Omega-3 Fatty Acid Supplementation and Cardiovascular Disease Risk: Glass Half Full or Time to Nail the Coffin Shut?

There has been a great deal of controversy in recent years about the potential role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) in the prevention of cardiovascular disease (CVD). Four recent meta-analyses have been published that evaluated randomized, controlled trial (RCT) data from studies that assessed the effects of supplemental n-3 PUFA intake on CVD endpoints. The authors of those reports reached disparate conclusions. This review explores the reasons informed experts have drawn different conclusions from the evidence, and addresses implications for future investigation. Although RCT data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with n-3 PUFA supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention. The most promising evidence supports n-3 PUFA supplementation for prevention of cardiac death. Two ongoing trials have enrolled high cardiovascular risk subjects with hypertriglyceridemia and are administering larger dosages of n-3 PUFA than employed in previous RCTs. These are expected to clarify the potential role of long-chain n-3 PUFA supplementation in CVD risk management.