Longitudinal associations between marine omega-3 supplement users and coronary heart disease in a UK population-based cohort

OBJECTIVES Assess the association between marine omega-3 polyunsaturated fatty acid (n-3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart disease (CHD) mortality. DESIGN Prospective cohort study, with three exposure measurements over 22 years. SETTING Norfolk-based European Prospective Investigation into Cancer (EPIC-Norfolk, UK). PARTICIPANTS 22 035 men and women from the general population, 39-79 years at recruitment. EXPOSURE Supplement use was assessed in three questionnaires (1993-1998; 2002-2004; 2004-2011). Participants were grouped into non-supplement users (NSU), n-3 PUFA supplement users (SU+n3) and non-n-3 PUFA supplement users (SU-n3). Cox regression adjusted for time-point specific variables: age, smoking, prevalent illnesses, body mass index, alcohol consumption, physical activity and season and baseline assessments of sex, social class, education and dietary intake (7-day diet diary). PRIMARY AND SECONDARY OUTCOME MEASURES During a median of 19-year follow-up, 1562 CHD deaths were registered for 22 035 included participants. RESULTS Baseline supplement use was not associated with CHD mortality, but baseline food and supplement intake of n-3 PUFA was inversely associated with CHD mortality after adjustment for fish consumption. Using time-varying covariate analysis, significant associations were observed for SU+n3 (HR: 0.74, 95% CI 0.66 to 0.84), but not for SU-n3 versus NSU. In further analyses, the association for SU+n3 persisted in those who did not take other supplements (HR: 0.83, 95% CI 0.71 to 0.97). Those who became SU+n3 over time or were consistent SU+n3 versus consistent NSU had a lower hazard of CHD mortality; no association with CHD was observed in those who stopped using n-3 PUFA-containing supplements. CONCLUSIONS Recent use of n-3 PUFA supplements was associated with a lower hazard of CHD mortality in this general population with low fish consumption. Residual confounding cannot be excluded, but the findings observed may be explained by postulated biological mechanisms and the results were specific to SU+n3.