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European Journal of Applied Physiology

, Volume 113, Issue 3, pp 793–802 | Cite as

Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise

  • Jenna M. Apicella
  • Elaine C. Lee
  • Brooke L. Bailey
  • Catherine Saenz
  • Jeffrey M. Anderson
  • Stuart A. S. Craig
  • William J. Kraemer
  • Jeff S. Volek
  • Carl M. MareshEmail author
Original Article

Abstract

Our aim was to examine the effect of betaine supplementation on selected circulating hormonal measures and Akt muscle signaling proteins after an acute exercise session. Twelve trained men (age 19.7 ± 1.23 years) underwent 2 weeks of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following a 2-week washout period, subjects underwent supplementation with the other treatment (B or P). Before and after each 2-week period, subjects performed an acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70 S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH (mean ± SD (Area under the curve, AUC), B: 40.72 ± 6.14, P: 38.28 ± 5.54, p = 0.060) and significantly increased IGF-1 (mean ± SD (AUC), B: 106.19 ± 13.45, P: 95.10 ± 14.23, p = 0.010), but significantly decreased cortisol (mean ± SD (AUC), B: 1,079.18 ± 110.02, P: 1,228.53 ± 130.32, p = 0.007). There was no difference in insulin (AUC). B increased resting Total muscle Akt (p = 0.003). B potentiated phosphorylation (relative to P) of Akt (Ser473) and p70 S6 k (Thr389) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK (Thr172) decreased during both treatments (both p = 0.001). Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis.

Keywords

Ergogenic aids Supplements GH IGF-1 Muscle signaling 

Notes

Acknowledgments

The authors would like to thank the DuPont Nutrition & Health for funding this study. Also, we wish to thank Kathleen N. Beasley, Brittanie M. Volk, Glenn Solomon-Hill, and Dr. Beth Joseph, M.D. for their assistance in data collection and the subjects for their participation.

Conflict of interest

This study was partially funded by DuPont Nutrition & Health.

References

  1. Adams GR (2002) Invited review: autocrine/paracrine IGF-I and skeletal muscle adaptation. J Appl Physiol 93:1159–1167. doi: 10.1152/japplphysiol.01264.2001 PubMedGoogle Scholar
  2. Alfieri RR, Bonelli MA, Cavazzoni A et al (2006) Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. J Physiol 576:391–401. doi: 10.1113/jphysiol.2006.115006 PubMedCrossRefGoogle Scholar
  3. 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
  4. Bergstrom J (1962) Muscle electrolytes in man. Scand J Clin Lab Invest 68:110–167Google Scholar
  5. Bloomer RJ, Farney TM, Trepanowski JF, McCarthy CG, Canale RE (2011) Effect of betaine supplementation on plasma nitrate/nitrite in exercise-trained men. J Int Soc Sports Nutr 8:5. doi: 10.1186/1550-2783-8-5 PubMedCrossRefGoogle Scholar
  6. Boden G, Chen X, Mozzoli M, Ryan I (1996) Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 81:3419–3423PubMedCrossRefGoogle Scholar
  7. 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 PubMedCrossRefGoogle Scholar
  8. Choe HS, Li HL, Park JH, Kang CW, Ryu KS (2010) Effects of dietary betaine on the secretion of insulin-like growth factor-I and insulin-like growth factor binding protein-1 and -3 in laying hens. Asian Australas J Anim Sci 23:379–384Google Scholar
  9. Coffey VG, Hawley JA (2007) The molecular bases of training adaptation. Sports Med 37:737–763PubMedCrossRefGoogle Scholar
  10. Coffey VG, Zhong Z, Shield A et al (2006) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J 20:190–192. doi: 10.1096/fj.05-4809fje PubMedGoogle Scholar
  11. Coffey VG, Pilegaard H, Garnham AP, O’Brien BJ, Hawley JA (2009) Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle. J Appl Physiol 106:1187–1197. doi: 10.1152/japplphysiol.91221.2008 PubMedCrossRefGoogle Scholar
  12. Courtenay ES, Capp MW, Anderson CF, Record MT Jr (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
  13. Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80:539–549PubMedGoogle Scholar
  14. Del Favero S, Roschel H, Artioli G et al (2011) Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids. doi: 10.1007/s00726-011-0972-5 Google Scholar
  15. Dinan TG, Thakore J, O’Keane V (1994) Lowering cortisol enhances growth hormone response to growth hormone releasing hormone in healthy subjects. Acta Physiol Scand 151:413–416PubMedCrossRefGoogle Scholar
  16. Doessing S, Heinemeier KM, Holm L et al (2010) Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis. J Physiol 588:341–351. doi: 10.1113/jphysiol.2009.179325 PubMedCrossRefGoogle Scholar
  17. Dreyer HC, Fujita S, Cadenas JG, Chinkes DL, Volpi E, Rasmussen BB (2006) Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol 576:613–624. doi: 10.1113/jphysiol.2006.113175 PubMedCrossRefGoogle Scholar
  18. 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
  19. Eliasson J, Elfegoun T, Nilsson J, Kohnke R, Ekblom B, Blomstrand E (2006) Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol Endocrinol Metab 291:E1197–E1205. doi: 10.1152/ajpendo.00141.2006 PubMedCrossRefGoogle Scholar
  20. Guezennec CY, Serrurier B, Aymonod M, Merino D, Pesquies PC (1984) Metabolic and hormonal response to short term fasting after endurance training in the rat. Horm Metab Res 16:572–575. doi: 10.1055/s-2007-1014854 PubMedCrossRefGoogle Scholar
  21. Hawley JA (2009) Molecular responses to strength and endurance training: are they incompatible? Appl Physiol Nutr Metab 34:355–361. doi: 10.1139/h09-023 PubMedCrossRefGoogle Scholar
  22. Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD (2009) Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr 6:7. doi: 10.1186/1550-2783-6-7 PubMedCrossRefGoogle Scholar
  23. 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
  24. Hulmi JJ, Tannerstedt J, Selanne H, Kainulainen H, Kovanen V, Mero AA (2009) Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men. J Appl Physiol 106:1720–1729. doi: 10.1152/japplphysiol.00087.2009 PubMedCrossRefGoogle Scholar
  25. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25. doi: 10.1016/j.cmet.2004.12.003 PubMedCrossRefGoogle Scholar
  26. Kimball SR (2006) Interaction between the AMP-activated protein kinase and mTOR signaling pathways. Med Sci Sports Exerc 38:1958–1964. doi: 10.1249/01.mss.0000233796.16411.13 PubMedCrossRefGoogle Scholar
  27. Kraemer WJ, Ratamess NA (2005) Hormonal responses and adaptations to resistance exercise and training. Sports Med 35:339–361PubMedCrossRefGoogle Scholar
  28. Kraemer WJ, Dunn-Lewis C, Comstock BA, Thomas GA, Clark JE, Nindl BC (2010) Growth hormone, exercise, and athletic performance: a continued evolution of complexity. Curr Sports Med Rep 9:242–252. doi: 10.1249/JSR.0b013e3181e976df PubMedGoogle Scholar
  29. 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 PubMedCrossRefGoogle Scholar
  30. 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
  31. Liu H, Bravata DM, Olkin I et al (2008) Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med 148:747–758PubMedGoogle Scholar
  32. Marliss EB, Vranic M (2002) Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes. Diabetes 51(Suppl 1):S271–S283PubMedCrossRefGoogle Scholar
  33. Matthews JO, Southern LL, Bidner TD, Persica MA (2001a) Effects of betaine, pen space, and slaughter handling method on growth performance, carcass traits, and pork quality of finishing barrows. J Anim Sci 79:967–974PubMedGoogle Scholar
  34. Matthews JO, Southern LL, Higbie AD, Persica MA, Bidner TD (2001b) Effects of betaine on growth, carcass characteristics, pork quality, and plasma metabolites of finishing pigs. J Anim Sci 79:722–728PubMedGoogle Scholar
  35. Minana MD, Hermenegildo C, Llsansola M, Montoliu C, Grisolia S, Felipo V (1996) Carnitine and choline derivatives containing a trimethylamine group prevent ammonia toxicity in mice and glutamate toxicity in primary cultures of neurons. J Pharmacol Exp Ther 279:194–199PubMedGoogle Scholar
  36. Nindl BC, Sharp MA, Mello RP, Rice VJ, Murphy MM, Patton JF (1998) Gender comparison of peak oxygen uptake: repetitive box lifting versus treadmill running. Eur J Appl Physiol Occup Physiol 77:112–117PubMedCrossRefGoogle Scholar
  37. Ortiz-Costa S, Sorenson MM, Sola-Penna M (2002) Counteracting effects of urea and methylamines in function and structure of skeletal muscle myosin. Arch Biochem Biophys 408:272–278PubMedCrossRefGoogle Scholar
  38. QiChun H, ZiRong X, XinYan H, WeiFen L (2006) Changes in hormones, growth factor and lipid metabolism in finishing pigs fed betaine. Livest Sci 105:78–85. doi: 10.1016/j.livsci.2006.04.031 CrossRefGoogle Scholar
  39. Sartin JL, Kemppainen RJ, Coleman ES, Steele B, Williams JC (1994) Cortisol inhibition of growth hormone-releasing hormone-stimulated growth hormone release from cultured sheep pituitary cells. J Endocrinol 141:517–525PubMedCrossRefGoogle Scholar
  40. Shah OJ, Kimball SR, Jefferson LS (2000a) Among translational effectors, p70S6k is uniquely sensitive to inhibition by glucocorticoids. Biochem J 347:389–397PubMedCrossRefGoogle Scholar
  41. Shah OJ, Kimball SR, Jefferson LS (2000b) Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle. Am J Physiol Endocrinol Metab 278:E76–E82PubMedGoogle Scholar
  42. Shah OJ, Iniguez-Lluhi JA, Romanelli A, Kimball SR, Jefferson LS (2002) The activated glucocorticoid receptor modulates presumptive autoregulation of ribosomal protein S6 protein kinase, p70 S6K. J Biol Chem 277:2525–2533. doi: 10.1074/jbc.M105935200 PubMedCrossRefGoogle Scholar
  43. Somero GN, Yancey PH (2010) Osmolytes and cell-volume regulation: physiological and evolutionary principles. In: Anonymous comprehensive physiology. John Wiley & Sons, Inc, New YorkGoogle Scholar
  44. Spiering BA, Kraemer WJ, Anderson JM et al (2008a) Effects of elevated circulating hormones on resistance exercise-induced Akt signaling. Med Sci Sports Exerc 40:1039–1048. doi: 10.1249/MSS.0b013e31816722bd PubMedCrossRefGoogle Scholar
  45. Spiering BA, Kraemer WJ, Anderson JM et al (2008b) Resistance exercise biology: manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med 38:527–540PubMedCrossRefGoogle Scholar
  46. Terzis G, Spengos K, Mascher H, Georgiadis G, Manta P, Blomstrand E (2010) The degree of p70 S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume. Eur J Appl Physiol 110:835–843. doi: 10.1007/s00421-010-1527-2 PubMedCrossRefGoogle Scholar
  47. Thompson K, Coleman ES, Hudmon A, Kemppainen RJ, Soyoola EO, Sartin JL (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
  48. Trepanowski JF, Farney TM, McCarthy CG, Schilling BK, Craig SA, Bloomer RJ (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. doi: 10.1519/JSC.0b013e318217d48d PubMedGoogle Scholar
  49. Ueland PM (2011) Choline and betaine in health and disease. J Inherit Metab Dis 34:3–15. doi: 10.1007/s10545-010-9088-4 PubMedCrossRefGoogle Scholar
  50. 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
  51. Widdowson WM, Healy ML, Sonksen PH, Gibney J (2009) The physiology of growth hormone and sport. Growth Horm IGF Res 19:308–319. doi: 10.1016/j.ghir.2009.04.023 PubMedCrossRefGoogle Scholar
  52. Wilkinson SB, Phillips SM, Atherton PJ et al (2008) Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol 586:3701–3717. doi: 10.1113/jphysiol.2008.153916 PubMedCrossRefGoogle Scholar
  53. Yancey PH, Clark ME, Hand SC, Bowlus RD, Somero GN (1982) Living with water stress: evolution of osmolyte systems. Science 217:1214–1222PubMedCrossRefGoogle Scholar
  54. 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 2012

Authors and Affiliations

  • Jenna M. Apicella
    • 1
  • Elaine C. Lee
    • 1
  • Brooke L. Bailey
    • 1
  • Catherine Saenz
    • 1
  • Jeffrey M. Anderson
    • 1
  • Stuart A. S. Craig
    • 2
  • William J. Kraemer
    • 1
  • Jeff S. Volek
    • 1
  • Carl M. Maresh
    • 1
    Email author
  1. 1.Human Performance Laboratory, Department of KinesiologyUniversity of ConnecticutStorrsUSA
  2. 2.DuPont Nutrition and HealthTarrytownUSA

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