- beta-hydroxy-beta-methylbutyrate monohydrate
For Patients & Caregivers
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.
- 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.
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.
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.
For Healthcare Professionals
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 was shown to 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) .
Conclusions of a systematic review indicate that HMB is effective in preventing exercise-related muscle damage in healthy trained and untrained individuals, as well as muscle loss during chronic disease (17).
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). However, supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine and glutamine was effective in preventing radiation dermatitis in a study of head and neck cancer patients (18).
In muscle cells, HMB is thought to restore the balance between intracellular protein synthesis and proteolysis, likely by activating the PI3K/Akt-dependent mammalian target of rapamycin (mTOR) and FoxO1/FoxO3a signaling pathway and the reduction of tumor necrosis factor alpha-interferon gamma-induced MuRF-1 expression, improving atrophy due to aging (19).
In animal models, HMB caused reductions in the total subcutaneous fat content and LDL cholesterol (15). But it did not affect circulating plasma levels of testosterone (4), cortisol, insulin-like growth factor-1 (IGF-1), or insulin (14).
Supplemental HMB has been shown to enhance protein synthesis in skeletal muscle of neonatal pigs by stimulating translation initiation (20).
In a study of mice, HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, and significantly attenuated diaphragm weakness, preserving the generation of muscle force. This may potentially be of use in infected patients by reducing the duration of mechanical ventilation and decreasing mortality (21).
HMB was also shown to improve the proliferation of muscle stem cells in fast twitch plantaris muscles in aged rats. This is thought to be due to reduced apoptotic index in HMB treated muscles associated with enhanced satellite cell proliferation leading to increased differentiated myonuclei (22).
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).
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.