Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence

Abstract

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.

Fig. 1

Advances in nutritional science research paradigms. For causal inference about how dietary habits affect chronic disease, the best evidence is derived from randomized controlled trials (RCTs) of multiple risk pathways, observed differences in disease endpoints in prospective cohort studies, and effects on disease endpoints in RCTs. Conclusions can be considered most robust when these complementary lines of evidence provide concordant results. Adapted with permission from Harris, Mozaffarian, et al. 2009 [90]

Fig. 2

Changes in blood lipid levels for consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or trans fatty acids (TFA) as an isocaloric replacement for carbohydrate (CHO) as a reference, based on two meta-analyses of randomized controlled feeding trials [5, 6]. β reflects the change for each 1% energy isocaloric replacement; *P < 0.05

Fig. 3

Changes in blood lipid levels for consumption of different chain-length saturated fatty acids (SFA) as an isocaloric replacement for carbohydrate (CHO), based on meta-analysis of randomized controlled feeding trials [5]. β reflects the change for each 1% energy isocaloric replacement; *P < 0.05

Fig. 4

Relative risk of incident diabetes associated with consumption of saturated fat (SFA). Multivariable-adjusted results from prospective cohort studies and the overall pooled result using fixed-effects meta-analysis are shown. Results from the Women’s Health Initiative randomized controlled trial are also shown comparing controls (higher SFA intake) to the intervention group in which SFA was reduced by ~3.2%E over 8 years [79]. CI’s for Harding et al.[56] were estimated based on the numbers of cases

Fig. 5

Effects on coronary heart disease (CHD) risk of consuming polyunsaturated fat (PUFA), carbohydrate (CHO), or monounsaturated fat (MUFA) in place of saturated fat (SFA). Predicted effects are based on changes in the TC:HDL-C ratio in short-term trials [5], coupled with observed associations between the TC:HDL-C ratio and CHD disease events in middle-aged adults [91]. Evidence for effects of dietary macronutrients on actual CHD events comes from a meta-analysis of eight randomized controlled trials (RCTs) for PUFA replacing SFA, including 13,614 participants with 1,042 CHD events [78]; and from the Women’s Health Initiative (WHI) RCT for CHO replacing SFA, including 46,558 individuals with 1,185 CHD events and ~3.2%E reduction in SFA over 8 years [79]. Evidence for observed relationships of usual dietary habits with CHD events comes from a pooled analysis of 11 prospective cohort studies, including 344,696 individuals with 5,249 CHD events [69]. Reproduced with permission from Mozaffarian et al., in press [78]