Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development: A Mendelian randomization study

BACKGROUND: Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome (PCOS). However, the effectiveness of vitamin, vitamin-like nutrient, or mineral supplementation in reducing the risk of PCOS remains a subject of debate. AIM: To investigate the impact of plasma levels of vitamins A, B12, D, E, and K on PCOS and key pathways implicated in its development, namely, insulin resistance, hyperlipidemia, and obesity, through Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies. The primary analysis was performed using the random-effects inverse-variance-weighted approach. Complementary analyses were conducted using the weighted median, MR-Egger, MR-robust adjusted profile score, and MR-PRESSO approaches. RESULTS: The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E (odds ratio [OR] = 0.118; 95% confidence interval [CI]: 0.071–0.226; P < 0.001) and vitamin B12 (OR = 0.753, 95%CI: 0.568–0.998, P = 0.048). An association was observed between vitamin E levels and insulin resistance (OR = 0.977, 95%CI: 0.976–0.978, P < 0.001). Additionally, genetically predicted higher concentrations of vitamins E, D, and A were suggested to be associated with a decreased risk of hyperlipidemia. Increased vitamins K and B12 levels were linked to a lower obesity risk (OR = 0.917, 95%CI: 0.848–0.992, P = 0.031). CONCLUSION: The findings of this MR study suggest a causal relationship between increased vitamins A, D, E, K, and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.