Mendelian randomization analysis of 1.4 million Europeans found eicosapentaenoic acid (EPA) showed no protective effect against ischemic heart disease, with odds ratio of 1.05 suggesting potential slight harm rather than benefit. EPA lowered triglycerides and large VLDL particles but increased smaller, potentially atherogenic particles including remnant cholesterol and total cholesterol. This finding challenges the omega-3 cardiovascular narrative that has dominated supplement marketing for decades. While EPA does remodel lipoproteins through apparent lipolysis of large particles, the incomplete clearance of resulting smaller particles may create mixed cardiovascular implications. The genetic approach sidesteps confounding factors that plague observational omega-3 studies, providing stronger causal inference than previous research. However, this preprint awaits peer review, and results may change following scientific scrutiny. The analysis contradicts some recent trials suggesting EPA benefits in high-triglyceride patients, raising questions about population-specific effects versus general applicability. For the millions taking EPA supplements for heart health, these results suggest the mechanism may be more complex than simple cardiovascular protection, warranting careful reconsideration of blanket omega-3 recommendations.