A groundbreaking study conducted by The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, in collaboration with various institutions, has cast doubt on the widely accepted notion that high cholesterol levels directly correlate with coronary artery disease in metabolically healthy individuals. Published in the Journal of the American College of Cardiology: Advances, the research focused on a group of 100 metabolically healthy individuals adhering to a long-term low-carbohydrate ketogenic diet who exhibited elevated LDL cholesterol levels. These individuals, termed Lean Mass Hyper-Responders (LMHRs), showed no connection between traditional cholesterol markers and baseline heart disease or its progression. This finding underscores the need for further personalized treatment strategies and more nuanced risk assessments.

Cardiovascular disease remains the leading cause of death globally, making accurate diagnosis and risk evaluation paramount. Traditionally, the lipid hypothesis has dominated cardiovascular risk assessment, emphasizing elevated apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) as primary risk factors. However, this new research challenges this paradigm, particularly for metabolically healthy individuals whose cholesterol levels rise due to a ketogenic diet often used to manage significant mental or physical health issues.

The study delved into the relationship between LDL-C, ApoB, and the progression of arterial plaque in a subset of people following low-carbohydrate diets and exhibiting the LMHR phenotype. Characterized by elevated LDL-C and ApoB levels alongside otherwise healthy metabolic markers such as low triglycerides, high HDL, low blood pressure, low insulin resistance, and low body mass index, this unique metabolic profile warranted investigation. Researchers discovered no link between plaque progression and total exposure to, changes in, or baseline levels of ApoB and LDL-C. Instead, they identified baseline plaque burden as the strongest predictor of future plaque progression.

This revelation suggests that high cholesterol is not always indicative of cardiovascular plaque progression and highlights the potential benefits of cardiac imaging for assessing cardiovascular risk in individuals with the LMHR phenotype. The findings reinforce previous work demonstrating that LMHR individuals possess similar coronary plaque levels compared to carefully matched groups with normal LDL levels, suggesting that ketogenic diet-induced LDL increases may not signal heightened coronary plaque risk.

Co-led by Dr. Matthew Budoff, an investigator and program director at The Lundquist Institute, along with independent researchers, the study emphasizes the importance of personalized, data-driven approaches to risk assessment based on individual conditions. The existence of this phenotype indicates that alternative markers or tests should be employed to establish metabolic health in certain cases. Expanding cardiovascular disease risk assessment to incorporate a personalized approach prioritizing cardiac imaging is essential. An open-minded multidisciplinary strategy is also necessary to better understand heart disease risks in individuals with the LMHR phenotype, many of whom depend on low-carbohydrate and ketogenic diets to manage chronic diseases.

These findings challenge established medical beliefs and pave the way for more tailored and effective strategies in managing cardiovascular health, especially among those adopting ketogenic diets for their health benefits. By shifting focus towards personalized medicine and advanced diagnostic tools, healthcare providers can offer more precise evaluations and interventions for patients at risk of heart disease.