Muesli Intake May Protect Against Coronary Artery Disease: Mendelian Randomization on 13 Dietary Traits

Background Diet is a key modifiable risk factor of coronary artery disease (CAD). However, the causal effects of specific dietary traits on CAD risk remain unclear. With the expansion of dietary data in population biobanks, Mendelian randomization (MR) could help enable the efficient estimation of causality in diet-disease associations. Objectives The primary goal was to test causality for 13 common dietary traits on CAD risk using a systematic two-sample MR framework. A secondary goal was to identify plasma metabolites mediating diet-CAD associations suspected to be causal. Methods Cross-sectional genetic and dietary data on up to 420,531 UK Biobank and 184,305 CARDIoGRAMplusC4D individuals of European ancestry were used in two-sample MR. The primary analysis used fixed effect inverse-variance weighted regression, while sensitivity analyses used weighted median estimation, MR-Egger regression, and MR-Pleiotropy Residual Sum and Outlier. Results Genetic variants serving as proxies for muesli intake were negatively associated with CAD risk (OR: 0.74; 95% CI: 0.65-0.84; P = 5.385 × 10−4). Sensitivity analyses using weighted median estimation supported this with a significant association in the same direction. Additionally, we identified higher plasma acetate levels as a potential mediator (OR: 0.03; 95% CI: 0.01-0.12; P = 1.15 × 10−4). Conclusions Muesli, a mixture of oats, seeds, nuts, dried fruit, and milk, may causally reduce CAD risk. Circulating levels of acetate, a gut microbiota-derived short-chain fatty acid, could be mediating its cardioprotective effects. These findings highlight the role of gut flora in cardiovascular health and help prioritize randomized trials on dietary interventions for CAD.