OBJECTIVE: Polycystic ovary syndrome (PCOS) affects many women and is linked to nutrient intake, but the causal role of nutrients is unclear. Our study used Mendelian randomization (MR) to explore this relationship. METHODS: We employed two-sample MR to investigate the causal effects of four macronutrients (carbohydrates, fats, sugars, proteins) and 12 micronutrients (vitamin A [retinol], folate, vitamin B6, vitamin B12, vitamin C [ascorbic acid], vitamin D, vitamin E [alpha-tocopherol], magnesium, calcium, iron, selenium, and zinc) on the risk of PCOS based on their circulating levels. We conducted analyses using the inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, and simple model approach, with IVW as the primary method. To correct for multiple testing, the false discovery rate (FDR) method was applied. The reliability and potential bias of the results were assessed by sensitivity analysis and F-statistics. RESULTS: From a genetic standpoint, higher circulating vitamin A (retinol) levels were found to be a protective factor for PCOS and closely associated with the risk of PCOS, consistent with recent research findings. The inverse variance-weighted (IVW) estimation indicated a protective effect of vitamin A (retinol) on PCOS (IVWOR = 0.97, 95% CI: 0.95-0.99, P = 0.002, FDR_P = 0.03). However, no causal relationship was found between other nutrients and PCOS. In addition, MR-PRESSO and MR-Egger regression showed that our results were not affected by horizontal pleiotropy (P >
0.05). Finally, leave-one-out sensitivity analysis confirmed the robustness of MR Results. CONCLUSION: Our findings suggest that circulating vitamin A (retinol) levels influence the risk of PCOS, but further research is needed.