Circulating and Dietary Omega 3 and Omega 6 Polyunsaturated Fatty Acids and Incidence of CVD in the Multi Ethnic Study of Atherosclerosis

Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self reported dietary assessment in relatively homogeneous populations. In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000 to 2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke) were prospectively identified through 2010 during 19 778 person years of followup. In multivariable adjusted Cox models, circulating n3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme quartile hazard ratios of 0.49 for eicosapentaenoic acid and 0.39 for docosahexaenoic acid. Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race per ethnicities. No significant associations with CVD were observed for circulating alpha linolenic acid or n6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial ethnic groups, except those of docosapentaenoic acid. Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha linolenic acid or n 6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n3 PUFA from seafood may prevent CVD development in a multiethnic population. (Authors abstract)   Current dietary guidelines emphasize increasing consumption of omega 3 and omega 6 (n 6) long chain polyunsaturated fatty acids (PUFAs), found in fish and vegetable oils, as a healthy substitute for saturated fatty acids. These recommendations are based on the beneficial effects of PUFAs on blood cholesterol and blood pressure, as well as epidemiologic and clinical trial evidence suggesting cardiovascular benefits of PUFA consumption.   However, a number of important questions remain unanswered. First, most prior observational studies have evaluated associations with self reported PUFA intake, which may be influenced by reporting bias and limited by nutrient database information.  The use of objective biomarkers of these fatty acids minimizes reporting bias and also allows direct investigation of individual circulating fatty acids. Yet few prior studies have evaluated both dietary and circulating PUFA biomarkers. Second, recent randomized, controlled trials of fish oil supplements in high risk patients have generally shown null results, raising concerns for true cardiovascular disease (CVD) benefits of n3 PUFAs. In addition, whereas meta analyses of prospective cohorts and of older clinical trials have seen lower CVD risk. In this large prospective cohort of multiethnic Americans, higher circulating EPA and DHA were each inversely associated with markers of inflammation and prospectively associated with lower CVD incidence. Circulating DPA, a fatty acid largely derived from endogenous metabolism, was inversely associated with CVD events in whites and Chinese, but not in African Americans and Hispanics. Conversely, circulating plant derived n3 PUFA (ALA) was not associated with most CVD risk factors or with CVD incidence. In addition, although higher total circulating n 6 PUFAs were inversely associated with systolic and diastolic blood pressure, plasma triglycerides, and total: HDL  C ratio, there were no significant associations between total or individual  n6 PUFAs and CVD risk. Although ALA improved several CVD risk factors in experimental studies, no significant associations between ALA and CVD events were shown.  This study found no evidence of inverse associations with CVD of circulating or dietary LA or AA; these findings contrast with evidence from meta analyses of observational studies and clinical trials that estimated a 10 per c ent  to 13 per cent reduction in incident CHD with replacement of 5 per cent  energy from saturated fat with PUFAs.  IA  non significant trend toward higher CVD risk with higher circulating LA was seen.   Differences in food sources of ALA and LA may at least partly explain inconsistencies across prior studies. For example, some of the largest sources of ALA and LA in the US diet are refined grain breads, desserts, pizza, popcorn, French fries, potato chips, burgers, and processed meats,  together accounting for 30 per cent and 40 per cent of ALA and LA intake, respectively.  In contrast, most randomized trials used vegetable oils as the source of PUFAs, whereas observational studies showing favorable associations evaluated replace replacement of saturated fat or carbohydrate with PUFA intake. These diverse potential sources suggest that other components present in less healthy food sources might be counterbalancing potential beneficial effects of ALA and LA. (Editors comments)