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Effect of varying the ratio of n–6 to n–3 fatty acids by increasing the dietary intake of -linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45–70 y: the OPTILIP Study^1,2,3

¹ From the Nutritional Sciences Research Division, King’s College London, London, United Kingdom (TABS, FL, and SS); the Centre for Food Safety and Nutrition, University of Surrey, Guildford, United Kingdom (BAG, MG, ID, DJM); the Centre for the Genetics of Cardiovascular Disease, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, United Kingdom (JAC); and the Medical Research Council Cardiovascular Research Group, Wolfson Institute, Barts and The London Queen Mary’s School Medicine and Dentistry, London, United Kingdom (GJM)

Background: Elevated fibrinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that lowering the dietary ratio of n–6 to n–3 polyunsaturated fatty acids (n–6:n–3) would modify these risk factors in older men and women.

Objective: The objective of the study was to measure fasting hemostatic risk factors and postprandial changes in activated FVII (FVIIa) concentrations after a 6-mo alteration in dietary n–6:n–3.

Design: In a randomized, parallel design in 258 subjects aged 45–70 y, we compared 4 diets providing 6% of energy as polyunsaturated fatty acids at an n–6:n–3 between 5:1 and 3:1 with a control diet that had an n–6:n–3 of 10:1. The diets were enriched in -linolenic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid, or both.

Results: Fasting and 3-h plasma triacylglycerol concentrations were 11.1% and 7.2% lower with the diet that had an n–6:n–3 of 3:1 and that was enriched with EPA and DHA than with the other diets. Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial FVIIa were not influenced by the diets. Avoiding foods high in fat the day before measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively. A test meal containing 50 g fat resulted in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6 h later, but the response did not differ by n–6:n–3.

Conclusion: Decreasing the n–6:n–3 to 3:1 by increasing the intake of EPA and DHA lowers fasting and postprandial plasma triacylglycerol concentrations in older persons but does not influence hemostatic risk factors.

Key Words: Factor VII • factor XII • n–3 fatty acids • ratio of n–6 to n–3 fatty acids • triacylglycerol • nonesterified fatty acids • fibrinogen

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