Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine

Am J Surg. 2002 Apr;183(4):471-9. doi: 10.1016/s0002-9610(02)00823-1.


Background: Cancer-related cachexia is caused by a diverse combination of accelerated protein breakdown and slowed protein synthesis. The hypothesis proposed in this study is that supplementation of specific nutrients known to positively support protein synthesis and reduce protein breakdown will reverse the cachexia process in advanced cancer patients.

Methods: Patients with solid tumors who had demonstrated a weight loss of at least 5% were considered for the study. Patients were randomly assigned in a double-blind fashion to either an isonitrogenous control mixture of nonessential amino acids or an experimental treatment containing beta-hydroxy-beta-methylbutyrate (3 g/d), L-arginine (14 g/d), and L-glutamine (14 g/d [HMB/Arg/Gln]). The primary outcomes measured were the change in body mass and fat-free mass (FFM), which were assessed at 0, 4, 8, 12, 16, 20, and 24 weeks.

Results: Thirty-two patients (14 control, 18 HMB/Arg/Gln) were evaluated at the 4-week visit. The patients supplemented with HMB/Arg/Gln gained 0.95 +/- 0.66 kg of body mass in 4 weeks, whereas control subjects lost 0.26 +/- 0.78 kg during the same time period. This gain was the result of a significant increase in FFM in the HMB/Arg/Gln-supplemented group (1.12 +/- 0.68 kg), whereas the subjects supplemented with the control lost 1.34 +/- 0.78 kg of FFM (P = 0.02). The response to 24-weeks of supplementation was evaluated by an intent-to-treat statistical analysis. The effect of HMB/Arg/Gln on FFM increase was maintained over the 24 weeks (1.60 +/- 0.98 kg; quadratic contrast over time, P <0.05). There was no negative effect of treatment on the incidence of adverse effects or quality of life measures.

Conclusions: The mixture of HMB/Arg/Gln was effective in increasing FFM of advanced (stage IV) cancer. The exact reasons for this improvement will require further investigation, but could be attributed to the observed effects of HMB on slowing rates of protein breakdown, with improvements in protein synthesis observed with arginine and glutamine.

Publication types

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

MeSH terms

  • Aged
  • Arginine / administration & dosage
  • Arginine / therapeutic use*
  • Body Composition / drug effects*
  • Cachexia / drug therapy*
  • Cachexia / etiology
  • Dietary Supplements*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Glutamine / administration & dosage
  • Glutamine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Neoplasms / complications*
  • Neoplasms / pathology
  • Treatment Outcome
  • Valerates / administration & dosage
  • Valerates / therapeutic use*


  • Drug Combinations
  • Valerates
  • Glutamine
  • beta-hydroxyisovaleric acid
  • Arginine