Key Findings
Evidence continues to support an equivalent role of omega-3 alpha-linolenic acid (ALA; 18:3n-3) and the long chain omega-3 fatty acids (LCn3PUFA) found in marine products, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in the reduction of coronary heart disease. This paper reports the first output from the Fatty Acids and Outcomes Research Consortium (FORCE), a collaboration of scientists who individually have conducted 19 different observational studies on omega 3 fats. The meta-analysis included data from 45,637 participants throughout 16 countries. The data showed that individuals with the highest omega 3 fatty acids in the blood levels had about a 25% lower risk of dying from a heart attack compared to those with the lowest levels. Overall, omega 3s from both plant and seafood sources were associated with a 10% lower risk of a fatal cardiac event.
Abstract
Importance: The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption, rather than biomarkers. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic (EPA; 20:5n-3), docosapentaenoic (DPA; 22:5n-3), and docosahexaenoic acid (DHA; 22:6n-3), and plant-derived α-linolenic acid (ALA; 18:3n-3), and incident CHD. Data Sources: A global consortium of 19 studies. Study Selection: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. Data Extraction and Synthesis: Each study conducted standardized individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using inverse-variance meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS-desaturase genes. Main Outcome(s) and Measure(s): Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). Results: The 19 studies comprised 16 countries, 45,637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 non-fatal MI events, with omega-3 measures in plasma, phospholipids, cholesterol esters, and adipose. In continuous (per 1 standard deviation increase) multivariable-adjusted analyses, omega-3 biomarkers ALA, DPA, and DHA were associated with lower risk of fatal CHD, with RRs (95% CI): ALA 0.91(0.84-0.98), DPA 0.90(0.85-0.96), and DHA 0.90(0.84-0.96), with EPA showing a trend towards lower risk (0.91 (0.82-1.00)). DPA, but not ALA, EPA, or DHA, was associated with lower risk of total CHD, with RRs (95% CI): 0.94(0.90-0.99), 1.00(0.95-1.05), 0.94(0.87-1.02), and 0.95(0.91-1.00), respectively. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence for nonlinearity in dose-responses. Conclusions and Relevance: Based on available studies of free-living populations globally, biomarker concentrations of both seafood and plant-derived omega-3s are associated with a modestly lower incidence of fatal CHD.
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