Some people follow a ketogenic diet seeking to lose weight, feel more energised, or gain control over their eating habits. Others may turn to this diet in an effort to treat conditions such as epilepsy, bipolar disorder, diabetes and inflammatory diseases. Regardless of their reasoning for adopting this eating pattern, a key question remains: is there ever an instance where having high LDL cholesterol levels on a ketogenic diet can be safe? In Episode #311, I’m joined by Dr William Cromwell, MD and Dave Feldman to explore this question.
“In lipidology, we don’t have models where we’re looking at people on a daily, weekly basis to see how quickly we can modify what are reasonably steady state [cholesterol] levels for most people. So just the fact that [Dave’s self-study] was reproducible, and the fact that he was going through this very methodically… [was] very interesting.” Dr William Cromwell
Dr William Cromwell is a lipidologist with over 35 years of clinical practice experience. Since 1990, Dr Cromwell’s practice has specialised in managing lipid and lipoprotein disorders. He has authored over two dozen peer-reviewed papers and book chapters on evaluating and managing lipoprotein disorders and lipoprotein analytics, and currently serves as the Medical Director and Principal Investigator at Velocity Clinical Research in Durham, NC, the Chief of the Lipoprotein and Metabolic Disorders Institute in Raleigh, NC, and an Adjunct Associate Professor in the Hypertension and Vascular Disease Center at Wake Forest University School of Medicine.
“Metabolic health is probably one of the most gigantic blind spots you can imagine in healthcare today.” Dave Feldman
Dave Feldman is a software and platform engineer, an entrepreneur, and founder of the Citizen Science Foundation. His life took a radical turn on seeing his cholesterol skyrocket after adopting a ketogenic diet and became obsessed with understanding why this is common with those who are likewise leaner and more metabolically healthy. While researching lipidology, he found the lipid system of the human body shares many commonalities with distributed networks, much like those he’s worked on in platform development. Through a series of self-experiments and partnering with formal researchers, he has since published the “Lipid Energy Model” which may explain this phenomenon.
In today’s discussion, Dr William Cromwell and Dave Feldman share their professional opinions on whether high cholesterol (specifically what’s known as the LMHR phenotype) on a ketogenic diet is a problem. We investigate where their opinions align and where they differ, where Dave’s hypotheses diverge from the norm (and standard patient care), and what we do and don’t know with the available evidence. We also explore the significance of ApoB, lifespan and healthspan considerations, research Dave is actively conducting, and much more.
Specifically, we cover:
- Intro (00:00)
- Dr. William Cromwell: Background as a Lipidologist and LDL Research (01:54)
- Dave Feldman’s Ketogenic Diet and Elevated LDL Experience (05:34)
- Unpacking the Lipid Hypothesis and Cardiovascular Risk (12:30)
- The history and evolution of the lipid hypothesis (20:40)
- The role of apoB lipoproteins in atherosclerosis (23:39)
- Factors beyond apoB involved in atherosclerosis and mortality risk (31:59)
- The complexity of interpreting mortality data in the context of apoB (41:40)
- Macrophages and the process of atherosclerosis (44:00)
- Beyond ApoB: Metabolic Vulnerability, Inflammation and Mortality Risk (52:57)
- Transcytosis: A New Perspective on LDL Movement and Atherosclerosis (1:10:36)
- Exploring Low Cholesterol Impacts and Genetic Disorders (1:17:30)
- Macrophage function and phenotype in the context of different drivers of high apoB (1:22:30)
- Defining Lean Mass Hyper-responders in the Context of a Ketogenic Diet (1:31:40)
- Investigating PCSK9 and Its Effects on Healthspan (1:38:00)
- Assessing cardiovascular risk in lean mass hyper-responders (1:43:50)
- Statin safety, adverse effects, and patient reluctance (2:01:54)
- Ketogenic Diets and Elevated LDL: Balancing Individual Risks and Benefits in the Absence of Long-term Data (2:10:40)
- Insulin Resistance, ApoB, and Cardiovascular Risk: Navigating the Challenges in Assessment and Imaging (2:18:12)
- Lean Mass Hyper-responder Study: Design, Recruitment, and Eligibility Criteria (2:32:45)
- Closing Perspectives on Research and Dietary Options (3:04:47)
- Outro (3:06:42)
For those interested in the specifics of lipids and atherosclerosis, this conversation is an incredibly interesting deep dive into the impact of a ketogenic diet. A sincere thank you to Dr William Cromwell and Dave Feldman for joining me for this discussion spanning multiple viewpoints and hypotheses.
Connect with Dr William Cromwell on Twitter/X, LinkedIn, and his website, https://www.mylipid.com/. Discover more of his work with Precision Health Reports on Twitter/X, LinkedIn, Facebook, Instagram, and at https://precisionhealthreports.com/.
Connect with Dave Feldman on Twitter/X, YouTube, and Instagram, and discover more of his work at https://citizensciencefoundation.org/, https://ownyourlabs.com/, and https://cholesterolcode.com/.
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More about William Cromwell, MD
Dr Cromwell received his doctoral degree in medicine from the Louisiana State University School of Medicine in New Orleans, LA. He completed residency training at the Trover Clinic Foundation in Madisonville, KY, where he received one of twenty national Mead Johnson Graduate Fellowships. Subsequently, he completed postgraduate work in Lipid Disorders at the Washington University School of Medicine Lipid Research Center in St. Louis, MO.
Since 1990, Dr Cromwell’s practice has specialised in managing lipid (cholesterol and triglyceride) and lipoprotein (particles that carry lipids) disorders. In addition to over 30 years of clinical practice experience, his career includes 14 years of service as Medical Director/Division Chief of Lipoprotein and Metabolic Disorders at multiple institutions, six years as Chief Medical Officer of LipoScience, and four years as Strategic Director / Discipline Director of Cardiovascular Disease at LabCorp.
Dr Cromwell currently serves as the Medical Director and Principal Investigator at Velocity Clinical Research in Durham, NC, the Chief of the Lipoprotein and Metabolic Disorders Institute in Raleigh, NC, and an Adjunct Associate Professor in the Hypertension and Vascular Disease Center at Wake Forest University School of Medicine.
Dr Cromwell is a Diplomate of the American Board of Clinical Lipidology, a Diplomate of the American Board of Family Medicine, a Fellow of the American Heart Association Council on Atherosclerosis, Thrombosis and Vascular Biology, a Fellow of the National Lipid Association, and a Fellow of the American Academy of Family Physicians.
Dr Cromwell has authored over two dozen peer-reviewed papers and invited book chapters on evaluating and managing lipoprotein disorders and lipoprotein analytics. He also has been an investigator in over 40 clinical research trials.
More about Dave Feldman
Dave Feldman is a software and platform engineer, an entrepreneur, and founder of the Citizen Science Foundation. His life took a radical turn on seeing his cholesterol skyrocket after adopting a ketogenic diet and became obsessed with understanding why this is common with those who are likewise leaner and more metabolically healthy. While researching lipidology, he found the lipid system of the human body shares many commonalities with distributed networks, much like those he’s worked on in platform development. Through a series of self-experiments and partnering with formal researchers, he has since published the “Lipid Energy Model” which may explain this phenomenon. In addition to this mechanistic research, he’s now spearheading a study out of UCLA that will gather advanced heart scans (CCTA) on participants with a likewise high LDL cholesterol and whether it will be associated with high risk for cardiovascular disease.
