Losing weight is more important than reducing saturated fat intake for improving atherogenic lipids

Cardiovascular disease (CVD) is the leading cause of death worldwide. In fact, it has been estimated^[1] that 17.9 million people died from CVD in 2015.

One of the strongest risk factors^[2] for CVD are elevated blood levels of low-density lipoprotein (LDL) cholesterol, also known as “bad” cholesterol. Dietary modifications are considered paramount for improving blood lipids and reducing CVD risk. One such modification involves the reduction of dietary saturated fatty acids (SFAs). The rationale is that saturated fatty acids have been shown to increase^[3] LDL cholesterol, contribute to the development of atherosclerosis^[4] (i.e., the build-up of plaque in the arteries) and increase CVD risk, while the replacement of dietary SFAs with polyunsaturated fatty acids (PUFAs) lowers^[5] LDL cholesterol and CVD risk. This is believed to happen because, as shown in Figure 1, replacing SFAs with PUFAs increases the levels and activity of LDL receptors^[6] in the liver, which are the primary route through which LDL cholesterol is cleared from the blood.

While the replacement of dietary SFAs with PUFAs is often recommended for reducing LDL cholesterol, the results of a recent meta-analysis^[7] of RCTs suggest that obesity may affect the lipid-lowering response of such dietary modifications. More specifically, it seems that there may be an inverse association^[8] between BMI and the size of the reduction in LDL cholesterol levels with dietary SFA restriction, such that individuals with a higher BMI experience a smaller reduction in LDL cholesterol levels. Given the high prevalence of overweight and obesity in the U.S. and other parts of the world, establishing whether there are differential effects of dietary changes on lipoproteins according to bodyweight status may have considerable implications.

Although the reasons for the potential variability in lipid responses to dietary changes according to bodyweight are not entirely clear, one proposed explanation is that obesity may impair LDL receptor^[9] activity, leading to decreased LDL clearance from the blood, and, therefore, to higher blood LDL levels. Moreover, since LDL receptor activity is mainly regulated by the proprotein convertase subtilisin/kexin type 9 (PCSK9)^[10], it may be the case that the beneficial effects of reducing dietary SFAs on LDL cholesterol are attributable to PCSK9 concentrations, and that PCSK9 concentrations are also affected by obesity. However, these hypotheses have not yet been clarified in research, and no studies have been done where the potential interactions between BMI and LDL changes were defined a priori. The study under review was the first to have defined these potential interactions between BMI and LDL a priori, and to have compared dietary substitution of SFAs with PUFAs on LDL concentrations in normal-weight and obese participants with elevated LDL cholesterol.

Elevated low-density lipoprotein (LDL) cholesterol is a strong risk factor for cardiovascular disease. Although replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs) generally decreases LDL cholesterol levels, some research suggests that individuals with obesity may experience a smaller reduction in LDL cholesterol levels when replacing dietary SFAs with PUFAs, compared to normal-weight individuals. However, there is currently a limited understanding of how obesity affects the lipid response to dietary substitution of SFAs with PUFAs, and the possible mechanisms behind these potential variable effects. The study under review aimed to fill these knowledge gaps by comparing the effects of dietary substitution of SFAs with PUFAs on LDL concentrations in normal-weight and obese participants with elevated LDL cholesterol.