New strategies in sport nutrition to increase exercise performance

In the paper

“The key trigger for the protein feeding induced increases in MPS seems to be the leucine content of the digested protein [107] and possibly the leucine metabolite HMB (β-Hydroxy β-methylbutyrate) [108].”

What the sources say

• Supported

  The Introduction raises the possibility that leucine metabolites mediate leucine’s anabolic effects. The Results report that oral HMB increased muscle protein synthesis by approximately 70%, supporting the citing sentence’s qualified suggestion that HMB may be a trigger. The study tested HMB alone, not HMB during protein feeding. (LLM, conf=0.88)

  cites [108] Wilkinson, 2013, Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism, J. Physiol. source

In the paper

“but also eradicated the effects of the exercise to reduce low-density lipoprotein, total cholesterol and triglyceride concentrations in the blood [177].”

What the sources say

• Partly supported

  The Results (page unavailable) show that exercise lowered LDL and triglycerides only in the placebo group, consistent with resveratrol abolishing those benefits. But total cholesterol concentration did not change with training in either group; the reported improvement was in the total-cholesterol/HDL ratio, not total cholesterol itself. (LLM, conf=0.94)

  cites [177] Gliemann, 2013, Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men, J. Physiol. sourceExperimental — accuracy not yet measured

In the paper

“similarly to 3.42 g Leucine (Leu), stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%).”

What the sources say

• Supported

  The Abstract states that oral consumption of 3.42 g free-acid HMB, providing 2.42 g pure HMB, stimulated MPS by about 70%, compared with about 110% after 3.42 g leucine. The Results section reports the corresponding increases in myofibrillar protein synthesis and notes that the responses were not statistically different (P = 0.12). (LLM, conf=0.95)

  cites [108] Wilkinson, 2013, Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism, J. Physiol. source

In the paper

“and IGF-1 activation following 8 weeks resistance training in healthy male participants [189].”

What the sources say

• Partly supported

  The Abstract reports increased IGF-1 after eight weeks of resistance training with UA in healthy men. However, the Methods (Ursolic acid supplementation; page unavailable) specify three 150 mg capsules daily, totaling 450 mg/day—not 1,350 mg/day. The study measured IGF-1 levels, rather than directly demonstrating activation of IGF-1 signaling. (LLM, conf=0.93)

  cites [189] Bang, 2014, Ursolic acid-induced elevation of serum irisin augments muscle strength during resistance training in men, Korean J. Physiol. Pharmacol. sourceExperimental — accuracy not yet measured

In the paper

“oral consumption of HMB (3.42 g free-acid (FA-HMB) providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle”

What the sources say

• Supported

  The Methods (Subject characteristics and study design) specify that participants drank 3.42 g of free-acid HMB solution providing 2.42 g of HMB. The Discussion reports that oral FA-HMB rapidly elevated plasma and intramuscular HMB, consistent with the concentrations reported in the Results. (LLM, conf=0.94)

  cites [108] Wilkinson, 2013, Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism, J. Physiol. source

In the paper

“These same pathways are shared with a number of the nutrient sensing mechanisms [3,4].”

What the sources say

• Not checked yetcites [3] Weigl, 2012, Lost in translation: regulation of skeletal muscle protein synthesis, Curr. Opin. Pharmacol. source
• Not checked yetcites [4] Hardie, 2011, Sensing of energy and nutrients by AMP-activated protein kinase, Am. J. Clin. Nutr. source

In the paper

“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”

In the paper

“Multiple molecular pathways are activated by exercise and these pathways have been shown to contribute to the adaptive remodelling of skeletal muscle [1,2].”

What the sources say

• Not checked yetcites [1] Baar, 2009, The signaling underlying FITness, Appl. Physiol. Nutr. Metab. source
• Not checked yetcites [2] Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab. source

In the paper

“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.”

In the paper

“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”

In the paper

“novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, βhydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training”

In the paper

“These adaptive processes are driven by transcriptional changes in response to each bout of exercise [2,8].”

What the sources say

• Not checked yetcites [2] Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab. source
• Not checked yetcites [8] Perry, 2010, Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle, J. Physiol. source

In the paper

“Structured endurance training leads to improvements in fatigue resistance partly by altering the phenotype of the skeletal muscle performing the work [7].”

What the sources say

• Not checked yetcites [7] Rivera-Brown, 2012, Principles of exercise physiology: responses to acute exercise and long-term adaptations to training, PM&R source

In the paper

“recent studies show that short duration high intensity interval training may in fact result in similar adaptations to typical endurance exercise [6]”

What the sources say

• Not checked yetcites [6] Gibala, 2006, Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance, J. Physiol. source

In the paper

“Activated AMPK phosphorylates and inhibits its downstream substrate Acetyl-CoA carboxylase (ACC) [12].”

What the sources say

• Not checked yetcites [12] Winder, 1996, Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise, Am. J. Physiol.

In the paper

“In this way, training with low CHO availability thereby leads to a co-ordinated up-regulation of both the nuclear and mitochondrial genomes.”

In the paper

“The AMPK dependent phosphorylation of PGC-1α additionally is associated with an increase in the expression of mitochondrial genes [28].”

What the sources say

• Not checked yetcites [28] Jager, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA source

In the paper

“Such data suggest that CHO feeding may also improve exercise performance via non-metabolic effects but through direct effects on the central nervous system [44].”

What the sources say

• Not checked yetcites [44] Carter, 2004, The effect of carbohydrate mouth rinse on 1-h cycle time trial performance, Med. Sci. Sports Exerc. source

In the paper

“When taken together, it is currently thought that CHO feeding during exercise may therefore augment exercise performance via multiple mechanisms consisting of muscle glycogen sparing [39], liver glycogen sparing [40] and maintenance of plasma glucose and CHO oxidation rates [41].”

What the sources say

• Not checked yetcites [39] Stellingwerff, 2007, Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use, Pflugers Arch. source
• Not checked yetcites [40] Gonzalez, 2015, Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists, Am. J. Physiol. Endocrinol. Metab.
• Not checked yetcites [41] Coyle, 1986, Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate, J. Appl. Physiol. source

In the paper

“In a feed forward fashion AMPK can translocate to the nucleus [24,27] where it regulates Histone de-aceytlases, transcription factors and transcriptional co-activators such as histone deacetylase 5 (HDAC5), myocyte enhancing factor 2 (MEF2) and peroxisome proliferator activated receptor-γ co-activator-1α (PGC-1α) respectively (Figure 1) [28][29][30].”

What the sources say

• Not checked yetcites [24] Philp, 2013, Glycogen content regulates peroxisome proliferator activated receptor- partial differential (PPAR-partial differential) activity in rat skeletal muscle, PLoS One source
• Not checked yetcites [27] McGee, 2003, Exercise increases nuclear AMPK alpha2 in human skeletal muscle, Diabetes source
• Not checked yetcites [28] Jager, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA source
• Not checked yetcites [29] McGee, 2006, Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle, FASEB J. source
• Not checked yetcites [30] McGee, 2008, AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5, Diabetes source

In the paper

“These data suggest that when glycogen is depleted AMPK is more active.”

What the sources say

• Not checked yetcites [20] McBride, 2009, The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor, Cell Metab. source

In the paper

“Interestingly, in rodent studies when exercise occurs in the low glycogen state AMPK nuclear content is increased [24].”

What the sources say

• Not checked yetcites [24] Philp, 2013, Glycogen content regulates peroxisome proliferator activated receptor- partial differential (PPAR-partial differential) activity in rat skeletal muscle, PLoS One source

In the paper

“Carbohydrate restriction and/or glycogen depletion during exercise leads to further enhances in mitochondrial biogenesis through increased activity of AMPK, p38 and SIRT1.”

In the paper

“AMPK also plays a key role in controlling running capacity and certain adaptive processes in response to endurance exercise training [25,26].”

What the sources say

• Not checked yetcites [25] Tanner, 2013, Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1, Am. J. Physiol. Endocrinol. Metab. source
• Not checked yetcites [26] 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.

In the paper

“Indeed, whilst both low endogenous [55] and exogenous [56] CHO availability can undoubtedly impair training intensity”

What the sources say

• Not checked yetcites [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 yetcites [56] Widrick, 1993, Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration, J. Appl. Physiol. (1985) source

In the paper

“In addition to high endogenous pre-exercise muscle glycogen stores, it is widely accepted that exogenous CHO feeding during exercise also improves physical, cognitive and technical elements of performance [37].”

What the sources say

• Not checked yetcites [37] Stellingwerff, 2014, Systematic review: carbohydrate supplementation on exercise performance or capacity of varying durations, Appl. Physiol. Nutr. Metab. source

In the paper

“HDAC5 functions to acetylate histones, causing the chromatin to be wound tighter restricting the access of transcription factors to promoter regions [31].”

What the sources say

• Not checked yetcites [31] McGee, 2011, Histone modifications and exercise adaptations, J. Appl. Physiol. (1985) source

In the paper

“accumulating data have now demonstrated a potent effect of reduced carbohydrate availability in modulating those acute exercise-induced increase in cell signalling and gene expression responses that regulate endurance training adaptations [57,58]”

What the sources say

• Not checked yetcites [57] Hawley, 2014, Ramping up the signal: promoting endurance training adaptation in skeletal muscle by nutritional manipulation, Clin. Exp. Pharmacol. Physiol. source
• Not checked yetcites [58] Bartlett, 2015, Carbohydrate availability and exercise training adaptation: too much of a good thing?, Eur. J. Sport Sci. source

In the paper

“The AMPK dependent regulation of HDAC5 leads to the nuclear export of this de-acetylase [30].”

What the sources say

• Not checked yetcites [30] McGee, 2008, AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5, Diabetes source

In the paper

“For example, when exercise is commenced in the glycogen depleted state the phosphorylation of AMPK is greater in the post exercise recovery when muscle glycogen is low [21][22][23].”

What the sources say

• Not checked yetcites [21] Bartlett, 2013, Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis, Am. J. Physiol. Regul. Integr. Comp. Physiol. source
• Not checked yetcites [22] Wojtaszewski, 2003, Regulation of 5′AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle, Am. J. Physiol. Endocrinol. Metab. source
• Not checked yetcites [23] Yeo, 2010, Acute signalling responses to intense endurance training commenced with low or normal muscle glycogen, Exp. Physiol. source

In the paper

“Since this landmark study, a wealth of studies conducted over the next 40 years unequivocally confirmed that high preexercise muscle glycogen stores (i.e.>500 mmol.kg-1 dw) can improve endurance and team sport performance in those instances where exercise duration is >60-90 minutes [35].”

What the sources say

• Not checked yetcites [35] Hawley, 1997, Carbohydrate-loading and exercise performance. An update, Sports Med. source

In the paper

“In addition to this event exercise induced AMPK is also thought to phosphorylate and inhibit the Rab-GAP proteins TBC1D1/TBC1D4 [16][17][18].”

What the sources say

• Not checked yetcites [16] Pehmoller, 2009, Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle, Am. J. Physiol. Endocrinol. Metab. source
• Not checked yetcites [17] Howlett, 2008, The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle, Am. J. Physiol. Endocrinol. Metab. source
• Not checked yetcites [18] Howlett, 2007, Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle, Diabetes source

In the paper

“Furthermore, the increases in fat utilisation during exercise persisted in the face of abundant carbohydrate supplies.”

In the paper

“So while the data are clear that mTORC1 is required for load-induced growth [89], resistance exercise [91] and feeding [90], it is still very unclear if manipulating mTORC1 above what occurs physiologically will lead to enhanced muscle growth.”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [91] Drummond, 2009, Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis, J. Physiol. source
• Not checked yetcites [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

In the paper

“An appropriately structured resistance training program will lead to improved strength partly through improvements in muscle mass [80].”

What the sources say

• Not checked yetcites [80] Faigenbaum, 2015, Citius, Altius, Fortius: beneficial effects of resistance training for young athletes, Br. J. Sports Med.

In the paper

“The finding that shifts in substrate utilisation during exercise occurred in as little as 5 days of exposure to the LCHF paved the way for a further series of studies”

What the sources say

• Not checked yetcites [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

In the paper

“Through an unknown mechanism the GTPase activity of the RagGTPases (RagA/B and RagC/D) is sensitive to the intracellular amino acid content [101].”

What the sources say

• Not checked yetcites [101] Bar-Peled, 2014, Regulation of mTORC1 by amino acids, Trends Cell Biol. source

In the paper

“The mechanically sensitive pathways that respond to loading across the muscle to increase MPS converge with those that respond to increases in intracellular amino acid concentrations and insulin at mTORC1 [88] (Figure 2).”

What the sources say

• Not checked yetcites [88] McCarthy, 2010, Anabolic and catabolic pathways regulating skeletal muscle mass, Curr. Opin. Clin. Nutr. Metab. Care

In the paper

“Activation of mTORC1 is required for increases in protein synthesis with amino acids [90] and resistance exercise [91].”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [91] Drummond, 2009, Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis, J. Physiol. source

In the paper

“Cell based work has shown that this amino acid sensing system is incredibly sensitive with an ~7% increase in intracellular leucine leading to 50% maximal activation of mTORC1 [97].”

What the sources say

• Not checked yetcites [97] Christie, 2002, Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner, J. Biol. Chem. source

In the paper

“The key trigger for the protein feeding induced increases in MPS seems to be the leucine content of the digested protein [107] and possibly the leucine metabolite HMB (β-Hydroxy β-methylbutyrate) [108].”

What the sources say

• Not checked yetcites [107] Breen, 2012, Leucine: a nutrient ‘trigger’ for muscle anabolism, but what more?, J. Physiol. source

In the paper

“Furthermore, only a fraction of maximal mTORC1 activity (~30%) is required to fully saturate muscle protein synthesis [98,99].”

What the sources say

• Not checked yetcites [98] Crozier, 2005, Oral leucine administration stimulates protein synthesis in rat skeletal muscle, J. Nutr. source
• Not checked yetcites [99] Greenhaff, 2008, Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle, Am. J. Physiol. Endocrinol. Metab. source

In the paper

“However, not all stimuli that activate mTORC1 lead to improved protein synthesis.”

In the paper

“We have known for several decades that consuming essential amino acids in close proximity to resistance exercise can enhance the protein synthetic response in the skeletal muscle [104]”

What the sources say

• Not checked yetcites [104] Tipton, 1999, Postexercise net protein synthesis in human muscle from orally administered amino acids, Am. J. Physiol.

In the paper

“Here, it should be noted that a shift in measurements of respiratory exchange ratio during exercise, which are often used to mark shifts in substrate utilization, can reflect the prevailing availability of substrate rather than a true adaptation in the muscle.”

In the paper

“However, when insulin is infused to supra-physiological levels mTORC1 is potently activated without a concomitant increase in muscle protein synthesis [99].”

What the sources say

• Not checked yetcites [99] Greenhaff, 2008, Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle, Am. J. Physiol. Endocrinol. Metab. source

In the paper

“The multi-protein complex mechanistic Target of Rapamycin Complex 1 (mTORC1) is a key controller of protein synthesis through the control that it exerts on mRNA activity via increasing protein translation initiation [88] (Figure 2).”

What the sources say

• Not checked yetcites [88] McCarthy, 2010, Anabolic and catabolic pathways regulating skeletal muscle mass, Curr. Opin. Clin. Nutr. Metab. Care

In the paper

“It therefore seems that amino-acids and resistance exercise enhance MPS via a dual effect on increasing mTORC1 activity (Figure 2).”

In the paper

“Because the mechanically sensitive pathways and the resistance exercise pathways are distinct, consuming essential amino acids following resistance exercise significantly activates mTORC1 above resistance exercise alone [103].”

What the sources say

• Not checked yetcites [103] W. Apro, M. Moberg, D.L. Hamilton, B. Ekblom, O. Rooyackers, H.C. Holmberg, E. Blomstrand, Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise, FASEB J., 2015. source

In the paper

“As with endurance exercise, nutrition can play a critical role in augmenting the adaptive stimulus that comes from resistance exercise [84].”

What the sources say

• Not checked yetcites [84] Cermak, 2012, Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis, Am. J. Clin. Nutr. source

In the paper

“When mTORC1 activity [89] or the activity of its down stream target p70S6K1 [92,93] are impaired then muscle mass is impinged.”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [92] Mieulet, 2007, S6 kinase inactivation impairs growth and translational target phosphorylation in muscle cells maintaining proper regulation of protein turnover, Am. J. Physiol. Cell Physiol. source
• Not checked yetcites [93] Ohanna, 2005, Atrophy of S6K1(−/−) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control, Nat. Cell Biol. source

In the paper

“It therefore is logical to assume that increases in muscle protein synthesis could be enhanced by enhancing the activation of mTORC1.”

In the paper

“we now know that ~20g of high quality protein in the fasted [105] or fed [106] state is sufficient to saturate the protein synthetic response following resistance exercise in young men.”

What the sources say

• Not checked yetcites [106] Witard, 2014, Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise, Am. J. Clin. Nutr. source

In the paper

“When amino acids are above a certain threshold these Rags dimerise with the correct GTP loading status in such a way as to allow mTORC1 complex assembly [101].”

What the sources say

• Not checked yetcites [101] Bar-Peled, 2014, Regulation of mTORC1 by amino acids, Trends Cell Biol. source

In the paper

“Furthermore supplementation of protein during a program of resistance training is well proven to enhance lean mass/muscle gains [84].”

What the sources say

• Not checked yetcites [84] Cermak, 2012, Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis, Am. J. Clin. Nutr. source

In the paper

“we now know that ~20g of high quality protein in the fasted [105] or fed [106] state is sufficient to saturate the protein synthetic response following resistance exercise in young men.”

What the sources say

• Not checked yetcites [105] Moore, 2009, Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men, Am. J. Clin. Nutr. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“An individual's strength is highly, but not wholly dependent upon muscle mass [81,82].”

What the sources say

• Not checked yetcites [81] Moritani, 1979, Neural factors versus hypertrophy in the time course of muscle strength gain, Am. J. Phys. Med.
• Not checked yetcites [82] Seynnes, 2007, Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training, J. Appl. Physiol. (1985) source

In the paper

“The amino acid sensing by mTORC1 also seems to be driven not by extracellular, but instead by intracellular amino acid concentrations [100].”

What the sources say

• Not checked yetcites [100] Beugnet, 2003, Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability, Biochem. J. source

In the paper

“However, the situations in which this results in benefits to sports performance are presently unclear, particularly in the case of elite athletes who seem to be less responsive to nitrate supplementation protocols [131,132].”

What the sources say

• Not checked yetcites [131] Jonvik, 2015, Can elite athletes benefit from dietary nitrate supplementation?, J. Appl. Physiol. (1985) source
• Not checked yetcites [132] Hultstrom, 2015, Commentaries on Viewpoint: can elite athletes benefit from dietary nitrate supplementation?, J. Appl. Physiol. (1985) source

In the paper

“There is however considerable evidence behind the effectiveness of caffeine, creatine, nitrates, beta alanine, antioxidants and vitamin D and therefore these have been given special consideration.”

In the paper

“A comprehensive meta-analysis of the lengthy history of bicarbonate supplementation and sports performance found a moderate (1.7 ± 2.0%, 90%CL) enhancement of a single 1minute sprint in male athletes with the typical protocol [134].”

What the sources say

• Not checked yetcites [134] Carr, 2011, Effects of acute alkalosis and acidosis on performance: a meta-analysis, Sports Med. source

In the paper

“In addition to a number of health and benefits in clinical populations, enhanced NO availability appears to be responsible for improved exercise capacity via mechanisms including an increase in oxygen economy and direct effects on muscle contractility [130].”

What the sources say

• Not checked yetcites [130] Jones, 2014, Dietary nitrate supplementation and exercise performance, Sports Med. source

In the paper

“These other nutrients can potentially have benefits beyond the protein content [110].”

What the sources say

• Not checked yetcites [110] Phillips, 2015, Commonly consumed protein foods contribute to nutrient intake, diet quality, and nutrient adequacy, Am. J. Clin. Nutr. source

In the paper

“It must be stressed that direct evidence indicating a performance enhancing effect of vitamin D in athletic populations is at best equivocal [142].”

What the sources say

• Not checked yetcites [142] Owens, 2015, Vitamin D and the athlete: emerging insights, Eur. J. Sport Sci. source

In the paper

“Supplements that enhance intracellular and/or extracellular buffering capacity may benefit these sports by managing the progressive increase in intracellular acidosis.”

In the paper

“Caffeine may also enhance training outcomes, especially when used to allow the athlete to train harder during key sessions that are deliberately fatiguing [122]”

What the sources say

• Not checked yetcites [122] Lane, 2013, Caffeine ingestion and cycling power output in a low or normal muscle glycogen state, Med. Sci. Sports Exerc. source

In the paper

“Several protein dose response studies have demonstrated that ~20g of high quality protein (egg white protein or whey protein) following resistance exercise with a small amount of muscle mass (single leg training) is sufficient to maximally stimulate MPS in the trained leg [105,106].”

What the sources say

• Not checked yetcites [105] Moore, 2009, Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men, Am. J. Clin. Nutr. source
• Not checked yetcites [106] Witard, 2014, Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise, Am. J. Clin. Nutr. source

In the paper

“For instance, whole milk consumed after resistance exercise may be more effective at stimulating amino acid incorporation into skeletal muscle than fat free milk [115].”

What the sources say

• Not checked yetcites [115] Elliot, 2006, Milk ingestion stimulates net muscle protein synthesis following resistance exercise, Med. Sci. Sports Exerc. source

In the paper

“More recently, muscle concentrations of the dipeptide carnosine have been shown to respond to supplementation with β-alanine, the rate-limiting precursor for carnosine synthesis.”

What the sources say

• Not checked yetcites [136] Stellingwerff, 2012, Optimizing human in vivo dosing and delivery of beta-alanine supplements for muscle carnosine synthesis, Amino Acids source

In the paper

“Creatine supplementation may have important clinical roles and benefits to ageing populations [127].”

What the sources say

• Not checked yetcites [127] Gualano, 2012, In sickness and in health: the widespread application of creatine supplementation, Amino Acids source

In the paper

“Muscle creatine stores are elevated by ~ 20% to a threshold level by oral creatine supplementation, either by loading protocols (5 d @ 20 g/d in split doses) or by longer periods (~4 weeks) of a maintenance dose (~3 g/d) [125].”

What the sources say

• Not checked yetcites [125] Buford, 2007, International Society of Sports Nutrition position stand: creatine supplementation and exercise, J. Int. Soc. Sports Nutr. source

In the paper

“Recent changes to knowledge and practice around caffeine and sports performance include recognition that benefits apply across a large range of sports (highintensity events of 1-60 min, endurance/ultra-endurance events and team/racket/combat sports with intermittent efforts) [121].”

What the sources say

• Not checked yetcites [121] Burke, 2008, Caffeine and sports performance, Appl. Physiol. Nutr. Metab. source

In the paper

“Additionally, a number of studies have highlighted the benefits of milk-based protein, particularly whey, over plant based proteins for stimulating muscle protein synthesis [112].”

What the sources say

• Not checked yetcites [112] Devries, 2015, Supplemental protein in support of muscle mass and health: advantage whey, J. Food Sci.

In the paper

“The optimal loading protocol is unknown but intakes of 3-6 g/d for 4-12 weeks increase this intracellular buffer by 50-85% [136].”

What the sources say

• Not checked yetcites [136] Stellingwerff, 2012, Optimizing human in vivo dosing and delivery of beta-alanine supplements for muscle carnosine synthesis, Amino Acids source

In the paper

“Furthermore, evolving confirmation of genetic and other sources of individual variability in caffeine metabolism provides support for the well-known observations that some athletes are lowresponders [123] to caffeine or suffer side effects.”

What the sources say

• Not checked yetcites [123] Womack, 2012, The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine, J. Int. Soc. Sports Nutr. source

In the paper

“By increasing the muscle phosphocreatine reservoir, creatine supplementation can enhance the rapid regeneration of ATP during brief high-intensity exercise bouts, particularly when they are repeated with short recovery intervals.”

What the sources say

• Not checked yetcites [125] Buford, 2007, International Society of Sports Nutrition position stand: creatine supplementation and exercise, J. Int. Soc. Sports Nutr. source

In the paper

“The most relevant of caffeine's many pharmacological and physiological effects as an adenosine receptor antagonist and modifier of muscle contractility is the reduced perception of effort, fatigue or pain associated with exercise [120].”

What the sources say

• Not checked yetcites [120] Spriet, 2014, Exercise and sport performance with low doses of caffeine, Sports Med. source

In the paper

“endurance capacity also increased by ~25% in the NR supplemented mice”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“improved muscle mitochondrial respiration in response to a fatty acid-derived substrate [175].”

What the sources say

• Not checked yetcites [175] Timmers, 2011, Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans, Cell Metab. source

In the paper

“Certainly the human research to date suggests that resveratrol does not have the metabolic benefits in vivo as previously proposed in cell and rodent studies.”

In the paper

“NR has garnered recent attention, as it is a direct precursor for NAD + synthesis in skeletal muscle through the Nicotinamide Riboside Kinase 1/2 (NRK1/2) pathway [169].”

What the sources say

• Not checked yetcites [169] Bieganowski, 2004, Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss–Handler independent route to NAD+ in fungi and humans, Cell source

In the paper

“NR supplementation protected mice from the deleterious effects of 8 weeks high fat feeding”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“Thus, there are clear discrepancies between cell, rodent and human studies investigating resveratrol supplementation”

In the paper

“In addition, lower plasma glucose concentrations were observed following the supplementation [167].”

What the sources say

• Not checked yetcites [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

In the paper

“As a dietary derived NAD + donor in skeletal muscle, NR is thought to impact skeletal muscle mitochondrial function through the NAD + /SIRT1/PGC-1α signaling cascade [170] (Figure 1).”

What the sources say

• Not checked yetcites [170] Canto, 2015, NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus, Cell Metab. source

In the paper

“resveratrol supplementation also blunted training-induced decreases in protein carbonylation and tumour necrosis factor α (TNFα) mRNA within older individuals' skeletal muscle [178].”

What the sources say

• Not checked yetcites [178] Olesen, 2014, Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men, J. Physiol. source

In the paper

“As such these results indicate that (-)-epicatechin supplementation may be a nutritional approach to enhance skeletal muscle adaptation to endurance training (Figure 1).”

In the paper

“Resveratrol has been shown to promote fat oxidation and enhance endurance performance in mice [174].”

What the sources say

• Not checked yetcites [174] Murase, 2009, Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice, Biogerontology source

In the paper

“It is now well recognized that exercise-induced disruptions in skeletal muscle homeostasis regulate exercise adaptations with repeated activation [148,149] (Figure 1)”

What the sources say

• Not checked yetcites [148] Cobley, 2015, Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations, Free Radic. Biol. Med. source
• Not checked yetcites [149] Cobley, 2015, The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay, Front. Physiol. source

In the paper

“in addition to improving estimates of insulin sensitivity [175].”

What the sources say

• Not checked yetcites [175] Timmers, 2011, Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans, Cell Metab. source

In the paper

“and increased mitochondrial protein content.”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“numerous reports have identified resveratrol as a potent activator of mitochondrial biogenesis in skeletal muscle (Figure 1)”

What the sources say

• Not checked yetcites [173] de Ligt, 2015, Resveratrol and obesity: can resveratrol relieve metabolic disturbances?, Biochim. Biophys. Acta source

In the paper

“The authors proposed that the metabolic action of NR supplementation was mediated through SIRT1”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“Noguiera et al. (2011) were the first to report that fifteen days (-)-epicatechin supplementation increased skeletal muscle fatigue resistance, mitochondrial volume and angiogenesis in mice compared to activitymatched controls [166].”

What the sources say

• Not checked yetcites [166] Nogueira, 2011, (–)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle, J. Physiol. source

In the paper

“Unfortunately, many of the assays in the sports science literature merely serve to create confusion as they are fundamentally ill suited to deciphering whether a compound with antioxidant activity is actually acting as an antioxidant.”

What the sources say

• Not checked yetcites [156] Halliwell, 2004, Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?, Br. J. Pharmacol. source
• Not checked yetcites [157] Sies, 2007, Total antioxidant capacity: appraisal of a concept, J. Nutr. source

In the paper

“This is important because just because one is using an antioxidant it is not to say that it is acting as an antioxidant, which is especially important for nutritional antioxidants.”

In the paper

“Resveratrol has been shown to promote fat oxidation and enhance endurance performance in mice [174].”

What the sources say

• Not checked yetcites [174] Murase, 2009, Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice, Biogerontology source

In the paper

“NR feeding to mice (400 mg/kg/day) resulted in modest increases in skeletal muscle NAD + (~5%) following 1-week supplementation [171].”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“resveratrol supplementation in combination with high-intensity training in older men not only blunted the increase in maximal oxygen uptake observed in the placebo group”

What the sources say

• Not checked yetcites [177] Gliemann, 2013, Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men, J. Physiol. source

In the paper

“in addition to protecting skeletal muscle from the deleterious effects of high fat feeding in mice [173].”

What the sources say

• Not checked yetcites [173] de Ligt, 2015, Resveratrol and obesity: can resveratrol relieve metabolic disturbances?, Biochim. Biophys. Acta source

In the paper

“As such, there is growing support that resveratrol may be a beneficial approach to remodel skeletal muscle in humans.”

In the paper

“Recently, Canto et al (2012) who showed that NR supplementation in C2C12 myotubes increased NAD + content”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“resveratrol supplementation during exercise training in healthy individuals can result in a maladaptive response in exercise-stimulated gene expression [176].”

What the sources say

• Not checked yetcites [176] Scribbans, 2014, Resveratrol supplementation does not augment performance adaptations or fibre-type-specific responses to high-intensity interval training in humans, Appl. Physiol. Nutr. Metab. source

In the paper

“resveratrol supplementation increased skeletal muscle citrate synthase activity without a change in mitochondrial content”

What the sources say

• Not checked yetcites [175] Timmers, 2011, Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans, Cell Metab. source

In the paper

“30 days resveratrol supplementation (150mg/day resVida) can reduce intrahepatic lipid content, circulating glucose, triglycerides, alanineaminotransferase, and inflammation markers”

What the sources say

• Not checked yetcites [175] Timmers, 2011, Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans, Cell Metab. source

In the paper

“coupled to an increase in mitochondrial to nuclear DNA ratios (a marker of mitochondrial mass)”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“the adaptive response of C2C12 myotubes to NR supplementation was lost following SIRT1 siRNA mediated knockdown.”

What the sources say

• Not checked yetcites [171] Canto, 2012, The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity, Cell Metab. source

In the paper

“Therefore, it is presently unclear whether UA supplementation in humans can reproduce the anti-atrophy or pro-hypertrophic data reported previously [187].”

What the sources say

• Not checked yetcites [187] Kunkel, 2011, mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass, Cell Metab. source