The Cardiovascular Risk Reduction Benefits of a Low-Carbohydrate Diet Outweigh the Potential Increase in LDL-Cholesterol

ByCrossFitMarch 19, 2020

Question
It is well established that low-carbohydrate diets increase LDL cholesterol levels. Does this increase indicate an overall increase in cardiovascular risk?
Takeaway
This 2016 letter argues the complete profile of metabolic changes induced by a low-carbohydrate diet — increased LDL and HDL cholesterol, a reduction in triglycerides, and a reduction in insulin resistance — indicates a reduction in cardiovascular risk. Researchers who argue the increase in LDL cholesterol is atherogenic fail to consider more recent data suggesting LDL cholesterol levels are at best inferior to alternative markers of disease, and in fact may have little predictive value at all.

This 2016 letter to the editor of the BMJ was written as a response to Nadia Mansoor et al.’s meta-analysis of trials comparing the use of low-carbohydrate diets and low-fat diets for weight loss and cardiovascular benefit. Mansoor et al. found the low-carbohydrate diets, relative to the low-fat diets, led to increases in LDL and HDL and a reduction in triglycerides. Arguing the increase in LDL indicated elevated cardiovascular risk, they concluded the evidence did not support the use of low-carbohydrate diets.

Thomas Wood et al., the authors of the 2016 letter, do not disagree with the data presented by Mansoor et al. but disagree with their interpretation of it. Specifically, Wood et al. argue the sum of the evidence suggests the surveyed low-carbohydrate diets reduced cardiovascular disease (CVD) risk and any increase in risk associated with an increase in LDL cholesterol is inconsequential in the context of the other changes observed.

First, they argue LDL has limited usefulness as a marker of CVD risk. Mansoor et al. cite two papers from Ronald Krauss et al. to support their claim that an increase in LDL cholesterol is associated with elevated cardiovascular risk (1). These papers in fact make the opposite claim, arguing LDL cholesterol is a weaker marker of disease risk than available alternatives such as triglyceride levels and the TG:HDL ratio. Krauss et al. argue an atherogenic lipoprotein phenotype, independent of the total level of LDL cholesterol, consists of small, dense LDL particles; this state is correlated with high triglyceride and low HDL levels. For this reason, in a subsequent analysis, Krauss et al. argued against diets designed to lower saturated fat intake and increase carbohydrate intake (such as a low-fat diet), as these diets increase triglycerides and lower HDL (2).

Other lines of evidence further undermine the predictive value of LDL cholesterol. A large study of hospitalized CVD patients found half had “normal” LDL levels (<100 mg/dL), which suggests lowering LDL cholesterol is at best insufficient to reduce heart disease risk. A growing body of evidence, drawn largely from the pharmaceutical literature, indicates therapies directly targeting LDL suppression or HDL elevation may have little to no effect on cardiovascular outcomes, and the beneficial effects of certain drugs, such as statins, may be entirely unrelated to their effects on serum cholesterol levels (3).

More broadly, evidence suggests insulin resistance and hyperglycemia may more accurately predict cardiovascular risk than any of these lipid markers. Insulin resistance is an independent risk factor for CVD and predisposes the lipid profile toward the atherogenic phenotype described above — i.e., high triglycerides, low HDL, and small, dense LDL particles (4). By elevating triglyceride levels, insulin resistance and high-carbohydrate diets reduce the size of LDL particles and increase their time in circulation, which leads to increased glycation and oxidation of LDL particles (i.e., generation of glycLDL and oxLDL). These small, oxidized LDL particles are more likely to infiltrate the arterial wall, which may explain the link between increased insulin resistance and increased CVD risk (5). Insulin resistance also increases (and low-carbohydrate diets decrease) oxidative stress and inflammation, which are additional independent CVD risk factors (6).

Wood et al. conclude the lipid changes observed by Mansoor et al., alongside the reduction in insulin resistance consistently associated with carbohydrate restriction, indicate a reduction in cardiovascular risk among subjects consuming a low-carbohydrate diet. Their conclusion is similar to that of a previous meta-analysis that found a more comprehensive assessment of CVD risk factors indicated low-carbohydrate diets reduce risk (7). This indicates use of a low-carbohydrate diet should not be discouraged on the basis of its effect on cardiovascular risk. It also indirectly provides further support for the broader argument that LDL cholesterol is no longer a useful tool for assessing risk of heart disease, and judging the relative merit of potential treatments due to their effect on LDL cholesterol can lead to misguided conclusions.

Read the letter

Notes