Budoff 2024: The KETO Trial Shows No Excess Plaque in High-LDL Dieters

In 2024, Dr. Matthew Budoff and colleagues published the highly anticipated KETO Trial—the first study to directly examine whether the dramatically elevated LDL cholesterol seen in ketogenic dieters translates to increased coronary atherosclerosis.

The Critical Question

The LMHR phenotype presented a clinical dilemma: these individuals had LDL levels sometimes exceeding 500 mg/dL—numbers that in other contexts would trigger immediate aggressive treatment. But their metabolic profiles were otherwise excellent. Do the standard cardiovascular risk rules apply?

Study Design

The researchers recruited 80 adults on sustained ketogenic diets (mean 4.7 years) with elevated LDL cholesterol (mean 272 mg/dL, range up to 591 mg/dL) and compared them to 80 matched controls with normal LDL (mean 123 mg/dL). Both groups underwent coronary CT angiography (CCTA), the gold standard for detecting coronary plaque.

Key Results

No significant difference in coronary plaque burden was found. Median coronary artery calcium (CAC) scores were 0 vs 1 (p=0.520). Total, calcified, and non-calcified plaque volumes were similar between groups.

Perhaps most striking: there was no correlation between LDL-C level and coronary plaque among the ketogenic dieters. Individuals with LDL of 300 did not have more plaque than those with LDL of 500.

Implications

These findings suggest that LDL cholesterol elevation in the context of carbohydrate restriction and metabolic health may not carry the same atherosclerotic risk as LDL elevation in the context of metabolic dysfunction. The lipid particle composition and function may differ fundamentally.

Limitations and Caveats

This was an observational study with 4.7 years mean exposure. Longer-term outcomes and randomized data are still needed. However, these results provide meaningful reassurance that aggressive LDL lowering may not be mandatory in metabolically healthy ketogenic dieters.