"Replacing SFAs with PUFAs has been associated with cardiovascular benefit in the majority of metabolic, epidemiological, and clinical trial data, but study design caveats including residual confounding in epidemiological studies and changes in multiple dietary variables in RCTs should be considered when weighing the evidence for specific nutrient effects. Epidemiological studies support a beneficial association of ω-3 fatty acids with CVD; however, clinical trial studies to date have not consistently confirmed this. In contrast, the replacement of SFAs with TFAs has been associated with adverse CVD risk factors and outcomes, whereas the replacement of SFAs with CHOs has not been associated with benefit and may be associated with increased CVD risk. These effects are likely multifactorial, including effects on atherogenic lipoproteins, particularly remnants and sdLDL particles. A particular concern with regard to the growing population of individuals with excess adiposity and insulin resistance is that they may be particularly sensitive to the adverse lipoprotein effects of refined and processed CHOs while being concomitantly resistant to LDL-C-reducing effects of reduced SFAs. The effects of various SFA replacement scenarios on CVD risk factors other than lipids and lipoproteins are ambiguous, with the strongest evidence for proinflammatory effects derived from cellular and animal studies. Importantly, accumulating evidence indicates that food sources of SFAs can vary in their associations with CVD risk independent of their SFA content. This is likely due to components within foods other than SFAs that may singly or synergistically affect the development and progression of CVD. Therefore, the SFA content of foods is not necessarily a useful criterion on which to base food choices. Overall dietary patterns that emphasize vegetables, fish, nuts, and whole versus processed grains are the mainstays of heart-healthy eating. Whether SFAs need to be reduced in the context of such dietary patterns is not established."