Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: A prospective randomized controlled trial

D. G. Armstrong, J. R. Hanft, V. R. Driver, A. P.S. Smith, J. L. Lazaro-Martinez, A. M. Reyzelman, G. J. Furst, D. J. Vayser, H. L. Cervantes, R. J. Snyder, M. F. Moore, P. E. May, J. L. Nelson, G. E. Baggs, A. C. Voss, Joseph Caporusso, Cyaandi Dove, F. Felix Sigal, Leon Brill, Harry PennyMaxine Theriot, David Abdoo, Julia Alvarez-Hernandez, Timothy Dutra, Richard Pollak, Thomas Zgonis, Ira Gottlieb, Eric Jaakola, Stephen Moss, James Wrobel, Robert Wunderlich, Jawl Shan Hwang, Susan Kemp, Adam Landsman, Neal Mozen, Lee Rogers, Thomas Serena, Ken Shimozaki, Josep Bianchini, H. Harry Kezelian, Kathleen Serracino-Inglott

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Aims: 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.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalDiabetic Medicine
Issue number9
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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