Association of a Low-carbohydrate High-fat Diet with Plasma Lipid Levels and Cardiovascular Risk

Background Low-carbohydrate high-fat (LCHF) diets have attracted interest for a variety of conditions. In some individuals, these diets trigger hypercholesterolemia. There are limited data on their effects on cardiovascular disease risk. Objectives To investigate the association between LCHF dietary patterns, lipid levels and incident major adverse cardiovascular events (MACE). Methods In a cohort from the UK Biobank, participants with ≥ one 24-hour dietary questionnaire were identified. A LCHF diet was defined as <100g and/or <25% total daily energy (TDE) from carbohydrates/day and >45% TDE fat, with participants on a standard diet (SD) not meeting these criteria. Each LCHF case was age- and sex-matched 1:4 to SD individuals. Results From 2034 LCHF and 8136 SD identified participants, 305 LCHF and 1220 SD individuals completed an enrollment assessment concurrently with lipids collection. In this cohort, low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) levels were significantly increased in the LCHF vs SD group (p<0.001). 11.1% LCHF and 6.2% SD individuals demonstrated severe hypercholesterolemia (LDL-C >5 mmol/L, p<0.001). After 11.8 years, 9.8% LCHF vs 4.3% participants experienced a MACE (p<0.001). This difference remained significant after adjustment for cardiovascular risk factors (HR 2.18, 95% CI 1.39-3.43, p<0.001). Individuals with an elevated LDL-C polygenic risk score had the highest concentrations of LDL-C on a LCHF diet. Similar significant changes in lipid levels and MACE associations were confirmed in the entire cohort and in ≥2 dietary surveys. Conclusions Consumption of a LCHF diet was associated with increased LDL-C and apoB, and an increased risk of incident MACE.