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Cited by 221Muscle metabolism and nutritionExercise and Physiological ResponsesSports Performance and Training

New strategies in sport nutrition to increase exercise performance

Open access
Close, G.L., Hamilton, D.L., Philp, A., Burke, L.M., Morton, J.P.·2016·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2016.01.016
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Abstract

Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximise competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, β-hydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger).

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Written from the paper’s full text.

TL;DR

This narrative review argues that sports nutrition is moving toward “targeted nutritional periodization,” separating competition nutrition (performance-focused) from training nutrition (adaptation-focused). It concludes that carbohydrate remains central for performance, while strategic low-carbohydrate training, protein/amino acid timing, selected traditional supplements, and several novel compounds may modulate skeletal muscle adaptations.

Key findings

  • Carbohydrate remains “king” for exercise performance: high pre-exercise muscle glycogen (>500 mmol·kg⁻¹ dw) improves endurance/team-sport performance when exercise is >60–90 min; elite athletes are advised to consume 6–12 g/kg body mass CHO in the 24–36 h before competition. Exogenous CHO oxidation can rise to 1.8 g/min with sucrose or fructose added to a CHO blend, versus ~1 g/min with glucose alone, and CHO mouth rinsing for 10 s every 5–10 min can be ergogenic.
  • Training with reduced CHO availability can enhance endurance-training adaptations—increased mitochondrial enzyme activity/protein content, whole-body and intramuscular lipid oxidation, and sometimes exercise capacity—via AMPK, p38MAPK, PGC-1α, p53, and PPARδ signaling, supporting a “train-low, compete-high” model. Potential pitfalls include immune perturbations, impaired training intensity, reduced exogenous CHO oxidation during competition, and increased muscle protein oxidation.
  • Traditional supplements with evidence include caffeine, creatine, nitrate/beetroot juice, sodium bicarbonate, beta-alanine, vitamin D, and antioxidants. Reported numbers include creatine elevating muscle creatine stores by ~20%; bicarbonate producing a moderate 1.7 ± 2.0% enhancement of a single 1-min sprint in male athletes; beta-alanine at 3–6 g/d for 4–12 weeks increasing muscle carnosine by 50–85%; and vitamin D deficiency below 30 nmol/L impairing muscle function, with no performance-enhancing effect when starting concentrations are around 50 nmol/L.
  • Novel compounds are mostly early-stage: nicotinamide riboside (400 mg/kg/day in mice) increased skeletal muscle NAD⁺ by ~5% and endurance capacity by ~25%; HMB (3 g/day) enhanced fat-free mass gains after 6 weeks resistance training and increased MPS by +70% versus leucine +110%, while attenuating MPB by −57%; phosphatidic acid (750 mg/day) during 8 weeks resistance training increased squat strength by 12.7% and lean body mass by 2.6% versus 9.3% and 0.1% in placebo in one study, but other data are inconsistent or negative. Resveratrol supplementation in humans has been reported to blunt exercise-training adaptations.

Methods

  • Design: Narrative review of sports nutrition strategies for exercise performance and training adaptation; it covers molecular regulation of endurance and resistance training, carbohydrate/fat/protein nutrition, traditional supplements, and novel compounds.
  • Data or sample: Not stated in the paper; no primary sample or systematic search strategy is reported. The review cites human, rodent, and cell-based studies.
  • Main analysis: Narrative synthesis of existing literature, including a table categorizing common supplements as Green, Amber, or Red based on the authors’ interpretation of published evidence.

Limitations

  • Stated by the paper: many unanswered questions remain, including the best way to implement train-low carbohydrate strategies, whether and for how long fat adaptation may enhance performance, whether novel compounds from rodent models translate to human performance, and how much research on non-elite performers translates to elite athletes.
  • Stated/evident: the supplement categorization in Table 1 is based on the authors’ interpretation of existing literature, not a systematic review or meta-analysis.
  • Evident: as a narrative review, it provides no primary data, no systematic search or quality appraisal, and several novel-compound conclusions rely heavily on rodent/cell studies or inconsistent human findings.

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Registry

Crossref · 10.1016/j.freeradbiomed.2016.01.016

Cites

189 of 189 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 225 cited sources checked · 0 supported · 0 flagged

  • Premisecitation
    § 2. Nutrition gene interactions

    The molecular pathways activated by exercise are shared with a number of nutrient sensing mechanisms.

    “These same pathways are shared with a number of the nutrient sensing mechanisms [3,4].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Weigl, 2012, Lost in translation: regulation of skeletal muscle protein synthesis, Curr. Opin. Pharmacol. source

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    • cites [4] Hardie, 2011, Sensing of energy and nutrients by AMP-activated protein kinase, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • Premisereasoning
    § Abstract

    Macronutrient and micronutrient availability regulates cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training.

    “emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training”
    • Also stated in: § 1. Introduction into the growing role of sport nutrition · boosted
      “accumulating data have now demonstrated a potent role of both macro-and micro-nutrient availability in regulating those exerciseinduced cell-signalling pathways that are thought to regulate skeletal muscle adaptations to exercise training”
    Quote in the paperSubstantial claim
  • Premisecitation
    § 2. Nutrition gene interactions

    Multiple molecular pathways activated by exercise contribute to the adaptive remodelling of skeletal muscle.

    “Multiple molecular pathways are activated by exercise and these pathways have been shown to contribute to the adaptive remodelling of skeletal muscle [1,2].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Baar, 2009, The signaling underlying FITness, Appl. Physiol. Nutr. Metab. source

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    • cites [2] Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab. source

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  • Interpretationreasoning
    § 2. Nutrition gene interactions

    Crosstalk between nutrient sensitive and exercise sensitive pathways opens the possibility that nutrient provision strategies could influence both acute exercise performance and the magnitude of the adaptive response following structured exercise training.

    “This crosstalk between nutrient sensitive and exercise sensitive pathways opens up the possibility that nutrient provision strategies could influence not only acute exercise performance through fuelling the activity, but also the magnitude of the adaptive response following a period of structured exercise training.”
    Quote in the paperSubstantial claim
  • Interpretationnone given
    § Abstract

    Strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations.

    “In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations”
    Quote in the paperNot a substantial claim
  • May combine two claims. 57
  • Classified as probably not a substantial claim. 26
  • The quote only partly states this claim. 2

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    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    Transcriptional changes accumulate over time such that the protein expression profile of muscle is changed, resulting in an altered phenotype.

    “The transcriptional changes accumulate over time such that the protein expression profile of muscle is changed resulting in an altered phenotype [2,8].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab. source

      Not checked in the free run.

    • cites [8] Perry, 2010, Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle, J. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given
    § Abstract

    In the context of exercise performance, carbohydrate (but not fat) remains the most important nutrient, and carefully chosen ergogenic aids (caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can promote performance in the correct exercise setting.

    “Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g.caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given
    § Abstract

    High carbohydrate availability and antioxidant supplementation may attenuate training adaptation.

    “whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    When the AMP:ATP ratio increases, the probability of AMPK being in the AMP-bound state increases; this allosterically activates AMPK and makes AMPK a more efficient substrate for LKB1, phosphorylation by which leads to full activation of the kinase.

    “When the AMP:ATP ratio increases the probability of AMPK being in the AMP bound state increases.This allosterically activates AMPK [13] and makes AMPK a more efficient substrate for its upstream kinase LKB1, phosphorylation by which leads to full activation of the kinase [14].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source

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    • cites [14] Sakamoto, 2004, Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR, Am. J. Physiol. Endocrinol. Metab. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisereasoning
    § 1. Introduction into the growing role of sport nutrition

    Increased dietary protein is a necessary nutrient to promote muscle growth by providing amino acids to both activate and promote muscle protein synthesis.

    “In the context of resistance exercise, it is also now well known that increased dietary protein is a necessary nutrient to promote muscle growth by providing those necessary amino acids to both activate and promote muscle protein synthesis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning
    § 1. Introduction into the growing role of sport nutrition

    Deliberate periods of reduced carbohydrate availability (and potentially high fat availability) can enhance adaptations fundamental to endurance performance, including mitochondrial biogenesis, increased lipid oxidation and increased fatigue resistance.

    “emerging data suggest that deliberate periods of reduced carbohydrate availability (and potentially, high fat availability) can enhance those adaptations fundamental to endurance performance including mitochondrial biogenesis, increased lipid oxidation and increased fatigue resistance”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § Abstract

    Vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise.

    “Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    The exercise-dependent increase in skeletal muscle AMP is thought to allosterically activate glycolysis and activate AMP-activated protein kinase (AMPK).

    “The exercise dependent increase in skeletal muscle AMP [10] is thought to not only allosterically activate glycolysis [11] but also activate the evolutionary conserved fuel gauge protein AMP-activated protein kinase (AMPK) [12].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Meyer, 1980, AMP deamination and IMP reamination in working skeletal muscle, Am. J. Physiol. source

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    • cites [11] Trigun, 1988, Changes in the modulations of kinetics and allosteric properties of muscle phosphofructokinase of young and old rats, Arch. Gerontol. Geriatr. source

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    • cites [12] Winder, 1996, Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise, Am. J. Physiol.

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisereasoning
    § 1. Introduction into the growing role of sport nutrition

    Competition nutrition strategies that focus on sufficient macronutrient intake and ergogenic aids to promote energy availability and delay the biochemical determinants of fatigue are now largely based on sound scientific evidence.

    “When taken together, it is clear that those competition nutrition strategies that focus on sufficient macronutrient intake and ergogenic aids to promote energy availability and delay the biochemical determinants of fatigue are now largely based on sound scientific evidence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    A period of endurance training leads to improvements in blood flow, mitochondrial content and an improved ability to extract and utilise oxygen during exercise.

    “At the level of the muscle a period of endurance training leads to improvements in blood flow, mitochondrial content and an improved ability to extract and utilise oxygen during exercise [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Rivera-Brown, 2012, Principles of exercise physiology: responses to acute exercise and long-term adaptations to training, PM&R source

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    Premisecitation
    § 2.2. Is carbohydrate still king?

    Reducing endogenous and/or exogenous carbohydrate availability during short-term (e.g. 3-10 week) endurance training increases mitochondrial enzyme activity and protein content, increases whole body and intramuscular lipid oxidation, and in some instances improves exercise capacity.

    “we and others have collectively observed that reducing endogenous and/or exogenous CHO availability during short-term (e.g.3-10 week) endurance training increases mitochondrial enzyme activity and protein content [55,59,60] increases both whole body [55] and intramuscular lipid oxidation [61] and in some instances, improves exercise capacity [62,63]”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [55] Yeo, 2008, Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens, J. Appl. Physiol. source

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    • cites [59] Morton, 2009, Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle, J. Appl. Physiol. source

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    • cites [60] Van Proeyen, 2011, Beneficial metabolic adaptations due to endurance exercise training in the fasted state, J. Appl. Physiol. (1985) source

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    • cites [61] Hulston, 2010, Training with low muscle glycogen enhances fat metabolism in well-trained cyclists, Med. Sci. Sports Exerc. source

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    • cites [62] Hansen, 2005, Skeletal muscle adaptation: training twice every second day vs. training once daily, J. Appl. Physiol. (1985) source

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    • cites [63] Cochran, 2015, Manipulating carbohydrate availability between twice-daily sessions of high-intensity interval training over 2 weeks improves time-trial performance, Int. J. Sport Nutr. Exerc. Metab. source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § 2.2. Is carbohydrate still king?

    The "train-low (or smart), compete-high" model surmises that athletes deliberately complete a portion of their training programme with reduced carbohydrate availability so as to augment training adaptation but always ensure high carbohydrate availability prior to and during competition to promote maximal performance.

    “These data have therefore led to the innovative “train-low (or smart), compete-high” model surmising that athletes deliberately complete a portion of their training programme with reduced CHO availability so as to augment training adaptation but yet always ensure high CHO availability prior to and during competition in an attempt to promote maximal performance [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Burke, 2010, Fueling strategies to optimize performance: training high or training low?, Scand. J. Med. Sci. Sports source

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  • May combine two claims.

    Premisecitation
    § 2.2. Is carbohydrate still king?

    Exogenous carbohydrate feeding during exercise improves performance when exercise duration is <60 minutes, an effect that is not apparent when glucose is directly infused to the bloodstream during exercise.

    “It is noteworthy, however, that exogenous CHO feeding during exercise also improves performance when exercise duration is <60 minutes [42], an effect that is not apparent when glucose is directly infused to the bloodstream during exercise [43].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [42] Jeukendrup, 1997, Carbohydrate–electrolyte feedings improve 1h time trial cycling performance, Int. J. Sports Med. source

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    • cites [43] Carter, 2004, The effect of glucose infusion on glucose kinetics during a 1-h time trial, Med. Sci. Sports Exerc. source

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  • May combine two claims.

    Interpretationreasoning
    § 2.1 The molecular regulation of endurance training adaptation.

    Exercise-dependent increases in the AMP:ATP ratio and depletion of glycogen lead to a co-ordinated metabolic response, partly through AMPK activation, which increases substrate uptake and oxidation to fuel the activity.

    “Partly through these mechanisms the exercise dependent increases in AMP:ATP ratio and depletion of glycogen lead to a co-ordinated metabolic response, partly through AMPK activation, which increases substrate uptake and oxidation to fuel the activity (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    Nuclear export of HDAC5 leads to a relaxation of the chromatin and, in an unknown manner, leads to increases in transcription of GLUT4.

    “The nuclear export of HDAC5 therefore leads to a relaxation of the chromatin and in an unknown manner leads to increases in transcription of GLUT4 [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] McGee, 2008, AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5, Diabetes source

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    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    PGC-1α acts as a transcriptional co-activator where it moderates the activity of multiple transcription factors including the PPARs, TFAM, NRF1/2 and ERR-α.

    “As we mentioned PGC-1α acts as a transcriptional co-activator where it moderates the activity of multiple transcription factors including the PPAR's (PPAR-γ, PPAR-α and PPAR-δ), mitochondrial transcription factor A (TFAM), nuclear respiratory factors 1/2 (NRF1/2) and estrogen related receptor-α (ERR-α) (Figure 1) [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Gilde, 2003, Peroxisome proliferator-activated receptors (PPARS): regulators of gene expression in heart and skeletal muscle, Acta Physiol. Scand. source

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    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    Inhibition of ACC by AMPK leads to a reduction in malonyl CoA, which allows activation of the mitochondrial fatty acid transporter CPT1 and greater flux of fatty acids into mitochondria for oxidation.

    “The inhibition of ACC by AMPK leads to a reduction in the levels of manonyl CoA, which allows for the activation of the mitochondrial fatty acid transporter Carnitine palmitoyltransferase I (CPT1) allowing for a greater flux of fatty acids into the mitochondria for oxidation [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Alam, 1998, Malonyl-CoA and the regulation of fatty acid oxidation in soleus muscle, Biochem. J. source

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    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    Reduced activity of these Rab-GAPs allows more of the Rabs that control GLUT4 translocation to be in the GTP-bound state, which increases GLUT4 translocation to the plasma membrane and increases glucose uptake and oxidation.

    “The reduced activity of these Rab-GAPs allows for more of the Rabs that control glucose transporter 4 (GLUT4) translocation to be in the GTP bound state which increases the translocation of GLUT4 to the plasma membrane increasing glucose uptake and oxidation [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Sakamoto, 2008, Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic, Am. J. Physiol. Endocrinol. Metab. source

      Not checked in the free run.

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    Premisecitation
    § 2.2. Is carbohydrate still king?

    Potential pitfalls to long-term training with low carbohydrate availability include perturbations to immune function, impaired training intensity, reduced ability to oxidise exogenous carbohydrate during competition and increased muscle protein oxidation.

    “Despite the theoretical rationale for the training-low paradigm, potential pitfalls to longterm training with low CHO availability include perturbations to immune function [67] impaired training intensity [55], reduced ability to oxidise exogenous CHO during competition [68] and increased muscle protein oxidation [69].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [67] Nieman, 2007, Marathon training and immune function, Sports Med. source

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    • cites [55] Yeo, 2008, Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens, J. Appl. Physiol. source

      Not checked in the free run.

    • cites [68] Cox, 2010, Daily training with high carbohydrate availability increases exogenous carbohydrate oxidation during endurance cycling, J. Appl. Physiol. (1985) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 2.2. Is carbohydrate still king?

    Exogenous carbohydrate oxidation rates can increase to 1.8 g/min with the addition of sucrose or fructose to the carbohydrate blend, whereas they were previously thought to be limited at approximately 1 g/min due to saturation of intestinal glucose transporters.

    “Whereas it was generally accepted that exogenous CHO oxidation rates were thought to be limited at approximately 1 g/min due to saturation of intestinal glucose transporters, it is now known that exogenous CHO oxidation rates can increase to 1.8 g/min with the addition of sucrose or fructose to the CHO blend [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Jeukendrup, 2014, A step towards personalized sports nutrition: carbohydrate intake during exercise, Sports Med. source

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  • May combine two claims.

    Premisecitation
    § 2.1 The molecular regulation of endurance training adaptation.

    AMPK has the capacity to be modulated by the glycogen storage status of a cell; the β-subunit of AMPK binds to specific branch points on glycogen, inhibiting the enzyme and preventing it from being phosphorylated by upstream kinases.

    “In addition to being a direct AMP:ATP ratio sensor, AMPK also has the capacity to be modulated by the glycogen storage status of a cell [20].The β-subunit of AMPK binds to specific branch points on glycogen inhibiting the enzyme and preventing it from being phosphorylated by upstream kinases [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] McBride, 2009, The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor, Cell Metab. source

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    Premisecitation
    § 2.3 Adaptation to high fat diets and exercise performance.

    Investigations failed to find evidence of universal performance benefits from LCHF, but uncovered mechanisms to explain metabolic changes in the muscle as well as information on scenarios in which fat adaptation might be useful/benign and those in which it would impair sports performance.

    “However, again, these investigations failed to find evidence of universal performance benefits, but uncovered mechanisms to explain metabolic changes in the muscle as well as information on scenarios in which fat adaptation might be useful/benign and those in which it would, in fact, impair sports performance [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] L. Burke, Re-Examining High-Fat Diets for Sports Performance: Did We Call the ‘Nail in the Coffin’ Too Soon? Sports Med., 2015 (November 9:epub ahead of print). source

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    Premisecitation
    § 2.3 Adaptation to high fat diets and exercise performance.

    In the 1983 study, results were skewed by a large increase in endurance in one subject, and the authors noted that enhanced utilisation of fat and sparing of carbohydrate at moderate intensity was a limitation of the intensity of exercise that can be performed and a throttling of function near VO2max.

    “Moreover, the results were skewed by a large increase in endurance in one subject, and the authors also noted that the enhanced utilisation of fat and sparing of carbohydrate at moderate intensity was “a limitation of the intensity of exercise that can be performed” and a “throttling of function near VO2max” [75].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Phinney, 1983, The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation, Metabolism source

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    Premisenone given
    § 2.2. Is carbohydrate still king?

    The small compounds epicatechins, nicotinamide riboside and resveratrol have all been suggested to enhance endurance-training responses in skeletal muscle through a number of signalling pathways.

    “In addition, the small compounds epicatechins, nicotinamide riboside (NR) and resveratrol have all been suggested to enhance endurance-training responses in skeletal muscle through a number of signalling pathways (blue).”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § 2.4 The molecular regulation of resistance training adaptation.

    Mechanical activation of mTORC1 is thought to be dependent upon phosphatidic acid derived from diacylglycerol kinase.

    “As we mentioned the amino acid induced activation of mTORC1 is distinct from the mechanical activation of mTORC1, which again is not yet fully defined, but is thought to be dependent upon the secondary messenger phosphatidic acid (PA) derived from diacylglycerol kinase (DGK) [102].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] You, 2014, The role of diacylglycerol kinase zeta and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy, J. Biol. Chem. source

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    Premisenone given
    § 2.3 Adaptation to high fat diets and exercise performance.

    Endurance athletes develop a high capacity to fuel exercise via fat oxidation as an adaptation to their training.

    “Endurance athletes develop a high capacity to fuel exercise via fat oxidation as an adaptation to their training.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 2.3 Adaptation to high fat diets and exercise performance.

    LCHF diet models include moderate (<20% of energy) to extreme (<50 g/d) carbohydrate restriction, with fat increasing to ~65% or ~80% of energy respectively.

    “Models have included moderate (<20% of energy) to extreme (< 50 g/d) carbohydrate restriction, with fat increasing to ~65% or ~80% of energy respectively [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] L. Burke, Re-Examining High-Fat Diets for Sports Performance: Did We Call the ‘Nail in the Coffin’ Too Soon? Sports Med., 2015 (November 9:epub ahead of print). source

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  • May combine two claims.

    Premisecitation
    § 2.4 The molecular regulation of resistance training adaptation.

    mTORC1 is essential to loading-induced muscle growth in rodents and stimulus-induced increases in MPS in humans.

    “mTORC1 is well defined as essential to loading induced muscle growth in rodents [89] and stimulus induced increases in MPS in humans [90,91].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [89] Bodine, 2001, Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo, Nat. Cell Biol. source

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    • cites [90] Dickinson, 2011, Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids, J. Nutr. source

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    • cites [91] Drummond, 2009, Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis, J. Physiol. source

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    Interpretationreasoning
    § 2.4 The molecular regulation of resistance training adaptation.

    mTORC1 activation can be achieved nutritionally with high quality protein or essential amino acids and with carbohydrate-driven increases in insulin.

    “This can be achieved nutritionally in several ways, 1) with high quality protein or essential amino acids and 2) with carbohydrate driven increases in insulin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § 2.3 Adaptation to high fat diets and exercise performance.

    Current sports nutrition guidelines and practices promote an individualized and periodized approach to avoid unnecessary and excessive intake of carbohydrate, to optimise training outcomes via modification of the timing, amount and type of carbohydrate-rich foods and drinks to balance periods of low and high carbohydrate availability, and to adopt well-practiced competition strategies that provide

    “Instead they promote an individualized and periodized approach to avoid unnecessary and excessive intake of carbohydrate per se, to optimise training outcomes via modification of the timing, amount and type of carbohydrate-rich foods and drinks to balance periods of low and high carbohydrate availability and to adopt wellpracticed competition strategies that provide appropriate carbohydrate”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] L. Burke, Re-Examining High-Fat Diets for Sports Performance: Did We Call the ‘Nail in the Coffin’ Too Soon? Sports Med., 2015 (November 9:epub ahead of print). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given
    § 2.3 Adaptation to high fat diets and exercise performance.

    Chronic consumption of a low-carbohydrate, high-fat (LCHF) diet can further up-regulate the contribution of fat as a substrate for exercise.

    “However, there have been cycles of interest in strategies that can further up-regulate the contribution of fat as a substrate for exercise; specifically, the chronic consumption of a low-carbohydrate, high-fat (LCHF) diet.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2.4 The molecular regulation of resistance training adaptation.

    Endurance exercise adaptations are believed to be driven primarily by transcriptional responses, whereas the muscle growth adaptation to resistance exercise is driven primarily by changes in translation, in particular by increases in mRNA activity.

    “Whilst endurance exercise adaptations are believed to be driven primarily by transcriptional responses [2,8], the muscle growth adaptation to resistance exercise is driven primarily by changes in translation, in particular by increases in mRNA activity (protein produced per unit of mRNA) [85][86][87].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [2] Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab. source

      Not checked in the free run.

    • cites [8] Perry, 2010, Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle, J. Physiol. source

      Not checked in the free run.

    • cites [85] Baar, 1999, Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise, Am. J. Physiol. source

      Not checked in the free run.

    • cites [86] Chen, 2002, Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling, J. Physiol. source

      Not checked in the free run.

    • cites [87] Chesley, 1992, Changes in human muscle protein synthesis after resistance exercise, J. Appl. Physiol. (1985) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 2.4 The molecular regulation of resistance training adaptation.

    Both leucine and HMB activate mTORC1 in human skeletal muscle when consumed.

    “Both of which activate mTORC1 in human skeletal muscle when consumed [108].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Wilkinson, 2013, Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism, J. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 2.4 The molecular regulation of resistance training adaptation.

    Resistance exercise builds muscle mass by increasing the remodelling of muscle proteins and by sensitising the skeletal muscle protein synthesis machinery to subsequent meals.

    “Resistance exercise builds muscle mass by increasing the remodelling of muscle proteins and by sensitising the skeletal muscle protein synthesis machinery to subsequent meals [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Churchward-Venne, 2012, Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism, Nutr. Metab. (Lond.) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sodium bicarbonate.

    Gastrointestinal disturbances often occur with bicarbonate use, but can be managed by consuming the dose in a split protocol with intake of a small meal/snack.

    “Gastrointestinal disturbances often occur with bicarbonate use, but can be managed by consuming the dose in a split protocol with the intake of a small meal/snack [135].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Carr, 2011, Effect of sodium bicarbonate on [HCO3-], pH, and gastrointestinal symptoms, Int. J. Sport Nutr. Exerc. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    There is good evidence that nitrate/BJ supplementation can enhance sports performance in moderate caliber athletes and individuals among elite athlete populations, with emphasis on adequate protocols and sports/scenarios relying on less-oxidative type II muscle fibres and conditions of hypoxia or acidosis.

    “Nevertheless, there seems good evidence that nitrate/BJ supplementation can enhance sports performance in moderate caliber athletes and individuals among elite athlete populations [130], with emphasis on adequate supplementation protocols and sports or scenarios which rely on the recruitment of the lessoxidative type II muscle fibres, and local or environmental conditions of hypoxia or acidosis (e”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [130] Jones, 2014, Dietary nitrate supplementation and exercise performance, Sports Med. source

      Not checked in the free run.

    • cites [131] Jonvik, 2015, Can elite athletes benefit from dietary nitrate supplementation?, J. Appl. Physiol. (1985) source

      Not checked in the free run.

    • cites [132] Hultstrom, 2015, Commentaries on Viewpoint: can elite athletes benefit from dietary nitrate supplementation?, J. Appl. Physiol. (1985) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Beta-alanine.

    A daily intake of approximately 1.2 g appears to maintain muscle carnosine elevations and a return to baseline may require 6-20 weeks of supplement withdrawal.

    “To date, no threshold for carnosine concentrations has been found, but a daily intake of ~ 1.2 g appears to maintain muscle carnosine elevations and a return to baseline may require 6-20 weeks of supplement withdrawal [137].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [137] Stegen, 2014, Beta-alanine dose for maintaining moderately elevated muscle carnosine levels, Med. Sci. Sports Exerc. source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning
    § Vitamin D.

    Both innate and acquired immune function, cardiovascular health and even muscle growth and repair may be regulated by vitamin D.

    “It is now clear that both innate and acquired immune function, cardiovascular health and even muscle growth and repair may be regulated by vitamin D.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 2.5. New/Underexplored areas in protein nutrition?

    Foods rich in high quality protein also tend to be rich in other nutrients.

    “In addition to the benefits of consuming high quality proteins on muscle mass and exercise recovery, foods rich in high quality protein also tend to be rich in other nutrients [110].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Phillips, 2015, Commonly consumed protein foods contribute to nutrient intake, diet quality, and nutrient adequacy, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    Caffeine can be considered safe, effective and legal when used according to established and practiced protocols.

    “Following its 2004 removal from the WADA Prohibited List, caffeine can be considered safe, effective and legal when used according to established and practiced protocols.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Vitamin D.

    Many athletes are vitamin D deficient, largely due to a sun-shy lifestyle and poor dietary sources, even those living in sunny climates.

    “This emerging knowledge, combined with a plethora of research suggesting that many athletes are vitamin D deficient [140], largely due to a sun-shy lifestyle and poor dietary sources of vitamin D, even those living in sunny climates [141] has resulted in vitamin D being one of the most widely supplemented vitamins in sports nutrition.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [140] Close, 2013, Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function, J. Sports Sci. source

      Not checked in the free run.

    • cites [141] Hamilton, 2010, Profound vitamin D deficiency in a diverse group of women during pregnancy living in a sun-rich environment at latitude 32°N, Int. J. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given
    § Beta-alanine.

    Review of accumulating literature shows some support for benefits of beta-alanine supplementation on high-intensity exercise and a potential additive effect when combined with bicarbonate supplementation.

    “Indeed, review of the accumulating literature shows some support for the benefits of beta-alanine supplementation on high-intensity exercise and a potential additive effect when combined with bicarbonate supplementation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Vitamin D.

    While some studies have shown improved markers of muscle function, the majority have failed to show any meaningful effects of vitamin D on performance.

    “Whilst some studies have shown improved markers of muscle function the majority have failed to show any meaningful effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Vitamin D.

    EFSA has stated that 4000 iU is the maximum dose of vitamin D that should be used, and this dose has been shown to be effective in correcting deficiencies.

    “In terms of a supplemental dose, the EFSA have recently stated that 4000iU is the maximum dose that should be used which we have also shown to be an effective dose in correcting deficiencies [146].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Agostoni, 2012, Scientific opinion on the tolerable upper intake level of vitamin D, Eur. Food Saf. Auth. J.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Vitamin D.

    Many tissues in the human body express the vitamin D receptor, suggesting vitamin D plays a fundamental physiological role.

    “It is now known that many tissues in the human body express the vitamin D receptor suggesting that Vitamin D (or more specifically active vitamin D metabolites) play a fundamental physiological role that have previously been somewhat ignored [reviewed by 139].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [reviewed by 139]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning
    § 2.5. New/Underexplored areas in protein nutrition?

    The higher leucine content of whey is thought to explain its greater benefit over plant-based proteins for stimulating MPS.

    “This finding is thought to be due to the higher leucine content of whey.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Beta-alanine.

    Supplementation with doses >800 mg of purified β-alanine is associated with symptoms of paresthesia, but this can be managed with slow-release tablets or spreading doses over the day.

    “Supplementation with doses > 800 mg of purified b-alanine is associated with symptoms of paresthesia (skin tingling), but this sometimes unpleasant side-effect can be managed with slow-release tablets or spreading doses over the day [136].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] Stellingwerff, 2012, Optimizing human in vivo dosing and delivery of beta-alanine supplements for muscle carnosine synthesis, Amino Acids source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data
    § Vitamin D.

    Vitamin D deficiencies may impair muscle regeneration, and this effect may occur even when vitamin D concentrations are around 50 nmol/L.

    “Recent work from our group [147] has also demonstrated that vitamin D deficiencies may impair muscle regeneration and perhaps more importantly this effect may occur even when vitamin D concentrations are around 50nmol/L.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [147] Owens, 2015, A systems based investigation into vitamin D and skeletal muscle repair, regeneration and hypertrophy, Am. J. Physiol. Endocrinol. Metab.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    Careful studies of established creatine supplementation protocols have not found evidence of increased health risks and have reported reduced rather than increased prevalence of muscle damage or impaired thermoregulation associated with exercise.

    “Despite publicity around safety aspects, careful studies of established creatine supplementation protocols have not found evidence of increased health risks4 and have reported reduced rather than increased prevalence of muscle damage or impaired thermoregulation associated with exercise [128].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] Dalbo, 2008, Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration, Br. J. Sports Med.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 2.5. New/Underexplored areas in protein nutrition?

    Milk-based proteins can be digested via gastrointestinal peptidases to tryptophan-containing peptides, which in cell and biochemical assays can have biological activities that may positively impact human physiology from blood pressure control to satiation.

    “Milk based proteins in particular can be digested via gastrointestinal peptidases to tryptophan containing peptides, which in cell and biochemical based assays can have biological activities which may positively impact human physiology from blood pressure control to satiation [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Nongonierma, 2015, Milk proteins as a source of tryptophan-containing bioactive peptides, Food Funct. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Sodium bicarbonate.

    The enhancement increases by approximately 0.5% (±0.5%) with a larger (+0.1 mg/kg) dose or five extra sprint bouts, and reduces by a similar magnitude with each 10-fold increase in test duration (e.g. 1-10 minutes) or females.

    “This increases by ~0.5% (±0.5%) with a larger (+0.1 mg/kg) dose or five extra sprint bouts, and reduces by a similar magnitude with each 10-fold increase in test duration (e.g.1-10 minutes) or females.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [134] Carr, 2011, Effects of acute alkalosis and acidosis on performance: a meta-analysis, Sports Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    Creatine monohydrate remains an effective form of supplemental creatine, with muscle uptake optimized by co-ingestion with carbohydrate.

    “Despite the marketing of exotic creatine compounds, creatine monohydrate remains an effective form of supplemental creatine, with muscle uptake being optimized by its co-ingestion with carbohydrate [125].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Buford, 2007, International Society of Sports Nutrition position stand: creatine supplementation and exercise, J. Int. Soc. Sports Nutr. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 2.5. New/Underexplored areas in protein nutrition?

    Dairy protein sources, due to high calcium content, have been lauded for benefits beyond protein.

    “In particular dairy protein sources, due to the high calcium content has been lauded for this reason [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] S.M. Phillips, M.B. Zemel, Effect of protein, dairy components and energy balance in optimizing body composition, Nestle Nutrition Institute Workshop Series, 69, 2011, pp. 97–108 (discussion 108–113) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Vitamin D.

    In our laboratory, detrimental effects on muscle function have been reported when vitamin D concentrations are below 30 nmol/L, with no performance-enhancing effects of vitamin D supplements if the starting concentration is around 50 nmol/L.

    “In our laboratory, we have reported detrimental effects on muscle function when concentrations are below 30nmol/L [140] with no performance enhancing effects of vitamin D supplements if the starting concentration is around 50nmol/L [145].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [140] Close, 2013, Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function, J. Sports Sci. source

      Not checked in the free run.

    • cites [145] Owens, 2014, Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males, Eur. J. Appl. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    Creatine supplementation can acutely benefit performance of sports involving brief high-intensity repeated bouts and chronically enhance capacity to undertake training sessions of this nature.

    “This can acutely benefit the performance of sports involving such work patterns (e.g.team sports), as well as chronically enhance the athlete' capacity to undertake training sessions of this nature (e.g.resistance or interval training) [125].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Buford, 2007, International Society of Sports Nutrition position stand: creatine supplementation and exercise, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 3. Traditional Sports Supplements -the ones that still work in 2015

    Reasons for elite athletes' lower responsiveness include greater dietary nitrate intake and/or greater capacity for arginine-derived NO production, as well as better genetic and training-supported muscle characteristics.

    “Reasons for this observation include a greater dietary nitrate intake and/or greater capacity for arginine-derived production of NO in highly trained individuals, as well as better genetic and training-supported characteristics in the muscle, which enhance oxygen delivery and buffer metabolic acidosis, thus reducing the conditions under which the nitrate-nitrite-NO pathway may be important [130].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Jones, 2014, Dietary nitrate supplementation and exercise performance, Sports Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 2.5. New/Underexplored areas in protein nutrition?

    The optimal dose of protein post exercise in healthy young men may be best quantified in a g/kg basis or g/kg lean mass basis, with approximately 0.25 g/kg body mass and 0.25 g/kg lean mass appearing to elicit maximum rates of MPS.

    “This retrospective analysis has suggested that the optimal dose of protein post exercise in healthy young men may be best quantified in a g/kg basis or even a g/kg lean mass basis with ~0.25 g/kg body mass and 0.25 g/kg lean mass appearing to elicit the maximum rates of MPS [109].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Moore, 2015, Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men, J. Gerontol. A: Biol. Sci. Med. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 4. Novel compounds 4.1 Supporting endurance training adaptation (-)-Epicatechins.

    Following supplementation of (-)-epicatechin (1 mg/kg), participants displayed a lower RER, indicative of increased lipid oxidation.

    “Following supplementation of (-)-epicatechin (1 mg/kg), participants displayed a lower RER, indicative of increased lipid oxidation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Gutierrez-Salmean, 2014, Acute effects of an oral supplement of (–)-epicatechin on postprandial fat and carbohydrate metabolism in normal and overweight subjects, Food Funct. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Antioxidants

    Antioxidants are heterogeneous, work in distinct ways, and do not solely regulate ROS.

    “Antioxidants are heterogeneous [159] they work in distinct ways and importantly they do not solely regulate ROS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Murphy, 2011, Unraveling the biological roles of reactive oxygen species, Cell Metab. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Antioxidants

    Short-term NAC supplementation may be beneficial when adaptation is inconsequential (e.g., competitive events), although effective doses may result in gastro-intestinal discomfort.

    “Thus when adaptation is inconsequential (e.g., competitive events) short-term NAC supplementation may be beneficial although it should be stressed that effective doses may result in gastro-intestinal discomfort [161].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Cobley, 2011, N-acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations, Int. J. Sport Nutr. Exerc. Metab. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given
    § Nicotinamide riboside (NR).

    To date, no studies have examined the effect of NR supplementation on mitochondrial adaptation in human skeletal muscle.

    “To date, no studies have examined the effect of NR supplementation on mitochondrial adaptation in human skeletal muscle.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premiseown data
    § Vitamin D.

    High-dose vitamin D supplementation in non-deficient individuals could have negative consequences related to the function of the vitamin D endocrine system.

    “emerging work form our group is beginning to suggest that high dose supplementation, in non-deficient individuals, could have negative consequences related to the function of the vitamin D endocrine system.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation
    § Nicotinamide riboside (NR).

    NR supplementation appears capable of altering skeletal muscle NAD+ content which in turn increases skeletal muscle mitochondrial biogenesis through a SIRT1-dependent process.

    “Thus NR supplementation appears capable of altering skeletal muscle NAD + content which in turn increases skeletal muscle mitochondrial biogenesis through a SIRT1-dependent process [171] (Figure 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Antioxidants

    NAC blunts training adaptations but enhances acute performance.

    “For example, NAC blunts training adaptations [160] but enhances acute performance [161,162].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [160] Petersen, 2012, Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle, Acta Physiol. (Oxf.) source

      Not checked in the free run.

    • cites [161] Cobley, 2011, N-acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations, Int. J. Sport Nutr. Exerc. Metab. source

      Not checked in the free run.

    • cites [162] Reid, 2008, Free radicals and muscle fatigue: of ROS, canaries, and the IOC, Free Radic. Biol. Med. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation
    § Antioxidants

    There could be a case for some polyphenolic compounds, such as tart cherry juice, to be supplemented post-exercise to attenuate muscle soreness, although whether this is through a direct scavenging effect remains unclear.

    “There could also be a case for some polyphenolic compounds to be supplemented post-exercise, such as tart cherry juice [163] to attenuate muscle soreness although if this is through a direct scavenging effect remains unclear (see point 2 above and reference [148] for criteria that need to fulfilled to satisfy a scavenging affect).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [163] Howatson, 2010, Influence of tart cherry juice on indices of recovery following marathon running, Scand. J. Med. Sci. Sports source

      Not checked in the free run.

    • cites [148] Cobley, 2015, Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations, Free Radic. Biol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Antioxidants

    Decreasing reactive oxygen species (ROS) generation with nutritional antioxidants attenuates exercise-induced redox signalling and thereby blunts exercise adaptation.

    “This is best exemplified by the notion that decreasing reactive oxygen species (ROS) generation with nutritional antioxidants, attenuates exercise-induced redox signalling, and thereby blunts exercise adaptation [150,151].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [150] Paulsen, 2014, Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training, J. Physiol. source

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    • cites [151] Morrison, 2015, Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans, Free Radic. Biol. Med. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § Resveratrol.

    It is currently unclear why resveratrol supplementation may display a negative effect on whole body/skeletal muscle adaptation when combined with endurance-exercise training in healthy individuals.

    “it is currently unclear as to why resveratrol supplementation may display a negative effect on whole body/skeletal muscle adaptation when combined with endurance-exercise training in healthy individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Nicotinamide riboside (NR).

    The protection from high fat feeding by NR supplementation was principally through an increase in energy expenditure and a reduction in cholesterol levels.

    “principally through an increase in energy expenditure and a reduction in cholesterol levels [171].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 4. Novel compounds 4.1 Supporting endurance training adaptation (-)-Epicatechins.

    (-)-Epicatechin supplementation was not as potent as endurance exercise in remodeling skeletal muscle, but in combination with exercise training had a synergistic effect.

    “Importantly, (-)-epicatechin supplementation was not as potent as endurance exercise in remodeling skeletal muscle, however (-)-epicatechin supplementation in combination with exercise training had a synergistic effect.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [166] Nogueira, 2011, (–)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle, J. Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Phosphatidic acid (PA).

    PA plays a fundamental role in the regulation of cellular metabolism.

    “As such, PA plays a fundamental role in the regulation of cellular metabolism [181].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [181] Athenstaedt, 1999, Phosphatidic acid, a key intermediate in lipid metabolism, Eur. J. Biochem. source

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given
    § 5. Summary and future directions

    Carbohydrate restriction may enhance mitochondrial biogenesis and potentially long term adaption although it may also impair performance in a given training session.

    “carbohydrate restriction may enhance mitochondrial biogenesis and potentially long term adaption although it may also impair performance in a given training session.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Phosphatidic acid (PA).

    PA has been reported to have no effect on resistance training.

    “the fact that PA has also been reported to have no effect on resistance training [183]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Hoffman, 2012, Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § 4.2 Novel compounds supporting resistance training adaptations β-hydroxy β-methylbutyrate (HMB).

    HMB is a derivative of leucine that appears to have potent anabolic properties in skeletal muscle.

    “One of the key leucine intermediates appears to be the derivative β-hydroxy β-methylbutyrate (HMB), which like leucine appears to have potent anabolic properties in skeletal muscle [179]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [179] Atherton, 2012, Muscle protein synthesis in response to nutrition and exercise, J. Physiol. source

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  • The quote only partly states this claim.

    Premisecitation
    § Phosphatidic acid (PA).

    PA supplementation (750mg/day) during 8 weeks resistance training resulted in a 12.7% increase in squat strength.

    “the authors reported a 12.7% increase in squat strength”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] Hoffman, 2012, Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Phosphatidic acid (PA).

    PA has been reported to have a negative effect on WPC-stimulated protein synthesis.

    “or even have a negative effect on WPC-stimulated protein synthesis”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [185] Mobley, 2015, Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle, J. Int. Soc. Sports Nutr. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Phosphatidic acid (PA).

    PA is a precursor for the synthesis of numerous lipids.

    “Phosphatidic acid (PA) is a precursor for the synthesis of numerous lipids [181].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [181] Athenstaedt, 1999, Phosphatidic acid, a key intermediate in lipid metabolism, Eur. J. Biochem. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Phosphatidic acid (PA).

    Placebo during 8 weeks resistance training resulted in a 9.3% improvement in squat strength.

    “compared to a 9.3% improvement in squat strength”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Hoffman, 2012, Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation
    § Phosphatidic acid (PA).

    PA supplementation (750mg/day) during 8 weeks resistance training resulted in a 2.6% increase in LBM.

    “and a 2.6% increase in LBM in the PA group”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] Hoffman, 2012, Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Phosphatidic acid (PA).

    Placebo during 8 weeks resistance training resulted in a 0.1% change in LBM.

    “and a 0.1% change in LBM in the placebo group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Hoffman, 2012, Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § Ursolic acid (UA).

    Whether UA administration promotes skeletal muscle hypertrophy in human skeletal muscle is less clear.

    “Whether UA administration promotes skeletal muscle hypertrophy in human skeletal muscle is less clear.”
    Quote in the paperNot a substantial claim
80 of 80

  • The paper relies on this without support.

    Performance of sports requiring high rates of energy production from anaerobic glycolysis is often limited by excessive accumulation of hydrogen ions (H+) in the muscle.

    “Performance of sports requiring high rates of energy production from anaerobic glycolysis is often limited by excessive accumulation of hydrogen ions (H+) in the muscle.”

  • The paper relies on this without support.

    Acute ingestion of dietary bicarbonate, if it achieves a meaningful albeit temporary increase in blood bicarbonate concentrations and pH, can enhance extracellular disposal of the H+ efflux from the working muscle.

    “Acute ingestion of dietary bicarbonate, if it achieves a meaningful albeit temporary increase in blood bicarbonate concentrations and pH, can enhance extracellular disposal of the H+ efflux from the working muscle.”

  • The paper relies on this without support.

    To date, there have been no data to suggest that eating high quality fruit and vegetables attenuates adaptations to exercise.

    “A final note is that to date there have been no data to suggest that eating high quality fruit and vegetables attenuates adaptations to exercise so it may be best to advise athletes to consume a high quality diet and avoid mega dose micronutrient supplementation, it really could be that simple [164].”

  • The paper relies on this without support.

    It is currently unknown whether (-)-epicatechin supplementation can promote mitochondrial biogenesis and enhance endurance-training adaptation in human skeletal muscle.

    “However, it is currently unknown whether (-)-epicatechin supplementation can promote mitochondrial biogenesis and enhance endurance-training adaptation in human skeletal muscle.”

  • The paper relies on this without support.

    No study has assessed if increasing the amount of muscle mass worked, or if the size of the individual, plays any role in the protein requirements post exercise.

    “However, no study has assessed if increasing the amount of muscle mass worked, or if the size of the individual, plays any role in the protein requirements post exercise.”

  • The paper relies on this without support.

    The role that the fat fraction plays in regulating the feeding response to the protein is very underexplored.

    “Finally, protein-containing foods also contain fat and the role that the fat fraction plays in regulating the feeding response to the protein is very underexplored.”

  • The paper relies on this without support.

    The possibility of digested peptides from ingested proteins having beneficial biological activities is highly speculated but very underexplored.

    “However, an area that has been highly speculated about, but very underexplored is the possibility of digested peptides from ingested proteins having beneficial, biological activities [113].”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The evidence does not seem convincing enough to formulate practical guidelines for the use of any of these small nutritional bioactive compounds.

    “although there are some promising findings in some areas, the evidence does not seem convincing enough to formulate practical guidelines for the use of any of these compounds.”

    From Periodized Nutrition for Athletes (2017) · cites this paper as [10]

  • Training adaptations and recovery can be maximised by optimal nutrition practices or impaired by suboptimal nutrition practices.

    “Training adaptations and recovery can be maximised by optimal nutrition practices or impaired by suboptimal nutrition practices [36,37,38].”

    From Sleep and Nutrition Interactions: Implications for Athletes (2019) · cites this paper as [38]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • HDAC5 is described as both a deacetylase and an enzyme that acetylates histones

    Minor

    The paper identifies HDAC5 as a deacetylase, but then says it functions to acetylate histones. These descriptions assign it opposite actions.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Fentz, 2015, AMPKalpha is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 00157, 02015

Cited by

Sorted by citations

Related

Authors
Close, G. L., Hamilton, D. L., Philp, A., Burke, L. M., & Morton, J. P.
Affiliations
  • Liverpool John Moores University (GB)
  • University of Stirling (GB)
  • University of Birmingham (GB)
Corresponding author
Close, G.L.
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2016-09
Volume
98
Pages
144-158
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2016.01.016
OpenAlex
W2272552897
Semantic Scholar
1a423aabeb4d65d30db1bade29cd54bc06eb04a0
Cited by
221
References
189
Citations by year
2026: 9 · 2025: 14 · 2024: 30 · 2023: 27 · 2022: 23 · 2021: 22 · 2020: 24 · 2019: 20 · 2018: 27 · 2017: 20 · 2016: 4
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion, cc-by)
  • Research Bank (Australian Catholic University) (submittedVersion)
  • Stirling Online Research Repository (University of Stirling) (submittedVersion, public-domain)
  • Figshare (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
Funders
Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) (BB/L023547/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
Keywords
sports nutrition, exercise performance, carbohydrate intake, ergogenic aids, caffeine, creatine, sodium bicarbonate, beta-alanine, dietary nitrate, macronutrients, micronutrients, dietary protein, carbohydrate restriction, antioxidant supplementation, training effects, skeletal muscle hypertrophy, muscle regeneration, vitamin D, epicatechin, nicotinamide riboside, resveratrol, beta-hydroxy-beta-methylbutyrate, phosphatidic acid, ursolic acid, endurance training, resistance training
MeSH terms
Dietary Proteins, Humans, Exercise, Carbohydrate Metabolism, Diet, High-Fat, Sports Nutritional Sciences, Sports Nutritional Physiological Phenomena

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

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