The Keto Craze and Lipid Anomalies
Ketogenic diets (KD), famed for their weight-loss potential and metabolic health benefits, have surged beyond mere obesity and diabetes management. Today, their applications span neurological disorders, inflammatory conditions, and even mental health treatments. Yet, despite widespread enthusiasm, one aspect persistently raises medical eyebrows—lipid alterations, specifically increases in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB).
Interestingly, these lipid spikes predominantly occur in lean, metabolically healthy individuals—a phenotype intriguingly termed “lean mass hyper-responders” (LMHR). Characterized by significantly elevated LDL-C and ApoB, combined with high HDL cholesterol and notably low triglycerides, LMHRs represent a curious paradox in lipidology. However, the essential question persists: do these elevated biomarkers actually indicate heightened cardiovascular risk?
ApoB and LDL-C: Villains or Innocent Bystanders?
The conventional wisdom in cardiology places ApoB and LDL-C squarely as culprits in atherosclerosis. However, recent evidence from the KETO-CTA trial brings this dogma into question, at least within a very particular subset of individuals. In this groundbreaking study, 100 participants who exhibited extreme elevations in LDL-C (>190 mg/dL) due to sustained ketogenic dieting were tracked for one year using advanced coronary imaging techniques.
Contrary to established assumptions, neither ApoB levels nor LDL-C exposure significantly influenced the progression of coronary plaque. Instead, plaque progression strongly correlated with baseline plaque presence itself—leading researchers to a compelling conclusion: plaque, rather ironically, begets plaque, but ApoB may not.
Understanding the Results: Plaque Begets Plaque
At baseline, most participants displayed negligible or low plaque volumes, yet high ApoB and LDL-C levels. Over the year-long follow-up, coronary computed tomography angiography (CCTA) revealed minimal or no plaque progression in most subjects. Intriguingly, the few individuals experiencing significant progression already had higher baseline plaque levels, suggesting existing plaque as the primary determinant for further plaque formation.
Notably, Bayesian analysis provided additional strength to these findings, with results significantly favoring the absence of an ApoB-related plaque progression connection. This sharply challenges conventional lipid theory, at least within metabolically optimized ketogenic dieters.
What Drives Plaque Progression in the Keto Context?
While these results provoke substantial reevaluation of lipid-centric cardiovascular risk management, they also prompt a critical question: what mechanisms truly drive plaque progression among keto dieters?
Several hypotheses stand out. One possibility involves inflammatory pathways activated by pre-existing plaque deposits, indicating a self-perpetuating cycle independent of traditional lipid risk markers. Another theory considers the unique metabolic state induced by sustained ketosis—alterations in lipoprotein metabolism, quality, and dynamics—which might drastically reduce atherogenic potential even at extremely elevated ApoB and LDL-C levels.
Moreover, it is essential to recognize that this phenomenon is uniquely tied to lean, metabolically healthy individuals. ApoB and LDL-C elevations in individuals with obesity, insulin resistance, or chronic inflammatory states continue to present undeniable cardiovascular risks.
Clinical Implications: Tailoring Treatment and Risk Assessment
This research challenges clinicians to rethink rigid lipid-centric cardiovascular risk assessments and tailor interventions according to individualized metabolic contexts. For instance, keto dieters with zero baseline coronary artery calcium (CAC) appear remarkably resilient to plaque progression despite substantial LDL-C elevations, potentially warranting a conservative management approach.
Conversely, keto adherents presenting with pre-existing plaque, possibly accrued from prior metabolic disturbances, represent a higher-risk subgroup necessitating more attentive monitoring and perhaps earlier intervention.
Ultimately, the KETO-CTA trial underscores the importance of a nuanced, individualized assessment of cardiovascular risk—moving beyond simplistic biomarker thresholds toward a comprehensive metabolic and plaque-centric evaluation.
FAQ: Clarifying Key Questions
1. Should I be worried about high LDL-C on a keto diet if I’m healthy and lean?
Not necessarily. This study suggests elevated LDL-C and ApoB alone might not significantly drive plaque formation in metabolically healthy individuals on a ketogenic diet. However, baseline coronary plaque presence is critical, so individual assessments are advised.
2. Does high ApoB mean automatic heart risk?
Traditionally, yes—but this study challenges that assumption for specific populations. Context is key; metabolic health, inflammation, insulin sensitivity, and baseline plaque levels significantly influence actual risk.
3. How can I know my actual cardiovascular risk on keto?
Comprehensive risk assessment is best determined through advanced imaging methods like coronary calcium scoring or CCTA, alongside metabolic evaluations. High LDL-C alone may not reflect true risk without considering these factors.
Adrian Soto-Mota MD, PhD, Nicholas G. Norwitz PhD , Venkat S. Manubolu MD , April Kinninger MPH , Thomas R. Wood BM BCh, PhD, James Earls MD, David Feldman AA, Matthew Budoff MD
Metabolic Diseases Research Unit, National Institute for Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico
Tecnologico de Monterrey, School of Medicine, Mexico City, Mexico
Harvard Medical School Boston, Massachusetts, USA
Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA
Department of Pediatrics, University of Washington School of Medicine, Washington, USA
Cleerly, New York, New York, USA
Citizen Science Foundation, Las Vegas, Nevada, USA
