Abstract
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.
Highlights
There has been a great deal of controversy in recent years about the role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 Polyunsaturated Fatty Acids (PUFAs)) in the prevention of cardiovascular disease (CVD)
Based on results from prospective cohort studies, it is reasonable to speculate that supplementation with higher dosages of long-chain n-3 PUFA than used in most of the RCTs completed to date might be expected to produce larger reductions in cardiac death
A reduction in ST2 with long-chain n-3 PUFA supplementation in post-MI patients is consistent with the potential to reduce risk of cardiac death, especially because this was accompanied by improved left ventricular end systolic volume and reduced non-infarct cardiac fibrosis. These findings suggest further investigation of the effects of relatively high dosages of long-chain n-3 PUFA is warranted to evaluate the potential for reducing risk for cardiac death in high-risk subsets, such as those with recent MI or left ventricular hypertrophy, individuals with heart failure, and patients with end-stage renal disease
Summary
There has been a great deal of controversy in recent years about the 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 the available RCT data from studies that assessed the effects of n-3 PUFA intervention on CVD-related endpoints The authors of these papers reached disparate conclusions regarding the potential efficacy of long-chain n-3 PUFA supplementation for CVD risk reduction [11,16,17,18]. The objectives of this editorial review are to summarize results from recent meta-analyses of RCT data evaluating the effects of long-chain n-3 interventions on various CVD outcomes and to explain why we are of the opinion that additional research is warranted to evaluate potential cardiovascular benefits of higher dosages of long-chain n-3 PUFAs, for reducing risk of cardiac death in subgroups at high risk
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