A one-year prospective study found no correlation between atherosclerosis and extremely high cholesterol levels in 100 otherwise metabolically healthy individuals who had followed a ketogenic diet for an average of five years.
A new study from The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, in collaboration with researchers from multiple institutions, challenges the long-standing belief that high cholesterol directly causes coronary artery disease in metabolically healthy individuals.
Published in the Journal of the American College of Cardiology: Advances, the study examined 100 metabolically healthy adults who had followed a long-term low-carbohydrate ketogenic diet and developed elevated levels of LDL cholesterol. These individuals, known as Lean Mass Hyper-Responders (LMHRs), were found to have high LDL-C and ApoB levels without evidence of baseline coronary artery disease or disease progression over time.
The findings suggest that in this specific population, traditional cholesterol markers may not predict heart disease risk as previously assumed. The authors emphasize the need for further research and a more personalized approach to cardiovascular risk assessment and treatment.
Cardiovascular disease is the world’s leading cause of death, making diagnosis and risk assessment a high priority. The prevailing theory of cardiovascular disease risk is the lipid hypothesis, which posits that elevations in apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) are significant risk factors that should be primary treatment targets. However, this new research questions the relevance of the lipid hypothesis in metabolically healthy individuals whose cholesterol levels rise in response to a low-carb ketogenic diet–often adopted to address significant mental or physical health challenges.
The Role of Ketogenic Diets in Health and Risk
As evidence accumulates for the efficacy of therapeutic carbohydrate reduction to improve chronic conditions ranging from diabetes to inflammatory bowel disease to bipolar disorder, investigating the cardiovascular risk of diet-induced high cholesterol is becoming increasingly critical. Despite the striking beneficial effects that are seen following this therapy, adoption is often discouraged by medical doctors because of the presumed increased risk of heart disease.
The study investigated the relationship between LDL-C, ApoB, and heart plaque progression in a subpopulation of people who adopt low carbohydrate diets and fit the LMHR phenotype. This unique metabolic profile includes elevated LDL-C and ApoB levels despite otherwise healthy metabolic marker levels including low triglycerides, high HDL, low blood pressure, low insulin resistance, and low body mass index.
The researchers found no association between plaque progression and total exposure to, changes in, or baseline levels of ApoB and LDL-C. Rather, baseline plaque burden was identified as the strongest predictor of future plaque progression. These findings suggest that high cholesterol is not always a marker of cardiovascular plaque progression and that individuals with the LMHR phenotype may benefit from cardiac imaging to further assess their cardiovascular risk.
Implications for Risk Assessment and Medical Practice
The findings build on previous work from the research team demonstrating that LMHR individuals have similar levels of coronary plaque to a carefully matched comparison group with normal LDL levels, underscoring that ketogenic diet-induced LDL increases may not indicate a higher risk of coronary plaque.
The research was co-led by senior author Dr. Matthew Budoff, MD, Investigator and Program Director and Director of Cardiac CT, and the endowed chair of preventative cardiology at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center. The study leaders included independent researchers Nick Norwitz, PhD, Dr. Adrian Soto-Mota, MD, and Dave Feldman, founder of the Citizen Science Foundation, which, uniquely, crowd-sourced funding for the study.
“It is important that clinicians, along with the general public, are made aware that personalized, data-driven approaches to assessing risk should be considered based on individual conditions,” said Dr. Budoff, who is also a Professor of Medicine at David Geffen School of Medicine at UCLA. “The existence of this phenotype suggests that alternative markers or tests should be used to establish metabolic health in some cases.”
The study points to a clear need to expand cardiovascular disease risk assessment to include a personalized approach that can prioritize cardiac imaging. The researchers also call for an open-minded multidisciplinary approach to better understanding the heart disease risk of individuals with the LMHR phenotype, who often rely on low carbohydrate and ketogenic diets to keep chronic disease at bay.
Reference: “Plaque Begets Plaque, ApoB Does Not” by Adrian Soto-Mota, Nicholas G. Norwitz, Venkat S. Manubolu, April Kinninger, Thomas R. Wood, James Earls, David Feldman and Matthew Budoff, 7 April 2025, JACC: Advances.
DOI: 10.1016/j.jacadv.2025.101686
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14 Comments
Nice pseudoscience. No conflicts of interest here, nope.
The editorial board should be deeply ashamed to pollute the literature with this piece of garbage.
…call for an open-minded multidisciplinary approach… this is my call also to you Andrew
Any facts to support your wild accusations?
As it turns out, this study is also in line with the well-known Framingham Study data. That data also shows that LDL had little effect on heart disease for metabolically healthy people.
1 year follow up for coronary disease in 100 healthy patients. Hmm. And this is publishable??
It’s impressive they found any changes in a year regardless of previous pathology. I would think a minimum of 5 year f/u with an adequate sample size. What is the minimum number required to detect a significant change- way more than 100 for sure.
Note: “The authors emphasize the need for further research and a more personalized approach to cardiovascular risk assessment and treatment.”
100 healthy patients with *high cholesterol* who otherwise would have been put on statins by doctors who haven’t reexamined the science for 50 years! Good on these researchers!
Didn’t even publish their a priori findings, because it was opposite of what they wanted, and the associated table showing these findings was in the supplemental section. Finally posted it on X after much pushback. How scholarly of them.
Did you miss the citation? The Lundquist institute published in the JACC. I’ve read this. I read the first publication when the initial findings were reported, a year ago.
This piece is strongly in need of an editor. Many of the sentences are way too long and unnecessarily so.
Why are the PhDs not also referred to as “Dr.” and just the MDs? I have a PhD, and I am routinely addressed as “Dr.” (And if anyone thinks that only MDs or ODs deserve to be called “Dr.” then they should learn more about what a PhD or other non-medical doctor goes through to earn their degrees)
No surprise here! I’m HeFH; my typical LDL scores are on either side of 500 mg/d; total is around 600. At age 79, I finally got a non-zero coronary calcium score last year –4.1 Agatston; which is still off the charts low for even a normal male. Literature searches suggest a whole lot of FH individuals don’t develop plaque regardless of diet. I’ve been off all meds since my first zero EBCT around age 50. What is so depressing is that the medical community is so completely uninterested in understanding the differences between those of us without and those with plaque. Calcium scoring should be as universal as breast screening.
More proof that one size doesn’t fit all.
“Smoking didn’t cause cancer in this small group of healthy people over one year” → therefore smoking is harmless. 😜😭
Do your research, this study is very low quality evidence where much higher quality studies do in fact causally link high LDL to heart disease progression. Heart disease progression happens over decades, not one year like this study looked at. Also it’s unlikely a person would even be able to stay on a strict keto diet for decades and likely not healthy if they did. Of all super centenarians, not a single one has ever said they followed a keto/carnivore diet. Also all of the longest lived people groups ever studied (Okinawans and California Adventists for example) got the majority of their calories from carbs, fruit and vegetables are majority carbs and they are very good for you. It’s junk food, refined white sugar, corn syrup, chips, cookies, and fried foods that are unhealthy, so stop blaming “carbs“ and blame junk food.