Skip to main content

Supplements with purported effects on muscle mass and strength

European Journal of Nutrition volume 58, pages 2983–3008 (2019)Cite this article

Abstract

Purpose

Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear.

Methods

This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength.

Results

Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, β-Hydroxy-β-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid).

Conclusion

 In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. McGuigan MR, Wright GA, Fleck SJ (2012) Strength training for athletes: does it really help sports performance? Int J Sports Physiol Perform 7(1):2–5. https://doi.org/10.1123/ijspp.7.1.2

    Article  PubMed  Google Scholar 

  2. Spahillari A, Mukamal KJ, DeFilippi C, Kizer JR, Gottdiener JS, Djoussé L, Lyles MF, Bartz TM, Murthy VL, Shah RV (2016) The association of lean and fat mass with all-cause mortality in older adults: the cardiovascular health study. Nutr Metab Cardiovasc Dis 26(11):1039–1047. https://doi.org/10.1016/j.numecd.2016.06.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Volaklis KA, Halle M, Meisinger C (2015) Muscular strength as a strong predictor of mortality: a narrative review. Eur J Intern Med 26(5):303–310. https://doi.org/10.1016/j.ejim.2015.04.013

    Article  PubMed  Google Scholar 

  4. Egan B, Zierath JR (2013) Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 17(2):162–184. https://doi.org/10.1016/j.cmet.2012.12.012. (S1550-4131(12)00503-7 [pii])

    Article  CAS  PubMed  Google Scholar 

  5. Millward DJ, Garlick PJ, Stewart RJ, Nnanyelugo DO, Waterlow JC (1975) Skeletal-muscle growth and protein turnover. Biochem J 150(2):235–243

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Phillips SM (2014) A brief review of higher dietary protein diets in weight loss: a focus on athletes. Sports Med 44(Suppl 2):S149–S153. https://doi.org/10.1007/s40279-014-0254-y

    Article  PubMed  Google Scholar 

  7. Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ (2012) Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr 96(6):1454–1464. https://doi.org/10.3945/ajcn.112.037556

    Article  CAS  PubMed  Google Scholar 

  8. Naderi A, de Oliveira EP, Ziegenfuss TN, Willems MT (2016) Timing, optimal dose and intake duration of dietary supplements with evidence-based use in sports nutrition. J Exerc Nutr Biochem 20(4):1–12. https://doi.org/10.20463/jenb.2016.0031

    Article  Google Scholar 

  9. Ronis MJJ, Pedersen KB, Watt J (2018) Adverse Effects of Nutraceuticals and Dietary Supplements. Annu Rev Pharmacol Toxicol 58:583–601. https://doi.org/10.1146/annurev-pharmtox-010617-052844

    Article  CAS  PubMed  Google Scholar 

  10. Knapik JJ, Steelman RA, Hoedebecke SS, Austin KG, Farina EK, Lieberman HR (2016) Prevalence of dietary supplement use by athletes: systematic review and meta-analysis. Sports Med 46(1):103–123. https://doi.org/10.1007/s40279-015-0387-7

    Article  PubMed  Google Scholar 

  11. Wardenaar FC, Ceelen IJ, Van Dijk JW, Hangelbroek RW, Van Roy L, Van der Pouw B, De Vries JH, Mensink M, Witkamp RF (2017) Nutritional supplement use by dutch elite and sub-elite athletes: does receiving dietary counseling make a difference? Int J Sport Nutr Exerc Metab 27(1):32–42. https://doi.org/10.1123/ijsnem.2016-0157

    Article  CAS  PubMed  Google Scholar 

  12. Nissen SL, Sharp RL (2003) Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol (1985) 94(2):651–659. https://doi.org/10.1152/japplphysiol.00755.2002

    Article  CAS  Google Scholar 

  13. Beaudart C, Dawson A, Shaw SC, Harvey NC, Kanis JA, Binkley N, Reginster JY, Chapurlat R, Chan DC, Bruyère O, Rizzoli R, Cooper C, Dennison EM, Group I-ESW (2017) Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporos Int 28 (6):1817–1833. https://doi.org/10.1007/s00198-017-3980-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, Collins R, Cooke M, Davis JN, Galvan E, Greenwood M, Lowery LM, Wildman R, Antonio J, Kreider RB (2018) ISSN exercise and sports nutrition review update: research & recommendations. J Int Soc Sports Nutr 15(1):38. https://doi.org/10.1186/s12970-018-0242-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Goldman A, Basaria S (2017) Adverse health effects of androgen use. Mol Cell Endocrinol https://doi.org/10.1016/j.mce.2017.06.009

    Article  PubMed  Google Scholar 

  16. Thomas DT, Erdman KA, Burke LM (2016) American College of Sports Medicine Joint Position Statement. Nutrition and athletic performance. Med Sci Sports Exerc 48(3):543–568. https://doi.org/10.1249/MSS.0000000000000852

    Article  CAS  PubMed  Google Scholar 

  17. Davis JK, Green JM (2009) Caffeine and anaerobic performance: ergogenic value and mechanisms of action. Sports Med 39(10):813–832. https://doi.org/10.2165/11317770-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  18. Ganio MS, Klau JF, Casa DJ, Armstrong LE, Maresh CM (2009) Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res 23(1):315–324. https://doi.org/10.1519/JSC.0b013e31818b979a

    Article  PubMed  Google Scholar 

  19. Burke LM (2008) Caffeine and sports performance. Appl Physiol Nutr Metab 33(6):1319–1334. https://doi.org/10.1139/H08-130

    Article  CAS  PubMed  Google Scholar 

  20. Spriet LL (2014) Exercise and sport performance with low doses of caffeine. Sports Med 44 (Suppl 2):S175–S184. https://doi.org/10.1007/s40279-014-0257-8

    Article  PubMed  Google Scholar 

  21. Grgic J, Mikulic P, Schoenfeld BJ, Bishop DJ, Pedisic Z (2018) The influence of caffeine supplementation on resistance exercise: a review. Sports Med. https://doi.org/10.1007/s40279-018-0997-y

    Article  PubMed  Google Scholar 

  22. Warren GL, Park ND, Maresca RD, McKibans KI, Millard-Stafford ML (2010) Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med Sci Sports Exerc 42(7):1375–1387. https://doi.org/10.1249/MSS.0b013e3181cabbd8

    Article  CAS  PubMed  Google Scholar 

  23. Duncan MJ, Oxford SW (2011) The effect of caffeine ingestion on mood state and bench press performance to failure. J Strength Cond Res 25(1):178–185. https://doi.org/10.1519/JSC.0b013e318201bddb

    Article  PubMed  Google Scholar 

  24. Duncan MJ, Smith M, Cook K, James RS (2012) The acute effect of a caffeine-containing energy drink on mood state, readiness to invest effort, and resistance exercise to failure. J Strength Cond Res 26(10):2858–2865. https://doi.org/10.1519/JSC.0b013e318241e124

    Article  PubMed  Google Scholar 

  25. Jacobs I, Pasternak H, Bell DG (2003) Effects of ephedrine, caffeine, and their combination on muscular endurance. Med Sci Sports Exerc 35(6):987–994. https://doi.org/10.1249/01.MSS.0000069916.49903.70

    Article  CAS  PubMed  Google Scholar 

  26. Williams AD, Cribb PJ, Cooke MB, Hayes A (2008) The effect of ephedra and caffeine on maximal strength and power in resistance-trained athletes. J Strength Cond Res 22(2):464–470. https://doi.org/10.1519/JSC.0b013e3181660320

    Article  PubMed  Google Scholar 

  27. Astorino TA, Martin BJ, Schachtsiek L, Wong K, Ng K (2011) Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength Cond Res 25(6):1752–1758. https://doi.org/10.1519/JSC.0b013e3181ddf6db

    Article  PubMed  Google Scholar 

  28. Green JM, Wickwire PJ, McLester JR, Gendle S, Hudson G, Pritchett RC, Laurent CM (2007) Effects of caffeine on repetitions to failure and ratings of perceived exertion during resistance training. Int J Sports Physiol Perform 2(3):250–259

    PubMed  Google Scholar 

  29. Goldstein E, Jacobs PL, Whitehurst M, Penhollow T, Antonio J (2010) Caffeine enhances upper body strength in resistance-trained women. J Int Soc Sports Nutr 7:18. https://doi.org/10.1186/1550-2783-7-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Grgic J, Trexler ET, Lazinica B, Pedisic Z (2018) Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr 15:11. https://doi.org/10.1186/s12970-018-0216-0

    Article  PubMed  PubMed Central  Google Scholar 

  31. Maughan RJ, Burke LM, Dvorak J, Larson-Meyer DE, Peeling P, Phillips SM, Rawson ES, Walsh NP, Garthe I, Geyer H, Meeusen R, van Loon LJC, Shirreffs SM, Spriet LL, Stuart M, Vernec A, Currell K, Ali VM, Budgett RG, Ljungqvist A, Mountjoy M, Pitsiladis YP, Soligard T, Erdener U, Engebretsen L (2018) IOC consensus statement: dietary supplements and the high-performance athlete. Br J Sports Med 52(7):439–455. https://doi.org/10.1136/bjsports-2018-099027

    Article  PubMed  Google Scholar 

  32. Graham TE (2001) Caffeine and exercise: metabolism, endurance and performance. Sports Med 31(11):785–807. https://doi.org/10.2165/00007256-200131110-00002

    Article  CAS  PubMed  Google Scholar 

  33. Trexler ET, Smith-Ryan AE, Roelofs EJ, Hirsch KR, Mock MG (2016) Effects of coffee and caffeine anhydrous on strength and sprint performance. Eur J Sport Sci 16(6):702–710. https://doi.org/10.1080/17461391.2015.1085097

    Article  PubMed  Google Scholar 

  34. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80(3):1107–1213

    CAS  PubMed  Google Scholar 

  35. Walker JB (1979) Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 50:177–242

    CAS  PubMed  Google Scholar 

  36. Balsom PD, Söderlund K, Ekblom B (1994) Creatine in humans with special reference to creatine supplementation. Sports Med 18(4):268–280

    CAS  PubMed  Google Scholar 

  37. Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J (2007) International Society of sports nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 4:6. https://doi.org/10.1186/1550-2783-4-6

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL (2017) International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14:18. https://doi.org/10.1186/s12970-017-0173-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS (2009) The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr 6:6. https://doi.org/10.1186/1550-2783-6-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gill ND, Hall RD, Blazevich AJ (2004) Creatine serum is not as effective as creatine powder for improving cycle sprint performance in competitive male team-sport athletes. J Strength Cond Res 18(2):272–275. https://doi.org/10.1519/R-13193.1

    Article  PubMed  Google Scholar 

  41. Jagim AR, Oliver JM, Sanchez A, Galvan E, Fluckey J, Riechman S, Greenwood M, Kelly K, Meininger C, Rasmussen C, Kreider RB (2012) A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate. J Int Soc Sports Nutr 9(1):43. https://doi.org/10.1186/1550-2783-9-43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gualano B, Artioli GG, Poortmans JR, Lancha Junior AH (2010) Exploring the therapeutic role of creatine supplementation. Amino Acids 38(1):31–44. https://doi.org/10.1007/s00726-009-0263-6

    Article  CAS  PubMed  Google Scholar 

  43. Deane CS, Wilkinson DJ, Phillips BE, Smith K, Etheridge T, Atherton PJ (2017) “Nutraceuticals” in relation to human skeletal muscle and exercise. Am J Physiol Endocrinol Metab 312(4):E282–E299. https://doi.org/10.1152/ajpendo.00230.2016

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage FX, Dutheil F (2015) Creatine supplementation and lower limb strength performance: a systematic review and meta-analyses. Sports Med 45(9):1285–1294. https://doi.org/10.1007/s40279-015-0337-4

    Article  PubMed  Google Scholar 

  45. Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage FX, Dutheil F (2017) Creatine supplementation and upper limb strength performance: a systematic review and meta-analysis. Sports Med 47(1):163–173. https://doi.org/10.1007/s40279-016-0571-4

    Article  PubMed  Google Scholar 

  46. Johnston AP, Burke DG, MacNeil LG, Candow DG (2009) Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res 23(1):116–120

    PubMed  Google Scholar 

  47. Hespel P, Op’t Eijnde B, Van Leemputte M, Ursø B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA (2001) Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol 536(Pt 2):625–633

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Burke DG, Candow DG, Chilibeck PD, MacNeil LG, Roy BD, Tarnopolsky MA, Ziegenfuss T (2008) Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. Int J Sport Nutr Exerc Metab 18(4):389–398

    CAS  PubMed  Google Scholar 

  49. Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Moran M, Emanuele E, Joyner MJ, Lucia A (2015) Exercise attenuates the major hallmarks of aging. Rejuvenation Res 18(1):57–89. https://doi.org/10.1089/rej.2014.1623

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lobo DM, Tritto AC, da Silva LR, de Oliveira PB, Benatti FB, Roschel H, Nieß B, Gualano B, Pereira RM (2015) Effects of long-term low-dose dietary creatine supplementation in older women. Exp Gerontol 70:97–104. https://doi.org/10.1016/j.exger.2015.07.012

    Article  CAS  PubMed  Google Scholar 

  51. Cooper R, Naclerio F, Allgrove J, Jimenez A (2012) Creatine supplementation with specific view to exercise/sports performance: an update. J Int Soc Sports Nutr 9(1):33. https://doi.org/10.1186/1550-2783-9-33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Antonio J, Ciccone V (2013) The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength. J Int Soc Sports Nutr 10:36. https://doi.org/10.1186/1550-2783-10-36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Candow DG, Zello GA, Ling B, Farthing JP, Chilibeck PD, McLeod K, Harris J, Johnson S (2014) Comparison of creatine supplementation before versus after supervised resistance training in healthy older adults. Res Sports Med 22(1):61–74. https://doi.org/10.1080/15438627.2013.852088

    Article  PubMed  Google Scholar 

  54. Candow DG, Vogt E, Johannsmeyer S, Forbes SC, Farthing JP (2015) Strategic creatine supplementation and resistance training in healthy older adults. Appl Physiol Nutr Metab 40 (7):689–694. https://doi.org/10.1139/apnm-2014-0498

    Article  CAS  PubMed  Google Scholar 

  55. Gualano B, Roschel H, Lancha AH, Brightbill CE, Rawson ES (2012) In sickness and in health: the widespread application of creatine supplementation. Amino Acids 43(2):519–529. https://doi.org/10.1007/s00726-011-1132-7

    Article  CAS  PubMed  Google Scholar 

  56. Kley RA, Tarnopolsky MA, Vorgerd M (2008) Creatine treatment in muscle disorders: a meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry 79(4):366–367. https://doi.org/10.1136/jnnp.2007.127571

    Article  CAS  PubMed  Google Scholar 

  57. Candow DG, Chilibeck PD, Forbes SC (2014) Creatine supplementation and aging musculoskeletal health. Endocrine 45(3):354–361. https://doi.org/10.1007/s12020-013-0070-4

    Article  CAS  PubMed  Google Scholar 

  58. Moon A, Heywood L, Rutherford S, Cobbold C (2013) Creatine supplementation: can it improve quality of life in the elderly without associated resistance training? Curr Aging Sci 6(3):251–257

    CAS  PubMed  Google Scholar 

  59. Cañete S, San Juan AF, Pérez M, Gómez-Gallego F, López-Mojares LM, Earnest CP, Fleck SJ, Lucia A (2006) Does creatine supplementation improve functional capacity in elderly women? J Strength Cond Res 20(1):22–28. https://doi.org/10.1519/R-17044.1

    Article  PubMed  Google Scholar 

  60. Gotshalk LA, Volek JS, Staron RS, Denegar CR, Hagerman FC, Kraemer WJ (2002) Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc 34(3):537–543

    CAS  PubMed  Google Scholar 

  61. Pritchard NR, Kalra PA (1998) Renal dysfunction accompanying oral creatine supplements. Lancet 351(9111):1252–1253

    CAS  PubMed  Google Scholar 

  62. Anderson JE (2000) A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells. Mol Biol Cell 11(5):1859–1874. https://doi.org/10.1091/mbc.11.5.1859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Smith LW, Smith JD, Criswell DS (2002) Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. J Appl Physiol 92(5):2005–2011. https://doi.org/10.1152/japplphysiol.00950.2001

    Article  CAS  PubMed  Google Scholar 

  64. Stamler JS, Meissner G (2001) Physiology of nitric oxide in skeletal muscle. Physiol Rev 81(1):209–237

    CAS  PubMed  Google Scholar 

  65. Lundberg JO, Govoni M (2004) Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 37(3):395–400. https://doi.org/10.1016/j.freeradbiomed.2004.04.027

    Article  CAS  PubMed  Google Scholar 

  66. Jonvik KL, Nyakayiru J, van Dijk JW, Wardenaar FC, van Loon LJ, Verdijk LB (2017) Habitual dietary nitrate intake in highly trained athletes. Int J Sport Nutr Exerc Metab 27(2):148–157. https://doi.org/10.1123/ijsnem.2016-0239

    Article  CAS  PubMed  Google Scholar 

  67. Hoon MW, Jones AM, Johnson NA, Blackwell JR, Broad EM, Lundy B, Rice AJ, Burke LM (2014) The effect of variable doses of inorganic nitrate-rich beetroot juice on simulated 2,000-m rowing performance in trained athletes. Int J Sports Physiol Perform 9(4):615–620. https://doi.org/10.1123/ijspp.2013-0207

    Article  PubMed  Google Scholar 

  68. Peeling P, Cox GR, Bullock N, Burke LM (2015) Beetroot juice improves on-water 500 m time-trial performance, and laboratory-based paddling economy in national and international-level kayak athletes. Int J Sport Nutr Exerc Metab 25(3):278–284. https://doi.org/10.1123/ijsnem.2014-0110

    Article  CAS  PubMed  Google Scholar 

  69. Clements WT, Lee SR, Bloomer RJ (2014) Nitrate ingestion: a review of the health and physical performance effects. Nutrients 6(11):5224–5264. https://doi.org/10.3390/nu6115224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bescós R, Sureda A, Tur JA, Pons A (2012) The effect of nitric-oxide-related supplements on human performance. Sports Med 42(2):99–117. https://doi.org/10.2165/11596860-000000000-00000

    Article  PubMed  Google Scholar 

  71. Fulford J, Winyard PG, Vanhatalo A, Bailey SJ, Blackwell JR, Jones AM (2013) Influence of dietary nitrate supplementation on human skeletal muscle metabolism and force production during maximum voluntary contractions. Pflugers Archiv Eur J Physiol 465(4):517–528. https://doi.org/10.1007/s00424-013-1220-5

    Article  CAS  Google Scholar 

  72. Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AM (2010) Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol 109(1):135–148. https://doi.org/10.1152/japplphysiol.00046.2010

    Article  CAS  PubMed  Google Scholar 

  73. Mosher SL, Sparks SA, Williams EL, Bentley DJ, Mc Naughton LR (2016) Ingestion of a nitric oxide enhancing supplement improves resistance exercise performance. J Strength Cond Res 30(12):3520–3524. https://doi.org/10.1519/JSC.0000000000001437

    Article  PubMed  Google Scholar 

  74. Hoon MW, Fornusek C, Chapman PG, Johnson NA (2015) The effect of nitrate supplementation on muscle contraction in healthy adults. Eur J Sport Sci 15(8):712–719. https://doi.org/10.1080/17461391.2015.1053418

    Article  PubMed  Google Scholar 

  75. Schoenfeld BJ, Ogborn D, Krieger JW (2017) Dose-response relationship between weekly resistance training volume and increases in muscle mass: a systematic review and meta-analysis. J Sports Sci 35(11):1073–1082. https://doi.org/10.1080/02640414.2016.1210197

    Article  PubMed  Google Scholar 

  76. Bryan NS, Alexander DD, Coughlin JR, Milkowski AL, Boffetta P (2012) Ingested nitrate and nitrite and stomach cancer risk: an updated review. Food Chem Toxicol 50(10):3646–3665. https://doi.org/10.1016/j.fct.2012.07.062

    Article  CAS  PubMed  Google Scholar 

  77. Schoenfeld BJ, Aragon AA, Krieger JW (2013) The effect of protein timing on muscle strength and hypertrophy: a meta-analysis. J Int Soc Sports Nutr 10(1):53. https://doi.org/10.1186/1550-2783-10-53

    Article  PubMed  PubMed Central  Google Scholar 

  78. Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM (2009) Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107(3):987–992. https://doi.org/10.1152/japplphysiol.00076.2009

    Article  CAS  PubMed  Google Scholar 

  79. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM (2017) A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. https://doi.org/10.1136/bjsports-2017-097608

    Article  PubMed  Google Scholar 

  80. Xu ZR, Tan ZJ, Zhang Q, Gui QF, Yang YM (2014) Clinical effectiveness of protein and amino acid supplementation on building muscle mass in elderly people: a meta-analysis. PLoS One 9(9):e109141. https://doi.org/10.1371/journal.pone.0109141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Finger D, Goltz FR, Umpierre D, Meyer E, Rosa LH, Schneider CD (2015) Effects of protein supplementation in older adults undergoing resistance training: a systematic review and meta-analysis. Sports Med 45(2):245–255. https://doi.org/10.1007/s40279-014-0269-4

    Article  PubMed  Google Scholar 

  82. Thomas DK, Quinn MA, Saunders DH, Greig CA (2016) Protein supplementation does not significantly augment the effects of resistance exercise training in older adults: a systematic review. J Am Med Dir Assoc 17(10):959.e951–959.e959. https://doi.org/10.1016/j.jamda.2016.07.002

    Article  Google Scholar 

  83. Gillen JB, Trommelen J, Wardenaar FC, Brinkmans NY, Versteegen JJ, Jonvik KL, Kapp C, de Vries J, van den Borne JJ, Gibala MJ, van Loon LJ (2017) Dietary protein intake and distribution patterns of well-trained dutch athletes. Int J Sport Nutr Exerc Metab 27(2):105–114. https://doi.org/10.1123/ijsnem.2016-0154

    Article  CAS  PubMed  Google Scholar 

  84. Phillips SM, Moore DR, Tang JE (2007) A critical examination of dietary protein requirements, benefits, and excesses in athletes. Int J Sport Nutr Exerc Metab 17 Suppl:S58-76

    CAS  PubMed  Google Scholar 

  85. Areta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG (2013) Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol 591(9):2319–2331. https://doi.org/10.1113/jphysiol.2012.244897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Mamerow MM, Mettler JA, English KL, Casperson SL, Arentson-Lantz E, Sheffield-Moore M, Layman DK, Paddon-Jones D (2014) Dietary protein distribution positively influences 24-h muscle protein synthesis in healthy adults. J Nutr 144(6):876–880. https://doi.org/10.3945/jn.113.185280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Stark M, Lukaszuk J, Prawitz A, Salacinski A (2012) Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training. J Int Soc Sports Nutr 9(1):54. https://doi.org/10.1186/1550-2783-9-54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yang Y, Churchward-Venne TA, Burd NA, Breen L, Tarnopolsky MA, Phillips SM (2012) Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr Metab (Lond) 9(1):57. https://doi.org/10.1186/1743-7075-9-57

    Article  CAS  PubMed Central  Google Scholar 

  89. Burd NA, Yang Y, Moore DR, Tang JE, Tarnopolsky MA, Phillips SM (2012) Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men. Br J Nutr 108(6):958–962. https://doi.org/10.1017/S0007114511006271

    Article  CAS  PubMed  Google Scholar 

  90. Galvan E, Arentson-Lantz E, Lamon S, Paddon-Jones D (2016) Protecting skeletal muscle with protein and amino acid during periods of disuse. Nutrients 8 (7). https://doi.org/10.3390/nu8070404

    PubMed Central  Google Scholar 

  91. Volek JS, Volk BM, Gómez AL, Kunces LJ, Kupchak BR, Freidenreich DJ, Aristizabal JC, Saenz C, Dunn-Lewis C, Ballard KD, Quann EE, Kawiecki DL, Flanagan SD, Comstock BA, Fragala MS, Earp JE, Fernandez ML, Bruno RS, Ptolemy AS, Kellogg MD, Maresh CM, Kraemer WJ (2013) Whey protein supplementation during resistance training augments lean body mass. J Am Coll Nutr 32(2):122–135. https://doi.org/10.1080/07315724.2013.793580

    Article  CAS  PubMed  Google Scholar 

  92. Cribb PJ, Williams AD, Carey MF, Hayes A (2006) The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab 16(5):494–509

    CAS  PubMed  Google Scholar 

  93. Demling RH, DeSanti L (2000) Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann Nutr Metab 44(1):21–29. doi:12817

    CAS  PubMed  Google Scholar 

  94. Candow DG, Burke NC, Smith-Palmer T, Burke DG (2006) Effect of whey and soy protein supplementation combined with resistance training in young adults. Int J Sport Nutr Exerc Metab 16(3):233–244

    CAS  PubMed  Google Scholar 

  95. Wilborn CD, Taylor LW, Outlaw J, Williams L, Campbell B, Foster CA, Smith-Ryan A, Urbina S, Hayward S (2013) The effects of pre- and post-exercise whey vs. casein protein consumption on body composition and performance measures in collegiate female athletes. J Sports Sci Med 12(1):74–79

    PubMed  PubMed Central  Google Scholar 

  96. Institute-of-Medicine (2005) Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press, Washington

    Google Scholar 

  97. Jäger R, Kerksick CM, Campbell BI, Cribb PJ, Wells SD, Skwiat TM, Purpura M, Ziegenfuss TN, Ferrando AA, Arent SM, Smith-Ryan AE, Stout JR, Arciero PJ, Ormsbee MJ, Taylor LW, Wilborn CD, Kalman DS, Kreider RB, Willoughby DS, Hoffman JR, Krzykowski JL, Antonio J (2017) International society of sports nutrition position stand: protein and exercise. J Int Soc Sports Nutr 14:20. https://doi.org/10.1186/s12970-017-0177-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab 85(12):4481–4490. https://doi.org/10.1210/jcem.85.12.7021

    Article  CAS  PubMed  Google Scholar 

  99. Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, Phillips SM (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 70(1):57–62. https://doi.org/10.1093/gerona/glu103

    Article  CAS  PubMed  Google Scholar 

  100. Antonio J, Ellerbroek A, Silver T, Vargas L, Peacock C (2016) The effects of a high protein diet on indices of health and body composition–a crossover trial in resistance-trained men. J Int Soc Sports Nutr 13:3. https://doi.org/10.1186/s12970-016-0114-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Devries MC, Sithamparapillai A, Brimble KS, Banfield L, Morton RW, Phillips SM (2018) Changes in kidney function do not differ between healthy adults consuming higher- compared with lower- or normal-protein diets: a systematic review and meta-analysis. J Nutr 148(11):1760–1775. https://doi.org/10.1093/jn/nxy197

    Article  PubMed  PubMed Central  Google Scholar 

  102. Jeromson S, Gallagher IJ, Galloway SD, Hamilton DL (2015) Omega-3 fatty acids and skeletal muscle health. Mar Drugs 13(11):6977–7004. https://doi.org/10.3390/md13116977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fritsche KL (2008) Too much linoleic acid promotes inflammation-doesn’t it? Prostaglandins Leukot Essent Fatty Acids 79(3–5):173–175. https://doi.org/10.1016/j.plefa.2008.09.019

    Article  CAS  PubMed  Google Scholar 

  104. D’Antona G, Nabavi SM, Micheletti P, Di Lorenzo A, Aquilani R, Nisoli E, Rondanelli M, Daglia M (2014) Creatine, l-carnitine, and ω3 polyunsaturated fatty acid supplementation from healthy to diseased skeletal muscle. Biomed Res Int 2014:613890. https://doi.org/10.1155/2014/613890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B (2011) Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond) 121(6):267–278. https://doi.org/10.1042/CS20100597

    Article  CAS  Google Scholar 

  106. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B (2011) Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 93(2):402–412. https://doi.org/10.3945/ajcn.110.005611

    Article  CAS  PubMed  Google Scholar 

  107. Smith GI, Julliand S, Reeds DN, Sinacore DR, Klein S, Mittendorfer B (2015) Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Am J Clin Nutr 102(1):115–122. https://doi.org/10.3945/ajcn.114.105833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Rodacki CL, Rodacki AL, Pereira G, Naliwaiko K, Coelho I, Pequito D, Fernandes LC (2012) Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr 95(2):428–436. https://doi.org/10.3945/ajcn.111.021915

    Article  CAS  PubMed  Google Scholar 

  109. Edholm P, Strandberg E, Kadi F (2017) Lower limb explosive strength capacity in elderly women: effects of resistance training and healthy diet. J Appl Physiol 123(1):190–196. https://doi.org/10.1152/japplphysiol.00924.2016

    Article  CAS  PubMed  Google Scholar 

  110. Ryan AM, Reynolds JV, Healy L, Byrne M, Moore J, Brannelly N, McHugh A, McCormack D, Flood P (2009) Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial. Ann Surg 249(3):355–363. https://doi.org/10.1097/SLA.0b013e31819a4789

    Article  PubMed  Google Scholar 

  111. Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57(5):M326–M332

    PubMed  Google Scholar 

  112. Kris-Etherton PM, Harris WS, Appel LJ, Committee AHAN (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106(21):2747–2757

    PubMed  Google Scholar 

  113. From the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition (2008) Interim summary of conclusions and dietary recommendations on total fat and fatty acids. Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, Geneva

    Google Scholar 

  114. Candow DG, Forbes SC, Little JP, Cornish SM, Pinkoski C, Chilibeck PD (2012) Effect of nutritional interventions and resistance exercise on aging muscle mass and strength. Biogerontology 13(4):345–358. https://doi.org/10.1007/s10522-012-9385-4

    Article  CAS  PubMed  Google Scholar 

  115. Rundqvist HC, Esbjörnsson M, Rooyackers O, Österlund T, Moberg M, Apro W, Blomstrand E, Jansson E (2017) Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise. J Appl Physiol 123(6):1501–1515. https://doi.org/10.1152/japplphysiol.00244.2017

    Article  CAS  PubMed  Google Scholar 

  116. Børsheim E, Tipton KD, Wolf SE, Wolfe RR (2002) Essential amino acids and muscle protein recovery from resistance exercise. Am J Physiol Endocrinol Metab 283(4):E648–E657. https://doi.org/10.1152/ajpendo.00466.2001

    Article  PubMed  Google Scholar 

  117. Paddon-Jones D, Sheffield-Moore M, Zhang XJ, Volpi E, Wolf SE, Aarsland A, Ferrando AA, Wolfe RR (2004) Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 286(3):E321–E328. https://doi.org/10.1152/ajpendo.00368.2003

    Article  CAS  PubMed  Google Scholar 

  118. Dillon EL, Sheffield-Moore M, Paddon-Jones D, Gilkison C, Sanford AP, Casperson SL, Jiang J, Chinkes DL, Urban RJ (2009) Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women. J Clin Endocrinol Metab 94(5):1630–1637. https://doi.org/10.1210/jc.2008-1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wall BT, van Loon LJ (2013) Nutritional strategies to attenuate muscle disuse atrophy. Nutr Rev 71(4):195–208. https://doi.org/10.1111/nure.12019

    Article  PubMed  Google Scholar 

  120. Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, McComb A, Symons TB, Wolfe RR, Evans W (2010) EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 29(1):18–23. https://doi.org/10.1016/j.clnu.2009.03.009

    Article  CAS  PubMed  Google Scholar 

  121. Shimomura Y, Murakami T, Nakai N, Nagasaki M, Harris RA (2004) Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. J Nutr 134(6 Suppl):1583S–1587S

    CAS  PubMed  Google Scholar 

  122. Holeček M (2018) Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond) 15:33. https://doi.org/10.1186/s12986-018-0271-1

    Article  CAS  Google Scholar 

  123. Jackman SR, Witard OC, Philp A, Wallis GA, Baar K, Tipton KD (2017) Branched-chain amino acid ingestion stimulates muscle myofibrillar protein synthesis following resistance exercise in humans. Front Physiol 8:390. https://doi.org/10.3389/fphys.2017.00390

    Article  PubMed  PubMed Central  Google Scholar 

  124. Kobayashi H, Kato H, Hirabayashi Y, Murakami H, Suzuki H (2006) Modulations of muscle protein metabolism by branched-chain amino acids in normal and muscle-atrophying rats. J Nutr 136(1 Suppl):234S–236S

    CAS  PubMed  Google Scholar 

  125. Borgenvik M, Apró W, Blomstrand E (2012) Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle. Am J Physiol Endocrinol Metab 302(5):E510–E521. https://doi.org/10.1152/ajpendo.00353.2011

    Article  CAS  PubMed  Google Scholar 

  126. Apró W, Blomstrand E (2010) Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle. Acta Physiol (Oxf) 200(3):237–248. https://doi.org/10.1111/j.1748-1708.2010.02151.x

    Article  CAS  Google Scholar 

  127. Rahimi MH, Shab-Bidar S, Mollahosseini M, Djafarian K (2017) Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: a meta-analysis of randomized clinical trials. Nutrition 42:30–36. https://doi.org/10.1016/j.nut.2017.05.005

    Article  CAS  PubMed  Google Scholar 

  128. Fouré A, Bendahan D (2017) Is branched-chain amino acids supplementation an efficient nutritional strategy to alleviate skeletal muscle damage? A Systematic Review. Nutrients. https://doi.org/10.3390/nu9101047

    Article  PubMed  PubMed Central  Google Scholar 

  129. Atherton PJ, Smith K, Etheridge T, Rankin D, Rennie MJ (2010) Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids 38(5):1533–1539. https://doi.org/10.1007/s00726-009-0377-x

    Article  CAS  PubMed  Google Scholar 

  130. Buse MG, Reid SS (1975) Leucine. A possible regulator of protein turnover in muscle. J Clin Invest 56(5):1250–1261. https://doi.org/10.1172/JCI108201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Bratusch-Marrain P, Waldhäusl W (1979) The influence of amino acids and somatostatin on prolactin and growth hormone release in man. Acta Endocrinol (Copenh) 90(3):403–408

    CAS  Google Scholar 

  132. Anthony JC, Lang CH, Crozier SJ, Anthony TG, MacLean DA, Kimball SR, Jefferson LS (2002) Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab 282(5):E1092–E1101. https://doi.org/10.1152/ajpendo.00208.2001

    Article  CAS  PubMed  Google Scholar 

  133. English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E, Pattarini JM, Ploutz-Snyder R, Sheffield-Moore M, Paddon-Jones D (2016) Leucine partially protects muscle mass and function during bed rest in middle-aged adults. Am J Clin Nutr 103(2):465–473. https://doi.org/10.3945/ajcn.115.112359

    Article  CAS  PubMed  Google Scholar 

  134. Devries MC, McGlory C, Bolster DR, Kamil A, Rahn M, Harkness L, Baker SK, Phillips SM (2018) Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: a randomized, controlled trial. Am J Clin Nutr 107(2):217–226. https://doi.org/10.1093/ajcn/nqx028

    Article  PubMed  Google Scholar 

  135. Xu ZR, Tan ZJ, Zhang Q, Gui QF, Yang YM (2015) The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis. Br J Nutr 113(1):25–34. https://doi.org/10.1017/S0007114514002475

    Article  CAS  PubMed  Google Scholar 

  136. Komar B, Schwingshackl L, Hoffmann G (2015) Effects of leucine-rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta-analysis. J Nutr Health Aging 19(4):437–446. https://doi.org/10.1007/s12603-014-0559-4

    Article  CAS  PubMed  Google Scholar 

  137. Dickinson JM, Gundermann DM, Walker DK, Reidy PT, Borack MS, Drummond MJ, Arora M, Volpi E, Rasmussen BB (2014) Leucine-enriched amino acid ingestion after resistance exercise prolongs myofibrillar protein synthesis and amino acid transporter expression in older men. J Nutr 144(11):1694–1702. https://doi.org/10.3945/jn.114.198671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Ispoglou T, King RF, Polman RC, Zanker C (2011) Daily l-leucine supplementation in novice trainees during a 12-week weight training program. Int J Sports Physiol Perform 6(1):38–50

    PubMed  Google Scholar 

  139. Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB (2012) Determination of the tolerable upper intake level of leucine in acute dietary studies in young men. Am J Clin Nutr 96(4):759–767. https://doi.org/10.3945/ajcn.111.024471

    Article  CAS  PubMed  Google Scholar 

  140. Pasiakos SM, McClung JP (2011) Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids. Nutr Rev 69(9):550–557. https://doi.org/10.1111/j.1753-4887.2011.00420.x

    Article  PubMed  Google Scholar 

  141. Chen L, Chen Y, Wang X, Li H, Zhang H, Gong J, Shen S, Yin W, Hu H (2015) Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis. Nutr J 14:67. https://doi.org/10.1186/s12937-015-0056-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Sandonà D, Danieli-Betto D, Germinario E, Biral D, Martinello T, Lioy A, Tarricone E, Gastaldello S, Betto R (2005) The T-tubule membrane ATP-operated P2 × 4 receptor influences contractility of skeletal muscle. FASEB J 19(9):1184–1186. https://doi.org/10.1096/fj.04-3333fje

    Article  CAS  PubMed  Google Scholar 

  143. Heinonen I, Kemppainen J, Kaskinoro K, Peltonen JE, Sipilä HT, Nuutila P, Knuuti J, Boushel R, Kalliokoski KK (2012) Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 302(3):R385–R390. https://doi.org/10.1152/ajpregu.00245.2011

    Article  CAS  PubMed  Google Scholar 

  144. Rådegran G, Hellsten Y (2000) Adenosine and nitric oxide in exercise-induced human skeletal muscle vasodilatation. Acta Physiol Scand 168(4):575–591. https://doi.org/10.1046/j.1365-201x.2000.00705.x

    Article  PubMed  Google Scholar 

  145. Nyberg M, Mortensen SP, Thaning P, Saltin B, Hellsten Y (2010) Interstitial and plasma adenosine stimulate nitric oxide and prostacyclin formation in human skeletal muscle. Hypertension 56(6):1102–1108. https://doi.org/10.1161/HYPERTENSIONAHA.110.161521

    Article  CAS  PubMed  Google Scholar 

  146. Jäger R, Roberts MD, Lowery RP, Joy JM, Cruthirds CL, Lockwood CM, Rathmacher JA, Purpura M, Wilson JM (2014) Oral adenosine-5′-triphosphate (ATP) administration increases blood flow following exercise in animals and humans. J Int Soc Sports Nutr 11:28. https://doi.org/10.1186/1550-2783-11-28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Jordan AN, Jurca R, Abraham EH, Salikhova A, Mann JK, Morss GM, Church TS, Lucia A, Earnest CP (2004) Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc 36(6):983–990

    CAS  PubMed  Google Scholar 

  148. Freitas MC, Cholewa JM, Gerosa-Neto J, Gonçalves DC, Caperuto EC, Lira FS, Rossi FE (2017) A single dose of oral atp supplementation improves performance and physiological response during lower body resistance exercise in recreational resistance trained males. J Strength Cond Res. https://doi.org/10.1519/JSC.0000000000002198

    Article  PubMed  Google Scholar 

  149. Purpura M, Rathmacher JA, Sharp MH, Lowery RP, Shields KA, Partl JM, Wilson JM, Jäger R (2017) Oral Adenosine-5′-triphosphate (ATP) administration increases postexercise ATP levels, muscle excitability, and athletic performance following a repeated sprint bout. J Am Coll Nutr 36(3):177–183. https://doi.org/10.1080/07315724.2016.1246989

    Article  CAS  PubMed  Google Scholar 

  150. Rathmacher JA, Fuller JC, Baier SM, Abumrad NN, Angus HF, Sharp RL (2012) Adenosine-5′-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. J Int Soc Sports Nutr 9(1):48. https://doi.org/10.1186/1550-2783-9-48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier SM, Wilson SM, Rathmacher JA (2013) Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutr Metab (Lond) 10(1):57. https://doi.org/10.1186/1743-7075-10-57

    Article  CAS  Google Scholar 

  152. Coolen EJ, Arts IC, Bekers O, Vervaet C, Bast A, Dagnelie PC (2011) Oral bioavailability of ATP after prolonged administration. Br J Nutr 105(3):357–366. https://doi.org/10.1017/S0007114510003570

    Article  CAS  PubMed  Google Scholar 

  153. Rådegran G, Calbet JA (2001) Role of adenosine in exercise-induced human skeletal muscle vasodilatation. Acta Physiol Scand 171(2):177–185. https://doi.org/10.1046/j.1365-201x.2001.00796.x

    Article  PubMed  Google Scholar 

  154. Arts IC, Coolen EJ, Bours MJ, Huyghebaert N, Stuart MA, Bast A, Dagnelie PC (2012) Adenosine 5′-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans. J Int Soc Sports Nutr 9(1):16. https://doi.org/10.1186/1550-2783-9-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober L (2005) Almost all about citrulline in mammals. Amino acids 29(3):177–205. https://doi.org/10.1007/s00726-005-0235-4

    Article  CAS  PubMed  Google Scholar 

  156. Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun D (2011) Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study. Clin Nutr 30(6):807–811. https://doi.org/10.1016/j.clnu.2011.06.005

    Article  CAS  PubMed  Google Scholar 

  157. Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM (2015) l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol 119(4):385–395. https://doi.org/10.1152/japplphysiol.00192.2014

    Article  CAS  PubMed  Google Scholar 

  158. van Wijck K, Wijnands KA, Meesters DM, Boonen B, van Loon LJ, Buurman WA, Dejong CH, Lenaerts K, Poeze M (2014) l-citrulline improves splanchnic perfusion and reduces gut injury during exercise. Med Sci Sports Exerc 46(11):2039–2046. https://doi.org/10.1249/MSS.0000000000000332

    Article  CAS  PubMed  Google Scholar 

  159. Moinard C, Cynober L (2007) Citrulline: a new player in the control of nitrogen homeostasis. J Nutr 137(6 Suppl 2):1621S–1625S. https://doi.org/10.1093/jn/137.6.1621S

    Article  CAS  PubMed  Google Scholar 

  160. Ham DJ, Caldow MK, Lynch GS, Koopman R (2014) Arginine protects muscle cells from wasting in vitro in an mTORC1-dependent and NO-independent manner. Amino Acids 46(12):2643–2652. https://doi.org/10.1007/s00726-014-1815-y

    Article  CAS  PubMed  Google Scholar 

  161. Bouillanne O, Melchior JC, Faure C, Paul M, Canouï-Poitrine F, Boirie Y, Chevenne D, Forasassi C, Guery E, Herbaud S, Le Corvoisier P, Neveux N, Nivet-Antoine V, Astier A, Raynaud-Simon A, Walrand S, Cynober L, Aussel C (2018) Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: the Ciproage randomized controlled trial. Clin Nutr. https://doi.org/10.1016/j.clnu.2018.02.017

    Article  PubMed  Google Scholar 

  162. Moinard C, Nicolis I, Neveux N, Darquy S, Bénazeth S, Cynober L (2008) Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr 99(4):855–862. https://doi.org/10.1017/S0007114507841110

    Article  CAS  PubMed  Google Scholar 

  163. Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M (2006) l-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 38(4):660–666. https://doi.org/10.1249/01.mss.0000210197.02576.da

    Article  CAS  PubMed  Google Scholar 

  164. Glenn JM, Gray M, Jensen A, Stone MS, Vincenzo JL (2016) Acute citrulline-malate supplementation improves maximal strength and anaerobic power in female, masters athletes tennis players. Eur J Sport Sci 16(8):1095–1103. https://doi.org/10.1080/17461391.2016.1158321

    Article  PubMed  Google Scholar 

  165. Glenn JM, Gray M, Wethington LN, Stone MS, Stewart RW, Moyen NE (2017) Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. Eur J Nutr 56(2):775–784. https://doi.org/10.1007/s00394-015-1124-6

    Article  CAS  PubMed  Google Scholar 

  166. Pérez-Guisado J, Jakeman PM (2010) Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 24(5):1215–1222. https://doi.org/10.1519/JSC.0b013e3181cb28e0

    Article  PubMed  Google Scholar 

  167. Wax B, Kavazis AN, Weldon K, Sperlak J (2015) Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. J Strength Cond Res 29(3):786–792. https://doi.org/10.1519/JSC.0000000000000670

    Article  PubMed  Google Scholar 

  168. Cutrufello PT, Gadomski SJ, Zavorsky GS (2015) The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance. J Sports Sci 33(14):1459–1466. https://doi.org/10.1080/02640414.2014.990495

    Article  PubMed  Google Scholar 

  169. Hwang P, Morales Marroquín FE, Gann J, Andre T, McKinley-Barnard S, Kim C, Morita M, Willoughby DS (2018) Eight weeks of resistance training in conjunction with glutathione and l-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained males. J Int Soc Sports Nutr 15(1):30. https://doi.org/10.1186/s12970-018-0235-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Clarkson PM, Rawson ES (1999) Nutritional supplements to increase muscle mass. Crit Rev Food Sci Nutr 39(4):317–328. https://doi.org/10.1080/10408699991279196

    Article  CAS  PubMed  Google Scholar 

  171. Van Koevering M, Nissen S (1992) Oxidation of leucine and alpha-ketoisocaproate to beta-hydroxy-beta-methylbutyrate in vivo. Am J Physiol 262(1 Pt 1):E27–E31

    PubMed  Google Scholar 

  172. Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K (2015) Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr 61(2):168–175. https://doi.org/10.1016/j.archger.2015.06.020

    Article  CAS  PubMed  Google Scholar 

  173. Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR (2013) Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr 32(5):704–712. https://doi.org/10.1016/j.clnu.2013.02.011

    Article  CAS  PubMed  Google Scholar 

  174. Vukovich MD, Stubbs NB, Bohlken RM (2001) Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr 131(7):2049–2052

    CAS  PubMed  Google Scholar 

  175. Rowlands DS, Thomson JS (2009) Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis. J Strength Cond Res 23(3):836–846. https://doi.org/10.1519/JSC.0b013e3181a00c80

    Article  PubMed  Google Scholar 

  176. Sanchez-Martinez J, Santos-Lozano A, Garcia-Hermoso A, Sadarangani KP, Cristi-Montero C (2018) Effects of beta-hydroxy-beta-methylbutyrate supplementation on strength and body composition in trained and competitive athletes: a meta-analysis of randomized controlled trials. J Sci Med Sport 21(7):727–735. https://doi.org/10.1016/j.jsams.2017.11.003

    Article  PubMed  Google Scholar 

  177. Townsend JR, Hoffman JR, Gonzalez AM, Jajtner AR, Boone CH, Robinson EH, Mangine GT, Wells AJ, Fragala MS, Fukuda DH, Stout JR (2015) Effects of β-Hydroxy-β-methylbutyrate free acid ingestion and resistance exercise on the acute endocrine response. Int J Endocrinol 2015:856708. https://doi.org/10.1155/2015/856708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Teixeira FJ, Matias CN, Monteiro CP, Valamatos MJ, Reis J, Tavares F, Batista A, Domingos C, Alves F, Sardinha LB, Phillips SM (2018) Leucine metabolites do not enhance training-induced performance or muscle thickness. Med Sci Sports Exerc. https://doi.org/10.1249/MSS.0000000000001754

    Article  PubMed  Google Scholar 

  179. Portal S, Zadik Z, Rabinowitz J, Pilz-Burstein R, Adler-Portal D, Meckel Y, Cooper DM, Eliakim A, Nemet D (2011) The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double-blind, placebo-controlled study. Eur J Appl Physiol 111(9):2261–2269. https://doi.org/10.1007/s00421-011-1855-x

    Article  CAS  PubMed  Google Scholar 

  180. Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J (2013) International society of sports nutrition position stand: beta-hydroxy-beta-methylbutyrate (HMB). J Int Soc Sports Nutr 10(1):6. https://doi.org/10.1186/1550-2783-10-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ (2013) Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 591(11):2911–2923. https://doi.org/10.1113/jphysiol.2013.253203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Borack MS, Volpi E (2016) Efficacy and safety of leucine supplementation in the elderly. J Nutr 146(12):2625S–2629S. https://doi.org/10.3945/jn.116.230771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Lukaski HC (2000) Magnesium, zinc, and chromium nutriture and physical activity. Am J Clin Nutr 72(2 Suppl):585S–593S

    CAS  PubMed  Google Scholar 

  184. Ford ES, Mokdad AH (2003) Dietary magnesium intake in a national sample of US adults. J Nutr 133(9):2879–2882

    CAS  PubMed  Google Scholar 

  185. de Sousa EF, Da Costa TH, Nogueira JA, Vivaldi LJ (2008) Assessment of nutrient and water intake among adolescents from sports federations in the Federal District, Brazil. Br J Nutr 99(6):1275–1283. https://doi.org/10.1017/S0007114507864841

    Article  CAS  PubMed  Google Scholar 

  186. Mertens E, Kuijsten A, Dofková M, Mistura L, D’Addezio L, Turrini A, Dubuisson C, Favret S, Havard S, Trolle E, Van’t Veer P, Geleijnse JM (2018) Geographic and socioeconomic diversity of food and nutrient intakes: a comparison of four European countries. Eur J Nutr. https://doi.org/10.1007/s00394-018-1673-6

    Article  PubMed  PubMed Central  Google Scholar 

  187. Olza J, Aranceta-Bartrina J, González-Gross M, Ortega RM, Serra-Majem L, Varela-Moreiras G, Gil Á (2017) Reported dietary intake, disparity between the reported consumption and the level needed for adequacy and food sources of calcium, phosphorus, magnesium and vitamin d in the spanish population: findings from the ANIBES study. Nutrients 9 (2). https://doi.org/10.3390/nu9020168

    PubMed Central  Google Scholar 

  188. Wardenaar F, Brinkmans N, Ceelen I, Van Rooij B, Mensink M, Witkamp R, De Vries J (2017) Micronutrient intakes in 553 Dutch elite and sub-elite athletes: prevalence of low and high intakes in users and non-users of nutritional supplements. Nutrients. https://doi.org/10.3390/nu9020142

    Article  PubMed  PubMed Central  Google Scholar 

  189. van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M (2018) Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: a systematic review. J Am Med Dir Assoc 19(1):6–11.e13. https://doi.org/10.1016/j.jamda.2017.05.026

    Article  PubMed  Google Scholar 

  190. Musso CG (2009) Magnesium metabolism in health and disease. Int Urol Nephrol 41(2):357–362. https://doi.org/10.1007/s11255-009-9548-7

    Article  CAS  PubMed  Google Scholar 

  191. Zhang Y, Xun P, Wang R, Mao L, He K (2017) Can magnesium enhance exercise performance?. Nutrients. https://doi.org/10.3390/nu9090946

    Article  PubMed  PubMed Central  Google Scholar 

  192. Maggio M, De Vita F, Lauretani F, Nouvenne A, Meschi T, Ticinesi A, Dominguez LJ, Barbagallo M, Dall’aglio E, Ceda GP (2014) The interplay between magnesium and testosterone in modulating physical function in men. Int J Endocrinol 2014:525249. https://doi.org/10.1155/2014/525249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Dominguez LJ, Barbagallo M, Lauretani F, Bandinelli S, Bos A, Corsi AM, Simonsick EM, Ferrucci L (2006) Magnesium and muscle performance in older persons: the InCHIANTI study. Am J Clin Nutr 84(2):419–426

    CAS  PubMed  Google Scholar 

  194. Scott D, Blizzard L, Fell J, Giles G, Jones G (2010) Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort Study. J Am Geriatr Soc 58(11):2129–2134. https://doi.org/10.1111/j.1532-5415.2010.03147.x

    Article  PubMed  Google Scholar 

  195. Lukaski HC, Nielsen FH (2002) Dietary magnesium depletion affects metabolic responses during submaximal exercise in postmenopausal women. J Nutr 132(5):930–935

    CAS  PubMed  Google Scholar 

  196. Santos DA, Matias CN, Monteiro CP, Silva AM, Rocha PM, Minderico CS, Bettencourt Sardinha L, Laires MJ (2011) Magnesium intake is associated with strength performance in elite basketball, handball and volleyball players. Magnes Res 24(4):215–219. https://doi.org/10.1684/mrh.2011.0290

    Article  CAS  PubMed  Google Scholar 

  197. Brilla LR, Haley TF (1992) Effect of magnesium supplementation on strength training in humans. J Am Coll Nutr 11(3):326–329

    CAS  PubMed  Google Scholar 

  198. Kass LS, Poeira F (2015) The effect of acute vs chronic magnesium supplementation on exercise and recovery on resistance exercise, blood pressure and total peripheral resistance on normotensive adults. J Int Soc Sports Nutr 12:19. https://doi.org/10.1186/s12970-015-0081-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Newhouse IJ, Finstad EW (2000) The effects of magnesium supplementation on exercise performance. Clin J Sport Med 10(3):195–200

    CAS  PubMed  Google Scholar 

  200. Moslehi N, Vafa M, Sarrafzadeh J, Rahimi-Foroushani A (2013) Does magnesium supplementation improve body composition and muscle strength in middle-aged overweight women? A double-blind, placebo-controlled, randomized clinical trial. Biol Trace Elem Res 153(1–3):111–118. https://doi.org/10.1007/s12011-013-9672-1

    Article  CAS  PubMed  Google Scholar 

  201. Wang R, Chen C, Liu W, Zhou T, Xun P, He K, Chen P (2017) The effect of magnesium supplementation on muscle fitness: a meta-analysis and systematic review. Magnes Res 30(4):120–132. https://doi.org/10.1684/mrh.2018.0430

    Article  CAS  PubMed  Google Scholar 

  202. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73(1):79–118

    CAS  PubMed  Google Scholar 

  203. Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ (1996) Zinc status and serum testosterone levels of healthy adults. Nutrition 12(5):344–348

    CAS  PubMed  Google Scholar 

  204. Prasad AS (2014) Zinc is an antioxidant and anti-inflammatory agent: its role in human health. Front Nutr 1:14. https://doi.org/10.3389/fnut.2014.00014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Van Loan MD, Sutherland B, Lowe NM, Turnlund JR, King JC (1999) The effects of zinc depletion on peak force and total work of knee and shoulder extensor and flexor muscles. Int J Sport Nutr 9(2):125–135

    PubMed  Google Scholar 

  206. Krotkiewski M, Gudmundsson M, Backström P, Mandroukas K (1982) Zinc and muscle strength and endurance. Acta Physiol Scand 116(3):309–311. https://doi.org/10.1111/j.1748-1716.1982.tb07146.x

    Article  CAS  PubMed  Google Scholar 

  207. Ghavami-Maibodi SZ, Collipp PJ, Castro-Magana M, Stewart C, Chen SY (1983) Effect of oral zinc supplements on growth, hormonal levels, and zinc in healthy short children. Ann Nutr Metab 27(3):214–219

    CAS  PubMed  Google Scholar 

  208. Neek LS, Gaeini AA, Choobineh S (2011) Effect of zinc and selenium supplementation on serum testosterone and plasma lactate in cyclist after an exhaustive exercise bout. Biol Trace Elem Res 144(1–3):454–462

    Google Scholar 

  209. Gunanti IR, Al-Mamun A, Schubert L, Long KZ (2016) The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review. Public Health Nutr 19(16):2924–2939. https://doi.org/10.1017/S1368980016001154

    Article  PubMed  Google Scholar 

  210. Vincent JB (1999) Mechanisms of chromium action: low-molecular-weight chromium-binding substance. J Am Coll Nutr 18(1):6–12

    CAS  PubMed  Google Scholar 

  211. Hasten DL, Rome EP, Franks BD, Hegsted M (1992) Effects of chromium picolinate on beginning weight training students. Int J Sport Nutr 2(4):343–350

    CAS  PubMed  Google Scholar 

  212. Lukaski HC, Bolonchuk WW, Siders WA, Milne DB (1996) Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 63(6):954–965

    CAS  PubMed  Google Scholar 

  213. Volpe SL, Huang HW, Larpadisorn K, Lesser II (2001) Effect of chromium supplementation and exercise on body composition, resting metabolic rate and selected biochemical parameters in moderately obese women following an exercise program. J Am Coll Nutr 20(4):293–306

    CAS  PubMed  Google Scholar 

  214. Clancy SP, Clarkson PM, DeCheke ME, Nosaka K, Freedson PS, Cunningham JJ, Valentine B (1994) Effects of chromium picolinate supplementation on body composition, strength, and urinary chromium loss in football players. Int J Sport Nutr 4(2):142–153

    CAS  PubMed  Google Scholar 

  215. Campbell WW, Joseph LJ, Davey SL, Cyr-Campbell D, Anderson RA, Evans WJ (1999) Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men. J Appl Physiol 86(1):29–39

    CAS  PubMed  Google Scholar 

  216. Lukaski HC (2004) Vitamin and mineral status: effects on physical performance. Nutrition 20(7–8):632–644. https://doi.org/10.1016/j.nut.2004.04.001

    Article  CAS  PubMed  Google Scholar 

  217. Williams MH (2005) Dietary supplements and sports performance: minerals. J Int Soc Sports Nutr 2:43–49. https://doi.org/10.1186/1550-2783-2-1-43

    Article  PubMed  PubMed Central  Google Scholar 

  218. Reginster JY (2005) The high prevalence of inadequate serum vitamin D levels and implications for bone health. Curr Med Res Opin 21(4):579–586. https://doi.org/10.1185/030079905X41435

    Article  CAS  PubMed  Google Scholar 

  219. Montero-Odasso M, Duque G (2005) Vitamin D in the aging musculoskeletal system: an authentic strength preserving hormone. Mol Aspects Med 26(3):203–219. https://doi.org/10.1016/j.mam.2005.01.005

    Article  CAS  PubMed  Google Scholar 

  220. Vitale G, Cesari M, Mari D (2016) Aging of the endocrine system and its potential impact on sarcopenia. Eur J Intern Med 35:10–15. https://doi.org/10.1016/j.ejim.2016.07.017

    Article  CAS  PubMed  Google Scholar 

  221. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 dietary reference intakes for calcium and vitamin D: what dietetics practitioners need to know. J Am Diet Assoc 111(4):524–527. https://doi.org/10.1016/j.jada.2011.01.004

    Article  CAS  PubMed  Google Scholar 

  222. Verlaan S, Maier AB, Bauer JM, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Sieber C, Boirie Y, Cederholm T (2017) Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults—the PROVIDE study. Clin Nutr. https://doi.org/10.1016/j.clnu.2017.01.005

    Article  PubMed  Google Scholar 

  223. Buta B, Choudhury PP, Xue QL, Chaves P, Bandeen-Roche K, Shardell M, Semba RD, Walston J, Michos ED, Appel LJ, McAdams-DeMarco M, Gross A, Yasar S, Ferrucci L, Fried LP, Kalyani RR (2016) The association of vitamin D deficiency and incident frailty in older women: the role of cardiometabolic diseases. J Am Geriatr Soc. https://doi.org/10.1111/jgs.14677

    Article  PubMed  PubMed Central  Google Scholar 

  224. Fuller JC, Baier S, Flakoll P, Nissen SL, Abumrad NN, Rathmacher JA (2011) Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study. J Parenter Enteral Nutr 35(6):757–762. https://doi.org/10.1177/0148607111413903

    Article  CAS  Google Scholar 

  225. Muir SW, Montero-Odasso M (2011) Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 59(12):2291–2300. https://doi.org/10.1111/j.1532-5415.2011.03733.x

    Article  PubMed  Google Scholar 

  226. Tomlinson PB, Joseph C, Angioi M (2015) Effects of vitamin D supplementation on upper and lower body muscle strength levels in healthy individuals. A systematic review with meta-analysis. J Sci Med Sport 18(5):575–580. https://doi.org/10.1016/j.jsams.2014.07.022

    Article  PubMed  Google Scholar 

  227. Farrokhyar F, Sivakumar G, Savage K, Koziarz A, Jamshidi S, Ayeni OR, Peterson D, Bhandari M (2017) Effects of Vitamin D supplementation on serum 25-hydroxyvitamin D concentrations and physical performance in athletes: a systematic review and meta-analysis of randomized controlled trials. Sports Med. https://doi.org/10.1007/s40279-017-0749-4

    Article  PubMed  Google Scholar 

  228. Rosendahl-Riise H, Spielau U, Ranhoff AH, Gudbrandsen OA, Dierkes J (2017) Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. J Hum Nutr Diet 30(1):3–15. https://doi.org/10.1111/jhn.12394

    Article  CAS  PubMed  Google Scholar 

  229. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 22 (3):859–871. https://doi.org/10.1007/s00198-010-1407-y

    Article  CAS  PubMed  Google Scholar 

  230. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, Petermans J, Reginster JY, Bruyère O (2014) The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 99(11):4336–4345. https://doi.org/10.1210/jc.2014-1742

    Article  CAS  PubMed  Google Scholar 

  231. Agergaard J, Trøstrup J, Uth J, Iversen JV, Boesen A, Andersen JL, Schjerling P, Langberg H (2015) Does vitamin-D intake during resistance training improve the skeletal muscle hypertrophic and strength response in young and elderly men?—a randomized controlled trial. Nutr Metab (Lond) 12:32. https://doi.org/10.1186/s12986-015-0029-y

    Article  CAS  Google Scholar 

  232. Antoniak AE, Greig CA (2017) The effect of combined resistance exercise training and vitamin D. BMJ Open 7(7):e014619. https://doi.org/10.1136/bmjopen-2016-014619

    Article  PubMed  PubMed Central  Google Scholar 

  233. Makanae Y, Kawada S, Sasaki K, Nakazato K, Ishii N (2013) Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats. Acta Physiol (Oxf) 208(1):57–65. https://doi.org/10.1111/apha.12042

    Article  CAS  Google Scholar 

  234. Paulsen G, Hamarsland H, Cumming KT, Johansen RE, Hulmi JJ, Børsheim E, Wiig H, Garthe I, Raastad T (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 592(24):5391–5408. https://doi.org/10.1113/jphysiol.2014.279950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Bjørnsen T, Salvesen S, Berntsen S, Hetlelid KJ, Stea TH, Lohne-Seiler H, Rohde G, Haraldstad K, Raastad T, Køpp U, Haugeberg G, Mansoor MA, Bastani NE, Blomhoff R, Stølevik SB, Seynnes OR, Paulsen G (2016) Vitamin C and E supplementation blunts increases in total lean body mass in elderly men after strength training. Scand J Med Sci Sports 26(7):755–763. https://doi.org/10.1111/sms.12506

    Article  PubMed  Google Scholar 

  236. Stunes AK, Syversen U, Berntsen S, Paulsen G, Stea TH, Hetlelid KJ, Lohne-Seiler H, Mosti MP, Bjørnsen T, Raastad T, Haugeberg G (2017) High doses of vitamin C plus E reduce strength training-induced improvements in areal bone mineral density in elderly men. Eur J Appl Physiol 117(6):1073–1084. https://doi.org/10.1007/s00421-017-3588-y

    Article  CAS  PubMed  Google Scholar 

  237. Bobeuf F, Labonte M, Dionne IJ, Khalil A (2011) Combined effect of antioxidant supplementation and resistance training on oxidative stress markers, muscle and body composition in an elderly population. J Nutr Health Aging 15(10):883–889

    CAS  PubMed  Google Scholar 

  238. Labonté M, Dionne IJ, Bouchard DR, Sénéchal M, Tessier D, Khalil A, Bobeuf F (2008) Effects of antioxidant supplements combined with resistance exercise on gains in fat-free mass in healthy elderly subjects: a pilot study. J Am Geriatr Soc 56(9):1766–1768. https://doi.org/10.1111/j.1532-5415.2008.01810.x

    Article  PubMed  Google Scholar 

  239. Minisola S, Cianferotti L, Biondi P, Cipriani C, Fossi C, Franceschelli F, Giusti F, Leoncini G, Pepe J, Bischoff-Ferrari HA, Brandi ML (2017) Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens. Osteoporos Int 28 (11):3239–3249. https://doi.org/10.1007/s00198-017-4180-3

    Article  CAS  PubMed  Google Scholar 

  240. Hamishehkar H, Ranjdoost F, Asgharian P, Mahmoodpoor A, Sanaie S (2016) Vitamins, are they safe? Adv Pharm Bull 6(4):467–477. https://doi.org/10.15171/apb.2016.061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Bond P (2017) Phosphatidic acid: biosynthesis, pharmacokinetics, mechanisms of action and effect on strength and body composition in resistance-trained individuals. Nutr Metab (Lond) 14:12. https://doi.org/10.1186/s12986-017-0166-6

    Article  CAS  Google Scholar 

  242. Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294(5548):1942–1945. https://doi.org/10.1126/science.1066015

    Article  CAS  PubMed  Google Scholar 

  243. Mobley CB, Hornberger TA, Fox CD, Healy JC, Ferguson BS, Lowery RP, McNally RM, Lockwood CM, Stout JR, Kavazis AN, Wilson JM, Roberts MD (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 12:32. https://doi.org/10.1186/s12970-015-0094-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Gonzalez AM, Sell KM, Ghigiarelli JJ, Kelly CF, Shone EW, Accetta MR, Baum JB, Mangine GT (2017) Effects of phosphatidic acid supplementation on muscle thickness and strength in resistance-trained men. Appl Physiol Nutr Metab 42 (4):443–448. https://doi.org/10.1139/apnm-2016-0564

    Article  CAS  PubMed  Google Scholar 

  245. Shad BJ, Smeuninx B, Atherton PJ, Breen L (2015) The mechanistic and ergogenic effects of phosphatidic acid in skeletal muscle. Appl Physiol Nutr Metab 40 (12):1233–1241. https://doi.org/10.1139/apnm-2015-0350

    Article  CAS  PubMed  Google Scholar 

  246. Hoffman JR, Stout JR, Williams DR, Wells AJ, Fragala MS, Mangine GT, Gonzalez AM, Emerson NS, McCormack WP, Scanlon TC, Purpura M, Jäger R (2012) Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men. J Int Soc Sports Nutr 9(1):47. https://doi.org/10.1186/1550-2783-9-47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Joy JM, Gundermann DM, Lowery RP, Jäger R, McCleary SA, Purpura M, Roberts MD, Wilson SM, Hornberger TA, Wilson JM (2014) Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy. Nutr Metab (Lond) 11:29. https://doi.org/10.1186/1743-7075-11-29

    Article  CAS  PubMed Central  Google Scholar 

  248. Andre TL, Gann JJ, McKinley-Barnard SK, Song JJ, Willoughby DS (2016) eight weeks of phosphatidic acid supplementation in conjunction with resistance training does not differentially affect body composition and muscle strength in resistance-trained men. J Sports Sci Med 15(3):532–539

    PubMed  PubMed Central  Google Scholar 

  249. Campbell BI, La Bounty PM, Roberts M (2004) The ergogenic potential of arginine. J Int Soc Sports Nutr 1(2):35–38. https://doi.org/10.1186/1550-2783-1-2-35

    Article  PubMed  PubMed Central  Google Scholar 

  250. Castillo L, Ajami A, Branch S, Chapman TE, Yu YM, Burke JF, Young VR (1994) Plasma arginine kinetics in adult man: response to an arginine-free diet. Metabolism 43(1):114–122

    CAS  PubMed  Google Scholar 

  251. Wideman L, Weltman JY, Patrie JT, Bowers CY, Shah N, Story S, Weltman A, Veldhuis JD (2000) Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender. Am J Physiol Regul Integr Comp Physiol 279(4):R1455–R1466

    CAS  PubMed  Google Scholar 

  252. Wideman L, Weltman JY, Patrie JT, Bowers CY, Shah N, Story S, Veldhuis JD, Weltman A (2000) Synergy of l-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise. Am J Physiol Regul Integr Comp Physiol 279(4):R1467–R1477

    CAS  PubMed  Google Scholar 

  253. Chromiak JA, Antonio J (2002) Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 18(7–8):657–661

    CAS  PubMed  Google Scholar 

  254. Collier SR, Collins E, Kanaley JA (2006) Oral arginine attenuates the growth hormone response to resistance exercise. J Appl Physiol (1985) 101(3):848–852. https://doi.org/10.1152/japplphysiol.00285.2006

    Article  CAS  Google Scholar 

  255. Isidori A, Lo Monaco A, Cappa M (1981) A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 7(7):475–481. https://doi.org/10.1185/03007998109114287

    Article  CAS  PubMed  Google Scholar 

  256. Walberg-Rankin J, Hawkins CE, Fild DS, Sebolt DR (1994) The effect of oral arginine during energy restriction in male weight trainers. J Strength Cond Res 8(3):170–177

    Google Scholar 

  257. Forbes SC, Bell GJ (2011) The acute effects of a low and high dose of oral l-arginine supplementation in young active males at rest. Appl Physiol Nutr Metab 36 (3):405–411. https://doi.org/10.1139/h11-035

    Article  CAS  PubMed  Google Scholar 

  258. Blum A, Cannon RO, Costello R, Schenke WH, Csako G (2000) Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. J Lab Clin Med 135(3):231–237. https://doi.org/10.1067/mlc.2000.104909

    Article  CAS  PubMed  Google Scholar 

  259. Angeli G, Barros TLD, Barros DFLD, Lima M (2007) Investigation of the effects of oral supplementation of arginine in the increase of muscular strength and mass. Revista Brasileira de Medicina do Esporte 13(2):129–132

    Google Scholar 

  260. Pahlavani N, Entezari MH, Nasiri M, Miri A, Rezaie M, Bagheri-Bidakhavidi M, Sadeghi O (2017) The effect of l-arginine supplementation on body composition and performance in male athletes: a double-blinded randomized clinical trial. Eur J Clin Nutr 71(4):544–548. https://doi.org/10.1038/ejcn.2016.266

    Article  CAS  PubMed  Google Scholar 

  261. Chilosi A, Casarano M, Comparini A, Battaglia FM, Mancardi MM, Schiaffino C, Tosetti M, Leuzzi V, Battini R, Cioni G (2012) Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency. Orphanet J Rare Dis 7:43. https://doi.org/10.1186/1750-1172-7-43

    Article  PubMed  PubMed Central  Google Scholar 

  262. Valayannopoulos V, Boddaert N, Chabli A, Barbier V, Desguerre I, Philippe A, Afenjar A, Mazzuca M, Cheillan D, Munnich A, de Keyzer Y, Jakobs C, Salomons GS, de Lonlay P (2012) Treatment by oral creatine, l-arginine and l-glycine in six severely affected patients with creatine transporter defect. J Inherit Metab Dis 35(1):151–157. https://doi.org/10.1007/s10545-011-9358-9

    Article  CAS  PubMed  Google Scholar 

  263. Alvares TS, Conte-Junior CA, Silva JT, Paschoalin VM (2012) Acute l-Arginine supplementation does not increase nitric oxide production in healthy subjects. Nutr Metab (Lond) 9(1):54. https://doi.org/10.1186/1743-7075-9-54

    Article  CAS  Google Scholar 

  264. Alvares TS, Conte CA, Paschoalin VM, Silva JT, Meirelles CeM, Bhambhani YN, Gomes PS (2012) Acute l-arginine supplementation increases muscle blood volume but not strength performance. Appl Physiol Nutr Metab 37 (1):115–126. https://doi.org/10.1139/h11-144

    Article  CAS  PubMed  Google Scholar 

  265. Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS (2011) l-Arginine as a potential ergogenic aid in healthy subjects. Sports Med 41(3):233–248. https://doi.org/10.2165/11538590-000000000-00000

    Article  PubMed  Google Scholar 

  266. Pariza MW, Park Y, Cook ME (2001) The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 40(4):283–298

    CAS  PubMed  Google Scholar 

  267. Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello GA (2006) The effects of conjugated linoleic acid supplementation during resistance training. Med Sci Sports Exerc 38(2):339–348. https://doi.org/10.1249/01.mss.0000183860.42853.15

    Article  CAS  PubMed  Google Scholar 

  268. Tarnopolsky M, Zimmer A, Paikin J, Safdar A, Aboud A, Pearce E, Roy B, Doherty T (2007) Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS One 2(10):e991. https://doi.org/10.1371/journal.pone.0000991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL (2002) Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers. J Strength Cond Res 16(3):325–334

    PubMed  Google Scholar 

  270. Song HJ, Grant I, Rotondo D, Mohede I, Sattar N, Heys SD, Wahle KW (2005) Effect of CLA supplementation on immune function in young healthy volunteers. Eur J Clin Nutr 59(4):508–517. https://doi.org/10.1038/sj.ejcn.1602102

    Article  CAS  PubMed  Google Scholar 

  271. Curi R, Newsholme P, Procopio J, Lagranha C, Gorjão R, Pithon-Curi TC (2007) Glutamine, gene expression, and cell function. Front Biosci 12:344–357

    CAS  PubMed  Google Scholar 

  272. Wu G, Wu Z, Dai Z, Yang Y, Wang W, Liu C, Wang B, Wang J, Yin Y (2013) Dietary requirements of “nutritionally non-essential amino acids” by animals and humans. Amino acids 44(4):1107–1113. https://doi.org/10.1007/s00726-012-1444-2

    Article  CAS  PubMed  Google Scholar 

  273. Wernerman J (2008) Clinical use of glutamine supplementation. J Nutr 138 (10): 2040S–2044S

    CAS  PubMed  Google Scholar 

  274. Novak F, Heyland DK, Avenell A, Drover JW, Su X (2002) Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 30(9):2022–2029. https://doi.org/10.1097/01.CCM.0000026106.58241.95

    Article  CAS  PubMed  Google Scholar 

  275. Hammarqvist F, Wernerman J, Ali R, von der Decken A, Vinnars E (1989) Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg 209(4):455–461

    CAS  PubMed  PubMed Central  Google Scholar 

  276. Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lawin P, Fürst P (1989) Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1(8632):231–233

    CAS  PubMed  Google Scholar 

  277. Mok E, Eléouet-Da Violante C, Daubrosse C, Gottrand F, Rigal O, Fontan JE, Cuisset JM, Guilhot J, Hankard R (2006) Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy. Am J Clin Nutr 83(4):823–828

    CAS  PubMed  Google Scholar 

  278. Antonio J, Sanders MS, Kalman D, Woodgate D, Street C (2002) The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res 16(1):157–160

    PubMed  Google Scholar 

  279. Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T (2001) Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol 86(2):142–149. https://doi.org/10.1007/s00421-001-0523-y

    Article  CAS  PubMed  Google Scholar 

  280. Ramezani Ahmadi A, Rayyani E, Bahreini M, Mansoori A (2018) The effect of glutamine supplementation on athletic performance, body composition, and immune function: a systematic review and a meta-analysis of clinical trials. Clin Nutr. https://doi.org/10.1016/j.clnu.2018.05.001

    Article  PubMed  Google Scholar 

  281. Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P (2018) Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients. https://doi.org/10.3390/nu10111564

    Article  PubMed  PubMed Central  Google Scholar 

  282. Gleeson M (2008) Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr 138(10):2045S–2049S

    CAS  PubMed  Google Scholar 

  283. Lin Y, Chen F, Zhang J, Wang T, Wei X, Wu J, Feng Y, Dai Z, Wu Q (2013) Neuroprotective effect of resveratrol on ischemia/reperfusion injury in rats through TRPC6/CREB pathways. J Mol Neurosci 50(3):504–513. https://doi.org/10.1007/s12031-013-9977-8

    Article  CAS  PubMed  Google Scholar 

  284. Mattison JA, Wang M, Bernier M, Zhang J, Park SS, Maudsley S, An SS, Santhanam L, Martin B, Faulkner S, Morrell C, Baur JA, Peshkin L, Sosnowska D, Csiszar A, Herbert RL, Tilmont EM, Ungvari Z, Pearson KJ, Lakatta EG, de Cabo R (2014) Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab 20(1):183–190. https://doi.org/10.1016/j.cmet.2014.04.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM (2011) Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 21(11):851–856. https://doi.org/10.1016/j.numecd.2010.03.003

    Article  CAS  PubMed  Google Scholar 

  286. Dutt V, Gupta S, Dabur R, Injeti E, Mittal A (2015) Skeletal muscle atrophy: potential therapeutic agents and their mechanisms of action. Pharmacol Res 99:86–100. https://doi.org/10.1016/j.phrs.2015.05.010

    Article  CAS  PubMed  Google Scholar 

  287. Rathbone CR, Booth FW, Lees SJ (2009) Sirt1 increases skeletal muscle precursor cell proliferation. Eur J Cell Biol 88(1):35–44. https://doi.org/10.1016/j.ejcb.2008.08.003

    Article  CAS  PubMed  Google Scholar 

  288. Bennett BT, Mohamed JS, Alway SE (2013) Effects of resveratrol on the recovery of muscle mass following disuse in the plantaris muscle of aged rats. PLoS One 8(12):e83518. https://doi.org/10.1371/journal.pone.0083518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  289. Jackson JR, Ryan MJ, Alway SE (2011) Long-term supplementation with resveratrol alleviates oxidative stress but does not attenuate sarcopenia in aged mice. J Gerontol A Biol Sci Med Sci 66(7):751–764. https://doi.org/10.1093/gerona/glr047

    Article  CAS  PubMed  Google Scholar 

  290. Ballak SB, Jaspers RT, Deldicque L, Chalil S, Peters EL, de Haan A, Degens H (2015) Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol. Exp Gerontol 62:23–31. https://doi.org/10.1016/j.exger.2014.12.020

    Article  CAS  PubMed  Google Scholar 

  291. Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS (2017) Resveratrol enhances exercise-induced cellular and functional adaptations of skeletal muscle in older men and women. J Gerontol A Biol Sci Med Sci. https://doi.org/10.1093/gerona/glx089

    Article  PubMed  PubMed Central  Google Scholar 

  292. Katashima CK, Silva VR, Gomes TL, Pichard C, Pimentel GD (2017) Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review. Obes Rev 18(6):700–711. https://doi.org/10.1111/obr.12523

    Article  CAS  PubMed  Google Scholar 

  293. Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM (2011) mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab 13(6):627–638. https://doi.org/10.1016/j.cmet.2011.03.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM (2012) Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One 7(6):e39332. https://doi.org/10.1371/journal.pone.0039332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  295. Cho YH, Lee SY, Kim CM, Kim ND, Choe S, Lee CH, Shin JH (2016) Effect of loquat leaf extract on muscle strength, muscle mass, and muscle function in healthy adults: a randomized, double-blinded, and placebo-controlled trial. Evid Based Complement Alternat Med 2016:4301621. https://doi.org/10.1155/2016/4301621

    Article  PubMed  PubMed Central  Google Scholar 

  296. Church DD, Schwarz NA, Spillane MB, McKinley-Barnard SK, Andre TL, Ramirez AJ, Willoughby DS (2016) l-Leucine increases skeletal muscle IGF-1 but does not differentially increase Akt/mTORC1 signaling and serum IGF-1 compared to ursolic acid in response to resistance exercise in resistance-trained men. J Am Coll Nutr 35(7):627–638. https://doi.org/10.1080/07315724.2015.1132019

    Article  CAS  PubMed  Google Scholar 

  297. Bang HS, Seo DY, Chung YM, Oh KM, Park JJ, Arturo F, Jeong SH, Kim N, Han J (2014) Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Korean J Physiol Pharmacol 18(5):441–446. https://doi.org/10.4196/kjpp.2014.18.5.441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  298. Qureshi A, Naughton DP, Petroczi A (2014) A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect. J Diet Suppl 11(1):64–79. https://doi.org/10.3109/19390211.2014.887602

    Article  PubMed  Google Scholar 

  299. Neychev VK, Mitev VI (2005) The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men. J Ethnopharmacol 101(1–3):319–323. https://doi.org/10.1016/j.jep.2005.05.017

    Article  CAS  PubMed  Google Scholar 

  300. Ma Y, Guo Z, Wang X (2015) Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms: roles of androgen, IGF-1, and IGF binding protein-3. J Sport Health Sci 12:1–8

    CAS  Google Scholar 

  301. Rogerson S, Riches CJ, Jennings C, Weatherby RP, Meir RA, Marshall-Gradisnik SM (2007) The effect of five weeks of Tribulus terrestris supplementation on muscle strength and body composition during preseason training in elite rugby league players. J Strength Cond Res 21(2):348–353. https://doi.org/10.1519/R-18395.1

    Article  PubMed  Google Scholar 

  302. Antonio J, Uelmen J, Rodriguez R, Earnest C (2000) The effects of Tribulus terrestris on body composition and exercise performance in resistance-trained males. Int J Sport Nutr Exerc Metab 10(2):208–215

    CAS  PubMed  Google Scholar 

  303. Roaiah MF, El Khayat YI, GamalEl Din SF, Abd El Salam MA (2016) Pilot study on the effect of botanical medicine (Tribulus terrestris) on serum testosterone level and erectile function in aging males with partial androgen deficiency (PADAM). J Sex Marital Ther 42(4):297–301. https://doi.org/10.1080/0092623X.2015.1033579

    Article  PubMed  Google Scholar 

  304. Barillaro C, Liperoti R, Martone AM, Onder G, Landi F (2013) The new metabolic treatments for sarcopenia. Aging Clin Exp Res 25(2):119–127. https://doi.org/10.1007/s40520-013-0030-0

    Article  PubMed  Google Scholar 

  305. Yao K, Yin Y, Li X, Xi P, Wang J, Lei J, Hou Y, Wu G (2012) Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids 42(6):2491–2500. https://doi.org/10.1007/s00726-011-1060-6

    Article  CAS  PubMed  Google Scholar 

  306. Cai X, Zhu C, Xu Y, Jing Y, Yuan Y, Wang L, Wang S, Zhu X, Gao P, Zhang Y, Jiang Q, Shu G (2016) Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways. Sci Rep 6:26802. https://doi.org/10.1038/srep26802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  307. Riedel E, Nündel M, Hampl H (1996) Alpha-Ketoglutarate application in hemodialysis patients improves amino acid metabolism. Nephron 74(2):261–265

    CAS  PubMed  Google Scholar 

  308. Wirén M, Permert J, Larsson J (2002) Alpha-ketoglutarate-supplemented enteral nutrition: effects on postoperative nitrogen balance and muscle catabolism. Nutrition 18(9):725–728

    PubMed  Google Scholar 

  309. Cynober L (2004) Ornithine alpha-ketoglutarate as a potent precursor of arginine and nitric oxide: a new job for an old friend. J Nutr 134 (10 Suppl):2858S–2862S. (discussion 2895S)

    CAS  PubMed  Google Scholar 

  310. Le Bricon T, Coudray-Lucas C, Lioret N, Lim SK, Plassart F, Schlegel L, De Bandt JP, Saizy R, Giboudeau J, Cynober L (1997) Ornithine alpha-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion. Am J Clin Nutr 65(2):512–518

    PubMed  Google Scholar 

  311. Campbell B, Roberts M, Kerksick C, Wilborn C, Marcello B, Taylor L, Nassar E, Leutholtz B, Bowden R, Rasmussen C, Greenwood M, Kreider R (2006) Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition 22(9):872–881. https://doi.org/10.1016/j.nut.2006.06.003

    Article  CAS  PubMed  Google Scholar 

  312. Wax B, Kavazis AN, Webb HE, Brown SP (2012) Acute l-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men. J Int Soc Sports Nutr 9(1):17. https://doi.org/10.1186/1550-2783-9-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  313. Prosser JM, Majlesi N, Chan GM, Olsen D, Hoffman RS, Nelson LS (2009) Adverse effects associated with arginine alpha-ketoglutarate containing supplements. Hum Exp Toxicol 28(5):259–262. https://doi.org/10.1177/0960327109104498

    Article  CAS  PubMed  Google Scholar 

  314. Kokubo T, Maeda S, Tazumi K, Nozawa H, Miura Y, Kirisako T (2015) The effect of l-Ornithine on the phosphorylation of mTORC1 downstream targets in rat liver. Prev Nutr Food Sci 20(4):238–245. https://doi.org/10.3746/pnf.2015.20.4.238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  315. Tujioka K, Yamada T, Aoki M, Morishita K, Hayase K, Yokogoshi H (2012) Dietary ornithine affects the tissue protein synthesis rate in young rats. J Nutr Sci Vitaminol (Tokyo) 58(4):297–302

    CAS  Google Scholar 

  316. Evain-Brion D, Donnadieu M, Roger M, Job JC (1982) Simultaneous study of somatotrophic and corticotrophic pituitary secretions during ornithine infusion test. Clin Endocrinol (Oxf) 17(2):119–122

    CAS  Google Scholar 

  317. Demura S, Yamada T, Yamaji S, Komatsu M, Morishita K (2010) The effect of l-ornithine hydrochloride ingestion on human growth hormone secretion after strength training. Adv Biosci Biotechnol 1:7–11

    CAS  Google Scholar 

  318. Bucci L, Hickson JF, Pivarnik JM, Wolinsky I, McMahon JC, Turner SD (1990) Ornithine ingestion and growth hormone release in bodybuilders. Nutr Res 10(3):239–245

    CAS  Google Scholar 

  319. Peeling P, Binnie MJ, Goods PSR, Sim M, Burke LM (2018) Evidence-based supplements for the enhancement of athletic performance. Int J Sport Nutr Exerc Metab 28(2):178–187. https://doi.org/10.1123/ijsnem.2017-0343

    Article  CAS  PubMed  Google Scholar 

  320. Jones AM (2014) Dietary nitrate supplementation and exercise performance. Sports Med 44 (Suppl 1):S35–S45. https://doi.org/10.1007/s40279-014-0149-y

    Article  PubMed  Google Scholar 

  321. Molfino A, Gioia G, Rossi Fanelli F, Muscaritoli M (2014) The role for dietary omega-3 fatty acids supplementation in older adults. Nutrients 6(10):4058–4073. https://doi.org/10.3390/nu6104058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  322. Pencharz PB, Elango R, Ball RO (2012) Determination of the tolerable upper intake level of leucine in adult men. J Nutr 142(12):2220S–2224S. https://doi.org/10.3945/jn.112.160259

    Article  CAS  PubMed  Google Scholar 

  323. Kantartzis K, Fritsche L, Bombrich M, Machann J, Schick F, Staiger H, Kunz I, Schoop R, Lehn-Stefan A, Heni M, Peter A, Fritsche A, Häring HU, Stefan N (2018) Effects of resveratrol supplementation on liver fat content in overweight and insulin-resistant subjects: a randomized, double-blind, placebo-controlled clinical trial. Diabetes Obes Metab. https://doi.org/10.1111/dom.13268

    Article  PubMed  Google Scholar 

  324. Anton SD, Embry C, Marsiske M, Lu X, Doss H, Leeuwenburgh C, Manini TM (2014) Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study. Exp Gerontol 57:181–187. https://doi.org/10.1016/j.exger.2014.05.015

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

PLV is supported by University of Alcalá (FPI2016); JSM is supported by Spanish Ministry of Education, Culture and Sport (FPU14/03435); HPG is supported by Universidad Europea de Madrid (2017/UEM05) and Cátedra Real Madrid–Universidad Europea (2017/RM03); AL is supported by Spanish Ministry of Economy and Competitiveness and Fondos FEDER (PI15/00558).

Author information

Author notes

  1. Pedro L. Valenzuela, Javier S. Morales have contributed equally to this work.

Authors and Affiliations

  1. Department of Sport and Health, Spanish Agency for Health Protection in Sport (AEPSAD), Madrid, Spain

    Pedro L. Valenzuela

  2. Physiology Unit. Systems Biology Department, University of Alcalá, Madrid, Spain

    Pedro L. Valenzuela

  3. Faculty of Sport Sciences, Universidad Europea De Madrid, Villaviciosa De Odón, 28670, Madrid, Spain

    Javier S. Morales, Helios Pareja-Galeano & Alejandro Lucia

  4. 2E Science, Robbio, Pavia, Italy

    Enzo Emanuele

  5. Research Institute of the Hospital 12 De Octubre (i+12), Madrid, Spain

    Helios Pareja-Galeano & Alejandro Lucia

Authors
  1. Pedro L. Valenzuela
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Javier S. Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enzo Emanuele
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helios Pareja-Galeano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alejandro Lucia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors have contributed significantly to the work: HPG and EE conceived the original idea; JSM and PLV wrote the initial draft; HP-G, EE and AL reviewed the draft and contributed to the final version of the manuscript. All authors (PLV, JSM, EE, HP-G and AL) have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

Corresponding author

Correspondence to Helios Pareja-Galeano.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Additional information

Helios Pareja-Galeano, Alejandro Lucia share senior authorship.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Valenzuela, P.L., Morales, J.S., Emanuele, E. et al. Supplements with purported effects on muscle mass and strength. Eur J Nutr 58, 2983–3008 (2019). https://doi.org/10.1007/s00394-018-1882-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-018-1882-z

Keywords

  • Hypertrophy
  • Ergogenic aid
  • Skeletal muscle
  • Protein supplementation
  • Prevention of atrophy
  • Sarcopenia