Abstract
Recent evidence on the relationship between omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation and cardiovascular health suggests that n-3 LCPUFA may no longer be efficacious. This review summarises the randomised controlled trials (RCTs) that assess the effect of n-3 LCPUFA supplementation on cardiovascular mortality. It appears that in the RCTs that showed no effect of n-3 LCPUFA on cardiovascular mortality, the dose of n-3 LCPUFA (in particular docosahexaenoic acid (DHA)) and hence the n-3 LCPUFA status, may not have been sufficiently high to demonstrate the efficacy, and/or the baseline n-3 LCPUFA status was already too high. The intention-to-treat analysis (ITT) is the gold standard for analysing RCTs and ITT is used for drug intervention trials where exposure to the drug versus no drug exposure provides two clearly distinct groups to determine the efficacy of the drug being studied. This differs in nutrition trials as often the nutrient of interest being studied is already being consumed by both groups (placebo and active) and therefore a true placebo group with absolutely no intake of the nutrient being studied is highly unlikely. Therefore, in n-3 LCPUFA supplementation trials, as there is no clear distinction between the two groups (placebo and n-3 LCPUFA), a per-protocol analysis (comparison of groups that includes only those participants that fully completed the original intervention allocation) should be conducted in addition to ITT analysis. Furthermore, blood analysis pre- and post-supplementation should be conducted to ensure that: (1) that the baseline n-3 status is not too high, in order to alleviate a potential ceiling effect; and (2) that the dose is high enough and hence the increase in omega-3 status will be high enough in order to assess the efficacy of n-3 LCPUFA supplementation.
Highlights
IntroductionThe interest in n-3 LCPUFA originates from the documented evidence that Eskimos’ rates of cardiovascular disease (CVD) were much lower than those of the Danish population, despite the Eskimos’ high consumption of fat [9]
The health benefits of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are numerous and include neurological development [1,2,3], improved cognition [4,5,6], and reduced cognitive decline [7] as well as cardiovascular disease (CVD) benefits [8].The interest in n-3 LCPUFA originates from the documented evidence that Eskimos’ rates of CVD were much lower than those of the Danish population, despite the Eskimos’ high consumption of fat [9]
The eligibility criteria for inclusion in this review were research manuscripts that assessed the effect of n-3 LCPUFA supplementation on CVD mortality (including coronary heart disease (CHD), stroke, heart failure, and sudden cardiac death)
Summary
The interest in n-3 LCPUFA originates from the documented evidence that Eskimos’ rates of CVD were much lower than those of the Danish population, despite the Eskimos’ high consumption of fat [9]. Since there have been numerous publications on the cardiovascular health benefits of n-3 LCPUFA consumption, but recent meta-analyses suggest otherwise. When the Japanese move to Hawaii and adopt a diet much lower in n-3 LCPUFA, risk factors for CVD increase, suggesting that the Japanese protective effect is not purely due to genetics [14]. Total n-3 LCPUFA intakes of 750 mg per day showed the greatest protection in the age-adjusted mortality (from CVD, coronary heart disease and stroke) in a cross-sectional study of 38 countries [13]
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