Epidemiological Evidence of Relationships between Dietary Polyunsaturated Fatty Acids and Mortality in the Multiple Risk Factor Intervention Trial

Abstract

This evaluation of the Multiple Risk Factor Intervention Trial database investigated the effects of dietary PUFA on disease outcomes that may relate to polyunsaturated fatty acid (PUFA) biochemistry. The Multiple Risk Factor Intervention Trial was a randomized clinical trial in coronary heart disease (CHD) primary prevention involving 12,866 middle-aged men determined to be at high risk of CHD. They were assigned to either a special intervention group or a usual care group and returned to clinics on an annual basis for assessment of risk factor status. Only data on the usual care men (n = 6,250) are presented, since the multi-intervention effects on the special intervention group introduce considerable analytic complexities. Mean PUFA intake estimates were calculated from four dietary recall interviews at baseline and follow-up Years 1, 2, and 3 and estimates for PUFA were established using absolute grams, percentage of total kilocalories, and ratios. Proportional hazards regression analysis controlling for age, race and baseline diastolic blood pressure, smoking, high and low density lipoprotein cholesterol levels, and alcohol was used to analyze dietary PUFA intakes on 10.5-year mortality rates. Results were more significant when PUFA were expressed as percentage of total kilocalories. No significant associations with mortality were detected for linoleic acid (18:2n-6), the predominant dietary PUFA. Significant inverse associations were observed for linolenic acid (18:3n-3) on mortality from CHD (P < 0.04), all cardiovascular diseases (CVD) (P < 0.03), and all cause mortality (P < 0.02); the sum of fatty acids primarily derived from fish oils (20:5n-3 + 22:5n-3 + 22:6n-3) on CHD (P < 0.02), CVD (P < 0.006), and all cause (P < 0.02) mortality; and, the ratio of 18:3n-3 to 18:2n-6 on cancer mortality (P < 0.05). Analysis using the total n-3 (18:3 + 20:5 + 22:5 + 22:6) to total n-6 (18:2 + 18:4 + 20:4) ratio was also significant on cancer mortality (P < 0.04). These findings support reports that n-3 fatty acids are protective against CVD and suggest that composition of dietary PUFA may influence CVD and cancer rates.