Quick summary: A new study reveals that extremely high cholesterol levels triggered by ketogenic diets do not appear to drive coronary artery plaque build up in lean and metabolically healthy individuals. Researchers tracked participants with markedly elevated LDL cholesterol and ApoB who followed strict low carbohydrate eating for years and found no association between these markers and plaque progression over one year with pre existing plaque emerging as the key predictor instead. This challenges standard assumptions about cholesterol risks and supports more nuanced healthcare approaches focused on advanced imaging and personalised monitoring to better safeguard cardiovascular wellbeing for those on such diets.
A new study suggests that extremely high cholesterol levels triggered by ketogenic diets may not pose the same cardiovascular risk for everyone, especially among lean and metabolically healthy individuals. Researchers found that in people who followed a strict low-carbohydrate diet and exhibited very high levels of LDL cholesterol and apolipoprotein B (ApoB), these markers were not linked to the build-up of coronary artery plaque over a one-year period.
The research, published in JACC: Advances, followed 100 participants identified as “lean mass hyper-responders”: a term coined to describe those with normal body weight who experience dramatic rises in LDL cholesterol and ApoB when on a ketogenic diet. Despite these elevations, the study found no significant association between cholesterol levels and progression of noncalcified coronary plaque, a key marker of atherosclerosis.
Using advanced coronary computed tomography angiography and artificial intelligence-guided analysis, participants were scanned at the beginning and end of the study. Most had been on a ketogenic diet for nearly five years before enrolling, maintaining a high-fat, low-carbohydrate intake with notable consistency. The group’s average LDL cholesterol exceeded 250 mg/dL, and ApoB levels were similarly elevated. Yet, these metrics did not predict the growth of plaque within their arteries.
Instead, the clearest predictor of plaque progression was the amount of existing plaque at the beginning of the study. Those with even minimal pre-existing plaque were more likely to show further progression, regardless of cholesterol levels. In contrast, participants with no baseline coronary artery calcium showed little to no plaque growth over the year. This highlights the value of a coronary calcium score, which helps assess the presence of calcified plaque and may provide additional insight into cardiovascular risk beyond cholesterol levels alone.
This finding underpins the study’s central conclusion: “plaque begets plaque” but ApoB does not. The results challenge long-standing assumptions about cholesterol’s direct link to heart disease in all contexts and point to a more nuanced picture, especially for metabolically healthy individuals with unique lipid profiles induced by diet.
While these results offer some reassurance to those following ketogenic diets, researchers caution that this does not equate to a clean bill of cardiovascular health. Some participants did show progression, and the reasons behind this variation remain unclear. The study also acknowledges that one year is a relatively short time to fully assess long-term cardiovascular outcomes.
The researchers emphasise that individuals with high LDL cholesterol should still undergo regular cardiovascular monitoring, especially those with any evidence of existing plaque. Advanced imaging, such as the scans used in this research, may offer a more precise way to evaluate heart disease risk beyond standard cholesterol tests.
