Nadira Rifda UTAMI, Eddy ROFLIN, Pariyana PARIYANA
Endocrinology Research and Practice - 2026;30(3):183-194
Micronutrient supplementation has emerged as a potential adjunctive therapy to enhance wound healing in patients with diabetic foot ulcers (DFU). This systematic review synthesizes current evidence on the effectiveness of various micronutrients, including vitamin D, vitamin C, zinc, omega-3 fatty acids, magnesium combined with vitamin E, and multinutrient formulations, in improving wound-healing outcomes. A comprehensive literature search was conducted across PubMed, ScienceDirect, EuropePMC, and Google Scholar in accordance with PRISMA 2020 guidelines, and 9 randomized controlled trials (RCTs) were included. Overall, micronutrient supplementation was associated with improved wound-healing parameters, including reduced ulcer size, enhanced granulation tissue formation, and accelerated epithelialization. Several studies also reported favorable changes in inflammatory markers (e.g., interleukin-6, tumor necrosis factor-alpha, C-reactive protein), oxidative stress indicators, and metabolic parameters such as hemoglobin A1c and lipid profiles. These findings suggest that micronutrients may support wound repair through modulation of inflammatory, oxidative, and metabolic pathways. However, interpretation of these results is limited by heterogeneity in study design, intervention protocols, baseline nutritional status, and outcome assessment methods. Micronutrient supplementation may serve as a beneficial and generally well-tolerated adjunct in DFU management, but routine use should be approached cautiously. Further large-scale, well-designed RCTs are required to determine optimal dosing strategies, duration of therapy, and long-term safety outcomes.
