Can Omega-3 polyunsaturated fatty acids improve bone mineral density?: Evidence from a Mendelian randomization study

Previous studies have reported controversial associations between n-3 polyunsaturated fatty acids (n-3 PUFA) and bone mineral density (BMD). To clarify whether a causal relationship exists, this study employed a 2-sample Mendelian randomization analysis using single-nucleotide polymorphisms significantly associated with n-3 PUFA as instrumental variables; data for both exposure (n-3 PUFA) and outcome (BMD) were obtained from genome-wide association studies. The inverse variance weighting method served as the primary analytical approach, supplemented by multiple sensitivity analyses to assess the robustness of the findings. Results from the 2-sample Mendelian randomization analysis provided strong genomic evidence for a negative causal association between n-3 PUFA and BMD (inverse variance weighting: odds ratio = 0.94, 95% confidence interval: 0.90-0.98, P = .01). These findings indicate that higher n-3 PUFA is associated with an increased risk of reduced BMD, suggesting that elevated n-3 PUFA may be a risk factor for low BMD and potentially osteoporosis.