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

Abstract

AimsAmong 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.MethodsAlong 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.ResultsOverall, 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.ConclusionsWhile 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.

Mixture of Arginine, Glutamine, and β‐hydroxy‐β‐methyl Butyrate Enhances the Healing of Ischemic Wounds in Rats

“…This may suggest that the enhancement in the treatment group in the present study may rather be attributed to the efficacy of this amino acid combination in wound healing only in the presence of a factor that impairs wound healing, such as ischemia. This conclusion is further supported by the findings of Armstrong et al, 5 which show an enhancement in wound healing with the administration of this mixture in diabetic foot ulcers, not in the general population, but in patients with impaired limb perfusion.…”

“…Later, 2 small‐scale clinical trials—one with a historical control group and the other without a control group—demonstrated that this mixture could be beneficial in the healing of diabetic foot ulcers 6 , 24 . However, the only large‐volume randomized controlled study using this product showed no total overall benefit of the mixture in either shortening the healing time of the diabetic ulcers or reducing ulcer sizes at the end of the 16th week 5 . Still, in the mentioned study, post hoc analysis revealed a significantly higher proportion of subjects in the treatment group with wound closure at the 16th week when the patients with albumin levels <40 g/L and/or poor limb perfusion were considered.…”

“…It also has a role in nucleotide synthesis in fibroblasts, epithelial cells, and macrophages, and it is essential in gluconeogenesis, which provides energy during wound healing 2 . Recent reports presented evidence that a combination of these 2 amino acids with β‐hydroxy‐β‐methyl butyrate (HMB), a naturally occurring metabolite of the amino acid leucine, increases collagen accumulation in the tissues of elderly individuals 4 and may have a positive influence on the healing of some diabetic foot ulcers 5 , 6…”

The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial

“…The diabetic foot ulcer (DFU) is a common complication of diabetes mellitus affecting 10%-25% of people with diabetes (Armstrong et al, 2014). The annual incidence of ulceration and amputation among patients with DFU is as high as 2.5%-10.7% and 0.25%-1.8%, respectively (Tiaka, Papanas, Manolakis, & Maltezos, 2011).…”

The Use of an Arginine-Enriched Oral Nutrition Supplement to Enhance Wound Healing from a Cesarean Section

“…High-protein diets have been show to aid in healing of pressure ulcers and other open wounds [5, 6]. Some nutrients in particular that have been shown to enhance the healing process include vitamin C, vitamin E, zinc, and two important amino acids, arginine and glutamine [7, 8]. Research has shown that arginine, vitamin C, and zinc may be among the most important nutrients to promote wound healing.…”