Abstract

Introduction: The human diet consists of a complex mixture of fatty acids with differential effects on cardiovascular health. Saturated fatty acids have been shown to exert a hypercholesterolemic effect, while omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Advanced statistical approaches are needed however to address whether their covarying relationships may contribute to varying outcomes on cardiovascular health. Methods: We used data on adult participants from the 2003-2004 and 2011-2012 National Health and Nutrition Examination Survey. Blood lipid levels were measured in 2,926 participants, and C-reactive protein (CRP) was measured in 1,339 participants. Fatty acids were measured in serum or plasma and analyzed as the percentage of total fatty acids. We used covariate-adjusted quantile g-computation to assess the joint effects of 6 saturated, 6 monounsaturated, and 11 polyunsaturated fatty acids on log-transformed outcomes, as well as examine the relative contribution of each fatty acid to the joint mixture effect. Results: We estimated positive associations between the mixture of saturated fatty acids with total cholesterol and LDL, which was primarily driven by myristic acid and docosanoic acid. The mixture of monounsaturated fatty acids was associated with lower total cholesterol and LDL, but higher CRP with a quartile increase in monounsaturated fatty acids associated with 21.1% (95% CI: 7.9, 35.9) higher CRP. The mixture of omega-6 polyunsaturated fatty acids was positively associated with both total cholesterol and LDL. We found that the mixture of omega-3 polyunsaturated fatty acids was negatively associated with CRP and LDL. A quartile increase in omega-3 fatty acids was associated with -11.6% (95% CI: -18.8, -3.7) lower CRP, and -2.1% (95% CI: -3.6, -0.4) lower LDL. The relationship with CRP was primarily driven by docosapentaenoic n-3 acid and eicosapentaenoic acid, while the relationship with LDL was driven by docosapentaenoic n-3 acid and docosahexaenoic acid. Conclusions: Assessing the complex mixture of fatty acids, we found distinct beneficial relationships between omega-3 fatty acids with inflammation and lipid profiles, with an important role of docosapentaenoic n-3 acid.

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