#396 ‒ Breast cancer screening: understanding risk, deciding when to start and how often to screen, and choosing the right imaging strategyView the Show […]

#396 ‒ Breast cancer screening: understanding risk, deciding when to start and how often to screen, and choosing the right imaging strategyView the Show Notes […]

#395 – Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer’s disease risk, and the effects of lipid-lowering therapies on brain health | Tom Dayspring, M.D.View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Tom Dayspring is a world-renowned lipidologist and one of the most thoughtful teachers in the field of lipid metabolism. In this episode, Tom returns to The Drive for a deep dive into the relationship between lipids and brain health, beginning with the fundamentals of cholesterol transport before exploring why the brain’s cholesterol system operates almost entirely independently from the rest of the body. Tom examines the roles of apoB, apoA-I, and especially apoE in cholesterol homeostasis, discusses how APOE genotype influences Alzheimer’s disease risk, and unpacks the complex links between cholesterol metabolism, amyloid, and tau pathology. He also reviews what is currently known—and still uncertain—about the effects of statins, ezetimibe, omega-3 fatty acids, and emerging CETP inhibitors on brain health and neurodegenerative disease risk. Although highly technical, this conversation provides an essential framework for understanding the nuanced relationship between lipid-lowering therapies, cardiovascular disease prevention, and neurodegenerative diseases in an area often clouded by misinformation. We discuss: The fundamentals of cholesterol transport in the body, and how peripheral cholesterol metabolism differs from cholesterol handling in the brain [2:45]; How cholesterol is transported through plasma and stored within cells, and why lowering LDL cholesterol does not deplete the body or brain of cholesterol [11:45]; How apoB particles drive atherosclerosis, why lowering lipids matters, and the factors that influence individual cardiovascular risk [20:00]; How the brain produces and transports its own cholesterol using apoE lipoproteins independently of circulating cholesterol and apoB-containing lipoproteins [29:00]; How apoB structure influences LDL receptor binding and LDL clearance [39:00]; How neurons acquire cholesterol from apoE-containing lipoproteins and why desmosterol serves as a unique marker of cholesterol synthesis in the brain [41:45]; The difference between the APOE gene and the apoE protein, the major APOE genotypes found in humans, and how APOE4 influences Alzheimer’s disease risk [48:45]; HDL function beyond cholesterol: immune function, protein cargo, and communication with the brain [53:30]; How APOE4-associated defects in brain cholesterol transport may promote Alzheimer’s disease: amyloid production, neuronal cholesterol homeostasis, and cholesterol clearance [58:00]; Statins and brain health: reviewing the evidence of the potential impact of statins on cognition and Alzheimer’s disease risk [1:09:00]; Desmosterol and 24S-hydroxycholesterol as biomarkers of brain cholesterol metabolism and statin effects [1:17:15]; Possible cognitive benefits of ezetimibe beyond lowering apoB [1:19:30]; EPA, DHA, and the evidence for omega-3 fatty acids in brain health [1:23:15]; Obicetrapib: an emerging CETP inhibitor with potential implications for both cardiovascular and brain health [1:31:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and Yo […]

#395 – Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer’s disease risk, and the effects of lipid-lowering therapies on brain health | Tom Dayspring, M.D.View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Tom Dayspring is a world-renowned lipidologist and one of the most thoughtful teachers in the field of lipid metabolism. In this episode, Tom returns to The Drive for a deep dive into the relationship between lipids and brain health, beginning with the fundamentals of cholesterol transport before exploring why the brain’s cholesterol system operates almost entirely independently from the rest of the body. Tom examines the roles of apoB, apoA-I, and especially apoE in cholesterol homeostasis, discusses how APOE genotype influences Alzheimer’s disease risk, and unpacks the complex links between cholesterol metabolism, amyloid, and tau pathology. He also reviews what is currently known—and still uncertain—about the effects of statins, ezetimibe, omega-3 fatty acids, and emerging CETP inhibitors on brain health and neurodegenerative disease risk. Although highly technical, this conversation provides an essential framework for understanding the nuanced relationship between lipid-lowering therapies, cardiovascular disease prevention, and neurodegenerative diseases in an area often clouded by misinformation. We discuss: The fundamentals of cholesterol transport in the body, and how peripheral cholesterol metabolism differs from cholesterol handling in the brain [2:45]; How cholesterol is transported through plasma and stored within cells, and why lowering LDL cholesterol does not deplete the body or brain of cholesterol [11:45]; How apoB particles drive atherosclerosis, why lowering lipids matters, and the factors that influence individual cardiovascular risk [20:00]; How the brain produces and transports its own cholesterol using apoE lipoproteins independently of circulating cholesterol and apoB-containing lipoproteins [29:00]; How apoB structure influences LDL receptor binding and LDL clearance [39:00]; How neurons acquire cholesterol from apoE-containing lipoproteins and why desmosterol serves as a unique marker of cholesterol synthesis in the brain [41:45]; The difference between the APOE gene and the apoE protein, the major APOE genotypes found in humans, and how APOE4 influences Alzheimer’s disease risk [48:45]; HDL function beyond cholesterol: immune function, protein cargo, and communication with the brain [53:30]; How APOE4-associated defects in brain cholesterol transport may promote Alzheimer’s disease: amyloid production, neuronal cholesterol homeostasis, and cholesterol clearance [58:00]; Statins and brain health: reviewing the evidence of the potential impact of statins on cognition and Alzheimer’s disease risk [1:09:00]; Desmosterol and 24S-hydroxycholesterol as biomarkers of brain cholesterol metabolism and statin effects [1:17:15]; Possible cognitive benefits of ezetimibe beyond lowering apoB [1:19:30]; EPA, DHA, and the evidence for omega-3 fatty acids in brain health [1:23:15]; Obicetrapib: an emerging CETP inhibitor with potential implications for both cardiovascular and brain health [1:31:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and Yo […]

#394 ‒ Sleep pharmacology: the role of medications in healthy sleep, the promise of emerging therapies, and the evidence for common sleep supplementsView the […]

#394 ‒ Sleep pharmacology: the role of medications in healthy sleep, the promise of emerging therapies, and the evidence for common sleep supplementsView the […]

#393 ‒ AMA #85: A guide to medications and supplements: determining what to take, what to skip, and how to know if they’re working for youView the Show Notes […]

#393 ‒ AMA #85: A guide to medications and supplements: determining what to take, what to skip, and how to know if they’re working for youView the Show Notes […]

#392 – Genetic testing: when it’s valuable, how to choose the right test, and what to do with the resultsView the Show Notes Page for This Episode Become a Member to […]

#392 – Genetic testing: when it’s valuable, how to choose the right test, and what to do with the resultsView the Show Notes Page for This Episode Become a Member to […]

#391 ‒ Colorectal cancer screening: importance of early screening, colonoscopy as a screening and preventive tool, and how to build a personalized strategyVi […]

#391 ‒ Colorectal cancer screening: importance of early screening, colonoscopy as a screening and preventive tool, and how to build a personalized strategyView […]

#390 ‒ AMA #84: Family health history, preventing heart disease, metabolic health, strength training efficiency, dementia risk reduction, NAD supplements, and hydrationView the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on how to think through real-world trade-offs and apply scientific evidence in practice. He explores how to build and interpret a meaningful family health history, how individual risk tolerance influences decisions around testing and treatment, and why heart disease remains poorly prevented despite available tools. He also examines whether it’s possible to carry excess body fat while remaining metabolically healthy, outlines the minimum effective dose for strength training for those with limited time, and discusses the habits and interventions most likely to reduce dementia risk. Additional topics include what evidence would need to emerge for him to reconsider his current stance on NAD-boosting supplements, and when hydration and electrolyte strategies are truly beneficial versus unnecessary. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #84 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Topics overview [1:15]; Using family history to assess disease risk: why it matters more than genetic testing and how to analyze it effectively [2:30]; Peter’s views that differ from conventional medicine: approaches to cardiovascular risk, cancer screening, nutrition, and more [10:30]; Risk tolerance in health decisions: weighing action versus inaction and avoiding low-benefit, high-risk interventions [16:00]; Why cardiovascular disease persists: delayed treatment, insufficient thresholds, and missed opportunities for early intervention [22:00]; Whether someone can be overweight yet metabolically healthy, and how fat distribution influences metabolic risk [26:45]; Strength training with limited time: how to maximize results with intensity and efficiency [30:00]; Designing a sustainable exercise routine: balancing volume, recovery, and enjoyment over time [34:45]; Reducing dementia risk: prioritizing exercise, sleep, and cardiometabolic health based on individual gaps [38:00]; Peter’s current skepticism toward NAD-related supplements and what evidence would be needed to change his view [40:45]; Hydration and electrolytes: factors that impact needs and when supplementation might be necessary [43:30]; and More. Connect With Peter on Twitter, Instagram, Facebo […]

#390 ‒ AMA #84: Family health history, preventing heart disease, metabolic health, strength training efficiency, dementia risk reduction, NAD supplements, and hydrationView the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on how to think through real-world trade-offs and apply scientific evidence in practice. He explores how to build and interpret a meaningful family health history, how individual risk tolerance influences decisions around testing and treatment, and why heart disease remains poorly prevented despite available tools. He also examines whether it’s possible to carry excess body fat while remaining metabolically healthy, outlines the minimum effective dose for strength training for those with limited time, and discusses the habits and interventions most likely to reduce dementia risk. Additional topics include what evidence would need to emerge for him to reconsider his current stance on NAD-boosting supplements, and when hydration and electrolyte strategies are truly beneficial versus unnecessary. If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #84 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Topics overview [1:15]; Using family history to assess disease risk: why it matters more than genetic testing and how to analyze it effectively [2:30]; Peter’s views that differ from conventional medicine: approaches to cardiovascular risk, cancer screening, nutrition, and more [10:30]; Risk tolerance in health decisions: weighing action versus inaction and avoiding low-benefit, high-risk interventions [16:00]; Why cardiovascular disease persists: delayed treatment, insufficient thresholds, and missed opportunities for early intervention [22:00]; Whether someone can be overweight yet metabolically healthy, and how fat distribution influences metabolic risk [26:45]; Strength training with limited time: how to maximize results with intensity and efficiency [30:00]; Designing a sustainable exercise routine: balancing volume, recovery, and enjoyment over time [34:45]; Reducing dementia risk: prioritizing exercise, sleep, and cardiometabolic health based on individual gaps [38:00]; Peter’s current skepticism toward NAD-related supplements and what evidence would be needed to change his view [40:45]; Hydration and electrolytes: factors that impact needs and when supplementation might be necessary [43:30]; and More. Connect With Peter on Twitter, Instagram, Facebo […]

#389 – Thinking scientifically: why it’s hard, why it matters, and a practical toolkitView the Show Notes Page for This Episode Become a Member to Receive Exclusive […]

#389 – Thinking scientifically: why it’s hard, why it matters, and a practical toolkitView the Show Notes Page for This Episode Become a Member to Receive Exclusive […]

#388 — Prostate cancer screening: why current PSA guidelines are failing men and how modern tools improve early detection and save livesView the Show Notes Page for […]

#388 — Prostate cancer screening: why current PSA guidelines are failing men and how modern tools improve early detection and save livesView the Show Notes Page for […]

#387 – AMA #83: Peptides—evaluating the science, safety, and hype in a rapidly growing fieldView the Show Notes Page for This Episode Become a Member to Receive […]

#387 – AMA #83: Peptides—evaluating the science, safety, and hype in a rapidly growing fieldView the Show Notes Page for This Episode Become a Member to Receive […]