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

• Published in: The American journal of surgery 2002-04, Vol.183 (4), p.471-479
• Main Authors: May, Patricia Eubanks, Barber, Annabel, D’Olimpio, James T, Hourihane, Ann, Abumrad, Naji N
• Format: Article
• Language: English
• Subjects: Aged; Amino acids; Arginine; Arginine - administration & dosage; Arginine - therapeutic use; Biological and medical sciences; Body composition; Body Composition - drug effects; Body mass; Breakdown; Cachexia; Cachexia - drug therapy; Cachexia - etiology; Calories; Cancer; Cancer therapies; Cancer-related cachexia; Dietary Supplements; Double-Blind Method; Drug Combinations; Evaluation; Fat-free body mass; Female; General and cellular metabolism. Vitamins; Glutamine; Glutamine - administration & dosage; Glutamine - therapeutic use; Humans; Male; Medical prognosis; Medical sciences; Metabolism; Metabolites; Middle Aged; Mixtures; Morbidity; Mortality; Muscle, Skeletal - drug effects; Neoplasms - complications; Neoplasms - pathology; Nitrogen; Nutrients; Nutrition; Oral supplementation; Parenteral nutrition; Patients; Pharmacology. Drug treatments; Protein biosynthesis; Protein synthesis; Proteins; Proteolysis; Quality of life; Questionnaires; Solid tumors; Statistical analysis; Treatment Outcome; Tumors; Valerates - administration & dosage; Valerates - therapeutic use; Variance analysis; Weight loss; β-Hydroxy-β-methylbutyrate, arginine, and glutamine
• ISSN: 0002-9610; 1879-1883
• 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 β-hydroxy-β-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