Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study
Caslake, Muriel J. | Miles, Elizabeth A. | Kofler, Bettina M. | Lietz, Georg | Curtis, Peter | Armah, Christopher K. | Kimber, Alan C. | Grew, Jilly P. | Farrell, Lesley | Stannard, Julie | Napper, Frances L. | Sala-Vila, Aleix | West, Annette L. | Mathers, John C. | Packard, Christopher | Williams, Christine M. | Calder, Philip C. | Minihane, Anne M.
BACKGROUND:The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. OBJECTIVES:We aimed to determine the effect of moderate EPA and DHA intakes (<2 g EPA+DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. DESIGN:Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA+DHA/d (0.7FO), and 1.8 g EPA+DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. RESULTS:In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. CONCLUSIONS:Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.
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