HMB

• How It Works

  Studies of HMB to prevent or reverse cancer-related muscle-wasting is limited and results are mixed.

  HMB is a breakdown product of the amino acid leucine. Along with amino acids arginine and glutamine, these compounds are generally known to prevent or slow damage to muscle cells that occurs with intense exercise or in advanced cancers and AIDS. However, many of the findings stem from laboratory and animal studies, in healthy volunteers, or in athletes. Although more studies in elderly and ill patients have recently been conducted, only a few were in cancer patients, and those results are mixed.

• Purported Uses
  • To prevent or reverse cancer- or HIV-related weight loss and weakness
    There is limited research in these populations with conflicting results. Although two small studies in cancer patients showed some benefit, a larger study did not. Future trials should evaluate long-term safety and effects.
  • To increase muscle mass
    There is limited research in clinical populations and results are mixed. Small studies found that HMB may decrease muscle breakdown in bedridden elderly, but not hemodialysis patients. Another found that a formula containing HMB improved muscle strength in elderly women and hip fracture patients. However, further study is needed to confirm these effects.
  • To improve strength and endurance in athletes
    Clinical trials show mixed results regarding this use.
• Special Point
  • HMB stimulates a cell signal pathway called mTOR. Certain cancer drugs and immunosuppressants block this action and may reduce the effect of HMB. It is unclear if taking HMB would also interfere with these drugs.
  • HMB may alter lab results for cholesterol levels, including “bad” LDL cholesterol.
• Scientific Name

  Beta-hydroxy-beta-methylbutyrate

• Clinical Summary

  Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine. It is often used as a body building supplement to help improve muscle strength by reducing protein breakdown. HMB is also added to some medical foods for patients with muscle wasting and cachexia.

  Small studies were initially conducted in active and younger men with mixed results on body composition and physical performance ^{(1) (2) (3) (4) (5) (6)}. A systematic review suggests that HMB may prevent exercise-related muscle damage in healthy trained and untrained individuals, as well as muscle loss during chronic disease ⁽⁷⁾.

  However, research on HMB in clinical populations is limited. Studies in the eldery show that HMB benefits vascular endothelial function ⁽⁸⁾, reduces muscle breakdown ⁽⁹⁾, decreases abdominal fat mass ⁽¹⁰⁾, improves functional recovery after hip fracture ⁽¹¹⁾, and reduces mortality ⁽¹²⁾. Other study results are mixed. HMB improved pulmonary function in COPD patients ⁽¹³⁾ and nitrogen balance in critically injured patients ⁽¹⁴⁾, but did not reduce co-morbidities in hemodialysis patients ⁽¹⁵⁾.

  HMB is often used together with glutamine and arginine for muscle wasting and cachexia in patients with AIDS ⁽¹⁶⁾ and cancer ⁽¹⁷⁾. However, a large randomized trial in patients with cancer cachexia failed to demonstrate a significant effect ⁽¹⁸⁾. Additional research is needed ⁽¹⁹⁾. A small study showed that an HMB-containing supplement may help prevent radiation dermatitis in head and neck cancer patients ⁽²⁰⁾.

• Purported Uses
  • Cancer-related cachexia
  • HIV- and AIDS-associated wasting
  • Strength and stamina
  • Weight gain
• Mechanism of Action

  HMB is metabolized from the branched chain amino acid L-leucine endogenously through alpha-ketoisocaproic acid. Since only a small amount is converted from food sources, supplementation is used to increase intake. As a dietary supplement, HMB usually comes in calcium salt or free acid forms, the latter which is thought to have higher bioavailability ⁽²¹⁾. In muscle cells, HMB stimulates cell growth and survival through MAPK/ERK pathways ⁽²²⁾. HMB restored balance between intracellular protein synthesis and breakdown by activating PI3K/Akt-dependent mammalian target of rapamycin (mTOR) ^(23) (24). The stimulating effect of HMB on mTOR is eliminated with the introduction of rapamycin, an mTOR inhibitor ^(6) (25). However, it is unclear if HMB supplementation would also reduce the therapeutic effects of other mTOR inhibitors used in cancer treatment. HMB inhibits the ubiquitin-proteasome proteolytic pathway which governs the degradation of intracellular proteins ⁽²⁶⁾ . In murine neuroblastoma cells, HMB exihibited neurotrophic effects ⁽²⁷⁾.

  In animal models, HMB reduced total subcutaneous fat content and LDL cholesterol ⁽²⁸⁾, but did not affect circulating plasma levels of testosterone ⁽⁴⁾, cortisol, insulin-like growth factor-1 (IGF-1), or insulin ⁽²⁹⁾.

• Herb-Drug Interactions

  mTOR inhibitors: Laboratory studies suggest that the stimulating effect of HMB on mTOR is reduced by rapamycin, an mTOR inhibitor ^(6) (25). It is not known whether HMB may reduce the effectiveness of these drugs.

• Herb Lab Interactions

  May reduce low-density lipoprotein ⁽³⁰⁾.

• References

  1. Gallagher PM, Carrithers JA, Godard MP, et al. Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass. Med Sci Sports Exerc. Dec 2000;32(12):2109-2115.

  2. Vukovich MD, Slater G, Macchi MB, et al. beta-hydroxy-beta-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans. J Nutr Biochem. Nov 2001;12(11):631-639.

  3. O’Connor DM, Crowe MJ. Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on strength, power, and anthropometry of highly trained athletes. J Strength Cond Res. May 2007;21(2):419-423.

  4. Slater GJ, Logan PA, Boston T, et al. Beta-hydroxy beta-methylbutyrate (HMB) supplementation does not influence the urinary testosterone: epitestosterone ratio in healthy males. J Sci Med Sport. Mar 2000;3(1):79-83.

  5. Lamboley CR, Royer D, Dionne IJ. Effects of beta-hydroxy-beta-methylbutyrate on aerobic-performance components and body composition in college students. Int J Sport Nutr Exerc Metab. Feb 2007;17(1):56-69.

  6. Zanchi NE, Gerlinger-Romero F, Guimaraes-Ferreira L, et al. HMB supplementation: clinical and athletic performance-related effects and mechanisms of action. Amino Acids. Apr 2011;40(4):1015-1025.

  7. Molfino A, Gioia G, Rossi Fanelli F, et al. Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials. Amino Acids. Dec 2013;45(6):1273-1292.

  8. Ellis AC, Patterson M, Dudenbostel T, et al. Effects of 6-month supplementation with beta-hydroxy-beta-methylbutyrate, glutamine and arginine on vascular endothelial function of older adults. Eur J Clin Nutr. Feb 2016;70(2):269-273.

  9. Hsieh LC, Chow CJ, Chang WC, et al. Effect of beta-hydroxy-beta-methylbutyrate on protein metabolism in bed-ridden elderly receiving tube feeding. Asia Pac J Clin Nutr. 2010;19(2):200-208.

  10. Stout JR, Fukuda DH, Kendall KL, et al. beta-Hydroxy-beta-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men. Exp Gerontol. Apr 2015;64:33-34.

  11. Malafarina V, Uriz-Otano F, Malafarina C, et al. Effectiveness of nutritional supplementation on sarcopenia and recovery in hip fracture patients. A multi-centre randomized trial. Maturitas. Jul 2017;101:42-50.

  12. Deutz NE, Matheson EM, Matarese LE, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial. Clin Nutr. Feb 2016;35(1):18-26.

  13. Hsieh LC, Chien SL, Huang MS, et al. Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr. 2006;15(4):544-550.

  14. Kuhls DA, Rathmacher JA, Musngi MD, et al. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients. J Trauma. Jan 2007;62(1):125-131; discussion 131-122.

  15. Fitschen PJ, Biruete A, Jeong J, et al. Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in maintenance hemodialysis patients. Hemodial Int. Jan 2017;21(1):107-116.

  16. Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr. May-Jun 2000;24(3):133-139.

  17. May PE, Barber A, D’Olimpio JT, et al. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg. Apr 2002;183(4):471-479.

  18. Berk L, James J, Schwartz A, et al. A randomized, double-blind, placebo-controlled trial of a beta-hydroxyl beta-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122). Support Care Cancer. Oct 2008;16(10):1179-1188.

  19. Mochamat, Cuhls H, Marinova M, et al. A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project. J Cachexia Sarcopenia Muscle. Feb 2017;8(1):25-39.

  20. Imai T, Matsuura K, Asada Y, et al. Effect of HMB/Arg/Gln on the prevention of radiation dermatitis in head and neck cancer patients treated with concurrent chemoradiotherapy. Jpn J Clin Oncol. May 2014;44(5):422-427.

  21. Fuller JC, Jr., Sharp RL, Angus HF, et al. Free acid gel form of beta-hydroxy-beta-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt. Br J Nutr. Feb 2011;105(3):367-372.

  22. Kornasio R, Riederer I, Butler-Browne G, et al. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta. May 2009;1793(5):755-763.

  23. Kimura K, Cheng XW, Inoue A, et al. beta-Hydroxy-beta-methylbutyrate facilitates PI3K/Akt-dependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor alpha/interferon gamma-induced MuRF-1 expression in C2C12 cells. Nutr Res. Apr 2014;34(4):368-374.

  24. Wheatley SM, El-Kadi SW, Suryawan A, et al. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab. Jan 1 2014;306(1):E91-99.

  25. Eley HL, Russell ST, Baxter JH, et al. Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. Oct 2007;293(4):E923-931.

  26. Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review. Nutr Metab (Lond). Jan 3 2008;5:1.

  27. Salto R, Vilchez JD, Giron MD, et al. beta-Hydroxy-beta-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells. PLoS One. 2015;10(8):e0135614.

  28. Nissen S, Sharp RL, Panton L, et al. beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr. Aug 2000;130(8):1937-1945.

  29. Gallagher PM, Carrithers JA, Godard MP, et al. Beta-hydroxy-beta-methylbutyrate ingestion, part II: effects on hematology, hepatic and renal function. Med Sci Sports Exerc. Dec 2000;32(12):2116-2119.

  30. Slater GJ, Jenkins D. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength. Sports Med. Aug 2000;30(2):105-116.