Health Care Professional Information

Scientific Name
Beta-hydroxy-beta-methylbutyrate
Common Name

Beta-hydroxymethylbutyrate, beta-hydroxy-beta-methylbutyrate monohydrate

Brand Name

Juven® (contains arginine, glutamine, and HMB)

Clinical Summary

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine. Patients use HMB for body strength, muscle gain, AIDS wasting, and cancer-related cachexia. Clinical studies suggest that HMB increases lean weight gain and reduces adipose tissue (1) (2) . It does not increase muscle strength (3) nor affect plasma levels of androgens, cortisol, or insulin (4), but improves some components of aerobic performance (5). HMB may reduce muscle breakdown in bed-ridden elderly patients fed by nasogastric tube (9) . A formulation containing HMB, arginine, and lysine significantly improved muscle strength, health, and function in elderly women (10) . Data also indicate that HMB supplementation may improve pulmonary function in patients with chronic obstructive pulmonary disease (COPD), (11) and nitrogen balance in critically injured patients (12)
HMB may be of benefit in AIDS wasting (6), but additional research is necessary concerning use for cancer-related cachexia (7). A large randomized clinical study of HMB in patients with cancer cachexia failed to demonstrate a significant effect (8) .

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

The mechanism of action of HMB is unknown. Theoretically, HMB reduces skeletal muscle proteolysis (13). HMB may be metabolized to beta-hydroxy-beta-methylglutaryl CoA (HMG-CoA), which can elevate cholesterol and androgen synthesis. HMB does not affect circulating plasma levels of testosterone (4), cortisol, insulin-like growth factor-1 (IGF-1), or insulin (14). In animal studies, HMB causes a decrease in total subcutaneous fat content and a reduction in LDL cholesterol (15).

Pharmacokinetics

Following single dose administration of 3 grams HMB to healthy volunteers, peak plasma levels of nearly 480 nmol/L occur in about 1 hour. Concomitant administration of HMB and 75 grams of glucose appears to reduce the rate, but not extent of HMB absorption. The biologic half-life is approximately 2.4 hours with less than 30% of the parent compound excreted in the urine (6). Animal studies indicate there is no toxicity with doses up 5000 mg/kg/dose for up to 16 weeks (4).

Adverse Reactions

Chronic supplementation of HMB resulted in hyperinsulinemia in rats (16).

Herb Lab Interactions

May reduce Low-density lipoprotein.
(13)

Literature Summary and Critique

Hsieh LC, 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):200-8.
This randomized, controlled trial investigated the effect of HMB on body composition and protein metabolism in bed-ridden elderly patients fed by nasogastric tube. The subjects were randomized to either the HMB (n=39) or control group (n=40). Anthropometry measurements, blood sampling, and 24 hour urine samples were collected at baseline and 14 days after study initiation. A subset of patients (HMB, n=19; control, n=20) continued the study until day 28. Changes in body weight and BMI were not significantly different between the control and treatment groups on days 14 or 28. However, blood urea nitrogen significantly decreased in the HMB group (p<0.05), but remained unchanged in the control group after 14 days. Urinary urea nitrogen also significantly decreased in the HMB group (p<0.05), while it showed a trend toward increase in the control group at 14 and 28 days. The investigators concluded that HMB supplementation for 2 to 4 weeks could reduce muscle breakdown in elderly bed-ridden nursing home patients receiving tube feeding.

Berk L, 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. Support Care Cancer. 2008 Oct;16(10):1179-88.
This randomized, double-blind trial enrolled 472 advanced cancer patients who had between 2% and 10% weight loss. Patients were randomized to receive either an isonitrogenous, isocaloric control mixture (n=237) or, Juven® (n=235), a commercially available formula containing HMB, glutamine, and arginine. Patients received an 8-week supply of Juven or the control at the initial visit and were evaluated at 4- and 8-week follow-up. The primary endpoint was the percentage increase in lean body mass at 8 weeks as compared to baseline. Secondary endpoints were change in fatigue, quality of life, percent change in weight, and percent change in lean body mass. Based on an intent-to-treat analysis, there was no statistically significant difference in lean body mass between the control and treatment groups at 8 weeks. There were also no statistically significant differences in secondary endpoints between the two groups. However, patients on Juven showed a strongly higher trend throughout the study in a secondary lean body mass endpoint (measured using area under the curve [AUC]) evaluated by bioimpedance (p=0.08) and skin fold measurements (p=0.08). The investigators concluded that Juven failed to prevent lean body mass loss among cancer cachexia patients. However, the improving trend in lean body mass when measured using AUC suggests that further study is warranted.

Dosage (Inside MSKCC Only)
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References
  1. Gallagher PM, et al. Beta-hydroxy-beta-methylbutyrate ingestion, part I: effects on strength and fat free mass. Med Sci Sports Exerc. 2000;32:2109-15.
  2. Vukovich MD, et al. Beta-hydroxy-beta-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans. J Nutr Biochem. 2001;12:631-9.
  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. 2007;21(2):419-23.
  4. Slater GJ, et al. Beta-hydroxy beta-methylbutyrate (HMB) supplementation does not influence the urinary testosterone: epitestosterone ratio in healthy males. J Sci Med Sport. 2000;3:79-83.
  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. 2007 Feb;17(1):56-69.
  6. Clark RH, 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. J Parenteral Enteral Nutr. 2000;24:133-9.
  7. May PE, et al. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surgery. 2002;183:471-479.
  8. 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. Support Care Cancer. 2008 Oct;16(10):1179-88.
  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):200-8.
  10. 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 May;20(5):445-51.
  11. 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):544-50.
  12. Kuhls DA, Rathmacher JA, Musngi MD, et al. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients. J Trauma. 2007;62(1):125-31.
  13. Slater GJ, Jenkins D. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength. Sports Med. 2000;30:105-16.
  14. Gallagher PM, et al. Beta-hydroxy-beta-methylbutyrate ingestion, part II: effects on hematology, hepatic and renal function. Med Sci Sports Exerc. 2000;32:2116-9.
  15. Nissen S, et al. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk. J Nutr. 2000;130:1937-45.
  16. Gerlinger-Romero F, Guimarães-Ferreira L, Giannocco G, Nunes MT. Chronic supplementation of beta-hydroxy-beta methylbutyrate (HMβ) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats. Growth Horm IGF Res. 2011 Apr;21(2):57-62.

Consumer Information

How It Works

Bottom Line: HMB has not been shown to treat or prevent cancer.

HMB is a breakdown product of the amino acid leucine. It and other amino acids (such as arginine and glutamine) are generally known to prevent or slow the damage to muscle cells that occurs with intense exercise or in advanced cancer and AIDS. HMB has been shown to increase muscle health, strength, and function in elderly female patients. It also helps to prevent muscle breakdown in elderly bedridden nursing home patients receiving tube feedings. In studies in both animals and healthy volunteers, HMB caused a decrease in total cholesterol and LDL (“bad”) cholesterol. Scientists are not exactly certain how HMB exerts these effects. HMB does not affect blood levels of testosterone or growth factors.

Purported Uses
  • To prevent or reverse weight loss (cachexia) and weakness associated with diseases such as cancer and AIDS
    Two small clinical trials support this use, but larger trials that follow patients for longer periods of time are needed.
  • To increase muscle mass
    Clinical trials show mixed results regarding this use. The results of one small study found that HMB may decrease muscle breakdown in bed-ridden elderly patients. Another small study found that a formula containing HMB, arginine, lysine, and ascorbic acid may improve muscle strength, health, and function in elderly women. However, further study is needed to confirm these effects.
  • To improve strength and endurance in athletes
    Clinical trials show mixed results regarding this use.
Research Evidence

Muscle Health:
This randomized, controlled trial was conducted to study the effect of HMB on body composition and protein metabolism in bed-ridden elderly patients fed by nasogastric tube. The subjects were randomized to HMB and control groups. Anthropometry measurements, blood samples, and 24-hour urine samples were collected at baseline and 14 days after beginning study. A subset of patients continued the study until day 28. Changes in body weight and BMI were not significantly different between the control and treatment groups on days 14 or 28. The investigators concluded that HMB supplementation for 2 to 4 weeks can reduce muscle breakdown in elderly bed-ridden nursing home patients receiving tube feeding.

 

Cancer-related Cachexia:
This study involved 472 advanced cancer patients who had between 2% and 10% weight loss. Patients were randomized to receive either an isonitrogenous, isocaloric control mixture or Juven®, a commercially available formula containing HMB, glutamine, and arginine. Patients received an 8-week supply of Juven or the control at the initial visit and were evaluated at 4- and 8-week follow-up. There was no statistically significant difference in lean body mass between the control and treatment groups at 8 weeks. The investigators concluded that Juven failed to prevent lean body mass loss among cancer cachexia patients.

Side Effects

Chronic supplementation of HMB resulted in hyperinsulinemia (high insulin levels in the blood) in rats.

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