The Role of Vitamin D in Parkinson's Disease: Evidence from Serum Concentrations, Supplementation, and <i>VDR</i> Gene Polymorphisms.

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Background/aimVitamin D (VitD) has been implicated in neuroprotection, yet its role in Parkinson's disease (PD) remains unclear. This systematic review and meta-analysis aimed to evaluate the association between VitD status, supplementation, and vitamin D receptor (VDR) gene polymorphisms with PD risk and outcomes.MethodologyFollowing PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar through August 2025 for observational studies, clinical trials, and genetic association studies. Primary outcomes included serum VitD levels in PD versus healthy controls (HCs), prevalence of VitD insufficiency/deficiency, and effects of VitD supplementation on motor symptoms. Secondary outcomes assessed associations between VDR polymorphisms and PD susceptibility. Data were synthesized using random- and fixed-effects models, with heterogeneity and publication bias evaluated. PROSPERO (CRD420251133875).ResultsSixty-three studies (n ≈ 10,700 participants) met inclusion criteria. PD patients exhibited significantly lower VitD levels (SMD = -0.46; 95% CI: -0.51 to -0.41) and higher odds of insufficiency (OR = 1.52) and deficiency (OR = 2.20) compared to HC. Cohort data suggested sufficient VitD may reduce PD risk (HR = 0.83). Supplementation yielded modest, non-significant improvements in motor outcomes. Among 20 genetic studies, FokI (rs2228570) was most consistently associated with PD, while other VDR SNPs showed variable or null associations.ConclusionsVitD deficiency is common in PD and may influence disease risk and motor function. Current evidence indicates limited benefit of supplementation for motor outcomes, and genetic associations remain inconsistent.

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