The Impact of Omega-3 Fatty Acids, Polyphenols and Vitamin D on Neurodegenerative Diseases: A Meta-Analysis

Aim: This study is aimed to to assess the impact of vitamin D, omega-3 fatty acids (ω-3), and polyphenols on cognitive functioning, clinical outcomes, and inflammatory biomarkers in patients diagnosed with Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple Sclerosis (MS). Method: A systematic search was conducted in the PubMed, Scopus, and Google Scholar databases. Only clinical trials and randomized controlled trials (RCTs) were included. A total of 689 studies published between 2000 and 2025 were reviewed, and 14 studies that met the inclusion criteria were analyzed. Effect sizes were calculated using Hedges’ g value. Fixed and random effects models were used depending on heterogeneity. Funnel plots were used to assess publication bias. All statistical analyses were performed using the Comprehensive Meta-Analysis (CMA) program. Results: Vitamin D supplementation significantly raised blood 25-hydroxyvitamin D [25(OH)D] levels (g = 1.589, p< .001). The Mini-Mental State Examination (MMSE) showed no significant cognitive effects of omega-3 polyunsaturated fatty acids and polyphenols (p> 0.05). One study indicated that ellagic acid reduced Expanded Disability Status Scale (EDSS) scores, while vitamin D and omega-3 supplementation did not. Some studies showed considerable reductions in IL-6 and TNF-α levels, but the meta-analysis found no statistical significance. A substantial decrease in TNF-α was seen in the fixed effects model (p= .0029), but not in the random effects model (p= .132) Conclusion: Vitamin D supplementation markedly elevated serum 25(OH)D levels, indicating its potential as an effective intervention in neurodegenerative processes. The impact of omega-3 fatty acids and polyphenols on cognitive and clinical outcomes was observed to be inconsistent. Additional high-quality, long-term randomized controlled trials are necessary to more accurately assess the clinical efficacy of these compounds in neurodegenerative diseases.