Moore ZE, Corcoran MA, Patton D, et al.
The Cochrane database of systematic reviews. Date of publication 2020 Jul 17;volume 7():CD011378.
1. Cochrane Database Syst Rev. 2020 Jul 17;7:CD011378. doi:
10.1002/14651858.CD011378.pub2.
Nutritional interventions for treating foot ulcers in people with diabetes.
Moore ZE(1), Corcoran MA(2), Patton D(1).
Author information:
(1)School of Nursing & Midwifery, Royal College of Surgeons in Ireland, Dublin,
Ireland.
(2)Department of Endocrinology, Mater Misericordiae University Hospital, Dublin,
Ireland.
BACKGROUND: Foot ulcers in people with diabetes are non-healing, or poorly
healing, partial, or full-thickness wounds below the ankle. These ulcers are
common, expensive to manage and cause significant morbidity and mortality. The
presence of a wound has an impact on nutritional status because of the metabolic
cost of repairing tissue damage, in addition to the nutrient losses via wound
fluid. Nutritional interventions may improve wound healing of foot ulcers in
people with diabetes.
OBJECTIVES: To evaluate the effects of nutritional interventions on the healing
of foot ulcers in people with diabetes.
SEARCH METHODS: In March 2020 we searched the Cochrane Wounds Specialised
Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid
MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials
registries for ongoing and unpublished studies, and scanned reference lists of
relevant included studies as well as reviews, meta-analyses and health technology
reports to identify additional studies. There were no restrictions with respect
to language, date of publication or study setting.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that
evaluated the effect of nutritional interventions on the healing of foot ulcers
in people with diabetes.
DATA COLLECTION AND ANALYSIS: Two review authors, working independently, assessed
included RCTs for their risk of bias and rated the certainty of evidence using
GRADE methodology, using pre-determined inclusion and quality criteria.
MAIN RESULTS: We identified nine RCTs (629 participants). Studies explored oral
nutritional interventions as follows: a protein (20 g protein per 200 mL bottle),
1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals
and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate
supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements;
1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus
300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000
IU vitamin D supplements. The comparator in eight studies was placebo, and in one
study a different dose of vitamin D. Eight studies reported the primary outcome
measure of ulcer healing; only two studies reported a measure of complete
healing. Six further studies reported measures of change in ulcer dimension,
these studies reported only individual parameters of ulcer dimensions (i.e.
length, width and depth) and not change in ulcer volume. All of the evidence
identified was very low certainty. We downgraded it for risks of bias,
indirectness and imprecision. It is uncertain whether oral nutritional supplement
with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added
vitamins, minerals and trace elements, increases the proportion of ulcers healed
at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval
(CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and
β-hydroxy-β-methylbutyrate supplement increases the proportion of ulcers healed
at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain
whether the following interventions change parameters of ulcer dimensions over
time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg
elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid
from flaxseed oil supplement, magnesium and vitamin E co-supplementation and
vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D,
impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies
explored some of the secondary outcomes of interest for this review. It is
uncertain whether oral nutritional supplement with 20 g protein per 200 mL
bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace
elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or
amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain
whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases
health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI
-0.09 to 0.03). It is also uncertain whether arginine, glutamine and
β-hydroxy-β-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04,
95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than
placebo. None of the included studies reported the secondary outcomes cost of
intervention, acceptability of the intervention (or satisfaction) with respect to
patient comfort, length of patient hospital stay, surgical interventions, or
osteomyelitis incidence. One study exploring the impact of arginine, glutamine
and β-hydroxy-β-methylbutyrate supplement versus placebo did not report on any
relevant outcomes.
AUTHORS' CONCLUSIONS: Evidence for the impact of nutritional interventions on the
healing of foot ulcers in people with diabetes compared with no nutritional
supplementation, or compared with a different dose of nutritional
supplementation, remains uncertain, with eight studies showing no clear benefit
or harm. It is also uncertain whether there is a difference in rates of adverse
events, amputation rate, development of new foot ulcers, or quality of life,
between nutritional interventions and placebo. More research is needed to clarify
the impact of nutritional interventions on the healing of foot ulcers in people
with diabetes.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD011378.pub2
PMCID: PMC7388930 [Available on 2021-07-17]
PMID: 32677037 [Indexed for MEDLINE]
