title: Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients.
abstract: BACKGROUND
  Negative nitrogen balance and skeletal muscle loss are common in critically injured patients and may contribute to morbidity, mortality and resource utilization. Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and cancer patients. More recently HMB has been shown to attenuate cancer-induced muscle loss by decreasing muscle proteolysis. The purpose of this study was to analyze whether HMB alone or in combination with ARG and GLN would have a similar effect on critically injured trauma patients. We hypothesized that nitrogen balance would be improved and muscle proteolysis decreased with HMB and HMB/ARG/GLN supplementation.
  
  
  METHODS
  There were 100 adult trauma patients with Injury Severity Score (ISS) >18 were enrolled in this prospective, randomized, blinded study. All patients received standard tube feeds and one of three iso-nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo (PLAC) for 28 days. Urine, serum, and clinical data were collected for 72 patients receiving at least 7 days of supplementation during the first 14 days of treatment. Urinary 3-methylhistidine (3-MH) was used as a proxy for muscle proteolysis.
  
  
  RESULTS
  The three groups were similar in age, gender, mechanism, and severity of injury, with the average ISS being 31.9. Utilizing covariant (ISS) repeated measure (days 1-14) mixed model (SAS) analysis, there was a significant treatment effect (p = 0.05) on nitrogen balance (g/d). Change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group. 3-MH to creatinine ratios were not different in the PLAC group as compared with the HMB/ARG/GLN and HMB groups (Treatment Effect, p = 0.80).
  
  
  CONCLUSIONS
  These data suggest that supplementation with HMB alone may improve nitrogen balance in critically injured adult patients and that this effect is not a result of lowered muscle protein turnover as originally hypothesized.
authors.affiliation: Department of Surgery, University of Nevada School of Medicine, Las Vegas, Nevada 89102, USA. dkuhls@med.unr.edu
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Kuhls
authors.forename: John A
authors.initials: JA
authors.lastname: Rathmacher
authors.forename: M Diana
authors.initials: MD
authors.lastname: Musngi
authors.forename: Donald A
authors.initials: DA
authors.lastname: Frisch
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Nielson
authors.forename: Annabel
authors.initials: A
authors.lastname: Barber
authors.forename: Allan D
authors.initials: AD
authors.lastname: MacIntyre
authors.forename: Jay E
authors.initials: JE
authors.lastname: Coates
authors.forename: John J
authors.initials: JJ
authors.lastname: Fildes
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000627:therapeutic use*; D000328:Adult; D001120:Arginine / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D004750:Enteral Nutrition; D005260:Female; D005973:Glutamine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000517:prevention & control*; D009584:Nitrogen / Q000378:metabolism; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D015415:Biomarkers; D008762:Methylhistidines; D005973:Glutamine; D001120:Arginine; C028118:3-methylhistidine; D009584:Nitrogen; D020155:3-Hydroxybutyric Acid