Person:

Mozaffarian, Dariush

Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non-lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits.

Background: Few studies have examined the relationship of α‐linolenic acid (ALA 18:3n‐3), an intermediate‐chain essential n‐3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). Methods and Results: The study population included participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

Background: Evidence regarding the role of dairy fat intake in cardiovascular disease (CVD) has been mixed and inconclusive. Most earlier studies have used self‐reported measures of dietary intake and focused on relatively racially homogeneous populations. Circulating biomarkers of dairy fat in a multiethnic cohort provide objective measures of dairy fat intake and facilitate conclusions relevant to populations with different diets and susceptibility to CVD. Methods and Results: In a multiethnic cohort of 2837 US adults aged 45 to 84 years at baseline (2000–2002), phospholipid fatty acids including 15:0, 14:0, and trans‐16:1n7 were measured using standardized methods, and the incidence of CVD prospectively adjudicated. Self‐reported whole‐fat dairy and butter intakes had strongest associations with 15:0, rather than 14:0 or trans‐16:1n7. In multivariate models including demographics and lifestyle and dietary habits, each SD‐unit of 15:0 was associated with 19% lower CVD risk (hazard ratio [95% CI] 0.81 [0.68 to 0.98]) and 26% lower coronary heart disease (CHD) risk (0.74 [0.60 to 0.92]). Associations were strengthened after mutual adjustment for 14:0 and trans‐16:1n‐7 and were similar after adjustment for potential mediators. Plasma phospholipid 14:0 and trans‐16:1n‐7 were not significantly associated with incident CVD or CHD. All findings were similar in white, black, Hispanic, and Chinese American participants. Conclusion: Plasma phospholipid 15:0, a biomarker of dairy fat, was inversely associated with incident CVD and CHD, while no association was found with phospholipid 14:0 and trans‐16:1n‐7. These findings support the need for further investigation of CVD effects of dairy fat, dairy‐specific fatty acids, and dairy products in general.

Background: Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results: In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions: Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation.

Background: 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. Methods and Results: In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000–2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person‐years of follow‐up. In multivariable‐adjusted Cox models, circulating n‐3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme‐quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n‐3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P‐interaction=0.01). No significant associations with CVD were observed for circulating n‐3 alpha‐linolenic acid or n‐6 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. Conclusions: 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 n‐3 PUFA from seafood may prevent CVD development in a multiethnic population.

BACKGROUND: Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure. METHODS AND RESULTS: Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results. CONCLUSIONS: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.