Association Between Vitamin D Status and Peripheral Neuropathy: A GRADE-based Systematic Review and Meta-analysis
Asmaa Alnajjar1, Omar Khaled Abdelsalam2, Mesan Hijazy1, Ali Nagy Shelbaya3, Maha AbuZarifa4, Noha Hammad5, Moaz Abouelmagd6
1Faculty of Medicine, Al-Azhar University, Gaza, Palestine., 2Faculty of Medicine, New Mansoura University, New Mansoura, Egypt, 3Faculty of Medicine New Mansoura university, New Mansoura, Egypt, 4Faculty of Medicine, Al-Quds University- Al-Azhar branch, Gaza, Palestine, 5Faculty of Medicine, Port-Said University, Egypt, 6Faculty of Medicine Cairo University Cairo Egypt
Objective:
To evaluate the association between vitamin D status and the risk of peripheral neuropathy
Background:
Peripheral neuropathies (PNPs) are common disorders affecting approximately 2.4% of the global population and up to 8% in the elderly. Vitamin D deficiency has been linked to PNP. However, existing literature presents conflicting results, necessitating a meta-analysis.
Design/Methods:
This study adhered to the Cochrane Handbook and PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases until April 24, 2025, identified peer-reviewed observational studies quantifying serum vitamin D levels and their association with PNP. Data extraction and quality assessment (NOS for cohort/case-control, JBI for cross-sectional) were conducted independently by two reviewers. Meta-analyses used a random-effects model to calculate adjusted odds ratios (ORs) and 95% confidence intervals, with subgroup analyses by vitamin D status, assessment method, study design, and diabetes type.
Results:
Forty-four studies were included in the systematic review, with 31 in the meta-analysis, involving 420,311 participants. The pooled analysis demonstrated a significant association between vitamin D deficiency and increased risk of PNP (OR = 1.36; 95% CI: 1.18–1.56; p < 0.0001), while no significant relationship was observed for vitamin D insufficiency (OR = 0.97; 95% CI: 0.91–1.04; p = 0.45). Sensitivity analysis, after excluding two lower-quality studies, revealed a markedly higher pooled OR of 3.05 (95% CI: 1.76–5.30), confirming the robustness of the association. Among diabetic populations, vitamin D deficiency further elevated the risk of PNP (OR = 1.42; 95% CI: 1.23–1.65; p < 0.00001). Overall, these findings highlight that inadequate vitamin D levels are strongly linked to peripheral neuropathy, particularly in individuals with diabetes.
Conclusions:
Vitamin D deficiency is significantly associated with a higher risk of peripheral neuropathy, especially in diabetics. adequate vitamin D may protect against nerve damage. Despite heterogeneity, findings suggest a biological link needing further confirmation through future studies.
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