Journal Name:
Am. J. Clin. Nutr.
Article Title:
Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-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
Date Written:
2006
Volume:
84
Number:
NA
Page:
513
Author(s):
Sanders, T.A.B.; Lewis, F.; Slaughter, S.; Griffin, B.A.; Griffin, M.; Davies, I.; Millward, D.J.; Cooper, J.A.; Miller , G.J.
Article:
Hemostatic function impacts the risk of acute coronary syndromes. High fibrinogen concentrations and factor VII coagulant activity (FVIIc) is associated with a higher risk of fatal ischemic heart disease (IHD) while fasting FVIIc is positively associated with plasma cholesterol and triacylglycerol concentrations. *FVIIc and fibrinogen increase with age, especially in postmenopausal women, and are positively associated with obesity. Controlled feeding studies have found that total fat intake acutely influenced FVIIc, and FVIIc activity is related to recent fat intake in middle aged men. FVIIc is dependent on the concentration of both FVII zymogen and activated FVII (FVIIa).
Increasing the intake of omega 3 fatty acids may decrease the risk of fatal IHD. The Quantification of the Optimal omega 6/omega 3 Ratio in the UK Diet (OPTILIP) Study was designed to assess the effects of lowering the ratio of dietary n_6:n_3 on cardiovascular disease (CVD) risk factors in older persons. This objective was achieved by using a food-based intervention that involved increasing the intake of alpha-linolenic acid (ALA; 18:3), and eicosapentaenoic acid (EPA; 20:5n_3) or docosahexaenoic acid (DHA; 22:6), or both in relation to the intake of linoleic acid (LA). This report presents results for fasting fibrinogen, FXIIa, and FVII and the postprandial increase in FVIIa in response to a standardized high-fat meal.
This study tested the hypothesis that lowering the dietary ratio of omega 6/omega 3 polyunsaturated fatty acids would modify CVD risk factors in older men and women. 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 omega 6/omega 3. *In a randomized, parallel design in 258 subjects aged 45–70 years, 4 diets were compared which provided 6% of energy as polyunsaturated fatty acids at an omega 6/omega 3 between 5:1 and 3:1 with a control diet that had an omega 6/omega 3 of 10:1. The diets were enriched in ALA, EPA and DHA acid, or both.
The subjects had an estimated 18% risk of CVD within 10 year. In the designing of this study, it was recognized that a low intake of LA is associated with a higher risk of IHD.
Fasting and 3 hour plasma triacylglycerol concentrations were 11.1% and 7.2% lower with the diet that had an omega 6/omega 3 of 3:1 and that was enriched with 1.3 g 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% (42%, 52%) increase in FVIIa 6 h later, but the response did not differ by omega 6/omega 3.
In a secondary prevention of IHD trial, lower plasma fibrinogen were noted in subjects allocated to a diet with a low omega 6/omega 3, provided mainly by canola oil than in subjects following usual dietary advice. The findings of the current study suggest that moderate increases in omega 3 fatty acids in the diet, achieved by increasing fish consumption and by using canola oil with a lower omega 6/omega 3, have no measurable effect on plasma fibrinogen. However, there were large variations in FXIIa between subjects but little variation between measurements at baseline and follow-up. *Decreasing the omega 6/omega 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. In addition, lowering the omega 6/omega 3 by increasing the intake of ALA and decreasing that of LA affected neither plasma triacylglycerol nor hemostatic variables. The findings of this study suggest that other lifestyle factors, such as high BMI, alcohol intake, cigarette smoking, and the fat content of a meal, are significant determinants of these hemostatic factors.
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