Journal Name:
Circulation
Article Title:
Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men
Date Written:
2005
Volume:
111
Number:
0
Page:
157
Author(s):
Mozaffarian, D.; Ascherio, A.; Hu, F.B.; Stampfer, M.J.; Willett, W.C.; Siscovick, D.S.; Rimm, E.B.
Article:
Consumption of polyunsaturated fatty acids (PUFAs) may reduce coronary heart disease (CHD) risk, but n-6 PUFAs may compete with n-3 PUFA metabolism and attenuate benefits. n-6 PUFAs compete with n-3 PUFAs for common metabolic enzymes and thereby increase the production of prothrombotic rather than antithrombotic, aggregatory, and inflammatory leukotrienes, thromboxanes, and prostaglandins. Few prospective studies have evaluated the interplay between n-6 and n-3 PUFAs and CHD risk. Seafood-based, long-chain n-3 PUFAs may modify the effects of plant-based, intermediate-chain n-3 PUFAs. However, the interactions of these PUFAs in relation to CHD risk are not well established.
Thus this large prospective cohort study was organized to determine the interactions between the PUFAs in the total diet. Among 45722 men free of known cardiovascular disease in 1986, usual dietary intake was assessed at baseline and every 4 years by using validated food-frequency questionnaires. CHD incidence was prospectively ascertained. Over 14 years of follow-up, participants experienced 218 sudden deaths, 1521 nonfatal myocardial infarctions (MIs), and 2306 total CHD events (combined sudden death, other CHD deaths, and nonfatal MI). In multivariate-adjusted analyses, both long-chain and intermediate-chain n-3 PUFA intakes were associated with lower CHD risk, without modification by n-6 PUFA intake. For example, men with ≥median long-chain n-3 PUFA intake (≥250 mg/d) had a reduced risk of sudden death whether n-6 PUFA intake was below (≤11.2 g/d) or above (≥11.2 g/d) the median compared with men with a ≥ median intake of both. In similar analyses, median intake of intermediate-chain n-3 PUFAs (≥1080 mg/d) was associated with a reduced total CHD risk whether n-6 PUFA intake was lower or higher compared with a ≥median intake of both. Intermediate-chain n-3 PUFAs were particularly associated with CHD risk when long-chain n-3 PUFA intake was very low (≤100 mg/d); among these men, each 1 g/d of intermediate-chain n-3 PUFA intake was associated with an approximate 50% lower risk of nonfatal MI and total CHD. n-3 PUFAs from both seafood and plant sources may reduce CHD risk, with little apparent influence from background n-6 PUFA intake.
Plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish. The strongest relation between ALA intake and CHD risk was seen when EPA and DHA intake was very low (about 100 mg/d). Long-chain n-3 PUFAs inhibit metabolism of ALA via feedback inhibition. Many of the effects of long-chain n-3 PUFAs on heart health (in particular on myocardial infarction) are seen only at pharmacological doses. Conversely, ALA intake was associated with a lower risk of nonfatal myocardial infarction and total CHD, suggesting that in the absence of significant long-chain n-3 PUFA intake, ALA may influence CHD risk via multiple pathways, including non–arrhythmia related mechanisms. The data from this study also shows that the effects of ALA on CHD are influenced by background EPA and DHA intake, which may explain some reports on null associations between ALA intake and CHD risk.
In this study, a modest dietary intake of long-chain n-3 PUFAs (about 250 mg/d) was associated with a 40% to 50% lower risk of sudden death, regardless of background intake of n-6 PUFAs. Additionally, an inverse association between ALA and CHD risk was reported. n-6 PUFA intake did not appreciably counteract the effects of either intermediate- or long-chain n-3 PUFAs on the risk of CHD events.
The results of this study indicated that n-3 PUFAs from both seafood and plant sources reduce CHD risk, with little apparent influence from background n-6 PUFA intake. Of significance to canola oil, this study showed that plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish.
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