Commentary: New Meta‐Analysis Confirms the Long Established Triacylglycerol‐Lowering Effect of Omega‐3 Fatty Acids Given in Supplemental Form

Abstract

In this issue of European Journal of Lipid Science and Technology, Nam et al.[1] present the findings of a new meta-analysis of the impact of omega-3 supplements (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) on blood lipids; much of the focus of the paper is on the effect on blood triacylglycerol (TG) concentrations. Quite rightly, the analysis uses data from randomized, double blind, placebo controlled trials. In total, data from 53 such trials involving over 7000 participants are used to evaluate the effect on blood TG concentrations, 54, 55, and 50 trials are used to evaluate the effect on blood total cholesterol, high density lipoprotein (HDL)-cholesterol, and low density lipoprotein (LDL)-cholesterol concentrations, respectively. This seems a robust database from which to draw firm conclusions and the meta-analysis appears to be well performed. Overall, it is identified that supplemental omega-3 fatty acids lower blood TG concentrations by an average of 38.6 mg dL À1.[1] Although no value for p is provided, it is evident from the 95% confidence intervals (CI; À47.2 to À30.2 mg dL À1) that the TG lowering effect of omega-3 fatty acids is highly statistically significant. There was no overall effect of omega-3 fatty acids on total cholesterol concentration, but both HDL-cholesterol and LDLcholesterol concentrations were increased. For HDL-cholesterol the increase was 1.6 mg dL À1 (95% CI 0.9-2.3 mg dL À1), while for LDL-cholesterol it was 3.1 mg dL À1 (95% CI 1.1-5.0 mg dL À1 ). The authors present a number of sub-group analyses that are very important in understanding the nature of the evidence base around supplemental omega-3 fatty acids and blood TG lowering. The two most important sub-group analyses are regarding the dose of supplemental omega-3 fatty acids used and the starting (i.e., baseline) blood TG concentration. First, it is demonstrated that low doses of supplemental omega-3 fatty acids have a smaller effect than higher doses.[1] This identification of a dose-dependent effect of omega-3 fatty acids provides a biological plausibility to the findings. Importantly, the metaanalysis identifies that more than one g per day of EPA and/or DHA is required to have a significant impact on blood TGs. [1] Secondly, the effect of omega-3 fatty acids is shown to be greater if the starting blood TG concentration is higher; this finding provides a strong clinical rationale for use of supplemental omega-3 fatty acids in those with hypertriacylglycerolemia. Other subgroup analyses identified no difference in the effect of omega-3 fatty acids on blood TG according to whether the pharmaceutical industry provided the omega-3 supplements or not; to whether the pharmaceutical industry or an independent organization funded the trial; to which continent the trial was conducted on; or to the duration of supplementation.[1] These findings give confidence to the conclusion that supplemental omega-3 fatty acids can be used to lower blood TG concentrations.The findings of this new meta-analysis are entirely...

Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation

“…Although n-3 FA consumption overall significantly reduced TG concentrations, the authors asserted that evidence regarding the effectiveness of n-3 FAs in the management of dysipidemia, especially hypertriglyceridemia, is inconclusive, in part because of the heterogeneity in studies, low methodological quality of studies, and small sample sizes (33). As raised by Calder (34) in a commentary on the meta-analysis, their findings are very consistent with the literature and actually clearly confirm that n-3 FAs in supplemental form can lower TG concentrations. Moreover, this inconclusiveness regarding the beneficial effects of n-3 FA intake can probably be attributable to the lack of consideration of contributors to the interindividual variability in the metabolic response to n-3 FA, including genetic factors.…”