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Background and Aims Diabetic foot ulcers (DFUs) add billions of dollars to the direct annual costs associated with diabetes. Despite various treatments, many DFUs do not heal and become infected. Both skin‐associated microbial communities and glycemic control are believed to be important in nonhealing DFUs. Recent studies have linked serum Vitamin C levels with glycemic control and DFUs. This cross‐sectional study assessed skin microbiome in DFUs, intact diabetic skin, and nondiabetic skin to identify correlations between hemoglobin A1c (HbA1c), Vitamin C, and microbial community structure. Correlations between Vitamin C, HbA1c, wound size, and ulcer duration were also determined. Methods Participants had their DFUs or intact skin culture swabbed. HbA1c was obtained via point‐of‐care fingerstick testing and serum Vitamin C was obtained via venipuncture. All participants completed a dietary questionnaire. Participants with ulcers were stratified into the controlled (≤8.0%) or uncontrolled (>8.0%) HbA1c group. Analysis of microbial communities was performed via 16S ribosomal RNA (rRNA) gene amplicon sequencing and bacterial load was measured by the domain‐level quantitative polymerase chain reaction of the 16S rRNA gene. Results Forty‐two patients were recruited over 6 months. Bacteria from the genera Staphylococcus and Stenotrophomonas were present in all samples and often dominant, but a shift towards anaerobic pathogenic taxa was observed in ulcers. No global significant differences were observed for HbA1c and Vitamin C levels in the microbial community structure ( R < 0.013/ p > 0.375). Bacterial loads were 4–5 orders of magnitude higher in ulcers than in intact skin samples. Bacterial load was not significantly higher in the uncontrolled HbA1c group ( p = 0.67). Larger wound sizes ( p = 0.46) were observed in the uncontrolled HbA1c group compared to the control. Lower Vitamin C levels ( p = 0.002) were observed in the uncontrolled HbA1c group compared to nondiabetic controls. Conclusion Understanding the link between Vitamin C and HbA1c and DFU microbiome may aid in new therapies.

Objective: The lifetime risk of developing a diabetic foot ulcer (DFU) in people with diabetes is as high as 25%. A trio of factors constitute the diabetic foot syndrome that characterises DFUs, including neuropathy, vascular disease and infections. Vitamin C has important functions in the nervous, cardiovascular, and immune systems that are implicated in DFU development. Furthermore, vitamin C deficiency has been observed in individuals with DFUs, suggesting an important function of vitamin C in DFU management and treatment. Therefore, this literature review evaluates the role of vitamin C in the nervous, cardiovascular and immune systems in relation to wound healing and DFUs, as well as discussing vitamin C's lesser known role in depression, a condition that affects many individuals with a DFU. Method: A literature search was done using PubMed, Cochrane Library, Embase, Ovid, Computer Retrieval of Information on Scientific Projects, and NIH Clinical Center. Search terms included ‘diabetic foot ulcer,’ ‘diabetic foot,’ ‘vitamin C,’ and ‘ascorbic acid.’ Results: Of the 71 studies initially identified, seven studies met the inclusion criteria, and only three were human clinical trials. Overall, the literature on this subject is limited, with mainly observational and animal studies, and few human clinical trials. Conclusion: There is a need for additional human clinical trials on vitamin C supplementation in individuals with a DFU to fill the knowledge gap and guide clinical practice.