title: Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.
abstract: OBJECTIVE
  Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and β-hydroxy-β-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes.
  
  
  METHODS
  Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and β-hydroxy-β-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated.
  
  
  RESULTS
  Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and β-hydroxy-β-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal.
  
  
  CONCLUSIONS
  While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and β-hydroxy-β-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and β-hydroxy-β-methylbutyrate in these high-risk subgroups might prove clinically valuable.
authors.affiliation: Southern Arizona Limb Salvage Alliance (SALSA), Department of Surgery, University of Arizona College of Medicine, Tucson, AZ.
authors.forename: D G
authors.initials: DG
authors.lastname: Armstrong
authors.forename: J R
authors.initials: JR
authors.lastname: Hanft
authors.forename: V R
authors.initials: VR
authors.lastname: Driver
authors.forename: A P S
authors.initials: AP
authors.lastname: Smith
authors.forename: J L
authors.initials: JL
authors.lastname: Lazaro-Martinez
authors.forename: A M
authors.initials: AM
authors.lastname: Reyzelman
authors.forename: G J
authors.initials: GJ
authors.lastname: Furst
authors.forename: D J
authors.initials: DJ
authors.lastname: Vayser
authors.forename: H L
authors.initials: HL
authors.lastname: Cervantes
authors.forename: R J
authors.initials: RJ
authors.lastname: Snyder
authors.forename: M F
authors.initials: MF
authors.lastname: Moore
authors.forename: P E
authors.initials: PE
authors.lastname: May
authors.forename: J L
authors.initials: JL
authors.lastname: Nelson
authors.forename: G E
authors.initials: GE
authors.lastname: Baggs
authors.forename: A C
authors.initials: AC
authors.lastname: Voss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D001120:Arginine / Q000008:administration & dosage*; D017719:Diabetic Foot / Q000178:diet therapy / Q000503:physiopathology*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014631:Valerates / Q000008:administration & dosage*; D014945:Wound Healing
chemical_list: D014631:Valerates; D005973:Glutamine; C004961:beta-hydroxyisovaleric acid; D001120:Arginine