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Diabetic foot ulcers (DFUs) persist as a predominant clinical challenge, constituting the primary etiological factor in the pathway to lower-extremity amputation and a significant source of comorbidity and mortality among individuals with diabetes mellitus. The role of vitamin C in wound repair is critical, yet its specific impact on DFUs requires further synthesis. Deficiencies in this micronutrient can disrupt collagen formation, immune response, and oxidative defense mechanisms, potentially impeding healing. To investigate this, a systematic review was conducted to assess clinical evidence linking vitamin C status, via supplementation or biochemical deficiency, to DFU prevalence and healing outcomes. A search strategy was executed in major electronic databases, identifying relevant clinical trials and observational studies up to September 2025. From the identified records, 10 studies were selected for final inclusion. The quality of evidence was subsequently evaluated using the Cochrane RoB 2.0 tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for observational studies. Vitamin C supplementation (500-1000 mg/day) significantly enhanced DFU healing outcomes in all four RCTs, with improved wound closure, reduced ulcer size, and faster recovery compared with control groups. Observational data demonstrated that low serum vitamin C (<23 µmol/L) was strongly correlated with delayed healing, severe ulceration, and increased risk of amputation. Combination therapies using vitamin C with vitamin E, platelet-rich plasma (PRP), fibrin glue, or silver dressings yielded synergistic healing benefits. Vitamin C deficiency is highly prevalent among DFU patients and is consistently associated with poor healing outcomes. Oral supplementation, especially in deficient individuals, appears to enhance wound recovery. Future large-scale RCTs should determine optimal dosing and clarify mechanistic pathways for clinical translation.
Saad et al. (Wed,) studied this question.