Habitual Fish Consumption, n‐3 Fatty Acids, and Nuclear Magnetic Resonance Lipoprotein Subfractions in Women

BACKGROUND: Supplementation with omega‐3 (n‐3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride‐lowering effects and slight increases in LDL (low‐density lipoprotein) cholesterol. Limited evidence has examined n‐3 effects on more detailed lipoprotein biomarkers. METHODS AND RESULTS: We conducted a study of 26 034 healthy women who reported information on fish and n‐3 intake from a 131‐item food‐frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n‐3, and the n‐3 subtypes (eicosapentaenoic, docosahexaenoic, and α‐linolenic acids). Top‐ versus bottom‐quintile intake of fish and n‐3 were significantly associated with lower triglyceride and large VLDL (very‐low‐density lipoprotein) particles. Fish intake, but not total n‐3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α‐linolenic acid was associated with lower LDL cholesterol. Total n‐3, docosahexaenoic acid, and α‐linolenic acid intake were also positively associated with larger HDL (high‐density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n‐3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. CONCLUSIONS: Higher consumption of fish and n‐3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α‐linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis‐generating findings warrant further study in clinical trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.