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

Nuria Amigó, Akintunde O Akinkuolie, Stephanie E Chiuve, Xavier Correig, Nancy R Cook, Samia Mora, Nuria Amigó, Akintunde O Akinkuolie, Stephanie E Chiuve, Xavier Correig, Nancy R Cook, Samia Mora

Abstract

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.

Keywords: fish; nuclear magnetic resonance lipoprotein subfractions; n‐3.

Figures

Figure 1
Figure 1
Percentage difference in outcome between quintiles (Qs; Q2–Q5) compared with Q1 of fish and n‐3 intake after adjusting for all demographic, clinical, and dietary factors. Individual distribution: fish: Q1, n=5839; Q2, n=5035; Q3, n=5465; Q4, n=4078; Q5, n=5617; n‐3: Q1, n=5248; Q2, n=5406; Q3, n=4991; Q4, n=5266; Q5, n=5123. Apo indicates apolipoprotein; HDL, high‐density lipoprotein; HDL‐C, high‐density lipoprotein cholesterol; IDL, intermediate‐density lipoprotein; LDL, low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; n‐3, omega‐3; TC, total cholesterol; TG, triglycerides; VLDL, very‐low‐density lipoprotein.
Figure 2
Figure 2
Adjusted percentage difference in lipids and lipoproteins between quintiles (Qs; Q2–Q5) compared with Q1 of n‐3 subtype intakes. ALA indicates α‐linolenic acid; Apo, apolipoprotein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HDL, high‐density lipoprotein; HDL‐C, high‐density lipoprotein cholesterol; IDL, intermediate‐density lipoprotein; LDL, low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; n‐3, omega‐3; TC, total cholesterol; TG, triglycerides; VLDL, very‐low‐density lipoprotein.
Figure 3
Figure 3
Heat map of percentage differences between adjusted means of greater and lower intake groups of the exposure variables (Q5–Q1) according to intake of fish, total n‐3, and n‐3 subtypes. Outcome variables are sorted according to previously reported hazard ratios (HRs) adjusted for nonlipid risk factors. Green is associated with lower risk of cardiovascular disease (CVD), and red is associated with higher risk of CVD. The right‐lower scale bar illustrates the magnitude (length) of a 15% difference between Q5 and Q1, in which smaller bars represent <15% difference and larger bars represent >15% difference. When the consumption of higher amounts of exposure variables decreases the outcome variable, Q5<Q1; when the consumption of higher amounts of exposure variables increases the outcome variable, Q5>Q1 (fish: Q1, n=5839; Q5, n=5617; n‐3: Q1, n=5248; Q5, n=5123; EPA: Q1, n=5370; Q5, n=4947; DHA: Q1, n=6351; Q5, n=4797; ALA: Q1, n=5286; Q5, n=5097). ALA indicates α‐linolenic acid; Apo, apolipoprotein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HDL, high‐density lipoprotein; HDL‐C, high‐density lipoprotein cholesterol; IDL, intermediate‐density lipoprotein; LDL, low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; n‐3, omega‐3; Q, quintile; TC, total cholesterol; VLDL, very‐low‐density lipoprotein.
Figure 4
Figure 4
Percentage differences between the means of the greater and lower intake groups of the exposure variables (Q5–Q1) after adjusting for all demographic, clinical, and dietary factors that showed a significant association (PTrend<0.05) among fish, total n‐3, and the different n‐3 subtypes of fatty acid intake and lipid and lipoprotein subfractions. Blank spaces indicate no significant association (fish: Q1, n=5839; Q5, n=5617; n‐3: Q1, n=5248; Q5, n=5123; EPA: Q1, n=5370; Q5, n=4947; 6 DHA: Q1, n=6351; Q5, n=4797; ALA: Q1, n=5286; Q5, n=5097). ALA indicates α‐linolenic acid; Apo, apolipoprotein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; TC, total cholesterol; LDL, low density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; TG, triglycerides; VLDL, very‐low‐density lipoprotein; HDL, high‐density lipoprotein; HDL‐C, high‐density lipoprotein cholesterol. For the adjusted means please see Table S14.

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