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 this discussion, Dr William Cromwell and Dave Feldman share their professional opinions on whether high cholesterol on a keto diet is a problem. We investigate where their opinions align and where they differ, where Dave’s hypotheses diverge from the norm, 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 currently conducting, and much more. Specifically, we discuss: 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) Connect with Dr William Cromwell: Twitter/X, LinkedIn, and https://www.mylipid.com/. Discover more of his work with Precision Health Reports: Twitter/X, LinkedIn, Facebook, Instagram, and at https://precisionhealthreports.com/. Connect with Dave Feldman: Twitter/X, YouTube, and Instagram, and discover more of his work at https://citizensciencefoundation.org/, https://ownyourlabs.com/, and https://cholesterolcode.com/. This episode is brought to you by: InsideTracker If you want to improve your health, you need to measure where you’re currently at. InsideTracker analyses up to 48 blood biomarkers including ApoB, LDL, HDL, A1C, and more before giving you advice to optimise your health. Get a 20% discount on your first order at insidetracker.com/simon. Shopify Shopify, the world's leading e-commerce platform, helps you turn browsers into buyers with the internet’s best-converting check out–up to 36% better compared to other leading e-commerce platforms. To boost your conversion rate, and grow your business, sign up for a one-dollar-per-month trial period at shopify.com/proof. Sun Home Saunas Invest in your body and mind with Sun Home Saunas, pioneers in crafting premium saunas and cold plunges. Safe, effective, research-backed wellness tools to improve cardiovascular health, offer psychological benefits, and reduce muscle soreness. Head to sunhomesaunas.com/theproof for $300 off your purchase.