Hydroxymethyl butyrate (HMB)

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 3-Hydroxy-3-methyl-butanoic acid, 3-hydroxyisobutyric acid, {beta}-hydroxy-{beta}-methylbutyrate, beta-hydroxy-beta-methylbutyric acid, beta-hydroxy-beta-methylglutarate-CoA, b-hydroxy-b-methylbutyrate monohydrate, branched-chain amino acids (BCAA), calcium beta-hydroxy-beta-methylbutyrate, creatinine, glutamine, HMB, HMG-CoA, HMG-CoA reductase, hydroxymethyl butyrate, hydroxymethylglutarate, ketoisocaproate, KIC, leucine.

Background

  • Beta-hydroxy beta-methylbutyrate (hydroxymethylbutyrate, or HMB) a breakdown product of the amino acid leucine. It can be found naturally in small quantities in grapefruit, alfalfa, and catfish.

  • HMB is also naturally synthesized in the human body. Production of HMB occurs in the muscle and liver, and it is believed to be involved in muscle protein synthesis. Currently, HMB is widely available and a popular supplement among athletes, especially bodybuilders.

  • Clinical trials have also reported HMB to be effective when used orally, in combination with amino acids, to prevent cachexia (loss of muscle) in patients with AIDS, cancer, and rheumatoid arthritis. Preliminary clinical evidence has indicated that HMB may lower blood pressure and cholesterol.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Exercise recovery

HMB has been found to reduce muscle damage associated with exercise and to shorten recovery time. Supplementation has been found to inhibit muscle breakdown and enhance protein synthesis.

Cachexia

HMB in combination with arginine and glutamine has been shown to decrease both cancer- and AIDS-related cachexia (weight loss/wasting). Evidence remains insufficient for use of HMB alone in the treatment of cachexia.

Cardiovascular disease risk

In preliminary research, HMB supplementation was found to reduce cardiovascular disease risk factors. HMB lowered total and low-density lipoprotein (LDL) cholesterol and reduced systolic blood pressure. Well-designed clinical trials are needed to confirm these findings.

Exercise performance

Reviews examining HMB’s effects on exercise performance have noted increases in lean body mass and strength in response to supplementation. Other studies, however, did not support these findings. Additional research is required.

Wound healing

HMB in combination with arginine and glutamine has been shown to enhance collagen synthesis. Additional research is required before any recommendation can be made.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Duchenne muscular dystrophy, immune function, kidney failure.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • The common dose for HMB is three grams or less taken by mouth daily for up to eight weeks.

  • For cachexia (muscle loss), a combination of three grams of HMB with 14 grams of arginine and 14 grams of glutamine has been taken by mouth in two divided doses daily for up to 24 weeks.

  • For cardiovascular disease risk, three grams has been taken by mouth daily for up to eight weeks.

  • For exercise performance, three grams has been taken by mouth daily for up to nine weeks.

  • For exercise recovery, three grams has been taken by mouth daily for up to six weeks.

Children (under 18 years old)

  • There is no proven safe or effective dose for HMB in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in individuals with known allergy or hypersensitivity to HMB.

Side Effects and Warnings

  • HMB appears to be safe with short-term use. Currently, data regarding the long-term effects of HMB use are lacking.

  • HMB may cause low blood pressure. Caution is advised in patients taking drugs, herbs, or supplements that lower blood pressure.

  • Use cautiously in individuals with immune disorders or those using agents that affect the immune system, as HMB supplementation may stimulate the immune system.

  • Avoid in individuals with known allergy or hypersensitivity to HMB.

Pregnancy and Breastfeeding

  • There is currently a lack of reliable data on the use of HMB during pregnancy or lactation.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • HMB may cause low blood pressure. Caution is advised in patients taking drugs that lower blood pressure.

  • HMB may interact with agents that affect the immune system, antivirals, cholesterol-lowering agents, and weight loss agents.

Interactions with Herbs and Dietary Supplements

  • HMB may cause low blood pressure. Caution is advised in patients taking herbs or supplements that lower blood pressure.

  • HMB may interact with antivirals, arginine, athletic performance enhancers, cholesterol-lowering herbs and supplements, creatine, glutamine, herbs and supplements that affect the immune system, sugar, and weight loss herbs and supplements.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Flakoll P, Sharp R, Baier S, et al. Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 2004;20(5):445-451. View Abstract
  2. Hoffman JR, Cooper J, Wendell M, et al. Effects of beta-hydroxy beta-methylbutyrate on power performance and indices of muscle damage and stress during high-intensity training. J Strength Cond Res 2004;18(4):747-752. View Abstract
  3. Marcora S, Lemmey A, Maddison P. Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial. Clin Nutr 2005;24(3):442-454. View Abstract
  4. 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 2002;183(4):471-479. View Abstract
  5. Palisin T, Stacy JJ. Beta-hydroxy-beta-Methylbutyrate and its use in athletics. Curr Sports Med Rep 2005;4(4):220-223. View Abstract
  6. Payne ET, Yasuda N, Bourgeois JM, et al. Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Muscle Nerve 2006;33(1):66-77. View Abstract
  7. Ransone J, Neighbors K, Lefavi R, et al. The effect of beta-hydroxy beta-methylbutyrate on muscular strength and body composition in collegiate football players. J Strength Cond Res 2003;17(1):34-39. View Abstract
  8. Rathmacher JA, Nissen S, Panton L, et al. Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. JPEN J Parenter Enteral Nutr 2004;28(2):65-75. View Abstract
  9. Siddiqui R, Pandya D, Harvey K, et al. Nutrition modulation of cachexia/proteolysis. Nutr Clin Pract 2006;21(2):155-167. View Abstract
  10. Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss. Cancer Res 2005;65(1):277-283. View Abstract
  11. Smith HJ, Wyke SM, Tisdale MJ. Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by beta-hydroxy-beta-methylbutyrate. Cancer Res 2004;64(23):8731-8735. View Abstract
  12. Thomson JS. beta-Hydroxy-beta-Methylbutyrate (HMB) supplementation of resistance trained men. Asia Pac J Clin Nutr 2004;13(Suppl):S59. View Abstract
  13. Tisdale MJ. Clinical anticachexia treatments. Nutr Clin Pract 2006;21(2):168-174. View Abstract
  14. Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol 2005;3(3):209-217. View Abstract
  15. van Someren KA, Edwards AJ, Howatson G. Supplementation with beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC) reduces signs and symptoms of exercise-induced muscle damage in man. Int J Sport Nutr Exerc Metab 2005;15(4):413-424. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.