "text": "(%)\nAntihypertensive agents\n54 (26)\n58 (29)\n55 (27)\n61 (30)\n228 (28)\n192 (30)\nLipid-lowering agents\n32 (16)\n48 (24)\n40 (20)\n31 (15)\n151 (19)\n128 (20)\nSmoking status — no.(%)\nCurrent smoker\n8 (4)\n5 (2)\n8 (4)\n10 (5)\n31 (4)\n24 (4)\nFormer smoker\n84 (41)\n59 (29)\n80 (39)\n75 (37)\n298 (37)\n241 (37)\nNever smoked\n112 (55)\n138 (68)\n116 (57)\n116 (58)\n482 (59)\n380 (59)\nEducational level — no. (%)\nHigh school or less\n23 (11)\n15 (7)\n19 (9)\n19 (9)\n76 (9)\n65 (10)\nSome college\n47 (23)\n47 (23)\n45 (22)\n41 (20)\n180 (22)\n132 (20)\nCollege graduate or beyond \n134 (66)\n140 (69)\n140 (69)\n141 (70)\n555 (68)\n448 (69)\nMarital status — no."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 24,
    "text": "(%)\nMarried\n132 (65)\n146 (72)\n144 (71)\n143 (71)\n565 (70)\n448 (69)\nDivorced or separated\n36 (18)\n24 (12)\n33 (16)\n29 (14)\n122 (15)\n94 (15)\nWidowed\n8 (4)\n4 (2)\n4 (2)\n2 (1)\n18 (2)\n16 (2)\nNever married\n28 (14)\n28 (14)\n23 (11)\n27 (13)\n106 (13)\n87 (13)\n \nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 25,
    "text": "All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n863\nResults\nParticipants\nOf 1638 participants who were screened, 811 (50%) \nwere randomly assigned to a diet, and 645 (80% \nof those assigned) completed the study (i.e., pro-\nvided a body-weight measurement at 2 years) (Fig.1 \nin the Supplementary Appendix). Baseline charac-\nteristics were similar among participants assigned \nto the four diets and between those who were as-\nTable 1."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 26,
    "text": "(Continued.)\nCharacteristic\nLow-Fat, \nAverage- \nProtein Group\n(N = 204)\nLow-Fat, \nHigh-Protein \nGroup\n(N = 202)\nHigh-Fat,  \nAverage- \nProtein Group\n(N = 204)\nHigh-Fat, \nHigh-Protein \nGroup\n(N = 201)\nAll \nParticipants\n(N = 811)\nParticipants \nWho \nCompleted \nthe Study\n(N = 645)\nHousehold income — no."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 27,
    "text": "(%)\n<$50,000\n56 (27)\n45 (22)\n48 (24)\n46 (23)\n195 (24)\n153 (24)\n$50,000 to <$100,000\n79 (39)\n82 (41)\n78 (38)\n84 (42)\n323 (40)\n260 (40)\n$100,000 to $150,000\n46 (23)\n43 (21)\n43 (21)\n32 (16)\n164 (20)\n123 (19)\n>$150,000\n21 (10)\n30 (15)\n33 (16)\n36 (18)\n120 (15)\n100 (16)\nInformation not provided\n2 (1)\n2 (1)\n2 (1)\n3 (1)\n9 (1)\n9 (1)\nRisk factors\nBlood pressure — mm Hg\nSystolic \n118±13\n120±13\n120±13\n120±15\n119±13\n119±14\nDiastolic\n75±9\n75±9\n76±9\n76±10\n75±9\n75±9\nGlucose — mg/dl\n93±12\n92±17\n92±12\n92±13\n92±14\n92±12\nInsulin — μU/ml\n12±7\n12±8\n12±7.5\n12±8\n12±8\n12±7\nHOMA\n2.8±1.9\n2.8±2.2\n2.9±1.9\n2.8±1.9\n2.8±2\n2.8±1.9\nCholesterol — mg/dl\nTotal\n199±38\n203±36\n203±37\n204±35\n202±37\n202±37\nLDL\n124±33\n126±32\n128±32\n126±31\n126±32\n125±32\nHDL\n49±15\n49±13\n48±12\n51±16\n49±14\n49±15\nTriglycerides — mg/dl\n135±82\n144±79\n147±93\n141±85\n142±85\n144±87\nDietary intake per day§\nNo."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 28,
    "text": "of participants who provid-\ned information \n103\n106\n105\n102\n416\n330\nEnergy — kcal\n2015±505\n1862±566\n2012±597\n1979±599\n1966±570\n1978±563\nCarbohydrate — %\n44±8\n46±8\n45±8\n44±7\n45±8\n45±8\nFat — %\n38±6\n36±6\n37±5\n38±6\n37±6\n37±6\nSaturated fat — %\n12±3\n12±3\n12±3\n12±2\n12±3\n12±3\nProtein — %\n18±4\n18±4\n18±3\n18±3\n18±3\n18±3\nDietary fiber — g\n18±7\n17±7\n18±6\n17±6\n17±7\n18±7\nCholesterol — mg\n303±121\n278±120\n306±135\n305±134\n298±128\n298±128\nAlcohol — g\n6±8\n4±7\n6±9\n6±9\n5±8\n5±8\nRespiratory quotient\n0.84±0.04\n0.84±0.04\n0.85±0.05\n0.84±0.04\n0.84±0.04\n0.84±0.04\n* Plus–minus values are means ±SD.To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for \ncholesterol to millimoles per liter, multiply by 0.02586."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 29,
    "text": "To convert the values for triglycerides to millimoles per liter, multiply by 0.01129.\nHDL denotes high-density lipoprotein, HOMA homeostasis model assessment of insulin sensitivity, and LDL low-density lipoprotein.\n† Race or ethnic group was reported by the participants.\n‡ The body-mass index is the weight in kilograms divided by the square of the height in meters.\n§\tData are from a 50% random sample.\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025. For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 30,
    "text": "All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n864\nsigned to a diet and those who completed the study \n(Table 1).\nWeight Loss\nThe amount of weight loss after 2 years was sim-\nilar in participants assigned to a diet with 25% \nprotein and those assigned to a diet with 15% \nprotein (3.6 and 3.0 kg, respectively; P = 0.22) and \namong those who completed each of those diets \n(4.5 and 3.6 kg, respectively; P = 0.11) (Fig.1). Weight \nloss was the same in those assigned to a diet with \n40% fat and those assigned to a diet with 20% fat \n(3.3 kg, P = 0.94) and was similar among those who \ncompleted each of those diets (3.9 and 4.1 kg, re-\nspectively; P = 0.76)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 31,
    "text": "There was no effect on weight \nloss of carbohydrate level through the target range \nof 35 to 65% (Fig.1 and 2). The change in waist \ncircumference did not differ significantly among \nthe diet groups (Fig."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 32,
    "text": "1 and 2).\nMost of the weight loss occurred in the first \n 0.0\nChange in Weight (kg)\n−1.0\n−0.5\n−1.5\n−2.0\n−3.0\n−3.5\n−4.5\n−2.5\n−4.0\n−5.0\nProtein\nFat\nCarbohydrate\nA All Participants\nB Participants Who Completed the Study\nDifference, −0.6 \n(95% CI, −1.6 to 0.4)\nP=0.22\nDifference, 0.6 \n(95% CI, −0.8 to 1.9)\nP=0.42\n 0.0\nChange in Weight (kg)\n−1.0\n−0.5\n−1.5\n−2.0\n−3.0\n−3.5\n−4.5\n−2.5\n−4.0\n−5.0\nProtein\nFat\nCarbohydrate\nDifference, −0.9 \n(95% CI, −2.1 to 0.2)\nP=0.11\nDifference, 0.7 \n(95% CI, −0.9 to 2.3)\nP=0.37\nChange in Waist Circumference (cm)\nProtein\nFat\nCarbohydrate\nC All Participants\nD Participants Who Completed the Study\nDifference, −0.7 \n(95% CI, −1.7 to 0.4)\nP=0.22\nDifference, 0.7 \n(95% CI, −0.8 to 2.1)\nP=0.39\n 0\nChange in Waist Circumference (cm)\n−2\n−1\n−3\n−4\n−6\n−5\n−7\n 0\n−2\n−1\n−3\n−4\n−6\n−5\n−7\nProtein\nFat\nCarbohydrate\nDifference, −1.1 \n(95% CI, −2.3 to 0.2)\nP=0.10\nDifference, 1.0\n(95% CI, −0.7 to 2.8)\nP=0.24\nHigh protein, fat, or carbohydrate\nLow or average protein, fat, or carbohydrate\nDifference, 0.04 \n(95% CI, −0.9 to 1.0)\nP=0.94\nDifference, 0.2 \n(95% CI, −1.0 to 1.3)\nP=0.76\nDifference, 0.0 \n(95% CI, −1.0 to 1.0)\nP=0.99\nDifference, 0.0 \n(95% CI, −1.3 to 1.2)\nP=0.95\nFigure 1."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 33,
    "text": "Mean Change in Body Weight and Waist Circumference from Baseline to 2 Years According to Dietary Macronutrient Content.\nSolid bars represent high-protein, high-fat, or highest-carbohydrate diets. Open bars represent average-protein, low-fat, or lowest-carbo-\nhydrate diets. T bars indicate standard errors. Panels A and C show the change in body weight and the change in waist circumference, \nrespectively, for all participants who were randomly assigned to a diet (a total of 811); missing data were imputed. A total of 403 partici-\npants were assigned to a high-protein diet and 408 to an average-protein diet, 405 were assigned to a high-fat diet and 406 to a low-fat \ndiet, and 204 were assigned to the highest-carbohydrate diet and 201 to the lowest-carbohydrate diet."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 34,
    "text": "Panel B shows the change in body \nweight for the 645 participants who provided measurements at 2 years.Of these participants, 325 were assigned to a high-protein diet \nand 320 to an average-protein diet, 319 were assigned to a high-fat diet and 326 to a low-fat diet, and 169 were assigned to the highest-\ncarbohydrate diet and 168 to the lowest-carbohydrate diet. Panel D shows the change in waist circumference for the 599 participants \nwho provided measurements at 2 years. Of these participants, 303 were assigned to a high-protein diet and 296 to an average-protein \ndiet, 292 were assigned to a high-fat diet and 307 to a low-fat diet, and 159 were assigned to the highest-carbohydrate diet and 155 to \nthe lowest-carbohydrate diet."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 35,
    "text": "The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n865\n6 months. Changes from baseline differed among \nthe diet groups by less than 0.5 kg of body weight \nand 0.5 cm of waist circumference (Fig. 2). After \n12 months, all groups, on average, slowly regained \nbody weight."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 36,
    "text": "A total of 185 of the participants \n(23%) continued to lose weight from 6 months to \n2 years; the mean (±SD) additional weight loss was \n3.6±3.5 kg, for a mean total loss from baseline of \n9.3±8.2 kg, with no significant differences among \nthe diet groups.At 2 years, 31 to 37% of the par-\nticipants had lost at least 5% of their initial body \nweight, 14 to 15% of the participants in each diet \ngroup had lost at least 10% of their initial weight, \nand 2 to 4% had lost 20 kg or more (P>0.20 for the \ncomparisons between diets).\nRisk Factors for Cardiovascular Disease  \nand Diabetes\nAll the diets reduced risk factors for cardiovascu-\nlar disease and diabetes at 6 months and 2 years \n(Table 2)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 37,
    "text": "At 2 years, the two low-fat diets and the \nhighest-carbohydrate diet decreased low-density \nlipoprotein cholesterol levels more than did the \nhigh-fat diets or the lowest-carbohydrate diet (low-\nfat vs.high-fat, 5% vs. 1% [P = 0.001]; highest-\ncarbohydrate vs. lowest-carbohydrate, 6% vs."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 38,
    "text": "1% \nChange in Weight from Baseline (kg)\nA All Participants\nB Participants Who Provided Measurements at Various Time Points\nChange in Weight from Baseline (kg)\nC All Participants\nD Participants Who Provided Measurements at Various Time Points\n 0\n−2\n−1\n−3\n−4\n−7\n−5\n−9\n 0\n−2\n−1\n−3\n−4\n−7\n−5\n−9\n−6\n−8\n−6\n−8\n0\n6\n12\n18\n24\n0\n6\n12\n18\n24\nMonths\nMonths\nMonths\nCarbohydrate/Protein/Fat:\n65/15/20%\n55/25/20%\n45/15/40%\n35/25/40%\nChange in Waist Circumference\nfrom Baseline (cm)\n 0\n−2\n−1\n−3\n−4\n−7\n−5\n−9\n−6\n−8\n0\n6\n12\n18\n24\nMonths\n 0\nChange in Waist Circumference\nfrom Baseline (cm)\n−2\n−1\n−3\n−4\n−7\n−5\n−9\n−6\n−8\n0\n6\n12\n18\n24\nFigure 2.Mean Changes in Body Weight and Waist Circumference at Various Time Points."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 39,
    "text": "Panels A and C show the mean changes in body weight and waist circumference, respectively, for all participants who were assigned to a \ndiet (a total of 811 at every time point); missing data were imputed.Panel B shows the change in body weight for participants who pro-\nvided measurements at various time points: 176 to 180 participants at 6 months, 157 to 167 at 12 months, 140 to 152 at 18 months, and \n151 to 168 at 2 years. Panel D shows the change in waist circumference for participants who provided measurements at various time-\npoints: 176 to 179 at 6 months, 154 to 166 at 12 months, 135 to 148 at 18 months, and 137 to 159 at 2 years."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 40,
    "text": "I bars in all panels indicate \nstandard errors.\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n866\n[P = 0.01]). The lowest-carbohydrate diet increased \nHDL cholesterol levels more than the highest-car-\nbohydrate diet (9% vs. 6%, P = 0.02). All the diets \ndecreased triglyceride levels similarly, by 12 to 17%."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 41,
    "text": "All the diets except the one with the highest car-\nbohydrate content decreased fasting serum insu-\nlin levels by 6 to 12%; the decrease was larger with \nthe high-protein diet than with the average-protein \ndiet (10% vs.4%, P = 0.07). Blood pressure de-\ncreased from baseline by 1 to 2 mm Hg, with no \nsignificant differences among the groups (P>0.59 \nfor all comparisons). These changes in risk factors \nin the intention-to-treat population were about \n30 to 40% smaller than the changes seen among \nparticipants who provided data at 2 years, reflect-\ning the effect of the imputation of missing values \n(Table 1 in the Supplementary Appendix)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 42,
    "text": "The \nmetabolic syndrome35 was present in 32% of the \nparticipants at baseline, and the percentage was \nlower at 2 years, ranging from 19 to 22% in the \nfour diet groups (P = 0.81 for the four-way com-\nparison).\nAdherence, Diet Acceptability, Satiety,  \nand Satisfaction\nMean reported intakes at 6 months and 2 years \ndid not reach the target levels for macronutrients \n(Table 2).The reported intakes represented differ-\nTable 2."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 43,
    "text": "Risk Factors, Nutrient Intake, and Biomarkers of Adherence, According to Diet, at 6 Months and 2 Years.*\nVariable\nLow Fat, Average Protein\nLow Fat, High Protein\n6-Mo Value\nChange \nfrom \nBaseline\n2-Yr \nValue\nChange  \nfrom \nBaseline\n6-Mo Value\nChange \nfrom \nBaseline\n2-Yr \nValue\nChange \nfrom \nBaseline\nRisk factors†\nCholesterol (mg/dl)\nTotal \n188±36\n–5.9\n192±37\n–3.7\n193±39\n–4.9\n197±40\n–2.9\nLDL\n116±29\n–6.6\n117±31\n–5.9\n120±33\n–4.8\n121±33\n–3.9\nHDL\n49±13\n–0.4\n51±15\n5.6\n51±13\n2.7\n53±15\n6.5\nTriglycerides (mg/dl)\n116±73\n–14.2\n120±83\n–11.5\n114±63\n–20.4\n120±67\n–16.6\nBlood pressure (mm Hg)\nSystolic \n116±12\n–1.2\n117±12\n–0.8\n117±12\n–2.6\n118±13\n–1.7\nDiastolic\n74±9\n–1.4\n74±9\n–0.8\n73±9\n–3.1\n74±9\n–1.3\nGlucose (mg/dl)\n90±11\n–3.0\n94±12\n1.1\n90±16\n–2.6\n93±17\n1.0\nInsulin (μU/ml)\n10±7\n–16.2\n12±10\n–2.4\n10±6\n–19.9\n11±8\n–11.5\nHOMA\n2.3±1.6\n–18.7\n2.8±2.3\n–1.4\n2.2±1.6\n–22.7\n2.5±2.2\n–10.4\nNutrient intake per day\nEnergy (kcal)\n1636±484\n–477\n1531±480\n–554\n1572±568\n–353\n1560±461\n–402\nCarbohydrate (%)\n57.5±11.1\n12.8\n53.2±11\n9.3\n53.4±8.5\n7.4\n51.3±9.2\n6.8\nProtein (%)\n17.6±3.4\n0.2\n19.6±3.9\n2.1\n21.8±3.8\n3.9\n20.8±4\n2.5\nFat (%)\n26.2±8\n–11.8\n26.5±8\n–12.0\n25.9±6.8\n–10.1\n28.4±8.1\n–8.4\nSaturated fat (%)\n7.5±3.2\n–4.9\n8±3.1\n–4.3\n7.9±2.7\n–3.9\n8.9±3.8\n–3.1\nBiomarkers of adherence\nUrinary nitrogen (g)‡\n11.1±4.1\n–11.5\n11.8±4.6\n–9.1\n11.9±4.3\n–2.5\n11.8±3.9\n–2.8\nRespiratory quotient§\n0.84±0.04\n0.58\n0.83±0.04\n–0.48\n0.84±0.04\n0.16\n0.84±0.04\n–0.84\n*\tPlus–minus values are means ±SD."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 44,
    "text": "Change from baseline is percent change in the case of risk factors and biomarkers of adherence and ac-\ntual change in the case of nutrient intake per day.Nutrient intake was determined by three 24-hour recalls. To convert the values for choles-\nterol to millimoles per liter, multiply by 0.02586. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To con-\nvert the values for glucose to millimoles per liter, multiply by 0.05551. HDL denotes high-density lipoprotein, HOMA homeostasis model \nassessment of insulin sensitivity, and LDL low-density lipoprotein.\n†\tData were included for 201 participants per group; missing values were imputed."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 45,
    "text": "‡\tData were included for 200 to 204 participants per group at baseline, 139 to 153 at 6 months, and 88 to 109 at 2 years.\n§\tData were included for 201 to 204 participants per group at baseline, 157 to 164 at 6 months, and 113 to 132 at 2 years.\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 46,
    "text": "All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n867\nences from target levels of fat, protein, and car-\nbohydrate intake of 8.0, 4.2, and 14.4 percentage \npoints, respectively, at 6 months and 6.7, 1.4, and \n10.2 percentage points, respectively, at 2 years.Re-\nported energy intakes and physical activity were \nsimilar among the diet groups."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 47,
    "text": "The participants \nwho completed the study had a mean weight loss \nof 6.5 kg at 6 months, which corresponds to a \nreduction in daily energy intake of approximately \n225 kcal.\nThere was a larger increase from baseline in the \nHDL cholesterol level, a biomarker for dietary car-\nbohydrate, in the lowest-carbohydrate group than \nin the highest-carbohydrate group (a difference in \nthe change of 2 mg per deciliter at 2 years) (Ta-\nble 1 in the Supplementary Appendix); this dif-\nference corresponds to a predicted difference in \ncarbohydrate intake of 6%.36 There was a larger \ndecrease in urinary nitrogen excretion from base-\nline in the average-protein group than in the high-\nprotein group (a difference in the change of 1.6 g \nat 6 months and 0.8 g at 2 years) (Table 3); these \ndifferences correspond to a difference in dietary \nprotein of 10 g per day and 5 g per day, respec-\ntively."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 48,
    "text": "The respiratory quotient was 0.84 at baseline \nin both the high-fat and low-fat groups, and the \nbetween-group difference in the change at 2 years \n(the value in the high-fat group minus the value \nin the low-fat group) was −0.02 (P = 0.002) (Ta-\nble 3)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 49,
    "text": "Thus, changes in biomarkers confirmed \nthat differences among the groups in macronu-\ntrient intake were consistent with those recorded \nin the dietary reports and that participants modi-\nfied their intake of macronutrients in the direc-\ntion of the goals, although the targets were not \nfully achieved.\nCraving, fullness, and hunger and diet-satisfac-\ntion scores were similar at 6 months and at 2 years \namong the diets (Table 2 in the Supplementary \nAppendix).\nHigh Fat, Average Protein\nHigh Fat, High Protein\n6-Mo Value\nChange \nfrom \nBaseline\n2-Yr \nValue\nChange \nfrom \nBaseline\n6-Mo Value\nChange  \nfrom \nBaseline\n2-Yr \nValue\nChange \nfrom \nBaseline\n195±39\n–3.7\n202±39\n–0.3\n199±35\n–2.3\n202±38\n–0.8\n123±33\n–3.2\n127±33\n–0.2\n124±31\n–1.1\n124±31\n–1.3\n49±13\n2.9\n51±13\n6.3\n53±15\n4.0\n55±17\n8.8\n120±88\n–18.1\n129±89\n–12.4\n114±71\n–19.5\n118±71\n–16.7\n118±12\n–1.5\n118±12\n–1.3\n119±12\n–1.7\n120±14\n–0.7\n74±9\n–2.3\n75±9\n–1.5\n74±9\n–1.8\n76±9\n–0.3\n90±12\n–1.9\n93±13\n1.6\n91±12\n–1.2\n94±15\n2.8\n10±7\n–18.2\n12±8\n–6.4\n10±9\n–14.4\n11±7\n–9.2\n2.4±1.8\n–18.6\n2.8±2.1\n–3.5\n2.4±2.9\n–13.4\n2.6±1.9\n–6.3\n1607±499\n–456\n1521±530\n–434\n1624±484\n–385\n1413±427\n–389\n49.1±8.6\n5.0\n48.6±10\n2.4\n43±6.7\n–0.2\n42.9±8.3\n–0.4\n18.4±4.5\n0.5\n19.6±5.2\n2.1\n22.6±4.4\n4.3\n21.2±5.2\n3.4\n33.9±6.7\n–3.8\n33.3±8.2\n–3.5\n34.3±7.8\n–3.7\n35.1±7\n–3.4\n9±2.5\n–3.0\n9.8±3.3\n–2.1\n9±2.6\n–3.7\n10.5±2.7\n–1.7\n10.3±4.4\n–17.3\n11.2±3.8\n–8.8\n12.6±4.7\n0.7\n12.5±5.3\n–1.9\n0.84±0.04\n–1.58\n0.83±0.04\n–3.16\n0.84±0.04\n–0.52\n0.83±0.04\n–1.92\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 50,
    "text": "For personal use only.\n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n868\nTable 3."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 51,
    "text": "Factorial-Design Estimates of Effect of Diet Type on Mean Changes from Baseline in Risk Factors, Nutrient Intake, and Biomarkers of Adherence.*\nVariable\nChange with High Fat minus \nChange with Low Fat \nChange with High Protein minus \nChange with Average Protein \nChange with Highest Carbohydrate minus \nChange with Lowest Carbohydrate \nAt 6 Mo\nP Value\nAt 2 Yr\nP Value\nAt 6 Mo\nP Value\nAt 2 Yr\nP Value\nAt 6 Mo\nP Value\nAt 2 Yr\nP Value\nRisk factors†\nCholesterol (mg/dl)\nTotal \n4.7±1.8 \n0.01\n5.6±1.9\n0.003\n2.3±1.8\n0.20\n0.2±1.9\n0.92\n–7.0±2.6 \n0.007\n–5.8±2.6\n0.02\nLDL\n4.4±1.6\n0.005\n5.1±1.6\n0.001\n2.4±1.6\n0.13\n0.5±1.6\n0.74\n–6.8±2.3\n0.003\n–5.7±2.2\n0.01\nHDL\n1.1±0.5\n0.01\n0.7±0.5\n0.12\n1.1±0.5\n0.02\n0.9±0.5\n0.05\n–2.2±0.6 \n0.001\n–1.7±0.7\n0.01\nTriglycerides (mg/dl)\n–2.8±4.3\n0.52\n–1.2±4.0\n0.76\n–5.4±4.3 \n0.21\n–6.7±4.0\n0.10\n8.1±5.0\n0.10\n7.9±6.0\n0.19\nBlood pressure (mm Hg)\nSystolic \n0.4±0.7 \n0.59\n0.3±0.7\n0.64\n–1.0±0.7 \n0.14\n–0.2±0.7\n0.77\n0.6±0.9 \n0.51\n–0.1±0.9\n0.89\nDiastolic\n0.1±0.5\n0.77\n0.1±0.5\n0.85\n–0.5±0.5\n0.32\n0.2±0.5\n0.59\n0.3±0.7\n0.62\n–0.3±0.7\n0.61\nGlucose (mg/dl)\n1.2±0.6\n0.04\n1.1±0.5\n0.05\n0.5±0.6\n0.38\n0.5±0.6\n0.34\n–1.7±0.9\n0.04\n–1.6±0.8\n0.06\nInsulin (μU/ml)\n0.2±0.4\n0.68\n–0.1±0.4\n0.77\n0.0±0.4\n0.91\n–0.7±0.4\n0.07\n–0.2±0.7\n0.74\n0.8±0.6\n0.19\nHOMA\n0.13±0.13\n0.31\n0.03±0.10\n0.78\n0.03±0.13 \n0.84\n–0.16±0.10\n0.12\n–0.15±0.21\n0.46\n0.13±0.16\n0.42\nNutrient intake per day\nEnergy (kcal)\n11.4±53.9\n0.83\n–75.6±70.9\n0.29\n–23.2±53.9\n0.67\n–35.5±71.0\n0.62\n11.1±71.8\n0.88\n118.1±96.6\n0.23\nCarbohydrate (%)\n–9.5±1.0 \n<0.001\n–6.4±1.5\n<0.001\n–5.2±1.1\n<0.001\n–3.6±1.5\n0.02\n14.4±1.4 \n<0.001\n10.2±2.1 \n<0.001\nProtein (%)\n0.9±0.5\n0.06\n0.2±0.7 \n0.77\n4.2±0.4\n<0.001\n1.4±0.7\n0.05\n–5.0±0.6 \n<0.001\n–1.6±1.0\n0.10\nFat (%)\n8.0±0.8 \n<0.001\n6.7±1.2\n<0.001\n0.2±0.9\n0.82\n1.8±1.3\n0.15\n–8.1±1.2 \n<0.001\n–8.6±1.6 \n<0.001\nSaturated fat (%)\n1.3±0.3 \n<0.001\n1.7±0.5\n<0.001\n0.2±0.3\n0.43\n0.8±0.5\n0.12\n–1.5±0.4\n0.001\n–2.5±0.6 \n<0.001\nBiomarkers of adherence\nUrinary nitrogen (g)‡\n–0.11±0.39\n0.77\n0.08±0.42\n0.84\n1.64±0.38 \n<0.001\n0.81±0.42\n0.06\n–1.50±0.55\n0.006\n–0.89±0.65\n0.18\nRespiratory quotient§\n–0.01±0.00\n0.005\n–0.02±0.00\n0.002\n0.00±0.00\n0.52\n0.00±0.00\n0.51\n0.01±0.01\n0.13\n0.01±0.01\n0.07\n*\tPlus–minus values are means ±SE."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 52,
    "text": "Nutrient intake was determined by three 24-hour recalls.To convert the values for cholesterol to millimoles per liter, multiply by 0.02586. To convert \nthe values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for glucose to millimoles per liter, multiply by 0.05551. HDL denotes high-density lipopro-\ntein, HOMA homeostasis model assessment of insulin sensitivity, and LDL low-density lipoprotein.\n†\tData were included for 201 participants per group; missing values were imputed. \n‡\tData were included for 200 to 204 participants per group at baseline, 139 to 153 at 6 months, and 88 to 109 at 2 years.\n§\tData were included for 201 to 204 participants per group at baseline, 157 to 164 at 6 months, and 113 to 132 at 2 years."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 53,
    "text": "The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n869\nWeight Change According to Attendance  \nat Group Sessions and Dietary Adherence\nAttendance at group sessions strongly predicted \nweight loss at 2 years (0.2 kg for every session \nattended) and was similar among the diet groups \n(P = 0.22 for a test of difference in slopes) (Fig. 3)."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 54,
    "text": "Adherence to the goal for protein intake was as-\nsociated with more weight loss only in the high-\nprotein groups, and adherence to the goal for fat \nintake was associated with more weight loss only \nin the low-fat groups (P<0.001) (Fig.4). The rang-\nes of protein and fat intakes overlapped substan-\ntially in the diet groups. Thus, a low-fat intake of \n25% was associated with increased weight loss in \nthe low-fat groups but not in the high-fat groups, \nand a high-protein intake of 24 to 25% was associ-\nated with increased weight loss in the high-pro-\ntein groups but not in the average-protein groups. \nAttendance at group sessions was associated with \nadherence to the fat and protein goals only in the \nhigh-protein and low-fat groups (Fig."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 55,
    "text": "4).\nAdverse Effects\nSerious adverse events were reported by 57 par-\nticipants (7%); there were no significant differences \nin the rates among diets.The ratio of urinary mi-\ncroalbumin to creatinine was more than 30 in five \nparticipants in the average-protein group and in \nfive participants in the high-protein group at  \n6 months and in seven participants, all in the av-\nerage-protein groups, at 2 years.\nDiscussion\nIn this population-based trial, participants were \nassigned to and taught about diets that emphasized \ndifferent contents of carbohydrates, fat, and pro-\ntein and were given reinforcement for 2 years \nthrough group and individual sessions."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 56,
    "text": "The prin-\ncipal finding is that the diets were equally suc-\ncessful in promoting clinically meaningful weight \nloss and the maintenance of weight loss over the \ncourse of 2 years.Satiety, hunger, satisfaction with \nthe diet, and attendance at group sessions were \nsimilar for all diets. The diets improved lipid risk \nfactors and fasting insulin levels in the directions \nthat would be expected on the basis of macronu-\ntrient content. The study had a large sample, a high \nrate of retention, and the sensitivity to detect small \nchanges in weight. The population was diverse with \nrespect to age, income, and geography and includ-\ned a large percentage of men."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 57,
    "text": "The participants were \neager to lose weight and to attempt whatever type \nof diet they were assigned, and they did well in \nscreening interviews and questionnaires that eval-\nuated their motivation.Thus, the findings should \nbe directly applicable to both clinicians’ recom-\nmendations for weight loss in individual patients \nand the development of population-wide recom-\nmendations by public health officials.\nDespite the intensive behavioral counseling in \nour study, participants had difficulty achieving the \ngoals for macronutrient intake of their assigned \ngroup."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 58,
    "text": "The mean differences among the groups in \nfat, carbohydrate, or protein intake at 6 months \nwere nevertheless often greater than those in \nseveral previous trials comparing diets for weight \nloss.11,12,19,21,26 Substantially diminished adher-\nence after the first few months is typical in weight-\nloss trials5,6,8,10-12,19,21,24,26 and occurred between \n6 months and 2 years in our trial.Only two trials \nhave reported dietary intake beyond 1 year,12,26 \nand one of them provided foods to the partici-\npants.12 In addition, trials of low-carbohydrate di-\nets have reported a very low incidence of urinary \nketosis after 6 months,6,8,12 suggesting that in \nmost overweight people, it is futile to sustain a \nlow intake of carbohydrates."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 59,
    "text": "Overall, these find-\nings with respect to adherence to macronutrient \ngoals suggest that participants in weight-loss pro-\ngrams revert to their customary macronutrient in-\ntakes over time but may nonetheless be able to \nmaintain weight loss.\nWe explored the association of achieved nutri-\nent intakes with weight loss.We caution that these \npost hoc analyses do not have the strong validity \nof the main analysis of this controlled trial, which \ncompared randomized groups. Protein and fat in-\ntakes overlapped among the groups. A high-pro-\ntein intake was associated with weight loss only \nin the high-protein groups, and a low-fat intake \nwas associated with weight loss only in the low-\nfat groups."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 60,
    "text": "The protein and fat contents of the \nparticipants’ usual diet were closer to the goals \nfor the average-protein and high-fat diets than to \nthose for the high-protein and low-fat diets.Thus, \nthe participants assigned to an average-protein or \nhigh-fat diet did not have to change their custom-\nary level of dietary protein and fat very much and \ncould focus more on reducing dietary intake. In \ncontrast, the participants in the high-protein or \nlow-fat groups had more challenging dietary goals. \nIt is therefore not surprising that attendance at \ngroup sessions was strongly related to adherence \nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025. For personal use only."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 61,
    "text": "No other uses without permission.Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n870\nto high-protein or low-fat goals but not to the \ngoals in the average-protein or high-fat groups. \nHowever, attendance had a strong association with \nweight loss, and the association was similar across \ndiet groups. We view attendance at counseling ses-\nsions as a proxy for commitment to achieving \nweight loss and for engagement in the program. \nStudy participants who attended two thirds of the \nsessions over the course of 2 years lost about 9 kg \nof weight."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 62,
    "text": "Regain after 6 to 12 months was about \n20% of the regain reported in earlier trials.28 Sev-\neral recent trials have also shown that continued \ncontact with participants after weight loss is as-\nsociated with less regain.12,24,37,38 These findings \ntogether point to behavioral factors rather than \nmacronutrient metabolism as the main influences \non weight loss.\nConformity to cultural norms, scientific nov-\nChange in Weight from Baseline to 2 Yr (kg)\nChange in Weight from Baseline to 2 Yr (kg)\nChange in Weight from Baseline to 2 Yr (kg)\nChange in Weight from Baseline to 2 Yr (kg)\nA Low-Fat, Average-Protein\nB Low-Fat, High-Protein\nC High-Fat, Average-Protein\nD High-Fat, High-Protein \n 20\n10\n−20\n0\n−40\n−10\n−30\n 20\n10\n−20\n0\n−40\n−10\n−30\n 20\n10\n−20\n0\n−40\n−10\n−30\n 20\n10\n−20\n0\n−40\n−10\n−30\n0\n10\n20\n30\n40\n50\n60\n0\n10\n20\n30\n40\n50\n60\n0\n10\n20\n30\n40\n50\n60\n0\n10\n20\n30\n40\n50\n60\nNo."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 63,
    "text": "of Sessions Attended\nNo.of Sessions Attended\nNo. of Sessions Attended\nNo. of Sessions Attended\nN=169\nSlope=−0.179\nN=151\nSlope=−0.252\nN=157\nSlope=−0.191\nN=168\nSlope=−0.217\nFigure 3. Change in Body Weight from Baseline to 2 Years According to Attendance at Counseling Sessions for Weight Loss,  \namong the 645 Participants Who Completed the Study. \nPanel A shows data for the low-fat, average-protein group; Panel B, for the low-fat, high-protein group; Panel C, for the high-fat, average-\nprotein group; and Panel D, for the high-fat, high-protein group."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 64,
    "text": "There were no significant differences among the regression coefficients \n(P>0.2 for all comparisons; R2 = 0.2 for total cohort).\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n871\nelty, and media attention are nonbiologic reasons \nfor the success of specific diets. We used a generic \napproach to developing each diet and the instruc-\ntions for following it, in order to minimize such \ninfluences."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 65,
    "text": "No diet was considered to be a control \ndiet, and the dietary counseling and the attention \nthat we provided were the same for all diet groups \nthroughout the study period."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 66,
    "text": "We did not confirm \nprevious findings that low-carbohydrate or high-\nprotein diets caused increased weight loss at  \n6 months3-12 and that the advantage of these diets \nusually eroded by 12 months, with weight loss \nthat was nearly or fully equivalent to that with \nlow-fat diets6,11,18 or other diets.12 Other studies \nshowed increased weight loss at 1 to 2 years with \ndiets that were high in unsaturated fat12,21,26 or \nwith low-fat, high-carbohydrate vegetarian di-\nets.22,24 These divergent results suggest that any \ntype of diet, when taught for the purpose of weight \nloss with enthusiasm and persistence, can be ef-\nfective."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 67,
    "text": "When nonnutritional influences are min-\nimized, as they were in our study, the specific \nmacronutrient content is of minor importance, \nas was suggested many years ago.39\nIn conclusion, diets that are successful in caus-\ning weight loss can emphasize a range of fat, \nprotein, and carbohydrate compositions that have \nbeneficial effects on risk factors for cardiovascular \ndisease and diabetes.29,40 Such diets can also be \ntailored to individual patients on the basis of their \npersonal and cultural preferences and may there-\nfore have the best chance for long-term success.\nSupported by grants from the National Heart, Lung, and \nBlood Institute (HL073286) and the General Clinical Research \nCenter, National Institutes of Health (RR-02635).\nDr."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 68,
    "text": "Greenway reports receiving consulting fees from or serv-\ning on a paid advisory board for Anian, Bristol-Myers Squibb, \nClarus Health, Encore Pharmaceutical, Leptos Biomedical, \nMDRNA, Novo Nordisk, General Nutrition Corporation, Cata-\nlyst, Jenny Craig, Orexigen, Lithera, and Basic Research, receiv-\ning lecture fees from BAROnova, Lazard, and Biologene, and \nowning equity in Lithera.No other potential conflict of interest \nrelevant to this article was reported. Dr. Ryan is chairperson of \nthe Obesity Committee of the National Heart, Lung, and Blood \nInstitute’s Clinical Guidelines for Cardiovascular Risk Reduc-\ntion Expert Panel; Dr. Loria is a member of that committee; and \nDr."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 69,
    "text": "Sacks is a member of the Lifestyle Working Group of the \nExpert Panel that interacts with the Obesity Committee.Dr."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 70,
    "text": "Sacks is also vice-chair of the Nutrition Committee of the \nAmerican Heart Association, which advises the Association on nu-\ntrition topics, including those related to overweight and obesity.\nWe thank the participants in the trial for their dedication and \ncontribution to the research; the following research staff mem-\nWeight Loss (kg)\nA High Fat\nB Low Fat\nC High Protein\nD Average Protein \n0\n−5\n−10\nFat Intake (% kcal)\nSessions Attended (%)\n24.3\n54.5\n31.2\n53.1\n35.2\n54.9\n39.6\n47.3\n45.5\n48.7\nWeight Loss (kg)\n0\n−5\n−10\nFat Intake (% kcal)\nSessions Attended (%)\n19.4\n61.6\n25.1\n61.4\n28.7\n55.2\n34.5\n48.8\n41.5\n40.7\nWeight Loss (kg)\n0\n−5\n−10\nProtein Intake (% kcal)\nSessions Attended (%)\n15.3\n41.6\n18.2\n48.5\n20.3\n55.0\n22.0\n58.4\n25.6\n59.3\nWeight Loss (kg)\n0\n−5\n−10\nProtein Intake (% kcal)\nSessions Attended (%)\n14.5\n54.0\n16.8\n47.8\n18.4\n56.0\n20.3\n57.1\n24.1\n48.7\nFigure 4."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 71,
    "text": "Weight Loss at 2 Years According to Adherence to Dietary Fat and Protein Goals.\nIntake was determined from three 24-hour diet recalls.Quintiles of fat and protein intakes are shown for the combined high-fat groups \n(Panel A), low-fat groups (Panel B), high-protein groups (Panel C), and average-protein groups (Panel D); there were 45 to 51 partici-\npants per quintile. Rates of attendance at group sessions (percent of total sessions attended over the 2-year period) are shown for the \nquintiles of fat and protein intake. I bars indicate 95% confidence intervals."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 72,
    "text": "P values for a trend in weight loss across quintiles are as fol-\nlows: P<0.001 for fat intake in low-fat groups, P<0.001 for protein intake in high-protein groups, P = 0.36 for fat intake in high-fat groups, \nand P = 0.83 for protein intake in average-protein groups.The results were similar when determined within each of the four diet groups \n(data not shown).\nClinical Directions: \nVote and comment \non this article at \nNEJM.org\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025. For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 73,
    "text": "All rights reserved.\nThe new engl and jour nal of medicine\nn engl j med 360;9  nejm.org  february 26, 2009\n872\nbers for their assistance in conducting the trial: Jungnam Joo, \nPh.D., and Charlotte A.Pratt, Ph.D., at the National Heart, Lung, \nand Blood Institute; Patricia Copeland, M.S., R.D., at Harvard \nSchool of Public Health; Cassandra Carrington, Jacqueline Gal-\nlagher, Clota Heazel, Megan Reddy, Alison Barr, M.S., R.D., \nMary Dinehart, M.S., R.D., Marit Pywell, R.D., Dawn Quintino, \nM.S., R.D., Audrey Shweky, M.S., R.D., Benjamin Harshfield, \nand Melissa McEnery-Stonelake at Brigham and Women’s Hos-\npital; and  Julia St. Amant, Elizabeth Tucker, Heidi K. Millet, \nMarisa M. Smith, Sara J. Schoen, R.D., L.D.N., Betsy B."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 74,
    "text": "Bern-\nhard, Courtney Brock, R.D., Laura DeCuir Moran, R.D., Kather-\nine Lastor, R.D., Erma Levy, M.P.H., R.D., Lisa Miller, R.D., \nGina Pennington, R.D., Dana Vieselmeyer, M.P.H., R.D., Mar-\nlene Afton, Lindsay Coates, Dawn Turner, Richard Dale Achord, \nBridget Conner, Margaret Graves, Doris Hoffpauir, Carla Kim-\nmel, Steve Lee, Kelli Melancon, Sandra Richard, Stacey Roussel, \nElizabeth Soroe, Denise Stein, Jamie Tuminello, and Connie \nMurla at Pennington Biomedical Research Center; and the mem-\nbers of the data and safety monitoring board: Barbara V.How-\nard, Ph.D. (chair), Phyllis E. Bowen, Ph.D., Daniel W. Jones, \nM.D., Michael G. Perri, Ph.D., David M. Reboussin, Ph.D., and \nMarcia L. Stefanick, Ph.D.\nReferences\nJéquier E, Bray GA. Low-fat diets are \n1.\t\npreferred."
  },
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    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 75,
    "text": "Am J Med 2002;113:Suppl:41S-\n46S.\nWillett WC, Leibel RL.Dietary fat is \n2.\t\nnot a major determinant of body fat. Am J \nMed 2002;113:Suppl:47S-59S.\nFreedman MR, King J, Kennedy E. Pop-\n3.\t\nular diets: a scientific review. Obes Res \n2001;9:Suppl:1S-40S.\nSkov AR, Toubro S, Rønn B, Holm L, \n4.\t\nAstrup A. Randomized trial of protein vs \ncarbohydrate in ad libitum fat reduced diet \nfor the treatment of obesity. Int J Obes \nRelat Metab Disord 1999;23:528-36.\nBrehm BJ, Seeley RJ, Daniels SR, \n5.\t\nD’Alessio DA. A randomized trial com-\nparing a very low carbohydrate diet and a \ncalorie-restricted low fat diet on body \nweight and cardiovascular risk factors in \nhealthy women. J Clin Endocrinol Metab \n2003;88:1617-23.\nFoster GD, Wyatt HR, Hill JO, et al."
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    "filename": "NEJMoa0804748.pdf",
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    "text": "6.\t\nA randomized trial of a low-carbohydrate \ndiet for obesity.N Engl J Med 2003;348: \n2082-90.\nSamaha FF, Iqbal N, Seshadri P, et al. \n7.\t\nA low-carbohydrate as compared with a \nlow-fat diet in severe obesity. N Engl J Med \n2003;348:2074-81.\nYancy WS Jr, Olsen MK, Guyton JR, \n8.\t\nBakst RP, Westman EC. A low-carbohy-\ndrate ketogenic diet versus a low-fat diet \nto treat obesity and hyperlipidemia: a ran-\ndomized, controlled trial. Ann Intern Med \n2004;140:769-77.\nVolek J, Sharman M, Gómez A, et al. \n9.\t\nComparison of energy-restricted very low-\ncarbohydrate and low-fat diets on weight \nloss and body composition in overweight \nmen and women. Nutr Metab (Lond) \n2004;1:13.\nDue A, Toubro S, Skov AR, Astrup A."
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    "filename": "NEJMoa0804748.pdf",
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    "text": "10.\t\nEffect of normal-fat diets, either medium \nor high in protein, on body weight in over-\nweight subjects: a randomised 1-year trial.\nInt J Obes Relat Metab Disord 2004;28: \n1283-90.\nGardner CD, Kiazand A, Alhassan S, \n11.\t\net al. Comparison of the Atkins, Zone, Or-\nnish, and LEARN diets for change in weight \nand related risk factors among overweight \npremenopausal women: the A to Z Weight \nLoss Study: a randomized trial. JAMA \n2007;297:969-77. [Erratum, JAMA 2007;298: \n178.]\nShai I, Schwarzfuchs D, Henkin Y, et \n12.\t\nal. Weight loss with a low-carbohydrate, \nMediterranean, or low-fat diet. N Engl J \nMed 2008;359:229-41.\nNoakes M, Keough JB, Foster PR, Clif-\n13.\t\nton PM."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 78,
    "text": "Effect of an energy-restricted, \nhigh-protein, low-fat diet relative to a con-\nventional low-fat, high-carbohydrate diet \non weight loss, body composition, nutri-\ntional status, and markers of cardiovascu-\nlar health in obese women.Am J Clin Nutr \n2005;81:1298-306.\nMcLaughlin T, Carter S, Lamendola C, \n14.\t\net al. Effects of moderate variations in \nmacronutrient composition on weight loss \nand reduction in cardiovascular disease \nrisk in obese, insulin-resistant adults. Am \nJ Clin Nutr 2006;84:813-21.\nMcMillan-Price J, Petocz P, Atkinson \n15.\t\nF, et al. Comparison of 4 diets of varying \nglycemic load on weight loss and cardio-\nvascular risk reduction in overweight and \nobese young adults: a randomized con-\ntrolled trial."
  },
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    "filename": "NEJMoa0804748.pdf",
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    "text": "Arch Intern Med 2006;166: \n1466-75.\nDas SK, Gilhooly CH, Golden JK, et al.\n16.\t\nLong-term effects of 2 energy-restricted \ndiets differing in glycemic load on dietary \nadherence, body composition, and metab-\nolism in CALERIE: a 1-y randomized con-\ntrolled trial. Am J Clin Nutr 2007;85:1023-\n30.\nLecheminant JD, Gibson CA, Sullivan \n17.\t\nDK, et al. Comparison of a low carbohy-\ndrate and low fat diet for weight mainte-\nnance in overweight or obese adults en-\nrolled in a clinical weight management \nprogram. Nutr J 2007;6:36.\nStern L, Iqbal N, Seshadri P, et al. The \n18.\t\neffects of low-carbohydrate versus con-\nventional weight loss diets in severely \nobese adults: one-year follow-up of a ran-\ndomized trial."
  },
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    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
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    "text": "Ann Intern Med 2004;140: \n778-85.\nDansinger ML, Gleason JA, Griffith \n19.\t\nJL, Selker JP, Schaefer EJ.Comparison of \nthe Atkins, Ornish, Weight Watchers, and \nZone diets for weight loss and heart dis-\nease risk reduction: a randomized trial. \nJAMA 2005;293:43-53.\nLuscombe-Marsh ND, Noakes M, Wit-\n20.\t\ntert GA, Keough JB, Foster P, Clifton PM. \nCarbohydrate restricted diets high in ei-\nther monounsaturated fat or protein are \nequally effective in promoting fat loss and \nimproving blood lipids. Am J Clin Nutr \n2005;81:762-72.\nKeogh JB, Luscombe-Marsh ND,  \n21.\t\nNoakes M, Wittert GA, Clifton PM."
  },
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    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 81,
    "text": "Long-\nterm weight maintenance and cardiovas-\ncular risk factors are not different follow-\ning weight loss on carbohydrate-restricted \ndiets high in either monounsaturated fat \nor protein in obese hyperinsulinemic \nmen and women.Br J Nutr 2007;97: \n405-10.\nOrnish D, Scherwitz LW, Billings JH, \n22.\t\net al. Intensive lifestyle changes for rever-\nsal of coronary heart disease. JAMA 1998; \n280:2001-7. [Erratum, JAMA 1999;281: \n1380.]\nBarnard ND, Cohen J, Jenkins DJ, et \n23.\t\nal. A low-fat vegan diet improves glycemic \ncontrol and cardiovascular risk factors in \na randomized clinical trial in individuals \nwith type 2 diabetes. Diabetes Care 2006; \n29:1777-83.\nTurner-McGrievy GM, Barnard ND, \n24.\t\nScialli AR."
  },
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    "filename": "NEJMoa0804748.pdf",
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    "text": "A two-year randomized weight \nloss trial comparing a vegan diet to a more \nmoderate low-fat diet.Obesity (Silver \nSpring) 2007;15:2276-81.\nToubro S, Astrup A. Randomized com-\n25.\t\nparison of diets for maintaining obese \nsubjects’ weight after major weight loss: ad \nlib, low fat, high carbohydrate diet v fixed \nenergy intake. BMJ 1997;314:29-34.\nMcManus K, Antinoro L, Sacks F. \n26.\t\nA randomized controlled trial of a moder-\nate-fat, low-energy diet compared with a \nlow fat, low-energy diet for weight loss in \noverweight adults. Int J Obes Relat Metab \nDisord 2001;25:1503-11.\nSimons-Morton DG, Obarzanek E, \n27.\t\nCutler JA. Obesity research — limitations \nof methods, measurements, and medica-\ntions. JAMA 2006;295:826-8.\nDansinger ML, Tatsioni A, Wong JB, \n28.\t\nChung M, Balk EM."
  },
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    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
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    "text": "Meta-analysis: the ef-\nfect of dietary counseling for weight loss.\nAnn Intern Med 2007;147:41-50.\nLichtenstein AH, Appel LJ, Brands M, \n29.\t\net al. Diet and lifestyle recommendations \nrevision 2006: a scientific statement from \nthe American Heart Association Nutri-\ntion Committee. Circulation 2006;114: \n82-96. [Errata, Circulation 2006;114(1): \ne27, 114(23):e629.]\nBaecke JA, Burema J, Frijters JE. A short \n30.\t\nquestionnaire for the measurement of ha-\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025. For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 84,
    "text": "All rights reserved.\nWeight-Loss Diets with Different Compositions of Macronutrients\nn engl j med 360;9  nejm.org  february 26, 2009\n873\nbitual physical activity in epidemiological \nstudies.Am J Clin Nutr 1982;36:936-42.\nChampagne CM, Bogle ML, McGee \n31.\t\nBB, et al. Dietary intake in the lower Mis-\nsissippi delta region: results from the \nFoods of Our Delta Study. J Am Diet Assoc \n2004;104:199-207.\nFlint A, Raben A, Blundell JE, Astrup \n32.\t\nA. Reproducibility, power and validity of \nvisual analogue scales in assessment of ap-\npetite sensations in single test meal stud-\nies. Int J Obes Relat Metab Disord 2000; \n24:38-48.\nUrban N, White E, Anderson GL, Cur-\n33.\t\nry S, Kristal AR. Correlates of mainte-\nnance of a low-fat diet among women in \nthe Women’s Health Trial."
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    "text": "Prev Med 1992; \n21:279-91.\nWadden TA, Berkowitz RI, Sarwer DB, \n34.\t\nPrus-Wisniewski R, Steinberg C.Benefits \nof lifestyle modification in the pharmaco-\nlogic treatment of obesity: a randomized \ntrial. Arch Intern Med 2001;161:218-27.\nThird report of the National Choles-\n35.\t\nterol Education Program (NCEP) Expert \nPanel on Detection, Evaluation, and Treat-\nment of High Blood Cholesterol in Adults \n(Adult Treatment Panel III). Bethesda, \nMD: National Cholesterol Education Pro-\ngram, National Heart, Lung, and Blood \nInstitute, National Institutes of Health, \n2002. (NIH publication no. 02-5215.)\nMensink RP, Zock PL, Kester AD, Ka-\n36.\t\ntan MB."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 86,
    "text": "Effect of dietary fatty acids and \ncarbohydrates on the ratio of serum total \nto HDL cholesterol and on serum lipids \nand apolipoproteins: a meta-analysis of \n60 controlled trials.Am J Clin Nutr 2003; \n77:1146-55.\nWing RR, Tate DF, Gorin AA, Raynor \n37.\t\nHA, Fava JL. A self-regulation program \nfor maintenance of weight loss. N Engl J \nMed 2006;355:1563-71.\nSvetkey LP, Stevens VJ, Brantley PJ, et \n38.\t\nal. Comparison of strategies for sustain-\ning weight loss: the Weight Loss Mainte-\nnance randomized controlled trial. JAMA \n2008;299:1139-48.\nKinsell LW, Gunning B, Michaels GD, \n39.\t\nRichardson J, Cox SE, Lemon C. Calories \ndo count. Metabolism 1964;13:195-204.\nde Souza RJ, Swain JF, Appel LJ, Sacks \n40.\t\nFM."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 87,
    "text": "Alternatives for macronutrient intake \nand chronic disease: a comparison of the \nOmniHeart diets with popular diets and \nwith dietary recommendations.Am J Clin \nNutr 2008;88:1-11.\nCopyright © 2009 Massachusetts Medical Society.\nelectronic access to the journal’s cumulative index\nAt the Journal’s site on the World Wide Web (NEJM.org),  \nyou can search an index of all articles published since January 1975  \n(abstracts 1975–1992, full text 1993–present). You can search by author,  \nkey word, title, type of article, and date. The results will include the citations  \nfor the articles plus links to the full text of articles published since 1993."
  },
  {
    "filename": "NEJMoa0804748.pdf",
    "pdf_title": "new england journal medicine",
    "chunk_id": 88,
    "text": "For nonsubscribers, time-limited access to single articles and 24-hour site  \naccess can also be ordered for a fee through the Internet (NEJM.org).\nThe New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.\nDownloaded from nejm.org on April 7, 2025.For personal use only. \n No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 0,
    "text": "Sports Med 2004; 34 (7): 465-485\nREVIEW ARTICLE\n0112-1642/04/0007-0465/$31.00/0\n© 2004 Adis Data Information BV. All rights reserved.\nFactors Affecting Running Economy\nin Trained Distance Runners\nPhilo U. Saunders,1,2 David B. Pyne,1 Richard D. Telford3  and John A. Hawley2 \n1\nDepartment of Physiology, Australian Institute of Sport, Belconnen, ACT, Australia\n2\nExercise Metabolism Group, Faculty of Medical Sciences, RMIT University, Bundoora,\nVictoria, Australia\n3\nSchool of Physiotherapy and Exercise Science, Griffith University, Gold Coast,\nQueensland, Australia\nContents\nAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465\n1.\nMeasurement of Running Economy (RE) ."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 1,
    "text": ".. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467\n1.1\nTreadmill RE Compared with Outdoor Running . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467\n1.2\nReliability of RE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468\n1.3\nCorrecting RE for Body Mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468\n2.\nRE and Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469\n3.\nPhysiological Factors Affecting RE . . . . . . . . . . . . . . . . . . . ."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 2,
    "text": ".. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470\n4.\nBiomechanical Factors Affecting RE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471\n4.1\nAnthropometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473\n4.2\nKinematics and Kinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473\n4.3\nFlexibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474\n4.4\nGround Reaction Forces. . . . . . . . . . . . . . . . . . . . . . . . . . ."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 3,
    "text": ".. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475\n5.\nInterventions to Improve RE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477\n5.1\nStrength Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477\n5.2\nAltitude Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478\n5.3\nTraining in the Heat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480\n6.\nConclusions and Future Directions . . . . . . . . . . . . . . . . . . . . ."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 4,
    "text": ".. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480\nRunning economy (RE) is typically defined as the energy demand for a given\nAbstract\nvelocity of submaximal running, and is determined by measuring the steady-state\nconsumption of oxygen ( ˙VO2) and the respiratory exchange ratio. Taking body\nmass (BM) into consideration, runners with good RE use less energy and therefore\nless oxygen than runners with poor RE at the same velocity."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 5,
    "text": "There is a strong\nassociation between RE and distance running performance, with RE being a better\npredictor of performance than maximal oxygen uptake ( ˙VO2max) in elite runners\nwho have a similar ˙VO2max.\nRE is traditionally measured by running on a treadmill in standard laboratory\nconditions, and, although this is not the same as overground running, it gives a\ngood indication of how economical a runner is and how RE changes over time.In\norder to determine whether changes in RE are real or not, careful standardisation\nof footwear, time of test and nutritional status are required to limit typical error of\nmeasurement. Under controlled conditions, RE is a stable test capable of detecting\n466\nSaunders et al.\nrelatively small changes elicited by training or other interventions."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 6,
    "text": "When tracking\nRE between or within groups it is important to account for BM.As ˙VO2 during\nsubmaximal exercise does not, in general, increase linearly with BM, reporting\nRE with respect to the 0.75 power of BM has been recommended.\nA number of physiological and biomechanical factors appear to influence RE\nin highly trained or elite runners. These include metabolic adaptations within the\nmuscle such as increased mitochondria and oxidative enzymes, the ability of the\nmuscles to store and release elastic energy by increasing the stiffness of the\nmuscles, and more efficient mechanics leading to less energy wasted on braking\nforces and excessive vertical oscillation.\nInterventions to improve RE are constantly sought after by athletes, coaches\nand sport scientists."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 7,
    "text": "Two interventions that have received recent widespread\nattention are strength training and altitude training.Strength training allows the\nmuscles to utilise more elastic energy and reduce the amount of energy wasted in\nbraking forces. Altitude exposure enhances discrete metabolic aspects of skeletal\nmuscle, which facilitate more efficient use of oxygen.\nThe importance of RE to successful distance running is well established, and\nfuture research should focus on identifying methods to improve RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 8,
    "text": "Interventions\nthat are easily incorporated into an athlete’s training are desirable.\nThe ability to metabolise energy aerobically is a\nEfficient utilisation of available energy facilitates\nprerequisite for superior endurance performance.[1-3]\noptimum performance in any endurance running\nIn competitive distance running, successful per-\nevent."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 9,
    "text": "Efficiency refers to the ratio of work done to\nformance has been correlated to an athlete’s maxi-\nenergy expended.[8] RE is represented by the energy\nmal oxygen uptake ( ˙VO2max).[1,3-5] Performance in\nexpenditure and expressed as the submaximal ˙VO2\nendurance events is directly influenced by altera-\nat a given running velocity.[4,9-11] The energy cost of\ntions in the availability of oxygen, carbohydrate and\nrunning reflects the sum of both aerobic and anaer-\nfat, and the density of muscle mitochondria.[6]\nobic metabolism, and the aerobic demand (measured\n˙VO2max is influenced by a variety of factors includ-\nby the ˙VO2 in L/min) at a given speed does not\ning muscle capillary density, haemoglobin mass,\nnecessarily account for the total energy cost of run-\nstroke volume, aerobic enzyme activity and muscle\nning, which is measured in joules or kilojoules of\nfibre type composition.[6] Although a high ˙VO2max\nwork done.[8] Runners with good RE use less oxygen\nis required for distance running, other physiological\nthan runners with poor RE at the same steady-state\nand performance factors are important in determin-\nspeed.[12] Figure 1 illustrates two international cali-\ning endurance capacity.[4] These factors depend on\nbre 10km runners measured in our laboratory: both\nthe race distance and include the percentage of\nrunners had a similar ˙VO2max, with the more effi-\n˙VO2max a runner can sustain without accumulating\ncient runner (better RE) having a 10km time of 1\nlactic acid, the ability to utilise fat as a fuel at high\nminute faster than the less efficient runner."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 10,
    "text": "The\nwork rates and thereby ‘spare’ carbohydrate and\nsteady-state condition is verified by the maintenance\nrunning at race pace with relatively low energy\nof blood lactate concentration (La) at baseline\nexpenditure (i.e.good running economy [RE]). The\nlevels[13] and a respiratory exchange ratio (RER)\nvelocity associated with attainment of ˙VO2max\n<1.[4] RE can vary among runners with a similar\n(v ˙VO2max) and the velocity at the onset of blood\n˙VO2max by as much as 30%.[8] In elite or near-elite\nlactate accumulation are good indicators of distance\nrunners with a similar ˙VO2max, RE is a better predic-\nrunning performance.[7]\ntor of performance than ˙VO2max.[5,14] Accordingly, it\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 11,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n467\ntively eliminated during indoor running; however,\ntransferring treadmill data to overground running\nrequires caution.[8,17] Pugh[18] estimated that 8% of\nthe total energy cost of middle-distance track run-\nning (5000m) is expended overcoming air resis-\ntance."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 12,
    "text": "Another study estimated the amount of ener-\ngy required to overcome air resistance was 4% for\nmiddle-distance runners and 2% for marathon run-\nners.[19] When a tailwind velocity is equal to running\nvelocity, overground ˙VO2 was equivalent to tread-\nmill ˙VO2.[17] Differences between overground run-\nning and treadmill running are more likely to be\nobserved as speed increases and the effect of air\nresistance becomes more pronounced.[8] Hagerman\net al.[20] reported lower submaximal ˙VO2 values at\nan altitude where the air is less dense than at sea\nlevel.Using a 14.5 km/h headwind in order to simu-\nSpeed (km/h)  \n14\n16\n18\nMax\n30\n40\n50\n60\n70\n80\n90\nSubject 1\nSubject 2\nVO2 (mL/kg/min)\n·\nFig. 1."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 13,
    "text": "Comparison of oxygen uptake ( ˙VO2) [mL/kg/min] in two\ninternational calibre 10km runners, one with good economy (sub-\nject 1) and the other with poor economy (subject 2) [Saunders et al.\nunpublished data, 2003].Max = maximum.\nlate outdoor conditions, Costill and Fox[21] reported\na 15% difference in submaximal ˙VO2 between con-\nfollows that substantial improvements in RE could\ntrol conditions (no wind) and a simulated headwind.\nfacilitate improved performance in distance runners.\nIt is clear that running on the treadmill is not the\nIn summary, the relationship between RE and per-\nsame as running over ground, where wind resistance\nformance is well documented, with many indepen-\naffects ˙VO2."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 14,
    "text": "Furthermore, the technique of running\ndent reports demonstrating a strong relationship be-\non a treadmill is different to running over ground\ntween \nRE \nand \ndistance \nrunning \nperform-\nwhere the hamstrings are used to a greater extent to\nance.[1,4,5,10,15,16]\nproduce propulsive forces.However, we can be\nThe purposes of this review are to examine the\nconfident that RE measured on a treadmill is highly\nvalidity and reliability of currently used tests for\ncorrelated to RE over ground. It is reasonable, then,\nmeasuring RE, examine research relating to physio-\nlogical and biomechanical factors which influence\nto assume that interventions affecting RE on the\nRE, describe interventions that have attempted to\ntreadmill will similarly affect RE over ground."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 15,
    "text": "From\nimprove RE, and discuss potential areas for future\nwork in our laboratory, we have determined that\nresearch directions in this field.\nreliable measures of RE need to be obtained at\nspeeds eliciting ≤85% of ˙VO2max in highly trained\ndistance runners.\n1.Measurement of Running\nEconomy (RE)\nRecent technological advances have allowed\nmeasurement of overground RE using portable oxy-\ngen analysers. The K4 Cosmed analyser (Rome,\n1.1 Treadmill RE Compared with\nItaly) described by Hausswirth et al.[22] is a light-\nOutdoor Running\nweight, accurate, telemetric system that enables\nmeasurement of energy requirements during both\nMeasures of RE have typically been determined\nsubmaximal and maximal exercise in the laboratory\nin the laboratory by having the athlete run on a\nor field."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 16,
    "text": "The K4 system allows continuous recording\nmotorised treadmill.This practice partially over-\nof ˙VO2 during incremental progressive field tests to\ncomes many of the difficulties in obtaining reliable\naccurately determine an athlete’s ventilatory charac-\nmetabolic data in the field (i.e. during training and\nteristics. The validity of the K4 Cosmed telemetric\ncompetition).[14] Air and wind resistance are effec-\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 17,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\n468\nSaunders et al.\nsystem was demonstrated against a metabolic mea-\nvidual RE in 17 male runners following 30–60 min-\nsurement cart (CPX, Medical Graphics, Saint-Paul,\nutes of treadmill familiarisation at the same time of\nMinnesota, USA) during both submaximal and max-\nthe day, in the same pair of shoes and in a non-\nimal exercise, with no difference observed between\nfatigued state.[32] There was a high day-to-day corre-\nthe two oxygen analysis systems.[22] Recent research\nlation in RE (r = 0.95) with a mean coefficient of\nhas utilised the K4 portable oxygen analyser to\nvariation (CV) of 1.3%."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 18,
    "text": "Pereira et al.[34] reported a\nmeasure ˙VO2 in various intervention studies on\nCV of 1.5% for RE in five trained male runners by\nmoderate to highly trained distance runners.[23-26] It\ncareful control of extrinsic factors such as time of\nappears that overground RE can be measured in a\ntesting, diet, footwear and relative workload.\nnatural field setting with the K4 Cosmed telemetric\nPereira and Freedson[33] note that previous stud-\nsystem and similar devices, although careful atten-\nies investigating intra-individual variation in RE\ntion must be made to ensure post-testing results are\nhave not compared intra-individual variability be-\nnot influenced by changes in environmental condi-\ntween runners differing in training level."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 19,
    "text": "These in-\ntions.\nvestigators used seven highly trained males\n( ˙VO2max; 69.1 mL/kg/min) and eight moderately\ntrained males ( ˙VO2max 58.3 mL/kg/min) with test-\n1.2 Reliability of RE\ning being carried out for 3 weeks at ~88% of the\nConsideration of the typical intra-individual vari-\nvelocity associated with the individual lactate\nation in RE is essential when investigating the effec-\nthreshold (LT).Time of day, day of the week, diet\ntiveness of interventions aimed at modifying RE. As\nand footwear were controlled within each subject\nhas been previously noted,[14] small sample sizes\nacross the three tests."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 20,
    "text": "CVs of 1.8% for the highly\nand omission of the typical error (TE) restricts the\ntrained group and 2.0% for the moderately trained\ndegree to which meaningful conclusions on the im-\ngroup (average 1.9%) were reported.[33] After ac-\npact an intervention has on RE can be drawn.In\ncounting for technical error, biological variation ac-\norder to interpret the practical significance of vari-\ncounted for ~94% of the intra-individual variation in\nous interventions aimed at improving RE, a state-\nRE. The results suggest that workloads below LT\nment of the test-retest reliability or TE should be\nmay permit more stable measures of RE to be ob-\nprovided. In research settings, a rigorous experi-\ntained."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 21,
    "text": "Brisswalter and Legros[28] demonstrated that\nmental design is necessary to control confounding\nRE, respiratory measures and stride rate were stable\nvariables and to permit a valid determination of the\nmeasures for assessing energy cost associated with\nimpact of interventions on RE.Daniels et al.[27]\nrunning in elite middle-distance runners. The au-\nobserved an 11% variation in the stability of RE in\nthors reported a variation of 4.7% in RE in ten elite\nten trained males running at 16 km/h, even after\n800m runners ( ˙VO2max, 68 mL/kg/min; mean 800m\ncontrolling for variability associated with footwear\ntime, 1:49 minutes). In a study of elite French dis-\nand test equipment."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 22,
    "text": "Well controlled reliability stud-\ntance runners, subjects were tested three times over\nies measuring RE show intra-individual variations\na 12-month period to determine the stability of RE.\nbetween 1.5–5%,[28-34] indicating that test-retest in-\nRE was stable over the 12-month period despite an\ntra-individual results are relatively stable.\nimprovement in ˙VO2max."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 23,
    "text": "The authors concluded\nFactors such as treadmill running experience,\nthat in elite distance runners, RE is a difficult param-\nfootwear, time of day of testing, prior training activ-\neter to improve.[35]\nity and nutritional status may affect intra-individual\nvariation in RE.[29] Morgan[29] investigated 16 male\n1.3 Correcting RE for Body Mass\nsubjects who completed two 10-minute RE tests at\nthe same time of the day within a 4-day period,\nRE can be expressed as a ratio of a runners’ ˙VO2\nwearing the same pair of shoes.The intra-individual\n(L/min) divided by their body mass (BM) in kilo-\nRE was 1.6%. Another study examined intra-indi-\ngrams.[36] However, when comparing individuals or\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 24,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n469\ngroups who differ in BM this expression may induce\nfinding to the extra muscular effort required to pro-\nvide cushioning if the shoe itself does not provide\nerror because submaximal ˙VO2 during running does\nadequate shock absorption.\nnot increase proportionately to BM.[37] In animals,\nthe oxygen cost of running does not increase propor-\ntionately to BM[38] and in humans, the ˙VO2 per\n2.RE and Performance\nkilogram of BM is higher in children than\nThe relationship between RE and performance is\nadults.[8,39-50] Bergh et al.[37] suggests that, in\nwell documented."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 25,
    "text": "Early research comparing elite\nhumans, the higher submaximal ˙VO2 observed in\nAmerican distance runners ( ˙VO2max 79 mL/kg/min)\nchildren relates to differences in body size and not\nwith good distance runners ( ˙VO2max; 69.2 mL/kg/\nmerely growth and maturation.Sjodin and\nmin), indicated that the elite runners had better RE\nSvedenhag[51] concur with this, and suggest that the\nthan good runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 26,
    "text": "When expressed as a percentage\nimproved RE measured in relation to BM, observed\nof ˙VO2max this difference in RE was magnified,\nin adolescent boys during growth, may largely be\nwith the elite runners working at a lower percentage\nattributable to its measurement of ˙VO2 per kilogram\nof their ˙VO2max.[16] Di Prampero et al.[15] stated that\nof BM.\na 5% increase in RE induced an approximately 3.8%\nTheory associated with elastic components of\nincrease in distance running performance."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 27,
    "text": "As an\nmuscle and connective tissue estimates ˙VO2 to be\nexample of the relationship between RE and per-\nproportional to the 0.75 power of BM.[52] Bergh et\nformance, a case study of American mile record\nal.[37] suggested that submaximal ˙VO2 and ˙VO2max\nholder Steve Scott, reported that during a 6-month\nmeasures during running are better related to\nperiod of training, Scott improved his ˙VO2max by\nBM–0.66 or BM–0.75 than BM–1."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 28,
    "text": "Furthermore, sever-\n3.8% (74.4 to 77.2 mL/kg/min).[8] During the same\nal studies[40,53,54] have shown an inverse relationship\nperiod there was a 6.6% improvement in RE (48.5 to\nbetween BM and submaximal ˙VO2/kg, providing\n45.3 mL/kg/min) at a running velocity of 16 km/h.\nfurther support that ˙VO2 reported as mL/kg/min\nThe combined improvement of an increased\nmay provide misleading comparative results.[37,51]\n˙VO2max and a better RE reduced the relative intensi-\nAnother factor affecting RE is the pattern of\nty of running at 16 km/h by 10.0% (65.1% to 58.6%\ndistribution of mass in the body."
  },
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    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 29,
    "text": "Carrying mass\nof ˙VO2max) and was associated with improved per-\ndistally increases the aerobic demand of running to a\nformance during this period.[10]\ngreater extent than carrying mass closer to the centre\nSvedenhag and Sjodin[60] observed variations in\nof mass.[55-58] Aerobic demand is increased by 1%\nRE and performance in elite distance runners\nfor every extra kilogram carried on the trunk, how-\n( ˙VO2max 75 mL/kg/min) who undertook alternating\never, when the mass was carried in the shoes, aero-\nsessions of slow distance, uphill and interval train-\nbic demand increased by 10% for every additional\ning over a 22-month period."
  },
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    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 30,
    "text": "Athletes significantly\nkilogram.[58] Jones et al.[56] found an average in-\nreduced their ˙VO2 at 15 and 20 km/h accompanied\ncrease in ˙VO2 of 4.5% per kilogram of load carried\nby enhanced performances over 5000m.However,\non the feet when running at 12 km/h. Another study\nnot all studies have demonstrated a significant rela-\ninvestigated the effect of carrying mass on either the\ntionship between RE and performance. Williams\nthighs or feet and reported a 7% per kilogram in-\nand Cavanagh[54] failed to identify a significant rela-\ncrease in ˙VO2 when the mass was carried on the\ntionship between RE at 13 km/h and 10km perform-\nthigh compared with 14% per kilogram increase in\nance (~35 minutes) in a group of 16 runners."
  },
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    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 31,
    "text": "The\n˙VO2 when carried on the feet.[57] The cushioning of\npercentage of slow-twitch muscle fibres and the\nshoes also affects RE, with an approximate 2.8%\nrunners ˙VO2max correlated best with 10km perform-\nenergy saving realised for treadmill running in well\nance.Conley and Krahenbuhl[4] showed that RE was\ncushioned shoes compared with poorly cushioned\na good predictor of performance in runners of com-\nshoes of similar mass.[59] The authors attributed this\nparable ability. In that study, 12 highly trained male\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 32,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\n470\nSaunders et al.\nPerformance in \ndistance runners\nEnvironment \nAltitude\nHeat\nResistance\nTraining\nPlyometrics\nTraining phase\nSpeed, volume, \nintervals, hills, etc.\nRunning economy\nPhysiology\nAdolescent\ndevelopment\nMetabolic \nfactors\nInfluence of \ndifferent running\nspeeds\nBiomechanics\nElastic stored\nenergy\nMechanical \nfactors\nGround reaction \nforce\nFlexibility\nAnthropometry\nBodyweight\nand composition\nMuscle stiffness,\ntendon length\nLimb \nmorphology\nMaximal oxygen\nuptake (VO2max)\n·\nFig.2."
  },
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    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 33,
    "text": "Factors affecting running economy.\ndistance runners ( ˙VO2max ~72 mL/min and 10km\ntheir ˙VO2max but with similar La as the Caucasian\nrunners.\nperformance ~32 minutes) were tested 3–6 days\nThese studies indicate that improving athletes RE\nafter they had competed in a 10km race.There were\nis related to improvements in distance running per-\nsignificant correlations between submaximal ˙VO2\nformance. RE is likely to be influenced by a number\nand performance at running speeds of 14, 16 and 18\nof factors (figure 2) and any intervention (training,\nkm/h."
  },
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    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 34,
    "text": "Some 65% of the variation in race perform-\naltitude, heat) that can reduce the oxygen cost over a\nance could be attributed to differences in RE, with\nrange of running velocities will conceivably lead to\nthe more economical runners performing the best.\nenhanced performance.\nThe more economical runners were able to run at a\nlower percentage of their ˙VO2max, resulting in lower\n3.Physiological Factors Affecting RE\nLa at a given speed."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 35,
    "text": "The latter factor is closely\nFluctuations in physiological factors such as core\nassociated with the pace a runner is able to maintain\ntemperature (CTemp), heart rate (HR), ventilation\nfor races >15 minutes.[61] These data also provide\n(VE) and La, may be associated with changes in RE\nevidence that RE at slower speeds are useful in\nduring competition.[14,63-65] Thomas et al.[12] investi-\npredicting performance in races at faster speeds.\ngated the effect of a simulated 5km race on RE, VE,\nWeston et al.[62] investigated the RE and perform-\nCTemp, La and HR.RE was determined using a\nance of eight African (Kenyan) and eight Caucasian\nconstant treadmill speed eliciting 80–85% of the\ndistance runners. The Kenyan runners had similar\nathletes ˙VO2max."
  },
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    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 36,
    "text": "RE decreased significantly and\n10km race performance to the Caucasian group,\nVE, CTemp, La and HR all increased significantly\ndespite having a 13% lower ˙VO2max.The RE of the\nfrom the beginning to the end of the 5km run. The\nKenyan runners was 5% better than the Caucasian\nincreased VE was the only factor that correlated\ngroup, and when RE was normalised to BM–0.66 the\nmoderately with the decrease in RE (r = 0.64; p <\nKenyans had an 8% better RE. The Kenyan runners\n0.05), indicating a greater oxygen cost was associat-\nalso completed the 10km at a higher percentage of\ned with the increase in VE. A higher CTemp increases\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 37,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n471\n˙VO2 at a given speed.[66-69] Increases in the metabol-\ninvoke improvements in RE, a smaller disturbance\nin homeostasis and slower utilisation of muscle gly-\nic cost from augmented circulation, VE and sweating\ncogen in the working musculature.[86] Daniels and\nare the major factors that increase submaximal ˙VO2\nDaniels[87] found that 800/1500m specialists were\nand decrease RE.[68] In contrast, Rowell et al.[70]\nmore economical than marathon runners at veloci-\nstated that the mechanical efficiency of muscle in-\nties above 19 km/h, yet were less economical than\ncreases when CTemp is mildly elevated, reducing\nmarathon runners at slower speeds."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 38,
    "text": "Without a mea-\n˙VO2 by an amount equal to or greater than the\nsure of the anaerobic contribution to total metabo-\nincrease caused by changes in the cost of circulation,\nlism, it is difficult to conclude that the 800/1500m\nVE and sweating.The composition of muscle fibres\nspecialists were more economical than the marathon\nalso seems to influence RE. It has been suggested\nrunners at the faster running velocities. Males were\nthat a higher percentage of slow-twitch muscle fib-\nmore economical than females at common speeds\nres is associated with better RE,[54,71,72] indicating\nand relative intensities, but there was no difference\nthat metabolic activity or actual speed of contraction\nin RE between males and females at typical race\nof the muscle fibres may influence RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 39,
    "text": "Myocardial\nintensities for each sex.Another study was unable to\n˙VO2 also constitutes a significant fraction of whole\ndetect significant differences in RE between trained\nbody ˙VO2 during exercise. Reductions in myocardi-\nmale and female distance runners across four run-\nal ˙VO2 would result in improved RE from a more\nning velocities (12–16 km/h).[88]\nefficient combination of HR and stroke volume (i.e.\nFranch et al.[78] investigated the effects of three\na reduction in HR and increase in stroke volume).[73]\ntypes of intensive running training on RE in 36 male\nLittle consensus exists on the effects of training\nrecreational runners ( ˙VO2max ~55 mL/kg/min)."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 40,
    "text": "Sub-\nand RE, largely as a consequence of limitations in\njects were assigned to either continuous-distance\nexisting experimental designs such as small sample\ntraining, long-repetition training (4–6 × 4 minutes\nsizes, lack of multiple economy measures to account\nrun with 3 minutes rest) or short-repetition training\nfor normal intra-individual variation and failure to\n(30–40 × 15 seconds run with 15 seconds rest)\ncontrol for factors that influence RE (e.g.fatigue\ngroups, and trained three times a week for 6\nlevel, state of training, treadmill experience and\nweeks.[78] Runners undertaking continuous-distance\nfootwear)."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 41,
    "text": "Some,[10,74-81] but not all[5,42,82] studies\ntraining and long-repetition training increased their\nhave reported improvements in RE after various\nRE by approximately 3% while short-repetition\ntraining interventions.The initial level of fitness of\ntraining had little effect on RE (0.9% change), sug-\nthe subjects is an important factor when considering\ngesting that longer training is the best way to im-\nwhether training alters RE.[42] Numerous studies\nprove RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 42,
    "text": "Thomas et al.[65] suggests that those train-\nindicate that trained subjects are more economical\ning in an effort to improve RE need to concentrate\nthan untrained or less trained subjects[8,74,79,82-84] and\non improving physiological characteristics such as\nlong-distance runners are more economical than\nHR, VE, La and CTemp regulation in order to de-\nmiddle-distance runners.[8,16,84] The better RE in\ncrease the energy demand associated with these\nlong distance runners is largely attributable to a\nparameters."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 43,
    "text": "Interval training may be beneficial to\nlower vertical displacement of the runner’s centre of\nRE by reducing HR, VE and La at higher running\nmass during running probably related to neuromus-\nspeeds.[89]\ncular adaptations induced by long, slow distance\ntraining.[85] Endurance training leads to increases in\n4.Biomechanical Factors Affecting RE\nthe morphology and functionality of skeletal muscle\nmitochondria. An increase in the respiratory capaci-\nRunning involves the conversion of muscular\nty of skeletal muscle permits trained runners to use\nforces translocated through complex movement pat-\nless oxygen per mitochondrial respiratory chain for\nterns that utilise all the major muscle joints in the\na given submaximal running speed. These responses\nbody."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 44,
    "text": "High performance running is reliant on skill\n© 2004 Adis Data Information BV.All rights reserved.\nSports Med 2004; 34 (7)\n472\nSaunders et al.\nTable I."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 45,
    "text": "Biomechanical factors related to better economy in runners[9]\nFactor\nDescription for better running economy\nHeight\nAverage or slightly smaller than average for males and slightly greater than average for females\nPonderal index\nHigh index and ectomorphic or mesomorphic physique\nBody fat\nLow percentage\nLeg morphology\nMass distributed closer to the hip joint\nPelvis\nNarrow\nFeet\nSmaller than average\nShoes\nLightweight but well cushioned shoes\nStride length\nFreely chosen over considerable training time\nKinematics\nLow vertical oscillation of body centre of mass\nMore acute knee angles during swing\nLess range of motion but greater angular velocity of plantar flexion during toe-off\nArm motion that is not excessive\nFaster rotation of shoulders in the transverse plane\nGreater angular excursion of the hips and shoulders about the polar axis in the transverse plane\nKinetics\nLow peak ground reaction forces\nElastic energy\nEffective exploitation of stored elastic energy\nTraining\nComprehensive training background\nRunning surface\nIntermediate compliance\nand precise timing in which all movements have\ntrast, Hausswirth et al.[97] showed that RE was im-\npurpose and function.[9] Clearly, changing aspects of\npaired during the last 45 minutes of a marathon run\nrunning mechanics that result in a runner using less\non a treadmill, which was partly attributed to bi-\nenergy at any given speed is advantageous to per-\nomechanical factors such as a greater forward lean\nformance.[90,91] Biomechanical characteristics asso-\nand a decrease in stride length."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 46,
    "text": "In a similar study,\nciated with improved RE are shown in table I.[9] The\ninvestigating the effects of running a marathon on\nspring-mass model is an important factor associated\nRE, both submaximal ˙VO2 and RER increased dur-\nwith RE, where the bounce of the body on the\ning, and 2 hours after, the marathon.The impaired\nground is counteracted by the spring behaviour of\nRE observed could not be completely explained by\nthe support leg. During the eccentric phase of con-\nany changes observed in the mechanics, and was\ntact, mechanical energy is stored in the muscles,\nattributed to the increasing physiological stresses\ntendons and ligaments acting across joints. Recov-\n(e.g."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 47,
    "text": "heat accumulation and increased reliance of fat\nery during the concentric phase of the stored elastic\nutilisation) associated with running a marathon.[94]\nenergy reduces the energy expenditure.An oscillat-\nThomas et al.[65] investigated the effects of a simu-\ning system is also characterised by a resonant fre-\nlated 5km race on RE and running mechanics of\nquency. The resonant frequency is the frequency at\ntrained female athletes. RE decreased during the\nwhich a system freely vibrates after a mechanical\n5km race, with athletes metabolising more oxygen\nimpulse.[92] RE was significantly correlated with\nat the same intensity."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 48,
    "text": "The changes in RE observed in\nmuscle stiffness (r = 0.80) and resonant frequency (r\nthis study were not caused by any alterations in the\n= 0.79) of the propulsive leg, with stiffer muscles\nmechanics of running, indicating that physiological\noperating at lower resonant frequencies eliciting the\nfactors are more important in reducing RE.Taken\nbest RE.[92] Several studies that have examined RE\ncollectively, the weight of evidence from the ex-\nand running mechanics after previously fatiguing\nisting literature suggests that if previously fatiguing\nexercise and have reported little change in running\nexercise is to reduce RE, it is likely to be through\nkinematics to explain decreases in RE.[93-96] In con-\nphysiological rather than biomechanical factors.\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 49,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n473\n4.1 Anthropometry\nparticular stride length/stride frequency for a given\nrunning speed.[90]\nAnthropometric characteristics such as height,\nThe first studies comparing the biomechanical\nlimb dimensions, body fat, as well as BM, have been\ncharacteristics of elite and good runners indicated\naddressed as potential influences on RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 50,
    "text": "While leg\nthat elite runners had slightly less vertical oscilla-\nlength contributes to angular inertia and the meta-\ntion, were more symmetrical, and had better RE.[102]\nbolic cost of moving the legs during running,[9] there\nWilliams and Cavanagh[103] found that better RE in\nseems little consensus on whether leg length is an\nelite male distance runners was associated with a\nimportant factor in determining RE.In 31 male\nmore extended lower leg at foot strike, a lower\ndistance runners with a 10km performance time of\nvertical force peak and a longer contact time."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 51,
    "text": "More\n~35 minutes, a large variation in RE was observed in\neconomical runners tend to exhibit less arm move-\nthe absence of any differences associated with seg-\nment, as measured by wrist excursion during the\nmental lengths and masses.[54] In contrast, there is\nstride.[54,104] Greater maximal plantar flexion veloc-\nevidence that leg mass and distribution of mass may\nity and greater horizontal heel velocity at foot con-\ninfluence RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 52,
    "text": "Williams and Cavanagh[54] reported a\ntact are also associated with better RE in elite male\nmodest inverse relationship between BM and sub-\ndistance runners.[103] While these authors demon-\nmaximal ˙VO2/kg (r = –0.52) and between maximal\nstrated links with various kinematic parameters and\nthigh circumference and submaximal ˙VO2/kg (r =\nRE, it would appear that further research is war-\n–0.58), indicating that heavier than average runners\nranted to determine if changing a runner’s kinemat-\nuse less oxygen per kilogram of BM."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 53,
    "text": "Myers and\nics induces an improvement in RE.\nSteudel[58] hypothesised that a runner with a propor-\ntionally smaller amount of BM concentrated in the\nRecent research has comprehensively investigat-\nextremities, particularly the legs, would perform\ned biomechanical factors affecting RE.[105] ˙VO2 at\nless work moving their body segments during run-\n12–13 different running speeds was compared with\nning, assuming that all other factors are unchanged\nkinematic data and three-dimensional ground reac-\n(e.g.speed, BM, running style).\ntion forces (GRF) simultaneously with telemetric\nEMG recordings of selected leg muscles."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 54,
    "text": "Joint mo-\nments and power were calculated using two-dimen-\n4.2 Kinematics and Kinetics\nsional video analysis and the digitised segment coor-\ndinates were transferred to a computer system.The\nEarly research suggested that well trained run-\nbiomechanical parameters examined (angular dis-\nners running at 14 and 16 km/h were most economi-\nplacements between the ankle, knee and hip joints;\ncal at the runner’s self-selected stride length, com-\njoint angular velocities) were not good predictors of\npared with other pre-determined stride lengths.[98]\nRE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 55,
    "text": "However, force production during ground con-\nMore recent work has confirmed that the aerobic\ntact, coupled with the activation of the leg extensors\ndemand of running at a given speed is lowest at a\nduring the pre-activity and braking phases and their\nself-selected stride length.[90] Submaximal ˙VO2 in-\ncoordination with longer-lasting activation of the\ncreases curvilinearly as stride length is either length-\nhamstring muscles were of importance.The authors\nened or shortened from that self-selected by the\npointed out that co-activation of the muscles around\nrunner.[90,98-101] Cavanagh and Williams[90] conclud-\nthe knee and ankle joints increases the joint stiff-\ned that there is little need to dictate stride length for\nness, which appears to be related to better RE."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 56,
    "text": "The\nwell trained athletes since they display near optimal\naction of the hip extensors also becomes beneficial\nstride length.They postulated two mechanisms for\nin this respect during ground contact.[105] Refining\nthis phenomenon. Firstly, runners naturally acquire\nmechanical elements such as stride length and fre-\nan optimal stride length and stride rate over time,\nquency or the integration and timing of muscle\nbased on perceived exertion. Secondly, runners may\nactivity to utilise the storage and release of elastic\nadapt physiologically through repeated training at a\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 57,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\n474\nSaunders et al.\nenergy more effectively may lead to improvements\nthe springs to maximise the exploitation of elastic\nenergy.[112-114]\nin RE.[9]\nWilliams and Cavanagh[54] provided substantial\n4.3 Flexibility\nsupport for the notion that more economical runners\nhave identifiable kinetic patterns in their running\nSeveral studies contend that trunk and lower limb\nmechanics.They observed that ground-support time\nflexibility affects RE.[115-117] Godges et al.[117] ob-\nand peak medial force correlated with submaximal\nserved that moderately trained athletic college stu-\n˙VO2 (r = 0.49 and 0.50, respectively)."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 58,
    "text": "More eco-\ndents increased their RE at all speeds (40, 60 and\nnomical runners had lower first peaks in the vertical\n80% ˙VO2max) with improved hip flexion and exten-\ncomponent of the GRF, smaller antero-posterior and\nsion.Improved hip flexibility, myofascial balance,\nvertical peak forces, and a more predominant rear-\nand pelvic symmetry are thought to enhance neuro-\nfoot striking pattern.[54] The authors suggested that\nmuscular balance and contraction, eliciting a lower\nthese characteristics affect muscular demands both\n˙VO2 at submaximal workloads."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 59,
    "text": "These findings are\nbefore and during support, with forefoot strikers\ncompatible with the general belief among runners\nrelying on musculature to assist with cushioning,\nand coaches that improved flexibility is desirable for\nmaking them less economical.In contrast, rear foot\nincreasing RE.[115]\nstrikers tend to rely on footwear and skeletal struc-\nIn contrast, Gleim et al.[116] found that untrained\ntures to take the load and are more economical.[54]\nsubjects who exhibited the lowest flexibility were\nWell cushioned shoes reduce oxygen cost by up to\nthe most economical when running at speeds rang-\n2.8% over stiffer shoes of the same weight.[59,91]\ning from 3–11 km/h."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 60,
    "text": "This finding was explained by\nHowever, it appears that there may be an individual-\ninflexibility in the transverse and frontal planes of\nly optimal degree of cushioning, as shoes with a\nthe trunk and hip regions of the body, stabilising the\n‘spring rate’ that compliments the muscle-tendon\npelvis at the time of foot impact with the ground.\nunits contribute to the exploitation of stored elastic\nThis has the effect of reducing both excessive range\nenergy.[9] Elastic energy stored during the eccentric\nof motion and metabolically expensive stabilising\ncontractions of running substantially contributes to\nmuscular activity.[116] Elastic energy storage and\npropulsion via release during subsequent contrac-\nreturn could be enhanced by having a tighter mus-\ntions.[106-109]\nculo-tendinous system.[118-120] Tightness in the mus-\nIt has been estimated that the Achilles tendon and\ncles and tendons could increase elastic storage and\ntendons in the arch of the foot can store 35% and\nreturn of energy and reduce the submaximal ˙VO2\n17%, respectively, of the kinetic and potential ener-\ndemand.\ngy gained and dissipated in a step while running at\nCraib et al.[115] examined the relationship be-\nmoderate speeds.[110] Cavagna et al.[111] estimates\ntween RE and selected trunk and lower limb flexi-\nthat ˙VO2 during running might be 30–40% higher\nbility in well trained male distance runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 61,
    "text": "Inflexi-\nwithout contributions from elastic energy storage\nbility in the hip and calf regions was associated with\nand return.At higher speeds, elastic recovery of\nbetter RE by minimising the need for muscle\nenergy prevails over the contractile machinery and\nstabilising activity and increasing the storage and\naccounts for most of the work.[109,112] Elastic capaci-\nreturn of elastic energy."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 62,
    "text": "Another study found that\ntance is influenced by the rate and magnitude of\nlower limb and trunk flexibility was negatively re-\nstretch, the level of activation and stiffness of the\nlated to RE in international standard male distance\nmuscle tendon unit, muscle length at completion of\nrunners, with a significant relationship between the\nthe stretch and the time lag between completion of\nsit-and-reach test score and submaximal ˙VO2 at 16\nthe stretch and initiation of the succeeding concen-\nkm/h.[121] Improved RE may reflect greater stability\ntric contraction.[106,107,109] The major role of the mus-\nof the pelvis, a reduced requirement for additional\ncles during running is to modulate the stiffness of\nmuscular activity at foot strike, and a greater storage\n© 2004 Adis Data Information BV."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 63,
    "text": "All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n475\nand return of elastic energy due to inflexibility of the\nIn a well controlled study, Heise and Martin[123]\nlower body.[121] A short and rapid stretch with a\ninvestigated the support requirements during foot\nshort coupling time and a high force at the end of\ncontact of 16 moderately trained male runners\npre-stretch increases musculo-tendon elasticity.[105]\n( ˙VO2max 62 mL/kg/min).Less economical runners\nKyrolainen et al.[105] found that stiffer muscles\nexhibited greater total and net vertical impulse, indi-\naround the ankle and knee joints in the braking\ncating wasteful vertical motion. Correlations be-\nphase of running increased force potentiation in the\ntween total vertical impulse and ˙VO2, and net verti-\npush-off phase."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 64,
    "text": "Having stiffer, more inflexible mus-\ncal impulse and ˙VO2 were r = 0.62 and 0.60, respec-\ncles in the legs and lower trunk could enhance RE\ntively.The combined influence of vertical GRF and\nvia increased energy from elastic storage and return,\nthe time course of the force application explained\nwhich has no additional oxygen cost.\n38% of the inter-individual variability in RE. Al-\nTaken collectively, the findings from these stud-\nthough positive relationships were observed, other\nies suggest that there is an optimal level of flexibility\nGRF characteristics such as twisting, medial-lateral\nwhereby RE can benefit, although a certain degree\nor antero-posterior moments were not significantly\nof muscle stiffness is also required to maximise\ncorrelated with submaximal ˙VO2."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 65,
    "text": "Kyrolainen et\nelastic energy storage and return in the trunk and\nal.[105] found that GRF and the rate of force produc-\nlegs.Runners should not abandon stretching as part\ntion increased with increasing running speed. They\nof their training programmes, as a certain amount of\nsuggested that increasing the pre-landing and brak-\nflexibility is also required for optimal stride length\ning activity of the leg extensor muscles might pre-\nat high running speeds.\nvent unnecessary yielding of the runner during the\nbraking phase, helping them tolerate higher impact\n4.4 Ground Reaction Forces\nloads."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 66,
    "text": "Pre-activation of these muscles is a preparato-\nry requirement for the enhancement of EMG activity\nFresh insight into the inter-individual variations\nduring the braking phase and for the time of muscu-\nin RE has come from comparative biology.Kram\nlar action with respect to the ground contact. Cen-\nand Taylor[122] investigated the aerobic demand of\ntrally programmed pre-landing activity appears to\nrunning, hopping and trotting in a variety of animal\nregulate the landing stiffness and compensates for\nspecies. They presented a simple inverse relation-\nlocal muscular failure."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 67,
    "text": "Pre-activity increases the\nship between aerobic demand and stance time inde-\nsensitivity of the muscle spindle via enhanced alpha-\npendent of an animal’s size, indicating that the ener-\ngamma co-activation potentiating stretch reflexes,\ngy cost of running is determined by the cost of\nand enhancing musculo-tendon stiffness, with a re-\nsupporting an animal’s mass and the time course of\nsulting improvement in RE.[105]\ngenerating force.[122] GRF reflect the functional and\nThe requirement to support BM is a major meta-\nmechanical requirements during stance."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 68,
    "text": "During\nbolic cost of running.[124] Vertical GRF is the major\nground contact, a runner activates muscles for the\ndeterminant of the metabolic cost during run-\npurpose of stability and maintenance of forward\nning.[122,123,125] However, horizontal forces can sub-\nmomentum.Excessive changes in momentum in the\nstantially affect the metabolic cost of running, and\nvertical, antero-posterior and medial-lateral direc-\nthis is clearly observed when running on a windy\ntions are wasteful in terms of metabolic energy\nday.[124] Using a wind tunnel to apply a horizontal\nrequirements. Linear impulse measures the change\nimpeding force, Pugh[126] showed that the metabolic\nin momentum and quantifies the time course of the\ncost of running increased with the square of head-\nGRF."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 69,
    "text": "Quantifying the magnitude of support and\nwind velocity.Similarly, a harness to apply imped-\nforces during ground contact may explain at least in\ning forces increased the metabolic cost of running\npart the variability in RE among individuals of simi-\nproportionally with an increase in external\nlar fitness.[123] Figure 3 depicts typical vertical and\nwork.[127-129] In a recent study, horizontal force was\nhorizontal GRF for three steps of one subject.\n© 2004 Adis Data Information BV. All rights reserved.\nSports Med 2004; 34 (7)\n476\nSaunders et al.\nSpeed (km/h)  \n0.2\n0.0\n0.6\n0.4\n0.8\n1.0\n−500\n0\n500\n1000\n1500\nc\nForce (N)\nImpact \npeak\nActive\npeak\n−500\n0\n500\n1000\n1500\nb\nForce (N)\n−500\n0\n500\n1000\n1500\na\nForce (N)\nFv\nFh\nFig. 3."
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    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 70,
    "text": "Typical vertical (Fv) and horizontal (Fh) ground reaction forces for three steps of a single subject: for unloaded, 0% bodyweight\napplied horizontal force (AHF) control condition (a), with an impeding force of 6% bodyweight AHF (b), and with an aiding force of 15%\nbodyweight AHF (c) [reproduced from Chang and Kram,[124] with permission].\naltered to both impede and assist runners using a\nThe authors concluded that generating horizontal\npulley and rubber harness.At the two extreme con-\nforce is metabolically more expensive per unit of\nditions, a 33% reduction in metabolic cost with a\nforce than horizontal braking force during steady-\n15% assisting force and a 30% increase in metabolic\nstate running."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 71,
    "text": "It appears that the net resultant force\ncost with a 6% impeding force were observed.[124]\ngenerated on the ground affects net muscle moments\n© 2004 Adis Data Information BV.All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n477\nat each joint, as well as the force of each muscle\ntriathletes ( ˙VO2max 69 mL/kg/min).[137] In this\ncrossing the joint. Therefore, it may not be appropri-\nstudy, 14 weeks of a HWT intervention elicited in\nate to consider vertical and horizontal GRF as inde-\nthe endurance/strength group a significantly lower\npendent determinants of metabolic cost.[124]\n(11%) submaximal ˙VO2 compared with the endur-\nance-only group, and a marginal enhancement in RE\n5."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 72,
    "text": "Interventions to Improve RE\nin the endurance/strength group compared with their\npre-test.\nRE is influenced by many physiological and bi-\nA specific type of strength training, known as\nomechanical variables; however, little research ex-\nexplosive-strength or plyometric training, invokes\nists with regard to improving RE and endurance\nspecific neural adaptations such as an increased\nperformance by manipulation of these factors.[73]\nactivation of the motor units, with less muscle hy-\nEndurance training coupled with various other train-\npertrophy than typical heavy-resistance strength\ning methods has been shown to improve RE in\ntraining.[130,138,139] Plyometric training enhances the\nuntrained and moderately trained subjects, with\nmuscles’ ability to generate power by exaggerating\ntrained runners having a better RE than their un-\ntrained or less trained counterparts.[8,74,79,82-84] Most\nthe stretch-shorten cycle, using activities such as\nstudies demonstrating improvements in RE as a\nbounding, jumping and hopping.[140] Plyometric\nresult of training have used untrained or moderately\ntraining also has the potential to increase the stiff-\ntrained subjects, and improvement in fitness is a\nness of the muscle-tendon system, which allows the\nnatural adaptation from endurance training."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 73,
    "text": "In high-\nbody to store and utilise elastic energy more effec-\nly trained runners who already possess a well devel-\ntively.[141] Both these adaptations from plyometric\noped RE through years of endurance training, fur-\ntraining could conceivably improve RE by generat-\nther improvements in RE are seemingly difficult to\ning more force from the muscles without a propor-\nobtain.Three areas that have potential to improve\ntionate increase in metabolic energy requirement.\nRE are strength training, altitude exposure and train-\nPaavolainen et al.[80] indicated that 9 weeks of ex-\ning in a warm to hot environment.\nplosive-strength training improved RE (8%) and\n5km performance (3%) with no changes in ˙VO2max\n5.1 Strength Training\nin moderately trained runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 74,
    "text": "This group also mea-\nsured neuromuscular characteristics using a 20m\nEndurance athletes must be able to sustain a high\nsprint test, the distance covered in five alternate\naverage running velocity for the duration of a race.\nforward leg jumps and the corresponding contact\nThis emphasises the role of neuromuscular charac-\ntimes (shorter times being better), as well as vertical\nteristics in voluntary and reflex neural activation,\nand horizontal forces measured on a force plate\nmuscle force and elasticity, running mechanics, and\nduring a constant-speed 200m run."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 75,
    "text": "The experimen-\nthe anaerobic capacities in elite endurance run-\ntal group improved in all of these tests compared\nners.[80,130] The use of strength training is one inter-\nwith the control group.[80] These findings indicate\nvention thought to improve RE.Strength training\nthat explosive-strength training can improve RE and\ncan improve anaerobic characteristics such as the\nperformance as a consequence of enhanced neuro-\nability to produce high La and the production of\nmuscular function."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 76,
    "text": "Similarly, recent studies have\nshort contact times and fast forces.[131,132] Heavy\nshown improvements in RE and performance after 6\nresistance training improves the endurance perform-\nweeks of plyometric training in moderately trained\nance of untrained subjects[133-135] and RE of moder-\nsubjects with no change in ˙VO2max,[140,141] with the\nately trained female distance runners without con-\nformer study showing a 6% improvement in RE\ncomitant changes in ˙VO2max.[136] Recent work has\nacross three running speeds and a 3% increase in\nshown that a combination of heavy-weight training\n3km run performance."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 77,
    "text": "The study by Spurrs et al.[141]\n(HWT) and endurance training improved running\ndemonstrated improvement in muscle-tendon stiff-\nperformance and enhanced RE in well trained\n© 2004 Adis Data Information BV.All rights reserved.\nSports Med 2004; 34 (7)\n478\nSaunders et al.\nness and rate of force development during a seated\nlivery and utilisation,[147,158,168,170] mechanisms that\ncalf-raise test, a finding which also supports the\npotentially could improve an athlete’s RE. Howev-\ntheory that improved RE from plyometrics is attrib-\ner, to date little research has been undertaken on the\nutable to increased muscular power, and greater\neffects of altitude exposure on RE in highly trained\nstorage and return of elastic energy. To date, there is\ndistance runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 78,
    "text": "Three investigations have reported\nlittle research investigating the effects of plyometric\nno change in submaximal ˙VO2 after a period of\ntraining on elite ( ˙VO2max >70 mL/kg/min) distance\naltitude exposure,[145,156,164] while others have\nrunners.\ndemonstrated improved RE after various stints of\nhypoxic exposure.[155,171,172] Similarly, after a period\n5.2 Altitude Exposure\nof altitude acclimatisation, sea-level ˙VO2 during\nsubmaximal cycling is either reduced[151,153,154,157] or\nThe effect of altitude training on endurance per-\nunchanged.[146,160] A tentative interpretation of these\nformance has been researched extensively.[142-168]\nfindings is that altitude exposure for runners and\nThere is a widespread belief in the athletic commu-\ncyclists has no detrimental effects on economy and\nnity that altitude training can enhance sea-level ath-\nthere is good evidence to suggest that it may lead to\nletic performance.[149,156,166] The mechanisms for\nimprovements.\nthese improvements are not clear, but may include\nIn a study undertaken at sea level, RE of high-\nhaematological changes (i.e."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 79,
    "text": "increased red cell\naltitude residents was compared with that of sea-\nmass)[148,156] and local muscular adaptations (such as\nlevel residents.˙VO2 was significantly lower in the\nimproved skeletal muscle buffer capacity).[151] The\nhighlanders, indicating greater economy.[154] Green\ntraditional approach to altitude training involves\net al.[153] examined the effects of a 21-day expedition\nathletes living and training at a moderate\nto altitude on submaximal cycling economy. Exper-\n(1500–3000m) natural altitude. A more recent ap-\nienced mountain climbers were recruited for this\nproach is for athletes to live/sleep at altitude and\nstudy and were based at 2160m, ascending to\ntrain near sea level, the so-called live-high train-low\nheights of 6194m."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 80,
    "text": "Three days after the expedition,\n(LHTL) method.[156] Because the geography of\nsubjects had a significantly lower ˙VO2 during a\nmany countries does not readily permit LHTL, a\n40-minute submaximal cycling test (20 minutes at\nfurther refinement involves athletes living at simu-\n60% ˙VO2max and 20 minutes at 75% ˙VO2max) than\nlated altitude under normobaric conditions and\nbefore the expedition."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 81,
    "text": "With resting ˙VO2 unchanged\ntraining at, or close to, sea level.[161] In recent years,\npre- and post-acclimatisation, the authors concluded\nendurance athletes have utilised several new devices\nthat the altitude exposure was responsible for the\nand modalities to complement the LHTL approach.\nimproved economy, indicating net efficiency in-\nThese modalities include: normobaric hypoxia via\ncreased by ~21% post-altitude acclimatisation, inde-\nnitrogen dilution, which allows athletes to undertake\npendent of the power output."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 82,
    "text": "A similar study of\nLHTL; supplemental oxygen to simulate normoxic\nmountain climbers showed an ~8% reduction in\nor hyperoxic conditions during exercise/sleep at nat-\n˙VO2 during steady-state, two-legged kicking exer-\nural altitude; and hypoxic sleeping devices which\ncise, 3 days after a 21-day mountain climbing expe-\npermit athletes to sleep low and train high (LLTH).\ndition to 6194m.[157] These studies involved cycling\nIntermittent hypoxic exposure is another method\nand two-legged kicking as the mode of exercise to\ninvolving brief periods of hypoxic exposure via a\nmeasure economy.Evidence to suggest that altitude\nhypobaric chamber or inhalation of a hypoxic gas\nexposure improves economy of highly trained ath-\nmixture to stimulate erythropoietin production."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 83,
    "text": "Data\nto support these claims are minimal and inconclu-\nletes was demonstrated by Gore et al.[151] in a study\nsive.[169]\nwhere six highly trained triathletes ( ˙VO2max 73 mL/\nkg/min) improved cycling efficiency after 23 nights\nAltitude acclimatisation results in both central\nsleeping at a simulated altitude of 3000m, compared\nand peripheral adaptations that improve oxygen de-\n© 2004 Adis Data Information BV.All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n479\nwith seven control athletes ( ˙VO2max 73 mL/kg/min)\nof the excitation and contraction process to perform\nwho trained the same but slept at normal altitude\nwork at lower energy costs.[153] Roberts et al.[160]\n(~600m)."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 84,
    "text": "In the LHTL group, overall submaximal\nobserved that 4300m altitude acclimatisation for 21\ncycling efficiency improved significantly by 1%.[151]\ndays decreased the reliance on fat as a fuel during\nAlthough this group was highly trained and mainly\nrest and cycling at 50% ˙VO2max."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 85,
    "text": "The authors sug-\nconsisted of triathletes who undertook a lot of run-\ngested that the shift towards increased dependence\nning training, cycling was still the mode of exercise\non glucose metabolism and away from reliance on\nused to determine improved economy, and further\nfatty acid consumption under conditions of acute\nresearch is required to determine whether altitude\nand chronic hypoxia, is advantageous because glu-\ntraining improves RE in highly trained runners.\ncose is a more efficient fuel in terms of generating\nATP per mole of oxygen."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 86,
    "text": "Another suggested im-\nCurrently, three studies have demonstrated im-\nprovement in efficiency is the reduced energy re-\nproved economy in highly trained runners.[155,171,172]\nquirement of one or more processes involved in\nKatayama and colleagues[171] have demonstrated on\nexcitation and contraction of the working muscles as\ntwo occasions that intermittent hypoxic exposure\na result of metabolic adaptations from altitude accli-\nimproves RE in well trained runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 87,
    "text": "The first study\nmatisation.[153] The reduction in by-product accumu-\nreported that simulated hypoxic exposure using in-\nlation, such as adenosine diphosphate (ADP), inor-\ntermittent hypobaria of 4500m 3 hours per day for\nganic phosphate and hydrogen that occur after alti-\n14 consecutive days improved RE and performance\ntude acclimatisation, increases the amount of free\nin well trained runners ( ˙VO2max 68 mL/kg/min).\nenergy released from ATP hydrolysis and depresses\nAltitude exposure improved RE by 2.6% (14 km/h)\nthe need to maintain hydrolysis rates at pre-accli-\nand 3.3% (16 km/h), improved 3000m run time by\nmatised levels.[153,173]\n1% and time to exhaustion on the treadmill by 2.7%.\nThe improvement in RE accounted for 37% of the\nSaltin et al.[174] investigated the physiological\nimprovement observed in the 3000m time trial.[155]\ncharacteristics of Kenyan and Scandinavian runners.\nMore recently, it was demonstrated that 3 hours per\nThe Kenyan runners lived and trained at altitude\nday for 2 weeks of intermittent exposure to\nwhile the Scandinavian runners lived and trained at\nnormobaric hypoxia (12.3% oxygen) improved RE\nsea level."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 88,
    "text": "Kenyan runners did not accumulate La\nby 2.6% (14 km/h) and 2.9% (16 km/h) in well\nduring running until near very high or peak exercise\ntrained runners ( ˙VO2max 68 mL/kg/min)."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 89,
    "text": "The im-\nintensities, and had much lower La both at altitude\nproved RE was accompanied by a decreased HR\nand sea level at high relative exercise intensities.\n(3.3% and 3.9% at 14 and 16 km/h, respectively)\nSimilarly, Weston et al.[175] reported Kenyan runners\nand a trend towards improved 3000m run time\nhad higher resistance to fatigue when running at the\n(1.3%, p = 0.06).[171] Another recent study demon-\nsame percentage of peak treadmill velocity than\nstrated that 20 days of sleeping at simulated altitude\nCaucasian runners, despite similar ˙VO2max values in\n(2000–3100m) and training near sea level (600m)\nthe two groups."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 90,
    "text": "Whilst these studies of runners\nimproved (3.3%, p = 0.005) RE in elite distance\nnative to high altitude do not necessarily indicate the\nrunners ( ˙VO2max 73 mL/kg/min) in the absence of\neffect of training at altitude, it has been reported that\nany changes in cardiorespiratory measures or red\nexercise after altitude training results in reduced La\ncell mass.[172]\nproduction at submaximal exercise, with lower\nblood and muscle La being reported.[146,152,176] On\nMechanisms that have been suggested to improve\nthis basis, altitude training allows athletes to main-\neconomy after altitude exposure include: decreased\ntain a given exercise intensity with lower accumula-\ncost of VE, a shift towards a greater glycolytic\ntion of La during post-acclimatised sea-level exer-\ninvolvement of adenosine triphosphate (ATP) re-\ncise."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 91,
    "text": "One of the mechanisms for lower plasma La\ngeneration, greater carbohydrate utilisation for oxi-\ndative phosphorylation and/or an increased ability\naccumulation is an increase in skeletal muscle oxi-\n© 2004 Adis Data Information BV.All rights reserved.\nSports Med 2004; 34 (7)\n480\nSaunders et al.\ndative enzyme capacity[177] by shifting metabolism\nmoderately trained distance runners, and some evi-\naway from anaerobic to aerobic. Weston et al.[175]\ndence has been reported that HWT tended to im-\nshowed that Kenyan runners who live and train at\nprove RE in well trained triathletes."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 92,
    "text": "Training at\naltitude have higher oxidative enzyme activities\naltitude or even sleeping at altitude has demonstrat-\nthan their Caucasian counterparts of a similar\ned improved submaximal economy in trained moun-\n˙VO2max.\ntain climbers, cyclists and triathletes.Both the use of\nresistance training and altitude exposure appear to\n5.3 Training in the Heat\nhave potential in improving the RE of elite distance\nrunners, but further research into this area is still\nThe mildly elevated CTemp resulting from train-\nrequired. Training in warm to hot conditions is\ning in warm to hot conditions may improve RE by\nanother intervention that has the potential to im-\nincreasing the efficiency of the working muscles."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 93,
    "text": "A\nprove RE in distance runners, but again intervention\nlower CTemp and an increased plasma volume, asso-\nstudies looking at the effect of training in the heat on\nciated with acute and chronic bouts of exercise in the\nRE are limited, and further research is needed in this\nheat, may attenuate the magnitude of the thermoreg-\narea.Given that well designed resistance training,\nulatory response (increased ventilation, circulation\nmoderate altitude training and training in warm con-\nand sweating) and reduce the increased energy re-\nditions have other benefits besides the potential to\nquirements associated with heat stress.[178] Heat ac-\nimprove RE, it would seem sensible for runners to\nclimatisation, accompanied by training, can increase\nemploy these training methods where possible."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 94,
    "text": "An\nplasma volume by up to 12%.The increase in plas-\nimportant area of RE is the ability of the muscles to\nma volume assists in the maintenance of stroke\nstore and release elastic energy, as this energy re-\nvolume, which in turn minimises myocardial\nquires no metabolic cost and could be a critical\nwork.[73] It follows that whole blood viscosity is\nfactor in improving RE. A method to quantify the\nreduced from training in the heat, and a decreased\namount of elastic energy utilised has yet to be devel-\nviscosity has positive effects on endurance perform-\noped, and this would provide a useful means of\nance.[179] Adaptations from training in warm to hot\ndetermining the effectiveness of various training\nconditions may also allow runners to run at any\ninterventions."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 95,
    "text": "More precision in measuring the con-\ngiven speed with a lower HR and CTemp, with both\ntribution of both metabolic and mechanical aspects\nfactors associated with improved RE.[65] These find-\nof RE are required before we are able to gain better\nings support the premise that training in moderate\ninsight into how we can improve RE.Current work\nheat may improve RE and performance at normal\naimed at developing better overground measure-\ntemperatures, although insufficient data precludes\nments of metabolic and mechanical work offers\ndrawing any definitive conclusions.\npotential in improving our understanding of physio-\nlogical and training factors that affect RE in elite\n6."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 96,
    "text": "Conclusions and Future Directions\nrunners.\nRE has been researched extensively over the last\n4–5 decades and is considered a critical factor in the\nAcknowledgements\nperformance of elite distance runners.Factors that\ninfluence RE include VE, CTemp, muscle metabo-\nThe authors have provided no information on sources of\nlism, muscle fibre-type, body composition, running\nfunding or on conflicts of interest directly relevant to the\ntechnique, GRF, muscle stiffness, and storage and\ncontent of this review.\nreturn of elastic energy. Although RE has been\nresearched extensively, there are still relatively few\nReferences\ndocumented interventions that have been shown to\n1. Costill DL. The relationship between selected physiological\nimprove the RE of elite distance runners."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 97,
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  },
  {
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    "text": "Piehl Aulin K, Svedenhag J, Wide L, et al.Short-term intermit-\nRes 2003; 17 (1): 60-7\ntent normobaric hypoxia: haematological, physiological and\n141. Spurrs RW, Murphy AJ, Watsford ML. The effect of plyometric\nmental effects. Scand J Med Sci Sports 1998; 8 (3): 132-7\ntraining on distance running performance. Eur J Appl Physiol\n160. Roberts AC, Butterfield GE, Cymerman A, et al. Acclimatiza-\n2003; 89 (1): 1-7\ntion to 4300m altitude decreases reliance on fat as a substrate. J\n142. Ashenden MJ, Gore CJ, Dobson GP, et al. Simulated moderate\nAppl Physiol 1996; 81 (4): 1762-71\naltitude elevates serum erythropoietin but does not increase\n161. Rusko HR. New aspects of altitude training. Am J Sports Med\nreticulocyte production in well-trained runners."
  },
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    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
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    "text": "Eur J Appl\n1996; 24 (6 Suppl.): S48-52\nPhysiol 2000; 81 (5): 428-35\n162.Schmidt W, Heinicke K, Rojas J, et al. Blood volume and\n143. Ashenden MJ, Gore CJ, Dobson GP, et al. \"Live high, train low\"\nhemoglobin mass in endurance athletes from moderate alti-\ndoes not change the total haemoglobin mass of male endurance\ntude. Med Sci Sports Exerc 2002; 34 (12): 1934-40\nathletes sleeping at a simulated altitude of 3000m for 23 nights.\n163. Stray-Gundersen J, Chapman RF, Levine BD. ‘Living high-\nEur J Appl Physiol Occup Physiol 1999; 80 (5): 479-84\ntraining low’ altitude training improves sea level performance\n144. Ashenden MJ, Gore CJ, Martin DT, et al. Effects of a 12-day\nin male and female elite runners."
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    "text": "J Appl Physiol 2001; 91 (3):\n‘live high, train low’ camp on reticulocyte production and\n1113-20\nhaemoglobin mass in elite female road cyclists.Eur J Appl\n164. Telford RD, Graham KS, Sutton JR, et al. Medium altitude\nPhysiol Occup Physiol 1999; 80 (5): 472-8\ntraining and sea level performance [abstract]. Med Sci Sports\n145. Bailey DM, Davies B, Romer L, et al. Implications of moderate\nExerc 1996; 28 (5 Suppl.): S124\naltitude training for sea-level endurance in elite distance run-\n165. van Hall G, Calbet JA, Sondergaard H, et al. The re-establish-\nners. Eur J Appl Physiol Occup Physiol 1998; 78 (4): 360-8\nment of the normal blood lactate response to exercise in\nhumans after prolonged acclimatization to altitude. J Physiol\n146. Brooks GA, Butterfield GE, Wolfe RR, et al."
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    "text": "Increased depen-\n2001; 536 (Pt 3): 963-75\ndence on blood glucose after acclimatization to 4300m.J Appl\nPhysiol 1991; 70 (2): 919-27\n166. Wilber R. Altitude training for the enhancement of sea level\nendurance performance. Olympic Coach 1995; 5: 6-10\n147. Brooks GA, Wolfel EE, Groves BM, et al. Muscle accounts for\nglucose disposal but not blood lactate appearance during exer-\n167. Wolfel EE, Groves BM, Brooks GA, et al. Oxygen transport\ncise after acclimatization to 4300m. J Appl Physiol 1992; 72\nduring steady-state submaximal exercise in chronic hypoxia. J\n(6): 2435-45\nAppl Physiol 1991; 70 (3): 1129-36\n© 2004 Adis Data Information BV. All rights reserved.\nSports Med 2004; 34 (7)\nRunning Economy\n485\n168. Young AJ, Evans WJ, Cymerman A, et al."
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    "text": "Sparing effect of\nand higher oxidative enzyme activity.J Appl Physiol 1999; 86\nchronic high-altitude exposure on muscle glycogen utilization.\n(3): 915-23\nJ Appl Physiol 1982; 52 (4): 857-62\n176. Green HJ, Sutton JR, Wolfel EE, et al. Altitude acclimatization\n169. Wilber RL. Current trends in altitude training. Sports Med 2001;\nand energy metabolic adaptations in skeletal muscle during\n31 (4): 249-65\nexercise. J Appl Physiol 1992; 73 (6): 2701-8\n170. Sutton JR, Reeves JT, Wagner PD, et al. Operation Everest II:\n177. Gollnick PD, Saltin B. Significance of skeletal muscle oxidative\noxygen transport during exercise at extreme simulated altitude.\nenzyme enhancement with endurance training. Clin Physiol\nJ Appl Physiol 1988; 64 (4): 1309-21\n1982; 2 (1): 1-12\n171."
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    "text": "Katayama K, Sato K, Matsuo H, et al.Effect of intermittent\nhypoxia on oxygen uptake during submaximal exercise in\n178. Svedenhag J. Running economy. In: Bangsbo J, Larsen H,\nendurance athletes. Eur J Appl Physiol. Epub 2004 Feb 26\neditors. Running and science. Copenhagen: Munksgaard,\n172. Saunders PU, Telford RD, Pyne DB, et al. Improved running\n2000: 85-105\neconomy in elite runners after 20 days of simulated moderate-\n179. Telford RD, Kovacic JC, Skinner SL, et al. Resting whole blood\naltitude exposure. J Appl Physiol 2004; 96 (3): 931-7\nviscosity of elite rowers is related to performance. Eur J Appl\n173. Newsholme EA, Leech AR. Biochemistry for the medical sci-\nPhysiol Occup Physiol 1994; 68 (6): 470-6\nences. New York: Wiley, 1983: 357-79\n174. Saltin B, Larsen H, Terrados N, et al."
  },
  {
    "filename": "00007256-200434070-00005.pdf",
    "pdf_title": "Factors Affecting Running Economy in Trained Distance Runners",
    "chunk_id": 134,
    "text": "Aerobic exercise capacity\nat sea level and at altitude in Kenyan boys, junior and senior\nCorrespondence and offprints: Philo U.Saunders, Depart-\nrunners compared with Scandinavian runners. Scand J Med Sci\nment of Physiology, Australian Institute of Sport, PO Box\nSports 1995; 5 (4): 209-21\n176, Belconnen, ACT 2616, Australia.\n175. Weston AR, Karamizrak O, Smith A, et al. African runners\nexhibit greater fatigue resistance, lower lactate accumulation,\nE-mail: Philo.Saunders@ausport.gov.au\n© 2004 Adis Data Information BV. All rights reserved.\nSports Med 2004; 34 (7)"
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 0,
    "text": "The effectiveness of exercise interventions to prevent\nsports injuries: a systematic review and meta-analysis\nof randomised controlled trials\nJeppe Bo Lauersen,1 Ditte Marie Bertelsen,2 Lars Bo Andersen3,4\n▸Additional material is\npublished online only."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 1,
    "text": "To view\nplease visit the journal online\n(http://dx.doi.org/10.1136/\nbjsports-2013-092538).\n1Institute of Sports Medicine\nCopenhagen, Bispebjerg\nHospital, Copenhagen NV,\nDenmark\n2Faculty of Health and Medical\nSciences, Copenhagen N,\nDenmark\n3Department of Exercise\nEpidemiology, Institute of Sport\nSciences and Clinical\nBiomechanics University of\nSouthern Denmark, Odense,\nDenmark\n4Department of Sports\nMedicine, Norwegian School of\nSport Sciences, Oslo, Norway\nCorrespondence to\nJeppe Bo Lauersen,\nInstitute of Sports Medicine\nCopenhagen, Bispebjerg\nHospital, Building 8, 1."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 2,
    "text": "Floor,\nBispebjerg Bakke 23, 2400\nCopenhagen NV, Sealand\n2400, Denmark;\njeppelauersen@stud.ku.dk\nAccepted 31 August 2013\nPublished Online First\n7 October 2013\nTo cite: Lauersen JB,\nBertelsen DM, Andersen LB.\nBr J Sports Med\n2014;48:871–877.\nABSTRACT\nBackground Physical activity is important in both\nprevention and treatment of many common diseases, but\nsports injuries can pose serious problems.\nObjective To determine whether physical activity\nexercises can reduce sports injuries and perform stratified\nanalyses of strength training, stretching, proprioception and\ncombinations of these, and provide separate acute and\noveruse injury estimates.\nMaterial and methods PubMed, EMBASE, Web of\nScience and SPORTDiscus were searched and yielded 3462\nresults."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 3,
    "text": "Two independent authors selected relevant\nrandomised, controlled trials and quality assessments were\nconducted by all authors of this paper using the Cochrane\ncollaboration domain-based quality assessment tool.\nTwelve studies that neglected to account for clustering\neffects were adjusted.Quantitative analyses were\nperformed in STATAV.12 and sensitivity analysed by\nintention-to-treat. Heterogeneity (I2) and publication bias\n(Harbord’s small-study effects) were formally tested.\nResults 25 trials, including 26 610 participants with\n3464 injuries, were analysed. The overall effect estimate on\ninjury prevention was heterogeneous."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 4,
    "text": "Stratified exposure\nanalyses proved no beneficial effect for stretching (RR\n0.963 (0.846–1.095)), whereas studies with multiple\nexposures (RR 0.655 (0.520–0.826)), proprioception\ntraining (RR 0.550 (0.347–0.869)), and strength training\n(RR 0.315 (0.207–0.480)) showed a tendency towards\nincreasing effect.Both acute injuries (RR 0.647 (0.502–\n0.836)) and overuse injuries (RR 0.527 (0.373–0.746))\ncould be reduced by physical activity programmes.\nIntention-to-treat sensitivity analyses consistently revealed\neven more robust effect estimates.\nConclusions Despite a few outlying studies, consistently\nfavourable estimates were obtained for all injury prevention\nmeasures except for stretching."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 5,
    "text": "Strength training reduced\nsports injuries to less than 1/3 and overuse injuries could\nbe almost halved.\nINTRODUCTION\nIncreasing evidence exists, for all age groups, that\nphysical activity is important in both prevention and\ntreatment of some of the most sizable conditions of\nour time,1–3 including cardiovascular disease, dia-\nbetes, cancer, hypertension, obesity, osteoporosis,\nand depression."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 6,
    "text": "Although overall population levels of\nphysical activity is a general concern, increasing levels\nof leisure time physical activity and sports participa-\ntion have been reported in some population groups.4\nInjuries are virtually the sole drawback of exercise,\nbut may be a common consequence of physical activ-\nity and have been shown to pose substantial pro-\nblems.5–7 Management of sports injuries is difficult,\ntime-consuming and expensive, both for the society\nand for the individual.8–10 However, sports injury\nprevention by different kinds of strength training,\nproprioception exercises, stretching activities, and\ncombinations of these, is accessible to essentially\neveryone and requires limited medical staff assistance.\nThis adds several interesting aspects regarding the\npotential dispersion, applicability, and compliance to\nthese programmes.\nMost studies on musculoskeletal injuries have\nfocused on one particular intervention, injury type/\nlocation, sport or studied other relatively narrowly\ndefined research questions."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 7,
    "text": "This applies to most\nreviews and meta-analyses as well.11–18 However,\nParkkari et al19 described 16 controlled trials in a\nnarrative review.Central concepts of sports injury\nprevention such as extrinsic (including exposures,\nenvironment, equipment) and intrinsic (including\nphysical characteristics, fitness, ability, age, gender,\npsychology) risk factors and the ‘sequence of preven-\ntion’ model of van Mechelen20 were summarised.\nAaltonen et al21 presented an overview of all sports\ninjury prevention measures, but as in the literature up\nuntil their search in January 2006, the focus of this\nreview was primarily on extrinsic risk factors.22\nRecently, and with less restrictive exclusion criteria,\nSchiff et al23 covered the same topic with additional\nstudies."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 8,
    "text": "Aaltonen et al and Schiff et al were unable to\nobtain full quantification of intervention effect esti-\nmates.Steffen et al24 presented a narrative review of\nacute sports injury prevention written by field\nexperts for each location of injury, but an examin-\nation and quantification of specific training exposures\nand a differentiation of acute and overuse outcome\neffect estimates is still lacking.\nThis review and meta-analysis will broaden the\nscope of previous reviews and meta-analyses on\nsports injury prevention and focus on the preventive\neffect of several different forms of physical activity\nprogrammes and complement the existing summative\nliterature on extrinsic risk factor reduction."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 9,
    "text": "Valuable\nsummary literature exists for both neuromuscular\nproprioception14\n15 and stretching exercises.17\n18\nHowever, aggregation of effect estimates and com-\nparison with the effect of strength training and an\nintervention group with multiple exposures (combin-\ning ex strength, proprioception, stretch etc) could\nreveal new and interesting information, enabling pro-\nposals for future directions in the field of sports\ninjury prevention.This study consequently aimed at\nperforming stratified analyses of different injury pre-\nvention exercise programmes and additionally pro-\nvides separate effect estimates for acute and overuse\ninjuries.\nEditor’s choice\nScan to access more\nfree content\nLauersen JB, et al. Br J Sports Med 2014;48:871–877."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 10,
    "text": "doi:10.1136/bjsports-2013-092538\n1 of 8\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies.\n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nMATERIAL AND METHODS\nSearch strategy and study selection\nA review protocol was composed, comprising a priori specifica-\ntion of analyses, inclusion/exclusion criteria, injury definition\nand search strategy."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 11,
    "text": "Injury was defined according to the\nF-MARC consensus statement for football, merely broadened to\nfit all forms of physical activity.25 See online supplements\neMethods1–3 and eFigure 1 for full injury definition, detailed\nsearch entries, study selection description and flow chart.\nPubMed, EMBASE, Web of Science and SPORTDiscus databases\nwere searched to October 2012 with no publication date restric-\ntions.The search was performed by four blocks of keywords\nrelated to prevention, injury and diagnoses, sports, and rando-\nmised controlled trials. The searches were customised to accom-\nmodate the layout and search methods of each search engine\nand the application of additional free text words were based on\nthe coverage of subject terms."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 12,
    "text": "Reference lists of retrieved articles\nwere hand searched for trials of potential interest and the search\nwas later updated to January 2013.\nSearch results yielded 3462 hits, which were screened by title\nto yield 90 titles.After exclusion by abstract, 40 were read in\nfull text and 22 were included. Another three studies were\nincluded from reference lists and updated search."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 13,
    "text": "Study selec-\ntion followed a priori-specified inclusion and exclusion criteria.\nInclusion criteria\nExclusion criteria\n▸\nPrimary prevention\n▸\nFree of injury at inclusion\n▸\nSports/physical activity injuries\n▸\nRandomised controlled trials\n▸\nAppropriate intervention/control\narms\n▸\nConducted in humans\n▸\nReported in English\n▸\nPeer-reviewed publications\n▸Influencing pathology\n▸Surrogate measures of injury\n▸Any use of devices (kinesiotaping,\ninsoles, etc)\n▸Any means of transportation (bicycles,\nmotor driven, skies, equestrian, etc)\n▸Inadequate follow-up\nTwo reviewers ( JBL and DMB) independently assessed the eli-\ngibility criteria with subsequent consensus by discussion."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 14,
    "text": "If\nunanimous consensus could not be reached, this was arbitrated\nby a third person (LBA).\nIn total, 25 studies were included.26–50\nData extraction\nAll included studies were assessed using the domain-based evalu-\nation tool recommended by the Cochrane collaboration.51 Two\nreviewers ( JBL and DMB) independently collected the support\nfor judgement and final judgements required consensus from all\nauthors of this paper.If reporting was inadequate or unclear,\nefforts were made to contact the corresponding authors and ask\nby ‘open questions’ in order to reduce the risk of overly positive\nanswers."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 15,
    "text": "Weighting of studies by quality assessment was consid-\nered but not performed, as such appraisals would inevitably\ninvolve subjective decisions and no evidence in support of this\napproach exists.51\nData extraction for total estimate and exposure subgroup esti-\nmates covered the primary outcome, defined by each study.\nInjuries were classified as acute or overuse according to defini-\ntions used by each study and proprioception was defined as\nexercises aiming at improving joint proprioception and/or joint\nstability.For the outcome subgroups, acute and overuse injuries,\nwe additionally extracted appropriate secondary data from\nstudies where information was available in order to optimise the\npower of these analyses."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 16,
    "text": "Overlapping entities were omitted so\nno injury was analysed more than once.\nThe stratification of studies into less heterogeneous exposure\nsubgroups was, with the exception of Beijsterveldt et al,27 per-\nformed after completion of the literature search.Beijsterveldt\net al was added from the updated literature search and was\nunambiguously fitted into the multiple exposures group.\nAs compliance plays a central role in the robustness of results,\nsensitivity analyses without studies that neglected to analyse by\nintention-to-treat were conducted.\nDuring the iterative process of hypothesis generation and pre-\nliminary searches the prespecified eligibility criteria were elabo-\nrated but not changed."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 17,
    "text": "All a priori-specified analyses were\nperformed as planned.\nStatistics\nWhenever possible, only first-time injuries were taken into\naccount as repeated outcomes are likely to be dependent of each\nother and therefore would introduce bias.Most studies have\nanalysed by calculation of either RR, injury rate RR or Cox\nregression RR. When no appropriate effect estimates were\nreported or studies neglected to adjust for clustering effects, we\nadjusted for clustering effects and calculated a RR. Twelve\nincluded studies were not originally adjusted for cluster random-\nisation. As individuals in clusters potentially lack independence\nof each other, a regulation of sample size calculations is often\nrequired."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 18,
    "text": "The equation for cluster adjustment is\nIF¼1þ(n\u00021)r\nwhere ρ is the intracluster correlation coefficient, n the average\ncluster size and IF the inflation factor."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 19,
    "text": "Effective sample size is\ncalculated by dividing sample size with IF.52 The intracluster\ncorrelation coefficient was calculated by\nr¼s2\nc=(s2\nc þs2\nw)\nwhere s2\nw is the within cluster variance of observations taken\nfrom individuals in the same cluster and s2\nc the variance of true\ncluster means.53 In the nine studies where the corresponding\nauthors did not provide us with sufficient data for ρ calculation,\nwe achieved this by calculating an average intracluster correl-\nation coefficient based on p values from studies, which were\nappropriately adjusted for clustering effects.\nIn order to address reporting bias formally, we sought to test\nall analyses by the Harbord small-study effect test with a modified\nGalbraith plot.54 This follows the recommendations by the\nCochrane handbook for systematic reviews of interventions and\nis available in STATAV.12.51 55 Effective sample sizes for interven-\ntion and control group populations were used for the required\nbinary data input to achieve a cluster-adjusted result for this test.\nThe heterogeneity for all analyses was assessed by I2 and the\nχ2 (Q) p value."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 20,
    "text": "I2 is calculated from the Stata given Q value and\nnumber of studies (n) by\nI2 ¼Q\u0002ðn\u00021Þ\nQ\nA rough interpretation guide of I2 has been proposed by\nHiggins et al.51\nAll analyses were computed in STATA V.12 by user-written\ncommands described by Egger et al56 The random effects model\nwas used for the weighting of studies.Statistically heterogeneous\n2 of 8\nLauersen JB, et al. Br J Sports Med 2014;48:871–877. doi:10.1136/bjsports-2013-092538\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies. \n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 21,
    "text": "10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nestimates were graphically explored by the metainf command,\ndisplaying the influence of each individual study on the effect\nestimate.These analyses did not reveal conclusive information\nof particular studies primarily causing the heterogeneity and\nwill not be reported throughout this article.\nRESULTS\nStudy characteristics\nTable 1 summarises the characteristics of 25 included studies. A\nfull study characteristics table is available in the online supple-\nments eTable 2."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 22,
    "text": "In total 26 610 individuals were included in the\nanalysis and effect estimates were based on 3464 injuries.\nThirteen studies were performed on adult participants, 11\nstudies on adolescents and one study included both.\nWe contacted nine authors and four supplied clarifying\nanswers with subsequent change in their data or quality\nassessment.For detailed quality assessments and quality assess-\nment summary see online supplementary eMethods 4, eTable 1\nand eFigure 2.\nTotal estimate\nThe total effect estimate was RR 0.632 (95% CI 0.533 to\n0.750, I2=70% with a χ2 p<0.001). Brushoj et al,28 Eils\net al,30 Gilchrist et al,34 Holmich et al36 and Soderman et al46\ndid not report intention-to-treat data."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 23,
    "text": "When performing a sen-\nsitivity analysis on the 20 studies with intention-to-treat data,\nan estimate of RR 0.608 (0.503–0.736, I2=74%, χ2 p<0.001)\nwas found."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 24,
    "text": "A post hoc analysis stratified for age showed RR\n0.577 (0.453–0.736, I2=68%, χ2 p<0.001) for adolescents\nand RR 0.683 (0.526–0.885, I2=72%, p<0.001) for adults\n(figure 1).\nTable 1\nStudy characteristics summary\nStudy\nIntervention\nPopulation\nCompletion\nFollow-up\nInjuries\nPrimary out\nAskling et al26\nStrength\nSoccer, male, elite\nIntervention 15 Control 15\n10 weeks + 1\nseason\nIntervention 3 Control 10\nHamstring injury\nBeijsterveldt et al27\nMulti\nSoccer, 18–40, male\namateur\nIntervention 223 Control 233\n9 months\nIntervention 135 Control 139\nAll injuries\nBrushoj et al28\nMulti\nConscripts,\n19–26 years\nIntervention 487 Control 490\n12 weeks\nIntervention 50 Control 48\nOveruse knee injury\nCoppack et al29\nStrength\nRecruits, 17–30 years\nIntervention 759 Control 743\n14 weeks\nIntervention 10 Control 36\nOveruse ant."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 25,
    "text": "knee\npain\nEils et al30\nProprioception\nBasketball, 1st–7th\nleague\nIntervention 81 Control 91\n1 season\nIntervention 7 Control 21\nAnkle injury\nEmery et al31\nProprioception\nStudents, 14–19 years\nIntervention 60 Control 54\n6 weeks +\n6 months\nIntervention 2 Control 10\nAll injuries\nEmery and\nMeeuwisse32\nMulti\nSoccer, 13–18 years\nIntervention 380 Control 364\n1 year\nIntervention 50 Control 79\nAll injuries\nEmery et al33\nProprioception\nBasketball,\n12–18 years\nIntervention 494 Control 426\n1 year\nIntervention 130 Control 141\nAll injuries\nGilchrist et al34\nMulti\nSoccer, collegiate\nIntervention 583 Control 852\n12 weeks\nIntervention 2 Control 10\nNon-contact ACL\nHeidt et al35\nProprioception\nH."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 26,
    "text": "school, female,\nsoccer\nIntervention 42 Control 258\n1 year\nIntervention 6 Control 87\nAll injuries\nHolmich et al36\nMulti\nFootball, 2nd–5th\nlevel\nIntervention 477 Control 430\n42 weeks\nIntervention 23 Control 30\nGroin injuries\nJamtvedt et al37\nStretch\nInternet, >18 years\nIntervention 1079 Control 1046\n12 weeks\nIntervention 339 Control 348\nLower limb + trunk\ninjury\nLaBella et al38\nMulti\nAthletes, female\nIntervention 737 Control 755\n1 season\nIntervention 50 Control 96\nLower extremity\ninjury\nLongo et al39\nMulti\nBasketball, male\nIntervention 80 Control 41\n9 months\nIntervention 14 Control 17\nAll injuries\nMcGuine and\nKeene40\nProprioception\nBasketball, adolescent\nIntervention 373 Control 392\n4 weeks + 1\nseason\nIntervention 23 Control 39\nAnkle sprain\nOlsen et al41\nMulti\nHandball, 15–17 years\nIntervention 958 Control 879\n8 months\nIntervention 48 Control 81\nKnee and ankle\ninjury\nPasanen et al42\nMulti\nFloorball, female, elite\nIntervention 256 Control 201\n6 months\nIntervention 20 Control 52\nNon-contact injuries\nPetersen et al43\nStrength\nSoccer, male, elite\nIntervention 461 Control 481\n12 months\nIntervention 12 Control 32\nHamstring injuries\nPope et al44\nStretch\nRecruits, 17–35 years\nIntervention 549 Control 544\n12 weeks\nIntervention 23 Control 25\n4 specific LE injuries\nPope et al 200045\nStretch\nRecruits, male\nIntervention 666 Control 702\n12 weeks\nIntervention 158 Control 175\nLower limb injuries\nSoderman et al46\nProprioception\nSoccer, female, elite\nIntervention 62 Control 78\n7 months\nIntervention 28 Control 31\nLower extremity\ninjury\nSoligard et al47\nMulti\nFootball, 13–17,\nfemale\nIntervention 1055 Control 837\n8 months\nIntervention 121 Control 143\nLower extremity\ninjury\nSteffen et al48\nMulti\nSoccer, female\nIntervention 1073 Control 947\n8 weeks + 1\nseason\nIntervention 242 Control 241\nAll injuries\nWalden et al49\nStrength\nSoccer, 12–17, female\nIntervention 2479 Control 2085\n7 months\nIntervention 7 Control 14\nACL injuries\nWedderkopp et al50\nProprioception\nHandball, 16–18,\nfemale\nIntervention 111 Control 126\n10 months\nIntervention 11 Control 45\nAll injuries\nLauersen JB, et al."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 27,
    "text": "Br J Sports Med 2014;48:871–877.doi:10.1136/bjsports-2013-092538\n3 of 8\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies. \n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nStratified exposure analyses\nThe strength training estimate including four studies was RR\n0.315 (0.207–0.480, I2=0%, χ2 p=0.808). All studies in the\nstrength training group were analysed by intention-to-treat. For\nstratified\nexposure\nForest\nplots\nsee\nonline\nsupplementary\neFigure 4–7.\nThe pooled effect estimate for six studies with propriocep-\ntion training as the primary exposure showed a RR of 0.550\n(0.347–0.869, I2=66%, χ2 p=0.012)."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 28,
    "text": "Sensitivity analysis of\nintention-to-treat ruled out Eils et al30 and Soderman et al46\nand\nrevealed\nRR\n0.480\n(0.268–0.862,\nI2=71%,\nχ2\np=0.017).\nUnlike\nthe\nabove\ntwo\nexposures,\nthe\noverall\nestimate\nfor\nstretching\ndid\nnot\nprove\nsignificant\nwith\nRR\n0.963\n(0.846–1.095, I2=0%, χ2 p=0.975) based on three studies.\nAll\nstudies\nin\nthe\nstretching\ngroup\nwere\nanalysed\nby\nintention-to-treat.\nThe combined effect estimate for the 12 studies with multiple\nexposure interventions revealed a RR of 0.655 (0.520–0.826,\nI2=69%, χ2 p<0.001)."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 29,
    "text": "Sensitivity analysis of intention-to-treat\nexcluded Brushoj et al28 Gilchrist et al34 and Holmich et al36\nand revealed RR 0.625 (0.477–0.820, I2=75%, χ2 p<0.001;\nfigure 2).\nStratified outcome analyses\nOn the basis of primary or secondary data from nine studies,\nthe RR for all types of exposures against acute injury was 0.647\n(0.502–0.836, I2=73%, χ2 p<0.001).One study had strength\ntraining as exposure, two studies did proprioception training\nand the remaining six studies were from the group of multiple\nexposure studies."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 30,
    "text": "Sensitivity analysis of eight intention-to-treat\nanalysed studies (Soderman et al46 was excluded) showed a RR\n0.615 (0.470–0.803, I2=75%, χ2 p<0.001).\nFigure 1\nTotal estimate Forest plot.\nStretching studies are denoted by red,\nproprioception exercises yellow,\nstrength training green, and multiple\ncomponent studies blue.\nFigure 2\nExposure estimates Forest\nplot.Stretching studies are denoted by\nred, proprioception exercises yellow,\nstrength training green, and multiple\ncomponent studies blue.\n4 of 8\nLauersen JB, et al. Br J Sports Med 2014;48:871–877. doi:10.1136/bjsports-2013-092538\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies. \n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 31,
    "text": "10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nSix studies provided data on overuse injuries.RR from these\nsix studies was 0.527 (0.373–0.746, I2=19%, χ2 p=0.287). All\nstudies in this analysis, except one proprioception training study,\nwere multiple exposure studies. All analysed studies reported\nintention-to-treat data (figure 3A,B).\nSmall-study effect\nThe Harbord test for the total estimate of all 25 studies showed\na\nhighly significant\nsmall-study effect\ntest.\nExposure\nand\noutcome subgroups revealed significant test for only the mul-\ntiple exposures group."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 32,
    "text": "See online supplementary eFigure 7 for\nmodified-Galbraith plot and online supplementary eTable 3 for\nHarbord tests.\nDISCUSSION\nAn overall RR estimate for physical activity for injury preven-\ntion, adjusted for clustering effects, was 0.632 (0.532–0.750),\nand slightly lower when sensitivity analysed by intention-to-treat\n(RR 0.607 (0.501–0.735)).A preventive effect of this size\nshould be considered convincing, but the analysis was heteroge-\nneous and the result is, therefore, clinically useless. However, it\nalso suggests that some types of interventions may prove better\nthan others.\nStretching did not show any protective effect (RR=0.961\n(0.836–1.106)), while strength training proved highly significant\n(RR 0.315 (0.207–0.480))."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 33,
    "text": "Results from stretching and strength\ntraining studies were not heterogeneous despite different pro-\ngrammes were used and outcomes of interest were different.This\npoints towards a strong generalisability of results. Proprioception\ntraining and multiple exposure programmes were also effective\n(RR=0.480 (0.266–0.864) and 0.625 (0.477–0.820), respect-\nively), but results were relatively heterogeneous.\nThe effect estimate of stretching and proprioception training\nanalyses in this article corresponds to earlier reviews.14 15 17 18\nOur data do not support the use of stretching for injury preven-\ntion purposes, neither before or after exercise, however it\nFigure 3\n(A) Acute outcomes\nestimate Forest plot."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 34,
    "text": "Proprioception\nstudies are denoted by yellow, strength\ntraining green, and multiple\ncomponent studies blue.(B) Overuse\noutcomes estimate Forest plot.\nProprioception studies are denoted by\nyellow and multiple component studies\nblue.\nLauersen JB, et al. Br J Sports Med 2014;48:871–877. doi:10.1136/bjsports-2013-092538\n5 of 8\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies. \n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nshould be noted that this analysis only included two studies on\narmy recruits and one internet-based study on the general popu-\nlation."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 35,
    "text": "Strength training showed a trend towards better prevent-\nive effect than proprioception training and proved significantly\nbetter than multiple exposure studies, even though all multiple\nexposure\nstudies\nincluded\na\nstrength\ntraining\ncomponent.\nFurther research of strength training for a wider range of injur-\nies is still needed, as our analyses suggest great sports injury pre-\nvention potential for this type of intervention.With a growing\nnumber of randomised controlled trials containing numerous\nexposure types, it was of interest to assess intervention studies\nwith multiple exposures separately, although, as expected, still\nbeing a heterogeneous subgroup."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 36,
    "text": "Though it makes intuitive\nsense to design an array of exposures for prevention of all injur-\nies, it is important to note that each component may be reduced\nquantitatively and/or qualitatively by doing so.Multiple expos-\nure programmes may therefore reduce the proportion of proven\nbeneficial exposures and consequently reduce the overall pre-\nventive effect on sports injury. Additionally, the risk of designing\ntoo extensive prevention programmes will unavoidably be\nenhanced with growing amounts of applied exposures and com-\npliance may suffer as a consequence. Although most multiple\nintervention studies in this analysis were well designed and\ncarried out in a satisfactory way, this subgroup did not exhibit\nan unambiguous preventive effect on sports injuries."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 37,
    "text": "Our find-\nings suggest that designs of multiple exposure interventions\nshould at least be built from well-proven single exposures and\nthat further research into single exposures remains pivotal.\nWhen analyses were stratified by outcome, both acute (RR\n0.615 (0.470–0.803)) and overuse (RR 0.527 (0.373–0.746))\ninjuries were effectively reduced by preventive physical activity,\nalthough overuse injuries fared slightly better.\nFive of six studies analysing overuse injuries were multiple\nexposure studies, and estimates were not particularly heteroge-\nneous.Six of nine studies analysing acute injuries were multiple\nexposure studies with heterogeneous effect sizes. It is not pos-\nsible to derive which parts of these interventions manifested the\npreventive\neffect."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 38,
    "text": "Future\nstudies\nshould\nreport\nacute and\noveruse injuries separately and test specific exposures against\nthese in order to acquire further knowledge in this import area.\nStrengths and limitations\nThe aim of this meta-analysis was to aggregate a wide array of\npopulations, exposures and outcomes to augment the external\nvalidity while maintaining the suitability of combining studies.\nPhysical activity is broadly defined and populations include\narmy recruits, recreational and professional athletes.In this\nregard, it should be pointed out that the diversity of included\nstudies should not be interchanged with the I2 measure of statis-\ntical heterogeneity, which exclusively concerns inconsistency in\neffect sizes."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 39,
    "text": "The statistically homogeneous analyses of strength\ntraining and stretching studies differing in population, interven-\ntion, and outcome, prove the generalisability of results.The stat-\nistically heterogeneous analyses of this meta-analysis should be\ninterpreted with caution as this heterogeneity could arise from\ntrue variation (diversity in design) and/or artefactual variation\n(bias by conduct, attrition, etc).\nOmission of intention-to-treat analysis and cluster adjustment\nare two sources of potentially serious bias."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 40,
    "text": "As compliance to\nintervention programmes appears to vary and remains a dis-\nputed phenomenon, the analysis by intention-to-treat plays a\ncentral role in the robustness of results.57–61 In the present\nmeta-analysis we extracted data from intention-to-treat analyses\nwhenever\npossible\nand\nperformed\nsensitivity\nanalysis\nby\nexclusion of five studies with no report of intention-to-treat ana-\nlysis.Contrary to the expected more conservative effect esti-\nmate, the intention-to-treat sensitivity analyses revealed even\nmore beneficial effect estimates. As a result we can conclude\nthat physical activity as primary prevention against sports injur-\nies is effective, even if it has been argued that compliance issues\ncould diminish the implementation and effect of these pro-\ngrammes."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 41,
    "text": "We speculate the above to result from an association\nbetween using intention-to-treat analysis and study conduct in\ngeneral.For example, Brushoj et al28 added concurrent training\nin the critical high risk period of military training initiation,\nwhich\nintuitively\nappears\ndetrimental\nto\noveruse\ninjuries.\nSoderman et al46 exhibited several methodological issues and\nreported adverse effects of major injuries that have not been\nreproduced by other studies. None of them analysed by\nintention-to-treat and exclusion of such studies improved the\nquality of included studies and subsequently the effect estimate.\nCluster adjustment is similarly important in order not to over-\nestimate the power of the study."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 42,
    "text": "A strength of this meta-analysis\nis the adjustment of these studies that report the same effect esti-\nmate but underestimate the width of CIs.Corresponding\nauthors of studies without cluster adjustment were contacted\nand three provided data for ρ calculation. For the remaining\nnine studies we calculated an average p value extracted from 12\nreported values of 10 studies that performed correct adjustment\nmethods. This caused, in some cases, a dramatic, down-\nregulation of effective sample size which affected the study\nweight in the quantitative analyses.\nA short discussion of the allocation concealment and partici-\npant blinding quality assessments is advocated."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 43,
    "text": "As true partici-\npant blinding is frequently argued to be impossible in sports\ninjury prevention and allocation, concealment makes less sense\nin non-pharmacological interventions, these quality assessment\nitems should be interpreted with caution.In spite of this, some\nof the included studies made qualified efforts to alleviate these,\nwhich, in this review, resulted in a lower risk of bias judgement.\nThe domain-based tool was chosen as evaluation tool of this\nreview as recommended by the Cochrane collaboration with the\nmost convincing validation evidence in this area."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 44,
    "text": "Although not\nbeing perfectly suited for assessment of sports injury prevention\nstudies, assessment of these parameters still holds relevance as\nthese factors can greatly influence analyses.62 63\nA Harbord’s small-study effect test and a modified Galbraith’s\nplot were performed for this meta-analysis to assess publication\nbias.The small-study effect test for the total estimate was highly\nsignificant, while the multiple exposures subgroup was the only\nsubgroup showing a statistically significant test. According to\nEgger et al64 65 significant small-study effects may arise from a\nnumber of reasons, including true publication bias, heterogen-\neity, chance, and methodological differences between smaller\nand larger studies."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 45,
    "text": "As the p value of the small-study effects\nincreased when the total estimate test was divided into less het-\nerogeneous subgroups, it is likely that a substantial part of the\ntotal estimate small-study effect originates in heterogeneity.\nOwing to the relatively heavy burden of implementing physical\nactivity interventions, it should be noted that smaller studies\noften would be able to pay greater attention to the intervention\nfor each team/individual, thereby enabling them to obtain more\nthorough intervention quality.Hence, a methodological differ-\nence may exist as well.\nCONCLUSION\nIn general, physical activity was shown to effectively reduce\nsports injuries. Stretching proved no beneficial effect, whereas\n6 of 8\nLauersen JB, et al. Br J Sports Med 2014;48:871–877."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 46,
    "text": "doi:10.1136/bjsports-2013-092538\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies.\n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \nmultiple exposure programmes, proprioception training, and\nstrength training, in that order, showed a tendency towards\nincreasing effect. Strength training reduced sports injuries to less\nthan one-third. We advocate that multiple exposure interven-\ntions should be constructed on the basis of well-proven single\nexposures and that further research into single exposures, par-\nticularly strength training, remains crucial."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 47,
    "text": "Both acute and\noveruse injuries could be significantly reduced, overuse injuries\nby almost a half."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 48,
    "text": "Apart from a few outlying studies, consistently\nfavourable estimates were obtained for all injury prevention\nmeasures except for stretching.\nWhat this study adds\nThis meta-analysis provides quantitative effect estimates of\ndifferent exercise programmes on sports injury prevention.\nComparison of exposures reveals a highly effective strength\ntraining estimate, significantly better than multicomponent\nstudies.\nAcknowledgements The authors would like to thank Thor Einar Andersen,\nassociate professor, Department of Sport Medicine, Norwegian School of Sport\nSciences and Ashley Cooper, professor, Centre for Exercise, Nutrition and Health\nSciences, University of Bristol for comments and manuscript revision.\nContributors All authors of this paper have contributed substantially to conception\nand design, analysis and interpretation of the data, drafting the article or revising it\ncritically for important intellectual content and final approval of the version to be\npublished.\nCompeting interests None.\nProvenance and peer review Not commissioned; externally peer reviewed.\nREFERENCES\n1\nStrong WB, Malina RM, Blimkie CJ, et al."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
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  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 55,
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    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
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    "text": "Exercises to prevent lower limb\ninjuries in youth sports: cluster randomised controlled trial.BMJ 2005;330:449.\n42\nPasanen K, Parkkari J, Pasanen M, et al. Neuromuscular training and the risk of leg\ninjuries in female floorball players: cluster randomised controlled study. BMJ\n2008;337:a295.\n43\nPetersen J, Thorborg K, Nielsen MB, et al. Preventive effect of eccentric training on\nacute hamstring injuries in men’s soccer: a cluster-randomized controlled trial.\nAm J Sports Med 2011;39:2296–303.\n44\nPope R, Herbert R, Kirwan J. Effects of ankle dorsiflexion range and pre-exercise\ncalf muscle stretching on injury risk in Army recruits. Aust J Physiother 1998;\n44:165–72.\nLauersen JB, et al. Br J Sports Med 2014;48:871–877."
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    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
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    "text": "doi:10.1136/bjsports-2013-092538\n7 of 8\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies.\n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as \n45\nPope RP, Herbert RD, Kirwan JD, et al. A randomized trial of preexercise stretching\nfor prevention of lower-limb injury. Med Sci Sports Exerc 2000;32:271–7.\n46\nSoderman K, Werner S, Pietila T, et al. Balance board training: prevention of\ntraumatic injuries of the lower extremities in female soccer players? A prospective\nrandomized intervention study. Knee Surg Sports Traumatol Arthrosc\n2000;8:356–63.\n47\nSoligard T, Myklebust G, Steffen K, et al."
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    "text": "London, UK: BMJ Publishing Group, 2008.\n57\nBraham R, Finch C, McCrory P.Non-participation in sports injury research: why\nfootball players choose not to be involved. Br J Sports Med 2004;38:238–9.\n58\nFinch CF. No longer lost in translation: the art and science of sports injury\nprevention implementation research. Br J Sports Med 2011;45:1253–7.\n59\nKeats MR, Emery CA, Finch CF. Are we having fun yet? Fostering adherence to\ninjury preventive exercise recommendations in young athletes. Sports Med\n2012;42:175–84.\n60\nVerhagen EA, Hupperets MD, Finch CF, et al. The impact of adherence on sports\ninjury prevention effect estimates in randomised controlled trials: looking beyond the\nCONSORT statement. J Sci Med Sport 2011;14:287–92.\n61\nSoligard T, Nilstad A, Steffen K, et al."
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    "text": "Compliance with a comprehensive warm-up\nprogramme to prevent injuries in youth football.Br J Sports Med\n2010;44:787–93.\n62\nJuni P, Altman DG, Egger M. Systematic reviews in health care: assessing the\nquality of controlled clinical trials. BMJ 2001;323:42–6.\n63\nMoher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of\nmeta-analyses of randomised controlled trials: the QUOROM statement. Quality of\nReporting of Meta-analyses. Lancet 1999;354:1896–900.\n64\nSterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis:\npower of statistical tests and prevalence in the literature. J Clin Epidemiol\n2000;53:1119–29.\n65\nEgger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a\nsimple, graphical test. BMJ 1997;315:629–34.\n8 of 8\nLauersen JB, et al."
  },
  {
    "filename": "871.full.pdf",
    "pdf_title": "The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials",
    "chunk_id": 64,
    "text": "Br J Sports Med 2014;48:871–877.doi:10.1136/bjsports-2013-092538\nReview\nProtected by copyright, including for uses related to text and data mining, AI training, and similar technologies. \n. \nby guest\n \non April 7, 2025\n \nhttp://bjsm.bmj.com/\nDownloaded from \n7 October 2013. \n10.1136/bjsports-2013-092538 on \nBr J Sports Med: first published as"
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 0,
    "text": "Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.\nAerobic High-Intensity Intervals Improve\nV˙ O2max More Than Moderate Training\nJAN HELGERUD1,2, KJETILL HKYDAL1, EIVIND WANG1, TRINE KARLSEN1, PA˚ LR BERG1, MARIUS BJERKAAS1,\nTHOMAS SIMONSEN1, CECILIES HELGESEN1, NINAL HJORTH1, RAGNHILD BACH1, and JAN HOFF1,3\n1Department of Circulation and Imaging, Faculty of Medicine, Norwegian University of Science and Technology,\nTrondheim, NORWAY; 2Hokksund Medical Rehabilitation Centre, Hokksund, NORWAY; 3Department of Physical Medicine\nand Rehabilitation, St. Olav’s University Hospital, Trondheim, NORWAY\nABSTRACT\nHELGERUD, J., K. HKYDAL, E. WANG, T. KARLSEN, P. BERG, M. BJERKAAS, T. SIMONSEN, C. HELGESEN, N. HJORTH,\nR. BACH, and J."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 1,
    "text": "HOFF.Aerobic High-Intensity Intervals Improve V˙ O2max More Than Moderate Training. Med. Sci. Sports Exerc.,\nVol. 39, No. 4, pp. 665–671, 2007. Purpose: The present study compared the effects of aerobic endurance training at different\nintensities and with different methods matched for total work and frequency. Responses in maximal oxygen uptake (V˙ O2max), stroke\nvolume of the heart (SV), blood volume, lactate threshold (LT), and running economy (CR) were examined."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 2,
    "text": "Methods: Forty\nhealthy, nonsmoking, moderately trained male subjects were randomly assigned to one of four groups:1) long slow distance (70%\nmaximal heart rate; HRmax); 2) lactate threshold (85% HRmax); 3) 15/15 interval running (15 s of running at 90–95% HRmax followed\nby 15 s of active resting at 70% HRmax); and 4) 4 \u0001 4 min of interval running (4 min of running at 90–95% HRmax followed by 3 min\nof active resting at 70% HRmax).All four training protocols resulted in similar total oxygen consumption and were performed 3 dIwkj1\nfor 8 wk. Results: High-intensity aerobic interval training resulted in significantly increased V˙ O2max compared with long slow\ndistance and lactate-threshold training intensities (P G 0.01)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 3,
    "text": "The percentage increases for the 15/15 and 4 \u0001 4 min groups were 5.5 and\n7.2%, respectively, reflecting increases in V˙ O2max from 60.5 to 64.4 mLIkgj1Iminj1 and 55.5 to 60.4 mLIkgj1Iminj1.SV increased\nsignificantly by approximately 10% after interval training (P G 0.05). Conclusions: High–aerobic intensity endurance interval training\nis significantly more effective than performing the same total work at either lactate threshold or at 70% HRmax, in improving V˙ O2max.\nThe changes in V˙ O2max correspond with changes in SV, indicating a close link between the two."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 4,
    "text": "Key Words: LACTATE\nTHRESHOLD, AEROBIC POWER, 4 \u0001 4-MIN INTERVALS, 15/15 TRAINING, STROKE VOLUME, BLOOD VOLUME\nI\nt is important to know how different training intensities\ninfluence adaptations in physiological parameters when\nselecting an optimum training regimen for a specific\nsport or for improving fitness in the general community.\nCardiorespiratory endurance has long been recognized as\none of the fundamental components of physical fitness (1).\nBecause accumulation of lactic acid is associated with\nskeletal muscle fatigue, anaerobic metabolism cannot\ncontribute at a quantitatively significant level to the energy\nexpended (1)."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 5,
    "text": "Pate and Kriska (17) have described a model\nthat incorporates the three major factors accounting for\ninterindividual variance in aerobic endurance performance:\nmaximal oxygen uptake (V˙ O2max), lactate threshold (LT),\nand work economy (C).Several published studies support\nthis model (3,5,8,12). Thus, the model should serve as a\nuseful framework for comprehensive examination of the\neffects of aerobic training on endurance performance.\nV˙ O2max is probably the single most important factor\ndetermining success in an aerobic endurance sport (1,20).\nHowever, within the same person, peak oxygen uptake is\nspecific to a given type of activity."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 6,
    "text": "Therefore, to obtain\nrelevant values, emphasis is placed on testing in activity-\nspecific modes, such as walking and running, and in sport-\nspecific activities for participants (24).At maximal\nexercise, the majority of evidence points to a V˙ O2max\nthat is limited by oxygen supply, and cardiac output (Q)\nseems to be the major factor in determining oxygen\ndelivery (28). In most textbooks, stroke volume of the\nheart (SV) and heart frequency are described as increasing\nlinearly during upright increased work rates until about\n50% of V˙ O2max, where SV reaches a plateau or increases\nonly modestly in both trained and sedentary subjects (11).\nHowever, other studies have shown that SV continues to\nincrease beyond that rate. Zhou et al."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 7,
    "text": "(30) found that SV\nAddress for correspondence: Jan Helgerud, Ph.D., Medicine, Faculty of\nMedicine, Norwegian University of Science and Technology, NO-7489,\nTrondheim, Norway 7489; E-mail: Jan.Helgerud@ntnu.no.\nSubmitted for publication February 2006.\nAccepted for publication November 2006.\n0195-9131/07/3904-0665/0\nMEDICINE & SCIENCE IN SPORTS & EXERCISE\u0001\nCopyright \u0002 2007 by the American College of Sports Medicine\nDOI: 10.1249/mss.0b013e3180304570\n665\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine.Unauthorized reproduction of this article is prohibited.\nincreased continuously with increased workload up to\nV˙ O2max in well-trained subjects."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 8,
    "text": "However, in sedentary\nand moderately trained subjects, the classical leveling off\nwas found.\nLT is the intensity of work or V˙ O2 at which the blood\nlactate concentration gradually starts to increase during\ncontinuous exercise (5).Because LT reflects an onset of\nanaerobic metabolism and the coinciding metabolic alter-\nations, this in turn determines the fraction of maximal\naerobic power that can be sustained for an extended period\n(18). The blood lactate level ([Laj]b) represents a balance\nbetween lactate production and removal, and there are\nindividual patterns in these kinetics (2)."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 9,
    "text": "LT changes in\nresponse to training with the alteration of V˙ O2max and\nsometimes also as the percentage of V˙ O2max (9,15,17).\nWork economy, or C, is referred to as the ratio between\nwork output and oxygen cost.Bunc and Heller (3),\nHelgerud (8), and Helgerud et al. (9) have shown the\nindividual variations in gross oxygen cost of activity at a\nstandard running velocity (CR). A number of physiological\nand biomechanical factors seem to influence CR in trained\nor elite runners."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 10,
    "text": "These include metabolic adaptations\nwithin the muscle such as increased mitochondria and\noxidative enzymes, the ability of the muscles to store and\nrelease elastic energy by increasing the stiffness of the\nmuscles, and more efficient mechanics leading to less\nenergy wasted on braking forces and excessive vertical\noscillation (17).Work economy also is improved from\nincreased maximal strength and especially from improve-\nments in rate of force development (12). Running economy\nis commonly defined as the steady-rate V˙ O2 in milliliters\nper kilogram per minute at a standard velocity or as energy\ncost of running per meter (mLIkgj0.75Imj1) (5,8).\nMost authors focus on the effects on V˙ O2max when\nevaluating the response to endurance training."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 11,
    "text": "Pollock (18)\nhas shown that improvement in V˙ O2max is directly related\nto intensity, duration, and frequency of training.The\nminimum training intensity for improvement in V˙ O2max\nand LT seems to be approximately 55–65% of maximal\nheart rate (HRmax) (1). It has been suggested that lower-\nintensity work of longer duration can give the same\ntraining effect as high-intensity, short-duration work in\nsome subjects (18); however, Wenger and Bell (29)\nobserved higher training responses at higher intensities.\nThere are few studies where training protocols of\ndifferent intensities have been matched for total work and\nfrequency. Overend et al."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 12,
    "text": "(16) concluded that interval\ntraining (80% V˙ O2max) offered no advantage over con-\ntinuous training of the same average power output in\naltering the aerobic parameters in untrained adult males.\nHowever, Thomas et al.(27) have concluded that interval\ntraining (90% HRmax) may benefit aerobic capacity more\nso than continuous running (75% HRmax) in untrained men\nand women. This is in line with the conclusion of\nRognmo et al. (19) that high-intensity aerobic interval\nexercise (80–90% V˙ O2max) was superior to continuous\nlow-intensity exercise (50–60% V˙ O2max) in patients with\ncoronary artery disease. The aim of this study is, thus, to\ncompare training methods of different intensity matched\nfor energy consumption."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 13,
    "text": "The hypothesis is that long slow\ndistance running (LSD), that is, continuous work at 70%\nof HRmax and at LT level (85% HRmax), will show less\ntraining effects on V˙ O2max than a similar workload of\nshort-interval (15 s of work and 15 s of active recovery)\nand long-interval (4 \u0001 4 min, 3 min of active recovery)\naerobic endurance training at 90–95% HRmax.\nMETHODS\nSubjects.Fifty-five healthy, nonsmoking male\nuniversity students were recruited for participation in the\nstudy. All subjects were engaged in endurance training and\nleisure-time physical activity at least three times per week.\nEach subject reviewed and signed consent forms approved\nby the human research committee before participating in\nthe study. All subjects were randomly assigned to one of\nfour training groups."
  },
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    "text": "During the training period, 13\nsubjects dropped out of the study because of illness and\ninjuries not related to the study.In addition, two of the\nsubjects were excluded because they participated in fewer\nthan 90% of the training sessions. The age, height, and\nweight of the 40 participating subjects were 24.6 T 3.8 yr,\n182 T 6 cm, and 82.0 T 12.0 kg, respectively. Because of\ndifficulties in performing the procedures for single-breath\nacetylene uptake (SB) for measuring Q, four subjects in\neach group were not able to perform both pre and post\nmeasurements. As such, the Q and SV measurements\ninclude data from six subjects per group. The hemato-\nlogical responses were measured on a separate day."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
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    "chunk_id": 15,
    "text": "For\nreasons not related to the training, two subjects in the LSD\ntraining and one subject in the 4 \u0001 4 min training group\nwere not able to attend both pre- and postmeasuring\nsessions of hematological responses.\nTest procedures and material.A Technogym\nRunrace (Italy) treadmill calibrated for inclination and\nspeed, at an inclination of 5.3%, was used for all physical\ncapacity measurements. The measurements of V˙ O2max,\nlactate threshold, work economy, all ventilatory pa-\nrameters, and pulmonary gas exchange were obtained\nusing the Cortex Metamax II portable metabolic test\nsystem (Cortex Biophysik GmbH, Leipzig, Germany).\nRecently, Metamax II has been validated against the clas-\nsic Douglas bag technique (14)."
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    "text": "Mean differences in V˙ O2\n(0.03, 0.02, and 0.04 LIminj1 for 100, 200, and 250 W,\nrespectively), and pulmonary ventilation (V˙E; 1.6, 2.9,\n1.5 LIminj1 for 100, 200, and 250 W, respectively) were\nsmall but significant for 100 W (V˙ O2 and V˙E) and 200 W\n(V˙E).However, intraclass coefficients of correlation were\nhigh throughout. Bland–Altman plots revealed 95% limits\nof agreement of T 0.2 LIminj1 for V˙ O2 (bias 0.04 LIminj1)\nand slightly below T 6 LIminj1 for V˙E (bias 1.9 LIminj1).\nhttp://www.acsm-msse.org\n666\nOfficial Journal of the American College of Sports Medicine\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine."
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    "text": "Unauthorized reproduction of this article is prohibited.\nThe subjects were familiarized with treadmill running\n(45 min) twice before the start of the study.The test\nstarted with a warm-up period of 10 min at approximately\n60% of predicted V˙ O2max, before establishing a baseline\nvalue of blood lactate concentration [Laj]b. To determine\nLT, the subjects ran a maximum of five increasing\nintensities for 5 min at 60–95% V˙ O2max, with a 30-s break\nfor the determination of [Laj]b from a fingertip. For all\nsubjects, this included one 4-min step at 7 kmIhj1 at 5.3%\ninclination for the determination of running economy at this\nstandardized workload. The running speeds used to\ndetermine LT were exactly the same for a given subject in\nthe pre- and the posttraining tests."
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    "text": "Lactate measurements\nwere made using a YSI 1500 Sport Lactate Analyzer\n(Yellow Springs Instruments, Yellow Springs, OH).LT\nwas calculated as the velocity or V˙ O2 that corresponded\nwith [Laj]b 1.5 mmol higher than the warm-up values (10).\nAs soon as [Laj]b was 1.5 mmol higher than warm-up\nvalues, the subjects proceeded to the V˙ O2max-testing\nprotocol. For the measurement of V˙ O2max, the speed was\nincreased every minute to a level that brought the subject to\nexhaustion in 3–6 min. Achievement of V˙ O2max was\naccepted when V˙ O2 leveled off despite further increases in\nrunning speed and when a respiratory exchange ratio (R)\nabove 1.05 was present. The highest heart rate during the\nlast minute was measured and used as HRmax."
  },
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    "chunk_id": 19,
    "text": "For assessing\nHR, Polar Accurex heart rate monitors were used (Polar\nElectro, Finland).Q and SV were measured 2 d after the LT\nand V˙ O2max tests using a Sensormedics Vmax Spectra 229\napparatus. Before the test, the subjects started a 10-min\nwarm-up period at 70% of HRmax that included multiple\ntraining bouts for the procedures for single-breath acetylene\nuptake (SB). The testing procedure started by gradually\nincreasing velocity to the speed corresponding to V˙ O2max at\nthe maximal test (i.e., maximal aerobic velocity). When the\nsubjects were close to their V˙ O2max, they were instructed to\nstart the breathing cycle when they were ready."
  },
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    "text": "The Q\nmeasurement procedure started with a complete emptying of\nthe lungs and then maximal inspiration of a gaseous mixture\nof 0.3% carbon monoxide (CO), 0.3% methane (CH4), 0.3%\nacetylene (C2H2), 21% oxygen (O2), and 80% nitrogen (N2),\ndirectly followed by one continuous expiration.The SB has\nbeen validated with the indirect Fick CO2-rebreathing\nmethod and compared with open-circuit acetylene uptake\n(4). Both techniques were shown to be valid and reliable for\nmeasuring Q. Repeated measurements of Q were made\nusing the SB at rest, 100 W, and 200 W. There were no\nsignificant differences between repeated measures of this\ntechnique at any workload. The standard error of\nmeasurement decreased with increasing intensity and was\n8.5% at rest and 3.2% at 200 W."
  },
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    "chunk_id": 21,
    "text": "Standard error (absolute)\nwas similar at all levels of intensity, ranging from 0.47 to\n0.56 LIminj1.The coefficient of variation (CV) was 7.6% at\n200 W. However, the authors concluded that the SB, re-\nquiring a constant, slow exhalation rate, made the procedure\ndifficult to perform at the highest exercise intensities (4).\nHematological measurements. In two of the\ntraining groups, the LSD and 4 \u0001 4 min groups, blood\nvolume was measured by determining the concentration of\nEvans blue dye in blood sampled at 10, 20, and 30 min\nafter injection of approximately 2.5 mL of 1.5% Evans\nblue dye. Blood samples were centrifuged at 3500 rpm for\n10 min in an ultracentrifuge (Kubota 2010, Japan)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 22,
    "text": "Blood\nplasma was analyzed for blue dye concentration using a\nspectrophotometer (Shimadzu UV-1601, Japan) at wave-\nlengths of 620 and 740 nm.Hematocrit was analyzed using\na Cobas Micros CT16 (Bergman Instrumentering AS,\nNorway).\nTraining interventions. The present study consists of\nfour training interventions. To equate the total amount of\nwork for each of the training sessions, a thorough\ncalculation was carried out.\n1. Long slow distance running (LSD): The first group\nperformed a continuous run at 70% HRmax (137 T\n7 bpm) for 45 min.\n2. Lactate threshold running (LT): The second group\nperformed a continuous run at lactate threshold (85%\nHRmax, 171 T 10 bpm) for 24.25 min.\n3."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 23,
    "text": "15/15 interval running (15/15): The third group\nperformed 47 repetitions of 15-s intervals at 90–\n95% HRmax (180 to 190 T 6 bpm) with 15 s of active\nresting periods at warm-up velocity, corresponding to\n70% HRmax (140 T 6 bpm) between.\n4.4 \u0001 4-min interval running (4 \u0001 4 min): A fourth\ngroup trained 4 \u0001 4-min interval training at 90–95%\nHRmax (180 to 190 T 5 bpm) with 3 min of active\nresting periods at 70% HRmax (140 T 6 bpm) between\neach interval.\nTraining interventions 2–4 started with a 10-min warm-\nup and ended with a 3-min cool-down period at 70%\nHRmax. All training sessions were performed running on a\ntreadmill at 5.3% inclination (Fig."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 24,
    "text": "1).\nThe calculation of the total oxygen uptake for the\ndifferent training protocols was based on the relationship\nbetween %HRmax and %V˙ O2max established by the Amer-\nican College of Sports Medicine (ACSM) (26).ACSM\nstates that 70, 85, and 92.5% HRmax can be used as indices\nfor 60, 80, and 87.5% of V˙ O2max. A pilot study was\nperformed to assure that the total oxygen cost required for\neach training regimen was the same—warm-up, active\nrecovery, and cool-down periods included. Eight non-\nsmoking male subjects participated in the pilot study (age\n26.2 T 3.3 yr, height 180.5 T 6.8 cm, weight 82.1 T\n11.5 kg). V˙ O2max was 4.80 T 0.49 LIminj1 and 58.5 T\n5.9 mLIkgj1Iminj1. HRmax was 202 T 12 bpm. All subjects\nperformed all four training protocols with at least 1 d of\nrest in between."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 25,
    "text": "The results showed no significant differ-\nence between the measured values for total oxygen uptake\nin any of the protocols performed.Expressed as a\npercentage of the mean V˙ O2 expenditure, the coefficient\nof repeatability (COR) was 11.9%. On average, the\nAEROBIC ENDURANCE TRAINING RESPONSES\nMedicine & Science in Sports & Exercised\n667\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.\nmeasured total oxygen uptake for the training protocols\nwere LSD: 131.0 T 12.9 L; LT: 128.1 T 10.5 L; 15/15:\n133.6 T 16.0 L; 4 \u0001 4 min: 127.3 T 14.6 L. When the heart\nrate started to increase (drift) in the LSD and LT group,\nthe speed of the treadmill was reduced to secure the\ntarget intensity."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 26,
    "text": "In the 15/15 group, the subjects were\ninstructed to reach the target intensity in about 3–4 min\nand then adjust the speed to stay there.In the 4 \u0001 4 min\ngroup, the subjects were instructed to reach the target\nintensity in about 1–1.5 min and then stay there by\nadjusting the speed of the treadmill. The total distance\ncovered (including active recovery periods) in each\ntraining bout for each group at pretraining was, on\naverage, 5.9 km. The subjects carried out three training\nsessions per week for 8 wk.\nStatistical analysis. Statistical analyses were\nperformed using the software program SPSS, version\n11.0 (Statistical Package for Social Science, Chicago, IL).\nIn all cases, P G 0.05 were taken as the level of\nsignificance in two-tailed tests."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 27,
    "text": "The results are presented\nas mean T SD and mean T SE in Figure 2.To calculate\ndifferences between and within groups, a two-way\nanalysis of repeated-measures ANOVA (least significance\ndifference test) were used for comparison of means for\ncontinuous variables. The data were tested for normal\ndistribution using quantile–quantile (QQ) plots. The\nresults of the QQ plots were interpreted by examining\nthe shape of the plots and the closeness of the plot to its\nbest linear fit.\nRESULTS\nThe high–aerobic intensity training performed by the\n15/15 and 4 \u0001 4 min groups increased absolute V˙ O2max\n(LIminj1) significantly compared with LSD and LT train-\ning."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 28,
    "text": "Between the 15/15 and the 4 \u0001 4 min groups, no\nsignificant difference in training response was observed.\nV˙ O2max increased from pre- to posttraining in both the\n15/15 (5.5%) and 4 \u0001 4 min (7.2%) groups, but no\nchange was apparent in the LT or LSD group (Table 1,\nFig.2). Running economy (CR) was not significantly\ndifferent between groups (Table 1), but all of the training\ngroups significantly improved their running economy,\nranging from 7.5 to 11.7%. LT did not change for any\ngroup when expressed as %V˙ O2max. The velocity at LT\n(vLT) was, however, significantly improved by an average\nof 9.6% in all four groups as a consequence of changes in\nrunning economy and V˙ O2max.\nSV changed significantly from pre- to posttraining for\nthe 15/15 and 4 \u0001 4 min group (Table 2)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 29,
    "text": "No between-\ngroup differences were observed.The highest average\nSV was 0.16 LIbeatj1, and the highest average Q was\n32.6 LIminj1 at posttraining. Oxygen uptake at the\nmaximal aerobic velocity at which SV and Q were\nmeasured was, on average, 7.2% lower than when tested\nduring the V˙ O2max protocol. Similarly lower ventilations\n    \n    \n    \n    \nFIGURE 1—Examples of the heart rate response to the four different training regimens in a subject from each group. Subject a (HRmax 200 bpm);\nlong slow distance running (LSD) 70% HRmax. Subject b (HRmax 200 bpm): lactate threshold running (LT), 85% HRmax. Subject c (HRmax 189\nbpm): 15-s interval running at 90–95% HRmax, with 15 s of active recovery (15/15)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 30,
    "text": "Subject d (HRmax 199 bpm): 4 \u0001 4-min interval running at\n90–95%, with 3 min of active recovery (4 \u0001 4 min).\nFIGURE 2—Percent change in absolute V˙ O2max (LIminj1) and\nabsolute stroke volume of the heart (mLIbeatj1) from pre- to\nposttraining for each of the groups, presented as mean and SE.\nSignificantly different from pre- to posttraining: * P G 0.05, ** P G\n0.01, *** = P G 0.001.\nhttp://www.acsm-msse.org\n668\nOfficial Journal of the American College of Sports Medicine\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine.Unauthorized reproduction of this article is prohibited.\nwere measured when running at the calculated maximal\naerobic velocity (Table 2)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 31,
    "text": "No significant changes took\nplace in the hematological responses to training (Table 3).\nBlood volume was calculated to be, on average, 7.2% of\nsubject body weight.\nDISCUSSION\nThe major novel finding of this research is that high–\naerobic intensity endurance training is significantly more\neffective than moderate- and low-intensity training in\nimproving V˙ O2max during a training period of 8 wk.Up\nto the level of maximum aerobic velocity, the intensity of\ntraining determines the training response. Intensity and\nvolume of training are, thus, not interchangeable. The\nchanges in V˙ O2max correspond with changes in stroke\nvolume of the heart (SV), indicating a close link between\nthe two.\nV˙ O2max. V˙ O2max is one of the primary determinants of\naerobic endurance performance (1)."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 32,
    "text": "The high–aerobic\nintensity interval training regimens of 15/15 and the 4 \u0001\n4 min performed at the same intensity both revealed\nsignificantly higher absolute V˙ O2max responses of 5.5 and\n7.3%, respectively, over the moderate- and lower-intensity\ntraining of the O2 cost-matched LT and LSD training\ngroups.The effect of interval training is in line with\nprevious studies (7,13). It has been suggested a longer\nduration for training sessions could compensate for lower-\nintensity exercise (16,18). However, the present study,\nwhich matched four training protocols for total work and\nfrequency, does not support this claim. Instead, our results\nare consistent with those of Wenger and Bell (29) and\nThomas et al."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 33,
    "text": "(27), who found that intensity of training\ncannot be compensated for by longer duration.\nImprovements in V˙ O2max seem to be dependent on\nfitness level.In a recent paper, we have shown an\nimprovement in V˙ O2max of 7% for cardiovascular patients\nTABLE 1."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 34,
    "text": "Changes in physiological parameters from pre- to posttraining.\nLSD (N = 10)\nLT (N = 10)\n15/15 (N = 10)\n4 \u0001 4 min (N = 10)\nPretraining\nPosttraining\nPretraining\nPosttraining\nPretraining\nPosttraining\nPretraining\nPosttraining\nV˙O2max\n(LIminj1)\n4.77 T 0.49\n4.74 T 0.46\n4.58 T 0.38\n4.67 T 0.40\n4.91 T 0.60\n5.18 T 0.56***#a\n4.56 T 0.62\n4.89 T 0.52***#b\n(mLIkgj1Iminj1)\n55.8 T 6.6\n56.8 T 6.3\n59.6 T 7.6\n60.8 T 7.1\n60.5 T 5.4\n64.4 T 4.4**#a\n55.5 T 7.4\n60.4 T 7.3***#b\n(mLIkgj0.75Iminj1)\n169.4 T 17.5\n171.6 T 17.0\n176.1 T 18.0\n179.5 T 16.6\n183.1 T 16.4\n194.7 T 14.7**#a\n167.0 T 19.9\n181.7 T 19.1***#b\nHRmax (bpm)\n196 T 7\n195 T 8\n201 T 10\n198 T 9\n200 T 6\n199 T 4\n199 T 8\n197 T 7\nV˙ E (LIminj1)\n150.6 T 15.0\n155.0 T 17.8\n148.8 T 17.4\n153.6 T 15.9\n147.5 T 13.2\n160.3 T 14.2\n150.7 T 17.6\n164.8 T 18.1\nR\n1.10 T 0.04\n1.10 T 0.05\n1.10 T 0.05\n1.10 T 0.05\n1.09 T 0.05\n1.12 T 0.04\n1.10 T 0.05\n1.12 T 0.04\n[Laj]b\n8.57 T 1.61\n7.63 T 1.04\n7.72 T 0.82\n7.43 T 0.84\n9.50 T 1.90\n8.40 T 0.80\n8.50 T 1.14\n8.84 T 0.94\nRunning economy\nV˙O2 (mLIkgj0.75Imj1)\n0.80 T 0.09\n0.74 T 0.08*\n0.85 T 0.09\n0.75 T 0.09***\n0.79 T 0.06\n0.73 T 0.07*\n0.79 T 0.06\n0.71 T 0.05**\nHR (bpm)\n150 T 17\n140 T 9**\n151 T 15\n137 T 10***\n147 T 16\n125 T 9**\n154 T 22\n136 T 17***\nLactate threshold\nV˙O2 (LIminj1)\n3.55 T 0.50\n3.52 T 0.50\n3.54 T 0.49\n3.51 T 0.50\n3.96 T 0.54\n3.99 T 0.56\n3.73 T 0.46\n3.76 T 0.43\n%V˙O2max\n74.4 T 3.1\n74.3 T 5.7\n77.2 T 6.6\n75.2 T 5.5\n80.6 T 5.6\n77.3 T 2.8\n78.6 T 8.5\n76.9 T 4.5\n%HRmax\n87.1 T 3.2\n86.5 T 5.4\n84.7 T 4.3\n84.3 T 3.7\n89.7 T 2.8\n87.0 T 2.9\n88.8 T 7.6\n85.8 T 4.1\nvLT (kmIhj1)\n9.7 T 1.2\n10.5 T 1.2**\n9.5 T 1.6\n10.6 T 1.8**\n11.2 T 0.6\n12.3 T 0.8**\n10.3 T 2.3\n11.2 T 1.9**\n[Laj]b (mM)\n2.75 T 0.62\n2.41 T 0.24\n2.94 T 0.49\n2.46 T 0.31\n3.30 T 1.20\n2.70 T 0.50\n2.57 T 0.42\n2.50 T 0.44\nMass (kg)\n86.2 T 9.1\n83.9 T 7.6*\n78.2 T 13.1\n77.8 T 12.7\n80.6 T 10.7\n79.8 T 9.7\n82.9 T 13.0\n81.4 T 11.84\nData are presented as means T SD."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 35,
    "text": "The test was carried out running on a treadmill at 5.3% inclination.LSD, long slow distance running; LT, lactate threshold; V˙O2, oxygen uptake;\nHRmax, maximal\nheart\nrate;\nV˙ E, pulmonary ventilation; [Laj ]b, blood lactate concentration after V˙O2max testing; R, respiratory exchange ratio; vLT, velocity at lactate threshold.\n* Significant differences (P G 0.05) within groups from pre- to posttraining; ** significant difference (P G 0.01) within groups from pre- to posttraining; *** significant difference\nwithin groups (P G 0.001) from pre- to posttraining; # significant difference between groups from pre- to posttraining. a 15/15 vs LSD and LT is significant at P G 0.001 and P G 0.05,\nrespectively."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 36,
    "text": "b The difference between 4 \u0001 4 min vs the LSD and LT is significant at P G 0.001 and P G 0.01, respectively.\nTABLE 2."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 37,
    "text": "Changes in cardiac output and stroke volume from pre- to posttraining when running at the velocity of V˙O2max.\nLSD (N = 6)\nLT (N = 6)\n15/15 (N = 6)\n4 \u0001 4 min (N = 6)\nPretraining\nPosttraining\nPretraining\nPosttraining\nPretraining\nPosttraining\nPretraining\nPosttraining\nSV (mLIkgj1Ibeatj1)\n1.82 T 0.22\n1.86 T 0.35\n1.76 T 0.23\n1.78 T 0.35\n1.81 T 0.31\n1.99 T 0.31*\n1.76 T 0.38\n1.98 T 0.45**\nSV (mLIbeatj1)\n154.2 T 19.8\n152.9 T 22.4\n128.5 T 16.9\n129.7 T 15.9\n148.7 T 18.3\n162.7 T 20.7*\n144.2 T 21.9\n159.2 T 21.9**\nQ (LIminj1)\n30.29 T 4.50\n30.05 T 5.10\n25.73 T 2.06\n26.00 T 2.52\n29.78 T 3.32\n32.59 T 5.20*\n28.45 T 3.08\n31.43 T 2.50**\nHR (bpm)\n187 T 11\n185 T 9\n195 T 6\n194 T 9\n185 T 9\n182 T 10\n191 T 12\n186 T 7\nV˙O2\n(LIminj1)\n4.59 T 0.60\n4.48 T 0.41\n4.01 T 0.13\n4.20 T 0.16\n4.72 T 0.63\n4.99 T 0.43*\n4.39 T 0.64\n4.80 T 0.51*\n(mLIkgj1Iminj1)\n53.4 T 6.2\n54.0 T 6.1\n53.4 T 8.9\n56.5 T 9.8\n55.7 T 5.2\n60.1 T 3.5*\n51.8 T 7.3\n54.8 T 6.7*\n(mLIkgj0.75Iminj1)\n162.4 T 17.3\n162.8 T 15.7\n156.7 T 19.6\n166.8 T 22.1\n167.7 T 14.6\n180.9 T 8.6*\n156.8 T 19.6\n166.0 T 16.9**\nV˙ E (LIminj1)\n134.1 T 10.4\n135.3 T 15.5\n111.7 T 22.0\n127.0 T 18.0\n103.6 T 24.8\n121.6 T 24.8\n133.5 T 16.9\n143.8 T 10.3\nR\n1.09 T 0.05\n1.10 T 0.05\n1.03 T 0.14\n1.08 T 0.07\n1.07 T 0.03\n1.07 T 0.05\n1.09 T 0.02\n1.08 T 0.03\nData are presented as means T SD."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 38,
    "text": "The test was carried out running on a treadmill at 5.3% inclination.LSD, long slow distance running; LT, lactate threshold; Qmax, maximal cardiac\noutput; SVmax, maximal stroke volume; V˙O2, oxygen uptake; HRmax, maximal heart rate; V˙ E, pulmonary ventilation; R, respiratory exchange ratio. * Significant differences (P G 0.05)\nwithin groups from pre- to posttraining; ** significant difference (P G 0.01) within groups from pre- to posttraining.\nAEROBIC ENDURANCE TRAINING RESPONSES\nMedicine & Science in Sports & Exercised\n669\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 39,
    "text": "Unauthorized reproduction of this article is prohibited.\nusing LSD training three times per week for 10 wk,\nwhereas the work-matched 4 \u0001 4-min interval training\nresulted in a 17.9% increase in V˙ O2max (19).Training\nresponses of 5–10% have been shown using 4 \u0001 4 min\ntraining interventions twice per week for professional\nyouth soccer players (8) at a similar fitness level as in this\nexperiment, whereas the control group of football players\ndid not reveal any change. The lower improvement in\nV˙ O2max at higher fitness levels is in line with previous\nobservations (20).\nStroke volume of the heart. Q is determined by SV\nand HRmax. Because HRmax does not change with training,\nchanges in Q are determined by changes in SV."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 40,
    "text": "The SV in\nthe high–aerobic intensity interval groups at posttraining in\nthe present experiment were approximately 0.16 LIbeatj1,\nin line with what has been presented for highly trained\nendurance athletes (30).Q in this experiment for the 15/15\ngroup and the 4 \u0001 4 min group was approximately\n30 LIminj1. Using the single-breath technique of acetylene\nuptake (SB), the measurements are highly dependent on a\nsubject`s ability to perform the breathing task properly,\nwhich might be difficult when approaching intensity close\nto V˙ O2max."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 41,
    "text": "The slightly lower V˙ O2 and ventilation in the\nprotocol for Q measurements indicate that the real maximal\nQ in this experiment might actually be somewhat higher.\nThis experiment shows that improvements in V˙ O2max\nseem to be followed by similar improvements in SV,\nindicating a strong dependence between these parameters,\nin line with the hypothesis.\nBlood volume and hematological responses.In\nthis experiment, no significant change in blood volume was\nobserved in the two groups examined. Red blood cell mass\nor hemoglobin did not increase for any of the groups,\nindicating no change in oxygen-carrying capacity with\ntraining. Thus, blood volume and oxygen-carrying capacity\nof the blood do not seem to explain the changes in V˙ O2max\nin this experiment."
  },
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    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
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    "chunk_id": 42,
    "text": "This is partly supported by the lack of\nchange in cardiovascular function with acute plasma\nvolume expansion in trained athletes (21).\nRunning economy.In the present study, all training\ngroups significantly improved running economy (CR) at\n7 kmIhj1, 5.3% inclination, with no differences observed\nbetween the groups. The within-group comparison shows a\nsignificant improvement in CR from pre- to posttraining of\nabout 5%."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 43,
    "text": "Improved CR is to be expected because of the\nlarge amount of running training carried out during the\ntraining program and because the subjects did not\nparticipate in any regular running training before the study.\nThe present result is compatible with those from the study\nby Helgerud (8), who found that higher V˙ O2max in men\nversus performance-matched women is compensated for by\nsuperior CR as a result of more running.Helgerud et al. (9)\nfound that CR was improved by 6.7% in an 8-wk running\nprogram of 4 \u0001 4-min interval training compared with a\ncontrol group that only participated in regular soccer\ntraining. Although this may be expected, the current study\nand previous research (5,8,9) suggest that CR is not\naffected by the running speed used during training.\nLactate threshold."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 44,
    "text": "The present study found no\nsignificant change in LT in any training groups when\nexpressed as %V˙ O2max.Although commonly claimed (6),\nseveral studies have found no change in LT as %V˙ O2max\npreviously (9,15,22,23). All groups significantly improved\nrunning velocity at LT (vLT); on average, 9.6%. However,\nbecause vLT follows the improvement in V˙ O2max (9,15),\nand because all groups improved CR, higher vLT would be\nexpected. Similar results regarding vLT have been found\npreviously (25).\nCONCLUSIONS\nThe present study has revealed that the 15/15 and the\n4 \u0001 4 min training groups of healthy students that trained\nat aerobic high intensity (i.e., 90–95% HRmax) increased\ntheir V˙ O2max significantly. However, the LSD and the LT\ngroups training at 70 and 85% HRmax did not change their\nV˙ O2max."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 45,
    "text": "The increases in V˙ O2max seem to be a function\nof increased SV resulting in increased Q.Training at LSD\nand LT did not change the SV. We conclude that when\ntotal work and training frequency are matched, higher\naerobic intensity leads to larger improvements in V˙ O2max.\nIn all the training groups CR improved significantly, with\nno differences between groups. We conclude, then, that CR\nseems not to be velocity specific within the running\nintensities corresponding to 70–95% V˙ O2max for healthy\nsubjects. There were no significant group differences in\nTABLE 3."
  },
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    "pdf_title": "",
    "chunk_id": 46,
    "text": "Hematological responses to low- and high-intensity aerobic training.\nLSD (N = 8)\n4 \u0001 4 min (N = 9)\nPretraining\nPosttraining\nPretraining\nPosttraining\nBlood volume (L)\n5.81 T 0.83\n6.14 T 0.75\n5.81 T 0.84\n5.95 T 0.80\nBlood volume (mLIkgj1)\n65.67 T 6.27\n71.57 T 7.37\n73.56 T 6.85\n75.88 T 10.75\nRed cell mass (L)\n2.17 T 0.32\n2.36 T 0.33\n2.30 T 0.45\n2.27 T 0.38\nRed cell mass (mLIkgj1)\n24.58 T 2.49\n27.49 T 2.97\n26.53 T 4.43\n26.53 T 4.43\nHemoglobin (gIdLj1)\n14.73 T 0.74\n14.42 T 0.46\n14.60 T 0.88\n14.01 T 1.15\nHematocrit (%)\n43.1 T 2.2\n44.2 T 1.9\n43.5 T 3.4\n42.9 T 3.6\nGlucose (mM)\n5.30 T 0.56\n5.14 T 0.29\n4.77 T 0.39\n4.84 T 0.26\nTriglycerides (mM)\n0.94 T 0.48\n0.80 T 0.24\n1.04 T 0.43\n0.94 T 0.61\nHDL (mM)\n1.18 T 0.22\n1.23 T 0.23\n1.32 T 0.35\n1.26 T 0.31\nLDL (mM)\n2.86 T 0.81\n2.77 T 0.95\n2.84 T 0.52\n2.84 T 0.50\nCK (UILj1)\n206.1 T 131.0\n138.7 T 52.2\n161.5 T 122.4\n165.3 T 96.6\nData are presented as means T SD."
  },
  {
    "filename": "aerobic_high_intensity_intervals_improve_v_o2max.12.pdf",
    "pdf_title": "",
    "chunk_id": 47,
    "text": "LSD, long slow distance running; HDL, high-density lipoprotein; LDL, low-density lipoprotein; CK, creatine kinase.\nhttp://www.acsm-msse.org\n670\nOfficial Journal of the American College of Sports Medicine\nBASIC SCIENCES\nCopyright @ 2007 by the American College of Sports Medicine.Unauthorized reproduction of this article is prohibited.\nLT when expressed as a percentage of V˙ O2max. Although\nboth the 15/15 training group and the 4 \u0001 4 min training\ngroup improved V˙ O2max, the 47 repetitions of 15 \u0001 15 s\ntraining at a velocity that eventually gives a heart rate at\n90–95% HRmax is difficult to administer. Interval training\nwith longer intervals, like the 4 \u0001 4 min training ad-\nministered in this experiment, is thus recommended to\nimprove V˙ O2max.\nREFERENCES\n1. A˚ STRAND, P-O., and K. RODAHL."
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    "text": "Textbook of Work Physiology.\nNew York, NY: McGraw-Hill Book Company, 1986.\n2.BROOKS, G. A. Lactate production under fully aerobic conditions:\nthe lactate shuttle during rest and exercise. Fed. Proc. 45:\n2924–2929, 1986.\n3. BUNC, V., and J. HELLER. Energy cost of running in similarly\ntrained men and women. Eur. J. Appl. Physiol. 59:178–183,\n1989.\n4. DIBSKI, D. W., D. J. SMITH, R. JENSEN, S. R. NORRIS, and G. T.\nFORD. Comparison and reliability of two non-invasive acetylene\nuptake techniques for the measurement of cardiac output. Eur. J\nAppl. Physiol. 94:670–680, 2005.\n5. DI PRAMPERO, P. E., G. ATCHO, C. BRU¨ CKNER, and C. MOYA. The\nenergetics of endurance running. Eur. J. Appl. Physiol. 55:\n259–266, 1986.\n6. EVERTSEN, F., J. I. MEDBØ, and A. BONEN."
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    "text": "SLØRDAHL.\nHigh intensity aerobic interval exercise is superior to moderate\nintensity exercise for increasing aerobic capacity in patients with\ncoronary artery disease.Eur. J. Cardiov. Prev. Rehabil. 11:\n216–222, 2004.\n20. SALTIN, B. Maximal oxygen uptake: limitations and malleability.\nIn: International Perspectives in Exercise Physiology, K. Nazar\nand R. L. Terjung (Eds.). Champaign, IL: Human Kinetics\nPublishers, pp. 26–40, 1990.\n21. SAWKA, M. N., V. A. CONVERTINO, E. R. EICHNER, S. M.\nSCHNIEDER, and A. J. YOUNG. Blood volume: importance and\nadaptations to exercise training, environmental stresses, and\ntrauma/sickness. Med. Sci. Sports Exerc. 32:332–348, 2000.\n22. SHONO, N., H. URATA, B. SALTIN, et al."
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    "text": "Effects of low intensity\naerobic training on skeletal muscle capillary and blood lip-\noprotein profiles.J. Atheroscler. Thromb. 9:78–85, 2002.\n23. SJO¨ DIN, B., I. JACOBS, and J. SVEDENHAG. Changes in onset of blood\nlactate accumulation (OBLA) and muscle enzymes after training\nat OBLA. Eur. J. Appl. Physiol. 49:45–57, 1982.\n24. STRØMME, S., F. INGJER, and H. D. MEEN. Assessment of maximal\naerobic power in specifically trained athletes. J. Appl. Physiol.\n42:833–837, 1977.\n25. SVEDENHAG, J. Maximal and submaximal oxygen uptake during\nrunning: how should body mass be accounted for? Scand. J. Med.\nSci. Sports 5:175–180, 1995.\n26. SWAIN, D. P., K. S. ABERNATHY, C. S SMITH, S. J. LEE, and S. A.\nBUNN. Target heart rates for the development of cardiorespiratory\nfitness. Med. Sci. Sports. Exerc."
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    "text": "26:112–116, 1994.\n27.THOMAS, T. R., S. B. ADENIRAN, and G. L. ETHERIDGE. Effects of\ndifferent running programs on V˙ O2max, percent fat, and plasma\nlipids. Can. J. Sports Sci. 9:55–62, 1984.\n28. WAGNER, P. D. A theoretical analysis of factors determining\nV˙ O2max at sea level and altitude. Respir. Physiol. 106:329–343,\n1996.\n29. WENGER, H. A., and G. J. BELL. The interactions of intensity,\nfrequency and duration of exercise in altering cardio respiratory\nfitness. Sports. Med. 3:346–356, 1986.\n30. ZHOU, B., R. K. CONLEE, R. JENSEN, G. W. FELLINGHAM, J. D.\nGEORGE, and A. G. FISHER. Stroke volume does not plateau during\ngraded exrcise in elite male distance runners. Med. Sci. Sports\nExerc."
  },
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    "pdf_title": "",
    "chunk_id": 55,
    "text": "33:1849–1854, 2001.\nAEROBIC ENDURANCE TRAINING RESPONSES\nMedicine & Science in Sports & Exercised\n671\nBASIC SCIENCES"
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 0,
    "text": "REVIEW\nOpen Access\nHow much protein can the body use in a\nsingle meal for muscle-building?\nImplications for daily protein distribution\nBrad Jon Schoenfeld1* and Alan Albert Aragon2\nAbstract\nControversy exists about the maximum amount of protein that can be utilized for lean tissue-building purposes in a\nsingle meal for those involved in regimented resistance training. It has been proposed that muscle protein synthesis is\nmaximized in young adults with an intake of ~ 20–25 g of a high-quality protein; anything above this amount is\nbelieved to be oxidized for energy or transaminated to form urea and other organic acids. However, these findings are\nspecific to the provision of fast-digesting proteins without the addition of other macronutrients."
  },
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    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 1,
    "text": "Consumption of\nslower-acting protein sources, particularly when consumed in combination with other macronutrients, would delay\nabsorption and thus conceivably enhance the utilization of the constituent amino acids.The purpose of this paper was\ntwofold: 1) to objectively review the literature in an effort to determine an upper anabolic threshold for per-meal\nprotein intake; 2) draw relevant conclusions based on the current data so as to elucidate guidelines for per-meal daily\nprotein distribution to optimize lean tissue accretion. Both acute and long-term studies on the topic were evaluated\nand their findings placed into context with respect to per-meal utilization of protein and the associated implications to\ndistribution of protein feedings across the course of a day."
  },
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    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 2,
    "text": "The preponderance of data indicate that while consumption\nof higher protein doses (> 20 g) results in greater AA oxidation, this is not the fate for all the additional ingested AAs as\nsome are utilized for tissue-building purposes.Based on the current evidence, we conclude that to maximize anabolism\none should consume protein at a target intake of 0.4 g/kg/meal across a minimum of four meals in order to reach a\nminimum of 1.6 g/kg/day."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 3,
    "text": "Using the upper daily intake of 2.2 g/kg/day reported in the literature spread out over the\nsame four meals would necessitate a maximum of 0.55 g/kg/meal.\nKeywords: Protein feeding pattern, Amino acid oxidation, Protein intake, Protein metabolism, Lean tissue mass\nBackground\nControversy exists about the maximum amount of\nprotein that can be utilized for lean tissue-building pur-\nposes in a single meal for those involved in regimented\nresistance training.A long-held misperception in the lay\npublic is that there is a limit to how much protein can\nbe absorbed by the body. From a nutritional standpoint,\nthe term “absorption” describes the passage of nutrients\nfrom the gut into systemic circulation. Based on this\ndefinition, the amount of protein that can be absorbed is\nvirtually unlimited."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 4,
    "text": "Following digestion of a protein\nsource, the constituent amino acids (AA) are transported\nthrough the enterocytes at the intestinal wall, enter the\nhepatic portal circulation, and the AA that are not\nutilized directly by the liver, then enter the bloodstream,\nafter which almost all the AA ingested become available\nfor use by tissues.While absorption is not a limiting\nfactor with respect to whole proteins, there may be\nissues with consumption of individual free-form AA in\nthis regard."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 5,
    "text": "Specifically, evidence shows the potential for\ncompetition at the intestinal wall, with AA that are\npresent in the highest concentrations absorbed at the\nexpense of those that are less concentrated [1].\nIt has been proposed that muscle protein synthesis\n(MPS) is maximized in young adults with an intake\nof ~ 20–25 g of a high-quality protein, consistent with\nthe “muscle full” concept; anything above this amount\nis believed to be oxidized for energy or transaminated\n* Correspondence: brad@workout911.com\n1CUNY Lehman College, Department of Health Sciences, 250 Bedford Park\nBlvd West, Bronx, NY 10468, USA\nFull list of author information is available at the end of the article\n© The Author(s)."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 6,
    "text": "2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0\nInternational License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and\nreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to\nthe Creative Commons license, and indicate if changes were made.The Creative Commons Public Domain Dedication waiver\n(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition\n (2018) 15:10 \nhttps://doi.org/10.1186/s12970-018-0215-1\nto form alternative bodily compounds [2]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 7,
    "text": "The pur-\npose of this paper is twofold: 1) to objectively review\nthe literature in an effort to determine an upper ana-\nbolic threshold for per-meal protein intake; 2) draw\nrelevant conclusions based on the current data so as\nto elucidate guidelines for per-meal daily protein dis-\ntribution to optimize lean tissue accretion.\nSpeed of digestion/absorption on muscle anabolism\nIn a study often cited as support for the hypothesis that\nMPS is maximized at a protein dose of ~ 20–25 g, Areta\net al.[3] provided differing amounts of protein to\nresistance-trained subjects over a 12-h recovery period\nfollowing performance of a multi-set, moderate repeti-\ntion leg-extension exercise protocol."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 8,
    "text": "A total of 80 g of\nwhey protein was ingested in one of the following three\nconditions: 8 servings of 10 g every 1.5 h; 4 servings of\n20 g every 3 h; or 2 servings of 40 g every 6 h.Results\nshowed that MPS was greatest in those who consumed 4\nservings of 20 g of protein, suggesting no additional\nbenefit, and actually a lower rise in MPS when consum-\ning the higher dosage (40 g) under the conditions\nimposed in the study. These results extended similar\nfindings by Moore et al. [4] on whole-body nitrogen\nturnover.\nAlthough the findings of Areta et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 9,
    "text": "[3] provide inter-\nesting insight into the dose-related effects of protein\nintake on muscle development, it is important to note\nthat a number of factors influence dietary protein me-\ntabolism including the composition of the given protein\nsource, the composition of the meal, the amount of pro-\ntein ingested, and the specifics of the exercise routine\n[5].In addition, individual variables such as age, training\nstatus, and the amount of lean body mass also impact\nmuscle-building outcomes. A major limitation in the\nstudy by Areta et al. [3] is that total protein intake over\nthe 12-h study period was only 80 g, corresponding to\nless than 1 g/kg of body mass."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 10,
    "text": "This is far below the\namount necessary to maximize muscle protein balance\nin resistance-trained individuals who served as partici-\npants in the study [6, 7].Furthermore, the ecological\nvalidity of this work is limited since habitual protein\nintakes of individuals focused on muscle gain or reten-\ntion habitually consume approximately 2–4 times this\namount per day [8, 9].\nIt also should be noted that subjects in Areta et al. [3]\ningested nothing but whey protein throughout the post-\nexercise period. Whey is a “fast-acting” protein; its\nabsorption rate has been estimated at ~ 10 g per hour\n[5]. At this rate, it would take just 2 h to fully absorb a\n20-g dose of whey."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 11,
    "text": "While the rapid availability of AA\nwill tend to spike MPS, earlier research examining whole\nbody protein kinetics showed that concomitant oxida-\ntion of some of the AA may result in a lower net protein\nbalance when compared to a protein source that is\nabsorbed at a slower rate [10]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 12,
    "text": "For example, cooked egg\nprotein has an absorption rate of ~ 3 g per hour [5],\nmeaning complete absorption of an omelet containing\nthe same 20 g of protein would take approximately 7 h,\nwhich may help attenuate oxidation of AA and thus pro-\nmote greater whole-body net positive protein balance.\nAn important caveat is that these findings are specific to\nwhole body protein balance; the extent to which this re-\nflects skeletal muscle protein balance remains unclear.\nAlthough some studies have shown similar effects of\nfast and slow proteins on net muscle protein balance\n[11] and fractional synthetic rate [12–14], other studies\nhave demonstrated a greater anabolic effect of whey\ncompared to more slowly digested sources both at rest\n[15, 16], and after resistance exercise [16, 17]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 13,
    "text": "However,\nthe majority of these findings were during shorter testing\nperiods (4 h or less), whereas longer testing periods (5 h\nor more) tend to show no differences between whey and\ncasein on MPS or nitrogen balance [18].Furthermore,\nmost studies showing greater anabolism with whey used\na relatively small dose of protein (≤20 g) [15–17]; it re-\nmains unclear whether higher doses would result in\ngreater oxidation of fast vs slow-acting protein sources.\nCompounding these equivocal findings, research exam-\nining the fate of intrinsically labeled whey and casein con-\nsumed within milk found a greater incorporation of casein\ninto skeletal muscle [19]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 14,
    "text": "The latter finding should be\nviewed with the caveat that although protein turnover in\nthe leg is assumed to be mostly reflective of skeletal\nmuscle, it is also possible that non-muscle tissues might\nalso contribute.Interestingly, the presence versus absence\nof milk fat coingested with micellar casein did not delay\nthe rate of protein-derived circulating amino acid avail-\nability or myofibrillar protein synthesis [20]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 15,
    "text": "Furthermore,\nthe coingestion of carbohydrate with casein delayed diges-\ntion and absorption, but still did not impact muscle pro-\ntein accretion compared to a protein-only condition [21].\nThe implication is that accompanying macronutrients’\npotential to alter digestion rates does not necessarily\ntranslate to alterations in the anabolic effect of the protein\nfeeding – at least in the case of slow-digesting protein\nsuch as casein.More fat and/or carbohydrate coingestion\ncomparisons need to be made with other proteins, subject\nprofiles, and relative proximity to training before drawing\ndefinitive conclusions.\nHigher acute ‘anabolic ceiling’ than previously thought?\nMore recently, Macnaughton et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 16,
    "text": "[22] employed a ran-\ndomized, double-blind, within-subject design whereby\nresistance-trained men participated in two trials sepa-\nrated by ~ 2 weeks.During one trial subjects received\n20 g of whey protein immediately after performing a\ntotal body resistance training bout; during the other trial\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition  (2018) 15:10 \nPage 2 of 6\nthe same protocol was instituted but subjects received a\n40-g whey bolus following training. Results showed that\nthe myofibrillar fractional synthetic rate was ~ 20%\nhigher from consumption of the 40 g compared to the\n20 g condition."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 17,
    "text": "The researchers speculated that the large\namount of muscle mass activated from the total body\nRT bout necessitated a greater demand for AA that was\nmet by a higher exogenous protein consumption.It\nshould be noted that findings by McNaughton et al. [22]\nare somewhat in contrast to previous work by Moore\net al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 18,
    "text": "showing no statistically significant differences in\nMPS between provision of a 20 g and 40 g dose of whey\nin young men following a leg extension bout, although\nthe higher dose produced an 11% greater absolute\nincrease\n[23].\nWhether\ndifferences\nbetween\nintakes\nhigher than ~ 20 g per feeding are practically meaningful\nremain speculative, and likely depend on the goals of the\nindividual.\nGiven that muscular development is a function of the\ndynamic balance between MPS and muscle protein\nbreakdown (MPB), both of these variables must be\nconsidered in any discussion on dietary protein dosage.\nKim et al.[24] endeavored to investigate this topic by\nprovision of either 40 or 70 g of beef protein consumed\nas part of a mixed meal on two distinct occasions sepa-\nrated by a ~ 1 week washout period."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 19,
    "text": "Results showed that\nthe\nhigher\nprotein\nintake\npromoted\na\nsignificantly\ngreater whole-body anabolic response, which was pri-\nmarily attributed to a greater attenuation of protein\nbreakdown.Given that participants ate large, mixed\nmeals as whole foods containing not only protein, but\ncarbohydrates and dietary fats as well, it is logical to\nspeculate that this delayed digestion and absorption of\nAAs compared to liquid consumption of isolated protein\nsources. This, in turn, would have caused a slower\nrelease of AA into circulation and hence may have con-\ntributed to dose-dependent differences in the anabolic\nresponse to protein intake. A notable limitation of the\nstudy is that measures of protein balance were taken at\nthe whole-body level and thus not muscle-specific."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 20,
    "text": "It\ntherefore can be speculated that some if not much of\nanti-catabolic benefits associated with higher protein in-\ntake was from tissues other than muscle, likely the gut.\nEven so, protein turnover in the gut potentially provides\nan avenue whereby accumulated amino acids can be re-\nleased into the systemic circulation to be used for MPS,\nconceivably enhancing anabolic potential [25].This\nhypothesis remains speculative and warrants further in-\nvestigation. It would be tempting to attribute these\nmarked reductions in proteolysis to higher insulin re-\nsponses considering the inclusion of a generous amount\nof carbohydrate in the meals consumed. Although insu-\nlin is often considered an anabolic hormone, its primary\nrole in muscle protein balance is related to anti-catabolic\neffects [26]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 21,
    "text": "However, in the presence of elevated plasma\nAAs, the effect of insulin elevations on net muscle\nprotein balance plateaus within a modest range of 15–\n30 mU/L [27, 28].Given evidence that a 45 g dose of\nwhey protein causes insulin to rise to levels sufficient to\nmaximize net muscle protein balance [29], it would\nseem that the additional macronutrients consumed in\nthe study by Kim et al. [24] had little bearing on results.\nLongitudinal findings\nAlthough the previously discussed studies offer insight\ninto how much protein the body can utilize in a given\nfeeding, acute anabolic responses are not necessarily as-\nsociated with long-term muscular gains [30]."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 22,
    "text": "The topic\ncan only be answered by assessing the results of longitu-\ndinal studies that directly measure changes in lean mass\nwith provision of varying protein dosages, as well as pro-\nteins of varying speeds of digestion/absorption.\nWilborn et al.[31], found no difference in lean mass\ngains after 8 weeks of pre- and post-resistance exercise\nsupplementation with either whey or casein. Similarly, a\nlack of between-group differences in lean mass gain was\nfound by Fabre et al. [32] when comparing the following\nwhey/casein protein ratios consumed postexercise: 100/\n0, 50/50, 20/80.\nIn a 14-day study of elderly women, Arnal et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 23,
    "text": "[33]\ndemonstrated that providing a majority of daily protein\n(79%) in a single meal (pulse pattern) resulted in a\ngreater retention of fat-free mass compared to an evenly\ndistributed intake partitioned over four daily meals\n(spread pattern).A follow-up study by the same lab in\nyoung women reported similar effects of pulse versus\nspread patterns of protein intake [34]. The combined\nfindings of these studies indicate that muscle mass is\nnot negatively affected by consuming the majority of\ndaily protein as a large bolus. However, neither study\nemployed regimented resistance training thereby lim-\niting generalizability to individuals involved in intense\nexercise programs.\nInsights into the effects of protein dosage can also be\ngleaned from studies on intermittent fasting (IF)."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 24,
    "text": "Typical\nIF protocols require intake of daily nutrients, including\nprotein, in a narrow time-frame – usually less than 8 h\n– followed by a prolonged fast.A recent systematic re-\nview concluded that IF has similar effects on fat-free\nmass compared with continuous eating protocols [35].\nHowever, the studies reviewed in the analysis generally\ninvolved suboptimal protein intakes consumed as part of\na low-energy diet without a resistance training compo-\nnent, again limiting the ability to extrapolate findings to\nresistance-trained individuals.\nHelping to fill this literature gap is an 8-week trial by\nTinsley et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 25,
    "text": "[36], comparing a time-restricted feeding\n(TRF) protocol of 20-h fasting/4-h feeding cycles done\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition  (2018) 15:10 \nPage 3 of 6\n4 days per week, with a normal-diet group (ND) in un-\ntrained subjects doing resistance training 3 days per week.\nThe TRF group lost body weight via lower energy intake\n(667 kcal less on fasting vs.non-fasting days), but did not\nsignificantly lose lean mass (0.2 kg); ND gained lean mass\n(2.3 kg), but not to a statistically significant degree, al-\nthough the magnitude of differences raises the possibility\nthat these findings may be practically meaningful."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 26,
    "text": "Perhaps\nmost interestingly, biceps brachii and rectus femoris cross\nsectional area showed similar increases in both groups\ndespite the 20-h fasting cycles and concentrated feeding\ncycles in TRF, suggesting that the utilization of protein\nintake in the ad libitum 4-h feeding cycles was not ham-\npered by an acute ceiling of anabolism.Unfortunately,\nprotein and energy were not equated in this study. Subse-\nquently, an 8-week trial by Moro et al. [37] using\nresistance-trained subjects on a 16-h fasting/8-h TRF cycle\nfound significantly greater fat loss in TRF vs. ND (1.62 vs.\n0.31 kg) while lean mass remained unchanged in both\ngroups."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 27,
    "text": "These findings further call into question the con-\ncern for breaching a certain threshold of protein intake\nper meal for the goal of muscle retention.\nIn contrast to the above findings showing neutral-to-\npositive effects of a temporally concentrated meal intake,\nArciero et al.[38] compared 3 diets: 2 high-protein (35%\nof total energy) diets consisting of 3 (HP3) and 6 meals/\nday (HP6), and a traditional protein intake (15% of total\nenergy) consumed in 3 meals/day (TD3). During the ini-\ntial 28-day eucaloric phase, HP3 and HP6 consumed\nprotein at 2.27 & 2.15 g/kg, respectively, while TD3 con-\nsumed 0.9 g/kg. HP6 was the only goup that significantly\ngained lean mass."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 28,
    "text": "During the subsequent 28-day eucalo-\nric phase, HP3 and HP6 consumed protein at 1.71 &\n1.65 g/kg, respectively, while TD3 consumed 0.75 g/kg.\nHP6 maintained its lean mass gain, outperforming the\nother 2 treatments in this respect (HP actually showed a\nsignificant loss of lean mass compared to the control).\nThe discrepancy between the latter findings and those in\nthe IF/TRF trials remains to be reconciled."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 29,
    "text": "In any case,\nit is notable that comparisons in this vein specifically\ngeared toward the goal of muscle gain, hypercaloric\ncomparisons in particular, are lacking.\nConclusions\nAn important distinction needs to be made between\nacute\nmeal\nchallenges\ncomparing\ndifferent\nprotein\namounts (including serial feedings in the acute phase\nfollowing resistance training) and chronic meal feedings\ncomparing different protein distributions through the\nday, over the course of several weeks or months.Longi-\ntudinal studies examining body composition have not\nconsistently corroborated the results of acute studies\nexamining muscle protein flux."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 30,
    "text": "Quantifying a maximum\namount of protein per meal that can be utilized for\nmuscle anabolism has been a challenging pursuit due to\nthe multitude of variables open for investigation.Per-\nhaps the most comprehensive synthesis of findings in\nthis area has been done by Morton et al. [2], who con-\ncluded that 0.4 g/kg/meal would optimally stimulate\nMPS. This was based on the addition of two standard\ndeviations to their finding that 0.25 g/kg/meal maximally\nstimulates MPS in young men. In line with this hypoth-\nesis, Moore et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 31,
    "text": "[39] mentioned the caveat that their\nfindings were estimated means for maximizing MPS, and\nthat the dosing ceilings can be as high as ~ 0.60 g/kg for\nsome older men and ~ 0.40 g/kg for some younger men.\nImportantly, these estimates are based on the sole\nprovision of a rapidly digesting protein source that would\nconceivably increase potential for oxidation of AA when\nconsumed in larger boluses.It seems logical that a slower-\nacting protein source, particularly when consumed in\ncombination with other macronutrients, would delay\nabsorption and thus enhance the utilization of the con-\nstituent AA."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 32,
    "text": "However, the practical implications of this\nphenomenon remain speculative and questionable [21].\nThe collective body of evidence indicates that total daily\nprotein intake for the goal of maximizing resistance\ntraining-induced gains in muscle mass and strength is ap-\nproximately 1.6 g/kg, at least in non-dieting (eucaloric or\nhypercaloric) conditions [6].However, 1.6 g/kg/day should\nnot be viewed as an ironclad or universal limit beyond\nwhich protein intake will be either wasted or used for\nphysiological demands aside from muscle growth. A re-\ncent meta-analysis on protein supplementation involving\nresistance trainees reported an upper 95% confidence\ninterval (CI) of 2.2 g/kg/day [6]. Bandegan et al."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 33,
    "text": "[7] also\nshowed an upper CI of 2.2 g/kg/day in a cohort of young\nmale bodybuilders, although the method of assessment\n(indicator amino acid oxidation technique) used in this\nstudy has not received universal acceptance for determin-\ning optimal protein requirements.This reinforces the\npractical need to individualize dietary programming, and\nremain open to exceeding estimated averages. It is there-\nfore a relatively simple and elegant solution to consume\nprotein at a target intake of 0.4 g/kg/meal across a\nminimum of four meals in order to reach a minimum of\n1.6 g/kg/day – if indeed the primary goal is to build\nmuscle. Using the upper CI daily intake of 2.2 g/kg/day\nover the same four meals would necessitate a maximum\nof 0.55 g/kg/meal."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 34,
    "text": "This tactic would apply what is cur-\nrently known to maximize acute anabolic responses as\nwell as chronic anabolic adaptations.While research\nshows that consumption of higher protein doses (> 20 g)\nresults in greater AA oxidation [40], evidence indicates\nthat this is not the fate for all the additional ingested AAs\nas some are utilized for tissue-building purposes. Further\nresearch is nevertheless needed to quantify a specific\nupper threshold for per-meal protein intake.\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition  (2018) 15:10 \nPage 4 of 6\nAcknowledgements\nN/A\nFunding\nN/A\nAvailability of data and materials\nN/A\nAuthors’ contributions\nBrad Schoenfeld conceived of the article. Both authors equally contributed\nto the writing of the manuscript."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 35,
    "text": "Both authors read and approved the final\nmanuscript.\nEthics approval and consent to participate\nN/A\nConsent for publication\nN/A\nCompeting interests\nBrad Schoenfeld serves on the scientific advisory board for Dymatize\nNutrition.The authors declare no other conflicts of interest.\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in\npublished maps and institutional affiliations.\nAuthor details\n1CUNY Lehman College, Department of Health Sciences, 250 Bedford Park\nBlvd West, Bronx, NY 10468, USA."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 36,
    "text": "2California State University, 18111 Nordhoff\nSt, Northridge, CA 91330, USA.\nReceived: 19 September 2017 Accepted: 20 February 2018\nReferences\n1.\nGropper SS, Smith JL, Groff JL: Advanced Nutrition and Human Metabolism.\nBelmont, CA: Wadsworth Cengage Learning; 2009.\n2.\nMorton RW, McGlory C, Phillips SM.Nutritional interventions to augment\nresistance training-induced skeletal muscle hypertrophy. Front Physiol. 2015;\n6:245.\n3.\nAreta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA,\nMoore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Timing and\ndistribution of protein ingestion during prolonged recovery from resistance\nexercise alters myofibrillar protein synthesis. J Physiol."
  },
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    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 37,
    "text": "2013;591(Pt 9):2319–31.\n4.\nMoore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cleroux\nM, Godin JP, Hawley JA.Daytime pattern of post-exercise protein intake\naffects whole-body protein turnover in resistance-trained males. Nutr Metab\n(Lond). 2012;9(1):91. -7075-9-91\n5.\nBilsborough S, Mann N. A review of issues of dietary protein intake in\nhumans. Int J Sport Nutr Exerc Metab. 2006;16(2):129–52.\n6.\nMorton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms\nE, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic\nreview, meta-analysis and meta-regression of the effect of protein\nsupplementation on resistance training-induced gains in muscle mass and\nstrength in healthy adults. Br J Sports Med."
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    "chunk_id": 38,
    "text": "2017;\n7.\nBandegan A, Courtney-Martin G, Rafii M, Pencharz PB, Lemon PW.Indicator\namino acid-derived estimate of dietary protein requirement for male\nbodybuilders on a nontraining day is several-fold greater than the current\nrecommended dietary allowance. J Nutr. 2017;147(5):850–7.\n8.\nSpendlove J, Mitchell L, Gifford J, Hackett D, Slater G, Cobley S, O'Connor H.\nDietary intake of competitive bodybuilders. Sports Med. 2015;45(7):1041–63.\n9.\nAntonio J, Ellerbroek A, Silver T, Vargas L, Peacock C: The effects of a high\nprotein diet on indices of health and body composition–a crossover trial in\nresistance-trained men."
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    "text": "J Int Soc Sports Nutr 2016, 13:3–016–0114-2.\neCollection 2016.\n10.\nDangin M, Boirie Y, Guillet C, Beaufrere B: Influence of the protein digestion\nrate on protein turnover in young and elderly subjects.J Nutr 2002, 132(10):\n3228S–33S.\n11.\nTipton KD, Elliott TA, Cree MG, Wolf SE, Sanford AP, Wolfe RR. Ingestion of\ncasein and whey proteins result in muscle anabolism after resistance\nexercise. Med Sci Sports Exerc. 2004;36(12):2073–81.\n12.\nMitchell CJ, McGregor RA, D'Souza RF, Thorstensen EB, Markworth JF,\nFanning AC, Poppitt SD, Cameron-Smith D. Consumption of milk protein or\nwhey protein results in a similar increase in muscle protein synthesis in\nmiddle aged men. Nutrients."
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    "text": "2015;7(10):8685–99.\n13.\nReitelseder S, Agergaard J, Doessing S, Helmark IC, Lund P, Kristensen NB,\nFrystyk J, Flyvbjerg A, Schjerling P, van Hall G, Kjaer M, Holm L.Whey and\ncasein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of\nresistance exercise and protein ingestion. Am J Physiol Endocrinol Metab.\n2011;300(1):E231–42.\n14.\nDideriksen KJ, Reitelseder S, Petersen SG, Hjort M, Helmark IC, Kjaer M, Holm\nL. Stimulation of muscle protein synthesis by whey and caseinate ingestion\nafter resistance exercise in elderly individuals. Scand J Med Sci Sports. 2011;\n21(6):e372–83.\n15.\nPennings B, Boirie Y, Senden JM, Gijsen AP, Kuipers H, van Loon LJ."
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    "text": "Whey\nprotein stimulates postprandial muscle protein accretion more effectively\nthan do casein and casein hydrolysate in older men.Am J Clin Nutr. 2011;\n93(5):997–1005.\n16.\nBurd NA, Yang Y, Moore DR, Tang JE, Tarnopolsky MA, Phillips SM. Greater\nstimulation of myofibrillar protein synthesis with ingestion of whey protein\nisolate v. Micellar casein at rest and after resistance exercise in elderly men.\nBr J Nutr. 2012;108(6):958–62.\n17.\nTang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of\nwhey hydrolysate, casein, or soy protein isolate: effects on mixed muscle\nprotein synthesis at rest and following resistance exercise in young men.\nJ Appl Physiol (1985). 2009;107(3):987–92.\n18.\nWitard OC, Wardle SL, Macnaughton LS, Hodgson AB, Tipton KD."
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  },
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    "text": "Disassociation\nbetween the effects of amino acids and insulin on signaling, ubiquitin\nligases, and protein turnover in human muscle.Am J Physiol Endocrinol\nMetab. 2008;295(3):E595–604.\n28.\nRennie MJ, Bohe J, Smith K, Wackerhage H, Greenhaff P. Branched-chain\namino acids as fuels and anabolic signals in human muscle. J Nutr. 2006;\n136(1 Suppl):264S–8S.\n29.\nPower O, Hallihan A, Jakeman P. Human insulinotropic response to oral\ningestion of native and hydrolysed whey protein. Amino Acids. 2009;37(2):\n333–9.\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition  (2018) 15:10 \nPage 5 of 6\n30.\nMitchell CJ, Churchward-Venne TA, Parise G, Bellamy L, Baker SK, Smith K,\nAtherton PJ, Phillips SM."
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    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
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    "text": "Acute post-exercise myofibrillar protein synthesis is\nnot correlated with resistance training-induced muscle hypertrophy in\nyoung men.PLoS One. 2014;9(2):e89431.\n31.\nWilborn CD, Taylor LW, Outlaw J, Williams L, Campbell B, Foster CA, Smith-\nRyan A, Urbina S, Hayward S. The effects of pre- and post-exercise whey vs.\ncasein protein consumption on body composition and performance\nmeasures in collegiate female athletes. J Sports Sci Med. 2013;12(1):74–9.\n32.\nFabre M, Hausswirth C, Tiollier E, Molle O, Louis J, Durguerian A, Neveux N,\nBigard X. Effects of Postexercise protein intake on muscle mass and\nstrength during resistance training: is there an optimal ratio between fast\nand slow proteins? Int J Sport Nutr Exerc Metab."
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    "text": "2017;27(5):448–57.\n33.\nArnal MA, Mosoni L, Boirie Y, Houlier ML, Morin L, Verdier E, Ritz P, Antoine\nJM, Prugnaud J, Beaufrere B, Mirand PP.Protein pulse feeding improves\nprotein retention in elderly women. Am J Clin Nutr. 1999;69(6):1202–8.\n34.\nArnal MA, Mosoni L, Boirie Y, Houlier ML, Morin L, Verdier E, Ritz P, Antoine\nJM, Prugnaud J, Beaufrere B, Mirand PP. Protein feeding pattern does not\naffect protein retention in young women. J Nutr. 2000;130(7):1700–4.\n35.\nSeimon RV, Roekenes JA, Zibellini J, Zhu B, Gibson AA, Hills AP, Wood RE,\nKing NA, Byrne NM, Sainsbury A. Do intermittent diets provide physiological\nbenefits over continuous diets for weight loss? A systematic review of\nclinical trials. Mol Cell Endocrinol."
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    "chunk_id": 48,
    "text": "2015;418(Pt 2):153–72.\n36.\nTinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB,\nGrandjean PW.Time-restricted feeding in young men performing resistance\ntraining: a randomized controlled trial. Eur J Sport Sci. 2017;17(2):200–7.\n37.\nMoro T, Tinsley G, Bianco A, Marcolin G, Pacelli QF, Battaglia G, Palma A, Gentil P,\nNeri M, Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal\nmetabolism, maximal strength, body composition, inflammation, and\ncardiovascular risk factors in resistance-trained males. J Transl Med. 2016;14(1):290.\n38.\nArciero PJ, Ormsbee MJ, Gentile CL, Nindl BC, Brestoff JR, Ruby M. Increased\nprotein intake and meal frequency reduces abdominal fat during energy\nbalance and energy deficit. Obesity (Silver Spring)."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 49,
    "text": "2013;21(7):1357–66.\n39.\nMoore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD,\nPhillips SM.Protein ingestion to stimulate myofibrillar protein synthesis\nrequires greater relative protein intakes in healthy older versus younger\nmen. J Gerontol A Biol Sci Med Sci. 2015;70(1):57–62.\n40.\nWitard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar\nmuscle protein synthesis rates subsequent to a meal in response to\nincreasing doses of whey protein at rest and after resistance exercise.\nAm J Clin Nutr."
  },
  {
    "filename": "s12970-018-0215-1.pdf",
    "pdf_title": "How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution",
    "chunk_id": 50,
    "text": "2014;99(1):86–95.\n•  We accept pre-submission inquiries \n•  Our selector tool helps you to find the most relevant journal\n•  We provide round the clock customer support \n•  Convenient online submission\n•  Thorough peer review\n•  Inclusion in PubMed and all major indexing services \n•  Maximum visibility for your research\nSubmit your manuscript at\nwww.biomedcentral.com/submit\nSubmit your next manuscript to BioMed Central \nand we will help you at every step:\nSchoenfeld and Aragon Journal of the International Society of Sports Nutrition  (2018) 15:10 \nPage 6 of 6"
  }
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