Association of a Low-Carbohydrate High-Fat Diet With Plasma Lipid Levels and Cardiovascular Risk

Abstract

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: The purpose of this study was 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 ≥1 24-hour dietary questionnaire were identified. A LCHF diet was defined as <100 g/day and/or <25% total daily energy from carbohydrates/day and >45% total daily energy from 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: Of the 2034 LCHF and 8136 SD identified participants, 305 LCHF and 1220 SD individuals completed an enrollment assessment concurrently with lipid collection. In this cohort, low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B levels were significantly increased in the LCHF vs SD group (P < 0.001). 11.1% of LCHF and 6.2% of SD individuals demonstrated severe hypercholesterolemia (LDL-C >5 mmol/L, P < 0.001). After 11.8 years, 9.8% of LCHF vs 4.3% of SD 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 apolipoprotein B levels, and an increased risk of incident MACE.

Keywords: UK Biobank; atherosclerotic cardiovascular disease; hypercholesterolemia; incident major adverse cardiovascular events; low-carbohydrate high-fat diet; low-density lipoprotein polygenic risk score.

Graphical abstract

Figure 1

LDL-Cholesterol and Apolipoprotein B Distributions According to Diet (A) LDL-C and (B) apoB distributions according to LCHF diet and standard diet. Boxplots display the mean (red line) and median (black line). Dotted thresholds indicate severe hypercholesterolemia (LDL-C >5.0 mmol/L or apo B >1.45 g/L), which was significantly more frequent in LCHF participants than those on SD. ApoB = apolipoprotein B; LCHF = low-carbohydrate high-fat diet; LDL-C = low-density lipoprotein-cholesterol; SD = standard diet.

Figure 2

Risk of MACE in Participants on a LCHF Diet and Standard Diet (A) Upper panel: proportion of incident ASCVD events in participants on both diets. (A) Lower panel: risk of ASCVD events assessed with Cox regression model adjusted for diet, diabetes, smoking, hypertension, and BMI. (B) Kaplan-Meier curves for time to ASCVD events stratified by diet: x-axis, time since first assessment and completion of initial 24-hour dietary questionnaire; y-axis, event-free probability. ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; HR = hazard ratio; LCHF = low-carbohydrate high-fat diet; SD = standard diet.

Figure 3

ASCVD Risk According to LDL-Cholesterol and Dietary Pattern Participants were stratified by bins of LDL-C (LDL-C <3.5, ≥3.5-5.0, ≥5.0 mmol/L) and dietary pattern, with individuals on standard diet with LDL-C <3.5 mmol/L representing the reference group. HRs are plotted on a logarithmic scale. Abbreviations as in Figure 1.

Figure 4

LDL-Cholesterol Distributions Based on Polygenic Risk Scores and Dietary Patterns Violon plots represent LDL-C distributions based on high vs non-high LDL-PRS and dietary patterns: mean (red dot), median (black line), black dots (participants with significantly high LDL-C), dotted threshold line (severe hypercholesterolemia with LDL ≥5.0 mmol/L). PRS = polygenic risk score; other abbreviations as in Figure 1.

Central Illustration

Association of a LCHF Dietary Pattern With Hypercholesterolemia and Increased Risk of ASCVD Consumption of a LCHF diet was associated with significantly higher LDL-C and apoB levels, with severe hypercholesterolemia (LDL ≥5.0 mmol/L) being twice as frequent in individuals on a LCHF diet. Incidence of ASCVD events was significantly greater in LCHF participants than those on a standard diet. Consumption of this dietary pattern was associated with a 2.2-fold increased ASCVD risk after adjustment for cardiovascular risk factors. The highest cardiovascular risk was observed in individuals with LDL-C ≥5.0 mmol/L on a LCHF diet. Participants with an elevated LDL-PRS had the highest LDL-C on as carbohydrate-restrictive diet, with severe hypercholesterolemia being 3 times more frequent in these individuals. Abbreviations as in Figure 1 and 2.