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 Mar-Apr;28(2):65-75. doi: 10.1177/014860710402800265.


Background: Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events.

Methods: Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day.

Results: Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p < .05) when compared with placebo-supplemented subjects. Blood creatinine levels were not changed. However, blood urea nitrogen increased (p = .01) with HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation.

Conclusion: These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / administration & dosage
  • 3-Hydroxybutyric Acid / adverse effects
  • 3-Hydroxybutyric Acid / therapeutic use*
  • Arginine / administration & dosage
  • Arginine / adverse effects
  • Arginine / therapeutic use*
  • Blood Chemical Analysis
  • Blood Urea Nitrogen
  • Cachexia / drug therapy*
  • Dietary Supplements*
  • Drug Therapy, Combination
  • Female
  • Glutamine / administration & dosage
  • Glutamine / adverse effects
  • Glutamine / therapeutic use*
  • HIV Wasting Syndrome / drug therapy*
  • Humans
  • Male
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Randomized Controlled Trials as Topic
  • Safety


  • Glutamine
  • Arginine
  • 3-Hydroxybutyric Acid