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Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on Cardiovascular Mortality: The Importance of the Dose of DHA.

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.

SUBMITTER: Meyer BJ

PROVIDER: S-EPMC5748755 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on Cardiovascular Mortality: The Importance of the Dose of DHA.

Meyer Barbara J BJ Groot Renate H M de RHM

Nutrients 20171130 12

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 ...[more]

PMID: 29189735

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Project description:BackgroundAlthough omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.Methods and resultsAmong 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.ConclusionsHigh circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

Dataset Information

Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on Cardiovascular Mortality: The Importance of the Dose of DHA.

Publications

Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on Cardiovascular Mortality: The Importance of the Dose of DHA.

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