Examine publishes rigorous, unbiased analysis of the latest and most important nutrition and supplementation studies each month, available to all Examine Members. Click here to learn more or log in.
Study under review: BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial
Introduction
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.
Who and what was studied?
What were the findings?
What does the study really tell us?
The big picture
Frequently asked questions
What should I know?
Other Articles in Issue #59 (September 2019)
-
Mini: The best diets to control blood lipids in people with diabetes
Improving blood lipid profile is especially important for people with diabetes, who are already at a higher risk for cardiovascular problems. Are some diets better than others at achieving this goal?
-
Does essential amino acid supplementation cause insulin resistance?
Aging brings with it a loss in muscle mass, which can negatively impact insulin sensitivity. Amino acid supplementation can help maintain muscle mass, but some evidence also suggests it may promote insulin resistance. Are older adults stuck between a rock and a hard place?
-
Does the feeding window matter for muscle mass?
Time-restricted feeding (TRF) may have a negative impact on muscle mass, at least in theory. This study put the question to the test by examining both TRF’s and HMB supplementation’s effects in resistance-training women.
-
Vitamin D dosing downer: implications for bone density
More isn't always better when it comes to vitamin D preventing bone density loss.
-
Mini: The latest evidence on the nutritional interventions’ effects on cardiovascular health
How good is the evidence concerning different nutritional interventions' impact on cardiovascular endpoints? A recent umbrella review explored the issue.
-
Beyond brawn: can protein supplementation fuel aerobic improvement?
It's well known that protein supplementation pairs well with resistance training, but can casein outperform carbs when paired with cardio?
-
Omega-3s for peripheral artery disease
Recent evidence suggests that high-dose pharmaceutical grade omega-3s can impact cardiovascular disease. How well does it work for PAD, though?