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. 2024 Aug 28;3(8):101109.
doi: 10.1016/j.jacadv.2024.101109. eCollection 2024 Aug.

Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis: The KETO Trial

Matthew Budoff  1 , Venkat S Manubolu  1 , April Kinninger  1 , Nicholas G Norwitz  2 , David Feldman  3 , Thomas R Wood  4 , Jonathan Fialkow  5 , Ricardo Cury  5 , Theodore Feldman  5 , Khurram Nasir  6
Affiliations

Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis: The KETO Trial

Matthew Budoff et al. JACC Adv. .

Abstract

Background: Increases in low-density lipoprotein cholesterol (LDL-C) can occur on carbohydrate restricted ketogenic diets. Lean metabolically healthy individuals with a low triglyceride-to-high-density lipoprotein cholesterol ratio appear particularly susceptible, giving rise to the novel "lean mass hyper-responder" (LMHR) phenotype.

Objectives: The purpose of the study was to assess coronary plaque burden in LMHR and near-LMHR individuals with LDL-C ≥190 mg/dL (ketogenic diet [KETO]) compared to matched controls with lower LDL-C from the Miami Heart (MiHeart) cohort.

Methods: There were 80 KETO individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglyceride levels ≤80 mg/dL, without familial hypercholesterolemia, matched 1:1 with MiHeart subjects for age, gender, race, hyperlipidemia, hypertension, and smoking status. Coronary artery calcium and coronary computed tomography angiography (CCTA) were used to compare coronary plaque between groups and correlate LDL-C to plaque levels.

Results: The matched mean age was 55.5 years, with a mean LDL-C of 272 (maximum LDL-C of 591) mg/dl and a mean 4.7-year duration on a KETO. There was no significant difference in coronary plaque burden in the KETO group as compared to MiHeart controls (mean LDL 123 mg/dL): coronary artery calcium score (median 0 [IQR: 0-56]) vs (1 [IQR: 0-49]) (P = 0.520) CCTA total plaque score (0 [IQR: 0-2] vs [IQR: 0-4]) (P = 0.357). There was also no correlation between LDL-C level and CCTA coronary plaque.

Conclusions: Coronary plaque in metabolically healthy individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL on KETO for a mean of 4.7 years is not greater than a matched cohort with 149 mg/dL lower average LDL-C. There is no association between LDL-C and plaque burden in either cohort. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT057333255).

Keywords: LDL cholesterol; atherosclerosis; coronary CT angiography; ketogenic diet; lean mass hyper-responder; plaque.

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Conflict of interest statement

This study was funded by the Citizen Science Foundation, 7320 S Rainbow Blvd, #102-182, Las Vegas, NV, United States. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Plaque Scores and LDL-C Level Total plaque score (TPS) (green bars) and LDL-C (blue line) between n = 80 KETO subjects (left) matched 1:1 to 80 Miami Heart (MiHeart) subjects (right). Group TPS median, IQR, and mean LDL-C ± SD are provided in inset. KETO = ketogenic diet; LDL-C = low-density lipoprotein cholesterol.
Figure 2
Figure 2
LDL-C Does Not Correlate With Total Plaque Score Total plaque score (TPS) plotted against LDL-C (mg/dL), including between KETO subjects (top) matched 1:1 to 80 Miami Heart (MiHeart) subjects (bottom). X-axes are adjusted for group LDL-C range. Abbreviations as in Figure 1.
Central Illustration
Central Illustration
Coronary Plaque in Ketogenic Diet Hyper-Responders and Matched Controls Coronary plaque was assessed by coronary CT angiography in cholesterol hyper-responders to a ketogenic diet (KETO) and a matched cohort (Miami Heart) (n = 80 each). There was no difference in plaque score between groups, and there was no correlation between LDL-C level and plaque burden. CCTA = coronary computed tomography angiography; CT = computed tomography; LDL-C = low-density lipoprotein cholesterol.
See this image and copyright information in PMC

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