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Amino Acids

, Volume 46, Issue 8, pp 1785–1793 | Cite as

Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms

  • Jason M. Cholewa
  • Lucas Guimarães-Ferreira
  • Nelo Eidy Zanchi
Review Article

Abstract

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects.

Keywords

Hypertrophy Strength Ergogenic Methylation Lipogenesis Sarcopenia 

Notes

Acknowledgments

The authors thank Stuart A.S. Craig for his help refining the manuscript.

Conflict of interest

No funding was obtained for the preparation of this manuscript. The authors declare no conflicts of interest relevant to this manuscript.

References

  1. Abdelmalek MF, Sanderson SO, Angulo P et al (2009) Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology 50:1818–1826. doi: 10.1002/hep.23239 PubMedCrossRefGoogle Scholar
  2. Abe T, DeHoyos DV, Pollock ML, Garzarella L (2000) Time course for strength and muscle thickness changes following upper and lower body resistance training in men and women. Eur J Appl Physiol 81:174–180. doi: 10.1007/s004210050027 PubMedCrossRefGoogle Scholar
  3. Apicella JM, Lee EC, Bailey BL et al (2012) Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise. Eur J Appl Physiol. doi: 10.1007/s00421-012-2492-8
  4. Armstrong LE, Casa DJ, Roti MW et al (2008) Influence of betaine consumption on strenuous running and sprinting in a hot environment. J Strength Cond Res 22:851PubMedCrossRefGoogle Scholar
  5. Atkinson W, Elmslie J, Lever M et al (2008) Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects. Am J Clin Nutr 87:577–585PubMedGoogle Scholar
  6. Atkinson W, Slow S, Elmslie J et al (2009) Dietary and supplementary betaine: effects on betaine and homocysteine concentrations in males. Nutr Metab Cardiovasc Dis 19:767–773. doi: 10.1016/j.numecd.2009.01.004 PubMedCrossRefGoogle Scholar
  7. Barbarino A, Corsello SM, Della Casa S et al (1990) Corticotropin-releasing hormone inhibition of growth hormone-releasing hormone-induced growth hormone release in man. J Clin Endocrinol Metab 71:1368–1374PubMedCrossRefGoogle Scholar
  8. Bloomer RJ, Farney TM, Trepanowski JF et al (2011) Effect of betaine supplementation on plasma nitrate/nitrite in exercise-trained men. J Int Soc Sports Nutr 8:1–7. doi: 10.1186/1550-2783-8-5 Google Scholar
  9. Bonen A, Tandon NN, Glatz JF et al (2006) The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes. Int J Obes 30:877–883. doi: 10.1038/sj.ijo.0803212 CrossRefGoogle Scholar
  10. Borsook ME, Billig HK, Golseth JG (1952) Betaine and glycocyamine in the treatment of disability resulting from acute anterior poliomyelitis. Ann West Med Surg 6:423–427PubMedGoogle Scholar
  11. Borum PR, Broquist HP (1977) Purification of S-adenosylmethionine: epsilon-N-l-lysine methyltransferase. The first enzyme in carnitine biosynthesis. J Biol Chem 252:5651–5655PubMedGoogle Scholar
  12. Brigotti M, Petronini PG, Carnicelli D et al (2003) Effects of osmolarity, ions and compatible osmolytes on cell-free protein synthesis. Biochem J 369:369–374. doi: 10.1042/BJ20021056 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Caldas T, Demont-Caulet N, Ghazi A, Richarme G (1999) Thermoprotection by glycine betaine and choline. Microbiology 145(Pt 9):2543–2548PubMedGoogle Scholar
  14. Chmurzyńska A (2006) The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet 47:39–48. doi: 10.1007/BF03194597 PubMedCrossRefGoogle Scholar
  15. Cho E, Zeisel SH, Jacques P et al (2006) Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr 83:905–911PubMedCentralPubMedGoogle Scholar
  16. Cholewa JM, Wyszczelska-Rokiel M, Glowacki R et al (2013) Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr 10:39. doi: 10.1186/1550-2783-10-39 PubMedCentralPubMedCrossRefGoogle Scholar
  17. Courtenay ES, Capp MW, Anderson CF, Record MT (2000) Vapor pressure osmometry studies of osmolyte-protein interactions: implications for the action of osmoprotectants in vivo and for the interpretation of “osmotic stress” experiments in vitro. Biochemistry 39:4455–4471PubMedCrossRefGoogle Scholar
  18. Craig SAS (2004) Betaine in human nutrition. Am J Clin Nutr 80:539–549PubMedGoogle Scholar
  19. Craig SS, Craig SA, Ganio MS et al (2010) The betaine content of sweat from adolescent females. J Int Soc Sports Nutr 7:3. doi: 10.1186/1550-2783-7-3 PubMedCentralPubMedCrossRefGoogle Scholar
  20. Del Favero S, Roschel H, Artioli G et al (2011) Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 42:2299–2305. doi: 10.1007/s00726-011-0972-5 PubMedCrossRefGoogle Scholar
  21. Dietz J, Schwartz J (1991) Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes. Metabolism 40:800–806PubMedCrossRefGoogle Scholar
  22. Dragolovich J (1994) Dealing with salt stress in animal cells: the role and regulation of glycine betaine concentrations. J Exp Zool 268:139–144. doi: 10.1002/jez.1402680211 CrossRefGoogle Scholar
  23. Eklund M, Bauer E, Wamatu J, Mosenthin R (2005) Potential nutritional and physiological functions of betaine in livestock. Nutr Res Rev 18:31–48. doi: 10.1079/NRR200493 PubMedCrossRefGoogle Scholar
  24. Feng J, Xu ZR (2001) Effect of betaine on muscle, liver and serum amino acid composition in finishing swine. J Zhejiang Univ Agric Life Sci 27:107–110Google Scholar
  25. Fernández-Fígares I, Wray-Cahen D, Steele NC et al (2002) Effect of dietary betaine on nutrient utilization and partitioning in the young growing feed-restricted pig. J Anim Sci 80:421–428PubMedGoogle Scholar
  26. Ghyczy M, Boros M (2001) Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress: a hypothesis. Br J Nutr 85:409–414PubMedCrossRefGoogle Scholar
  27. Gilles R (1997) “Compensatory” organic osmolytes in high osmolarity and dehydration stresses: history and perspectives. Comp Biochem Physiol 117:279–290CrossRefGoogle Scholar
  28. Häussinger D (1996) The role of cellular hydration in the regulation of cell function. Biochem J 313(Pt 3):697–710PubMedCentralPubMedGoogle Scholar
  29. Häussinger D, Roth E, Lang F, Gerok W (1993) Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 341:1330–1332PubMedCrossRefGoogle Scholar
  30. Hayes KC, Pronczuk A, Cook MW, Robbins MC (2003) Betaine in sub-acute and sub-chronic rat studies. Food Chem Toxicol 41:1685–1700. doi: 10.1016/S0278-6915(03)00196-0 PubMedCrossRefGoogle Scholar
  31. Hoffman J, Ratamess N, Kang J et al (2006) Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. Int J Sport Nutr Exerc Metab 16:430–446PubMedGoogle Scholar
  32. Hoffman JR, Ratamess NA, Kang J et al (2009) Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr 6:7. doi: 10.1186/1550-2783-6-7 PubMedCentralPubMedCrossRefGoogle Scholar
  33. Hoffman JR, Ratamess NA, Gonzalez A et al (2010) The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students. J Int Soc Sports Nutr 7:39. doi: 10.1186/1550-2783-7-39 PubMedCentralPubMedCrossRefGoogle Scholar
  34. Hoffman JR, Ratamess NA, Kang J et al (2011) Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise. J Strength Cond Res 25:2235–2241. doi: 10.1519/JSC.0b013e3182162530 PubMedCrossRefGoogle Scholar
  35. Hoffmann L, Brauers G, Gehrmann T et al (2013) Osmotic regulation of hepatic betaine metabolism. Am J Physiol Gastrointest Liver Physiol 304:G835–G846. doi: 10.1152/ajpgi.00332.2012 PubMedCrossRefGoogle Scholar
  36. Huang QC, Xu ZR, Han XY, Li WF (2007) Effect of betaine on growth hormone pulsatile secretion and serum metabolites in finishing pigs. J Anim Physiol Anim Nutr (Berl) 91:85–90. doi: 10.1111/j.1439-0396.2006.00644.x CrossRefGoogle Scholar
  37. Huang Q, Xu Z, Han X, Li W (2008) Effect of dietary betaine supplementation on lipogenic enzyme activities and fatty acid synthase mRNA expression in finishing pigs. Anim Feed Sci Technol 140:365–375. doi: 10.1016/j.anifeedsci.2007.03.007 CrossRefGoogle Scholar
  38. Huang Q-C, Han X-Y, Xu Z-R et al (2009) Betaine suppresses carnitine palmitoyltransferase I in skeletal muscle but not in liver of finishing pigs. Livest Sci 126:130–135. doi: 10.1016/j.livsci.2009.06.015 CrossRefGoogle Scholar
  39. Iwasaki H (2008) Involvement of PRMT1 in hnRNPQ activation and internalization of insulin receptor. Biochem Biophys Res Commun 372:314–319. doi: 10.1016/j.bbrc.2008.05.051 PubMedCrossRefGoogle Scholar
  40. Iwasaki H, Yada T (2007) Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells. Biochem Biophys Res Commun 364:1015–1021. doi: 10.1016/j.bbrc.2007.10.113 PubMedCrossRefGoogle Scholar
  41. Jakubowski H (2006) Pathophysiological consequences of homocysteine excess. J Nutr 136:1741–1749Google Scholar
  42. Knicker AJ, Renshaw I, Oldham ARH, Cairns SP (2011) Interactive processes link the multiple symptoms of fatigue in sport competition. Sport Med 41:307–328. doi: 10.2165/11586070-000000000-00000 CrossRefGoogle Scholar
  43. Lee MS, Kim M-S, Park SY, Kang C-W (2006) Effects of betaine on ethanol-stimulated secretion of IGF-I and IGFBP-1 in rat primary hepatocytes: involvement of p42/44 MAPK activation. World J Gastroenterol 12:1718–1722PubMedGoogle Scholar
  44. Lee EC, Maresh CM, Kraemer WJ et al (2010) Ergogenic effects of betaine supplementation on strength and power performance. J Int Soc Sports Nutr 7:27. doi: 10.1186/1550-2783-7-27 PubMedCentralPubMedCrossRefGoogle Scholar
  45. Lever M, Slow S (2010) The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem 43:732–744. doi: 10.1016/j.clinbiochem.2010.03.009 PubMedCrossRefGoogle Scholar
  46. Lever M, Sizeland PC, Bason LM et al (1994) Glycine betaine and proline betaine in human blood and urine. Biochim Biophys Acta 1200:259–264PubMedCrossRefGoogle Scholar
  47. Lever M, Sizeland PC, Frampton CM, Chambers ST (2004) Short and long-term variation of plasma glycine betaine concentrations in humans. Clin Biochem 37:184–190. doi: 10.1016/j.clinbiochem.2003.11.004 PubMedCrossRefGoogle Scholar
  48. Li Y, Jiang C, Xu G et al (2008) Homocysteine upregulates resistin production from adipocytes in vivo and in vitro. Diabetes 57:817–827. doi: 10.2337/db07-0617 PubMedCrossRefGoogle Scholar
  49. Low SY, Rennie MJ, Taylor PM (1997) Signaling elements involved in amino acid transport responses to altered muscle cell volume. FASEB J 11:1111–1117PubMedGoogle Scholar
  50. Najib S, Sánchez-Margalet V (2005) Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol 34:119–126. doi: 10.1677/jme.1.01581 PubMedCrossRefGoogle Scholar
  51. Noer A, Sørensen AL, Boquest AC, Collas P (2006) Stable CpG hypomethylation of adipogenic promoters in freshly isolated, cultured, and differentiated mesenchymal stem cells from adipose tissue. Mol Biol Cell 17:3543–3556. doi: 10.1091/mbc.E06 PubMedCentralPubMedCrossRefGoogle Scholar
  52. Ortiz-Costa S, Sorenson MM, Sola-Penna M (2008) Betaine protects urea-induced denaturation of myosin subfragment-1. FEBS J 275:3388–3396. doi: 10.1111/j.1742-4658.2008.06487.x PubMedCrossRefGoogle Scholar
  53. Petronini PG, De Angelis EM, Borghetti P et al (1992) Modulation by betaine of cellular responses to osmotic stress. Biochem J 282:69–73PubMedCentralPubMedGoogle Scholar
  54. Pryor JL, Craig SA, Swensen T (2012) Effect of betaine supplementation on cycling sprint performance. J Int Soc Sports Nutr 9:12. doi: 10.1186/1550-2783-9-12 PubMedCentralPubMedCrossRefGoogle Scholar
  55. Rojas-Cano ML, Lara L, Lachica M et al (2011) Influence of betaine and conjugated linoleic acid on development of carcass cuts of Iberian pigs growing from 20 to 50 kg body weight. Meat Sci 88:525–530. doi: 10.1016/j.meatsci.2011.02.004 PubMedCrossRefGoogle Scholar
  56. Schwab U, Törrönen A, Toppinen L et al (2002) Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr 76:961–967PubMedGoogle Scholar
  57. Schwahn BC, Hafner D, Hohlfeld T et al (2003) Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria. Br J Clin Pharmacol 55:6–13PubMedCentralPubMedCrossRefGoogle Scholar
  58. Scott RA, Cornelius SG, Mersmann HJ (1981) Effects of age on lipogenesis and lipolysis in lean and obese swine. J Anim Sci 52:505–511PubMedGoogle Scholar
  59. Senesi P, Luzi L, Montesano A et al (2013) Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation. J Transl Med 11:174. doi: 10.1186/1479-5876-11-174 PubMedCentralPubMedCrossRefGoogle Scholar
  60. Slow S, Lever M, Chambers ST, George PM (2009) Plasma dependent and independent accumulation of betaine in male and female rat tissues. Acad Sci Bohemoslov 58:403–410Google Scholar
  61. Stead LM, Brosnan JT, Brosnan ME et al (2006) Is it time to reevaluate methyl balance in humans? Am J Clin Nutr 83:5–10PubMedGoogle Scholar
  62. Stoll B, Gerok W, Lang F, Häussinger D (1992) Liver cell volume and protein synthesis. Biochem J 287(Pt 1):217–222PubMedCentralPubMedGoogle Scholar
  63. Suarez MC, Machado CJV, Lima LMTR et al (2003) Role of hydration in the closed-to-open transition involved in Ca2+ binding by troponin C. Biochemistry 42:5522–5530. doi: 10.1021/bi027102h PubMedCrossRefGoogle Scholar
  64. Thompson K, Coleman ES, Hudmon A et al (1995) Effects of short-term cortisol infusion on growth hormone-releasing hormone stimulation of growth hormone release in sheep. Am J Vet Res 56:1228–1231PubMedGoogle Scholar
  65. Trepanowski JF, Farney TM, McCarthy CG, et al (2011) The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. J Strength Cond Res 1–11. doi: 10.1519/JSC.0b013e318217d48d
  66. Wang Y, Xu Z, Feng J (2000) Study on the effect of betaine on meat quality and the mechanism in finishing pigs. Sci Agric Sin 33:94–99Google Scholar
  67. Warren LK, Lawrence LM, Thompson KN (1999) The influence of betaine on untrained and trained horses exercising to fatigue. J Anim Sci 77:677–684PubMedGoogle Scholar
  68. Williams KT, Schalinske KL (2007) New insights into the regulation of methyl group and homocysteine metabolism. J Nutr 137:311–314PubMedGoogle Scholar
  69. Wise CK, Cooney CA, Ali SF, Poirier LA (1997) Measuring S-adenosylmethionine in whole blood, red blood cells and cultured cells using a fast preparation method and high-performance liquid chromatography. J Chromatogr 696:145–152CrossRefGoogle Scholar
  70. Wray-Cahen D, Fernández-Fígares I, Virtanen E et al (2004) Betaine improves growth, but does not induce whole body or hepatic palmitate oxidation in swine (Sus scrofa domestica). Comp Biochem Physiol 137:131–140. doi: 10.1016/j.cbpb.2003.09.015 CrossRefGoogle Scholar
  71. Xing J, Kang L, Jiang Y (2011) Effect of dietary betaine supplementation on lipogenesis gene expression and CpG methylation of lipoprotein lipase gene in broilers. Mol Biol Rep 38:1975–1981. doi: 10.1007/s11033-010-0319-4 PubMedCrossRefGoogle Scholar
  72. Yan XC (2001) Effects of betaine on growth hormone releasing factor (GRF) and approach to the mechanism in the hypothalamus of finishing pig. Zhejiang University, HangzhouGoogle Scholar
  73. Zeisel SH, Mar M-H, Howe JC, Holden JM (2003) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133:1302–1307PubMedGoogle Scholar
  74. Zhan XA, Li JX, Xu ZR, Zhao RQ (2006) Effects of methionine and betaine supplementation on growth performance, carcase composition and metabolism of lipids in male broilers. Br Poult Sci 47:576–580. doi: 10.1080/00071660600963438 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Jason M. Cholewa
    • 1
  • Lucas Guimarães-Ferreira
    • 2
  • Nelo Eidy Zanchi
    • 3
  1. 1.Department of Kinesiology Recreation and Sport StudiesCoastal Carolina UniversityConwayUSA
  2. 2.Laboratory of Experimental Physiology and BiochemistryFederal University of Espirito SantoVitoriaBrazil
  3. 3.Postgraduate Program in Health Sciences, Health Sciences UnitUniversidade do Extremo Sul CatarinenseCriciúmaBrazil

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