#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses emerging evidence from a study that explored the drug's effects on Alzheimer's-related blood biomarkers. He also highlights intriguing findings in individuals carrying the APOE4 allele and reflects on what these early results may mean for both cardiovascular disease prevention and potential implications for Alzheimer's risk, as well as how he is thinking about this therapy in the context of caring for his own patients. We discuss: Introducing obicetrapib: CETP inhibitor history, lipid biology, and early Alzheimer's biomarker signals in APOE4 carriers [2:15]; CETP biology explained: lipoproteins, reverse cholesterol transport, and how CETP inhibition alters HDL and LDL particles [5:15]; The early CETP inhibitor story: why raising HDL cholesterol alone failed to deliver cardiovascular protection [13:45]; The rise and fall of early CETP inhibitors: torcetrapib, dalcetrapib, evacetrapib, and anacetrapib [18:30]; Why obicetrapib may succeed where earlier CETP inhibitors failed [23:30]; The BROADWAY trial: obicetrapib's effects on LDL, ApoB, Lp(a), and residual cardiovascular risk [26:00]; Brain lipid metabolism and APOE4: how CETP inhibition may influence cholesterol transport in Alzheimer's disease [30:45]; Findings from the substudy of the BROADWAY trial which looked at changes in biomarkers of Alzheimer's disease [40:00]; Interpreting the BROADWAY Alzheimer's biomarker results: limitations, cautious optimism, and the need for a dedicated prevention trial [46:45]; Why Peter is optimistic about obicetrapib: cardiovascular benefits, Lp(a) reduction, and the path toward approval [50:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Lisa Mosconi is a world-renowned neuroscientist and the director of the Women's Brain Initiative at Weill Cornell Medicine, where she studies how sex differences and hormonal transitions influence brain aging and Alzheimer's disease risk. In this episode, Lisa explores why Alzheimer's disease disproportionately affects women and why longer lifespan alone does not explain their nearly twofold risk compared to men. She explains why Alzheimer's disease may be best understood as a midlife disease for women, beginning decades before symptoms appear, and how menopause represents a fundamental brain event that reshapes brain energy use, structure, and immune signaling. The conversation also examines what advanced brain imaging reveals about preclinical Alzheimer's disease, estrogen receptors in the brain, and why genetic risks such as APOE4 appear to affect women differently from men. Finally, Lisa discusses the nuanced evidence around menopause hormone therapy, the legacy of the WHI, her new CARE Initiative to cut women's Alzheimer's risk in half by 2050, and practical, evidence-based strategies to support brain health through midlife—including lifestyle, sleep, metabolism, mood, and emerging therapies such as GLP-1 agonists and SERMs (selective estrogen receptor modulators). We discuss: How Lisa's personal family history and scientific background led her to focus on the intersection of women's health, brain aging, and Alzheimer's disease (AD) [2:45]; The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [7:15]; How AD compares to other common forms of dementia: prevalence, pathology, symptoms, diagnostic challenges, and more [10:45]; Why AD disproportionately affects women: how AD is not simply a disease of old age or longevity but a midlife disease in which women develop pathology earlier [16:15]; Menopause as a leading explanation for women's increased Alzheimer's risk, and how advanced braining imaging can detect early changes in the brain [26:15]; How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition [35:45]; What estrogen receptor imaging can and cannot tell us about hormone therapy's potential impact on brain health [48:45]; Lisa's studies on the relationship between levels of systemic estrogen and density of estrogen receptors in the brain [58:00]; Why blood estrogen levels poorly reflect brain estrogen signaling, and how tightly regulated brain hormone dynamics complicate our understanding of menstrual-cycle and lifestyle effects [1:02:15]; The CARE Initiative: Lisa's research program looking to slash AD rates in women [1:07:45]; The dramatic difference in AD risk between men and women associated with APOE4 [1:10:45]; What the evidence suggests about menopausal hormone therapy (MHT) and AD risk, and why timing, formulation, and uterine status appear to matter [1:12:00]; How the CARE initiative plans to study MHT and AD risk, within the practical constraints of a three-year research window [1:17:30]; How to think about starting hormone therapy during perimenopause: balancing symptom relief, hormonal variability, and individualized care [1:21:00]; Investigating selective estrogen receptor modulators (SERMs) as a targeted approach to brain health during and after menopause [1:25:00]; Why estrogen became wrongly associated with cancer risk and what the evidence actually shows [1:29:30]; Why better biomarkers are central to advancing women's Alzheimer's research [1:38:30]; Modifiable risk factors for dementia, the limitations of risk models, and questionable conclusions drawn from observational data [1:44:15]; GLP-1 agonists and brain health: exploring potential neuroprotective effects of GLP-1 agonists beyond metabolic benefits [1:49:00]; The importance of lifestyle factors in reducing risk of dementia: practical strategies for women to support brain health [1:53:45]; Why long-term, consistent lifestyle habits are essential for building cognitive resilience and protecting brain health over decades [2:01:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show's usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL oxidation and atherosclerosis. Along the way, Layne unpacks the chemistry and processing of modern seed oils, assesses evolutionary and ancestral nutrition arguments, clarifies the relationship between seed oils, ultra-processed foods, and contemporary dietary patterns, and situates these questions within the larger context of lifestyle factors that drive cardiometabolic health. Layne concludes by offering practical considerations around dietary fats, cooking oils, and real-world food choices. We discuss: The idea behind this episode, biases, and evidence-based thinking [5:15]; The four core arguments behind claims that seed oils are harmful [12:30]; The Minnesota Coronary Experiment (MCE) [14:30]; The differences among saturated, monounsaturated, polyunsaturated, and trans fats, and why those differences matter for cardiovascular disease [18:30]; Missing trans fat data as a confounder in the Minnesota Coronary Experiment, other limitations of that study, and the challenge detecting meaningful differences in hard outcomes through nutrition research [24:00]; The Sydney Diet Heart Study (SDHS): an attempt to address the "duration problem" by enrolling a much higher-risk population [28:30]; Debating whether evidence from randomized trials supports the idea that seed oils are uniquely harmful once major confounders are removed [34:00]; The Rose Corn Oil trial: an often-cited study used to argue against polyunsaturated fats [36:30]; Three studies where replacing saturated fat with polyunsaturated fat produced different results than earlier trials [41:30]; Layne's explanation for why the evidence is pointing towards cardiovascular risk reduction when substituting polyunsaturated fat for saturated fat [47:30]; What Mendelian randomization says about the causal role of LDL cholesterol in ASCVD [56:45]; The compounding effects of life-long exposure to high LDL cholesterol [1:06:45]; Does the linoleic acid (omega-6) content of seed oils cause inflammation? [1:13:45]; Does the linoleic acid (omega-6) content of seed oils increase oxidized LDL? [1:19:30]; Layne's analogy to explain why lower LDL particle number outweighs higher per-particle oxidation risk when comparing polyunsaturated fats to saturated fats [1:26:15]; The role of oxidized LDL in CVD: exploring differences in a diet high in polyunsaturated fat (seed oils) versus high in saturated fat [1:28:00]; Examining whether industrial processing and solvent extraction of seed oils—especially residual hexane—could plausibly cause long-term harm [1:34:00]; The evolutionary and "ancestral diet" argument against seed oils [1:40:45]; Weighing concerns about industrial processing of seed oils against the totality of metabolic and cardiovascular evidence [1:47:30]; Practical considerations around dietary fats, cooking oils, and real-world food choices [1:50:00]; Comparing the health impact of seed oils with that of caloric intake and activity levels, and how to prioritize interventions [2:00:15]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View 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 brings together his most up-to-date thinking on cardiorespiratory fitness into a single, practical guide designed to help listeners structure training for maximal impact on healthspan, lifespan, and long-term independence. He explains why cardiorespiratory fitness is one of the strongest modifiable predictors of longevity, clarifies what zone 2 training actually represents and how it differs from higher-intensity work, and addresses persistent confusion around exercise volume, intensity, and time constraints. The discussion covers how to measure and track progress in zone 2, VO₂ max targets and age-adjusted goals, planning for the marginal decade, and how to balance zone 2 with higher-intensity training across different weekly volumes. Peter also outlines how cardio training should be tailored for beginners, experienced trainees, and older adults, with special considerations for women and guidance on avoiding the most common cardio-training mistakes. 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 #79 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Rational for discussing cardiorespiratory fitness, zone 2, and VO₂ max despite having covered the topic extensively [2:30]; Why cardiorespiratory fitness and VO₂ max are powerful and modifiable predictors of all-cause mortality compared with other health metrics [7:30]; How age-related declines in VO₂ max constrain healthspan and everyday physical function [12:30]; The cardiorespiratory fitness triangle: how different training intensities contribute to building the aerobic base, the aerobic peak, and overall aerobic capacity [14:15]; The cellular mechanics of cardiorespiratory fitness: mitochondria, lactate, muscle fiber recruitment, and intensity thresholds [18:45]; The debate over whether zone 2 training has unique benefits or whether higher-intensity exercise alone is sufficient [27:15]; Balancing intensity and sustainability as training volume increases, and the important role of zone 2 training [32:15]; How to identify your zone 2 training intensity [34:45]; How to measure and track improvements in zone 2 fitness [40:00]; How to accurately measure VO₂ max: lab testing, field tests, and the limits of wearables [45:15]; How to set meaningful VO₂ max targets based on age, sex, long-term decline, and desired physical capabilities later in life [51:15]; How to structure and execute a zone 2 workout [59:45]; How strictly should zone 2 be maintained during a workout? [1:04:00]; How to design a VO₂ max training session: interval length, intensity, recovery, and progression strategies [1:07:00]; Why heart rate is not a reliable metric for titrating VO₂ max interval intensity [1:12:00]; Practical ways to monitor VO₂ max improvements [1:13:30]; How to balance zone 2 and VO₂ max training [1:15:30]; How to structure training for someone limited to 150 minutes per week of total exercise [1:19:00]; How to allocate 150 minutes per week of dedicated cardiorespiratory training between zone 2 and VO₂ max work [1:23:00]; How to structure training for someone with substantial available time who wants to maximize cardiorespiratory fitness [1:24:30]; Why spreading aerobic training across the week beats compressing volume into one session [1:26:15]; How beginners and metabolically unhealthy individuals should start cardiorespiratory training safely [1:28:00]; How "training age" determines the intensity and workload needed to continue improving cardiorespiratory fitness [1:31:15]; Why zone 2 training still matters for women (including postmenopausal women) [1:32:45]; How cardiorespiratory training should adapt with aging [1:35:45]; The most common mistakes people make when training cardiorespiratory fitness and how to avoid them [1:37:45]; How to break through a VO₂ max plateau [1:40:45]; The main takeaways about cardiorespiratory fitness and longevity [1:41:30]; Peter's carve out: oral hygiene and Peter's two-toothbrush system [1:43:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Abbie Smith-Ryan is a leading researcher in exercise physiology whose work focuses on how training and nutrition influence body composition, metabolism, cardiovascular health, and women's health across the lifespan, with particular attention on perimenopause and post-menopause. In this episode, Abbie explains how early exercise and play help build the foundation for bone health, muscle development, and cardiorespiratory fitness in girls, as well as how puberty and menstruation shape athletic performance, motivation, and recovery. She also explores how women can tailor training and nutrition across the menstrual cycle through smart fueling, hydration, and inflammation management; examines the evidence behind supplements such as creatine, omega-3s, and magnesium; and unpacks the metabolic and body composition changes that accompany the transition into perimenopause and menopause. Finally, she covers practical exercise programming for busy women, training and nutrition considerations during pregnancy and postpartum, and the evolving role of hormone therapy alongside lifestyle-based, evidence-driven approaches that help women better advocate for their health. We discuss: Abbie's background in distance running and her interest in studying women's health around exercise [3:00]; The role of early-life exercise in building lifelong bone, muscle, and cardiovascular health in girls [4:00]; Training principles for premenstrual girls, the risks of early specialization and delayed puberty from intense training, and how youth sport participation can shape bone and spinal health [7:15]; Nutrition as fuel in young female athletes: supporting training, growth, and performance [11:00]; Training and recovery across the menstrual cycle: recovery, nutrition, supplements, and practical strategies for performance support [16:00]; The benefits of creatine supplementation and importance of protein intake across the menstrual cycle [27:15]; How women should approach training intensity and volume across the menstrual cycle [33:00]; How to identify and monitor the perimenopausal transition and why this phase represents a critical window for exercise and nutrition interventions [37:15]; Case study: time-efficient exercise program for a busy, perimenopausal woman [42:00]; Why improving body composition is a better goal than weight loss, and how to set realistic fat-loss targets in midlife women [53:30]; How to preserve muscle and bone while using GLP-1 medications: resistance training, protein intake, and more [58:15]; Designing a three-hour-per-week training plan for sustainable body recomposition [1:03:30]; Abbie's insights from her 20+ years of self-tracking: nutrient timing, injury prevention, excessive training, bone health, and more [1:07:15]; How pregnancy and the postpartum period affect body composition, and how consistent exercise and intentional nutrition can prevent a permanent shift in body fat or muscle mass [1:13:30]; Changes in muscle quality and metabolic flexibility during perimenopause and menopause, and how exercise may counteract hormonally driven sarcopenia [1:21:45]; The biggest open questions about women's health: combining menopause hormone therapy with exercise, GLP-1 drugs, minimizing injury risk, and more [1:32:00]; How the training response differs between men and women, and the importance of type IIa muscle fibers [1:39:15]; Training advice for the hypothetical 70-year-old woman who has never exercised deliberately [1:47:00]; Misinformation about exercise and nutrition for women, injury risk, supplement hype, and the need for more nuanced messaging around hormones, recovery, and midlife training [1:53:30]; Benefits of hormone therapy in midlife women and its interaction with exercise and lifestyle interventions [2:00:15]; Peter's overall take on how women should approach exercise volume and intensity at various life phases and time constraints [2:03:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the "Four Laws of Behavioral Change." In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one's self-identity. Finally, James breaks down his "Four Laws of Behavioral Change" and how to use them to create new habits, undo bad habits, and make meaningful changes in one's life. We discuss: Why James became deeply interested in habits [1:45]; Viewing habits through an evolutionary lens [6:00]; The power of immediate feedback for behavior change, and why we tend to repeat bad habits [9:15]; The role of genetics and innate predispositions in determining one's work ethic and success in a given discipline [14:30]; How finding one's passion can cultivate perseverance and discipline [23:15]; Advantages of creating systems and not just setting goals [29:15]; The power of habits combined with self-identity to induce change [36:30]; How a big environmental change or life event can bring on radical behavioral change [50:30]; The influence of one's social environment on their habits [54:15]; How and why habits are formed [1:00:30]; How to make or break a habit with the "Four Laws of Behavior Change" [1:09:30]; Practical tips for successful behavioral change—the best strategies when starting out [1:16:15]; Self-forgiveness and getting back on track immediately after slipping up [1:30:30]; Law #1: Make it obvious—Strategies for identifying and creating cues to make and break habits [1:39:45]; Law #2: Make it attractive—examples of ways to make a new behavior more attractive [1:47:45]; Law #3: Make it easy—the 2-minute rule [1:58:45]; Law #4: Make it satisfying—rewards and reinforcement [2:03:30]; Advice for helping others to make behavioral changes [2:06:00]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this special episode of The Drive, Peter presents a curated "best of" conversation with bestselling author and previous guest Arthur Brooks, organized around four core themes: happiness itself, the forces that undermine it, the tools and practices that help cultivate it, and the courage required to live and love well. The episode brings together the most meaningful moments from two past interviews into a single, focused discussion that distills Brooks' most insightful ideas and offers practical takeaways for building a life that's both successful and deeply happy. We discuss: Happiness vs. happy feelings, and how happiness and unhappiness can coexist [2:15]; The six fundamental emotions [5:30]; The three main "macronutrients" of happiness [15:00]; Enjoyment: one of the three macronutrients of happiness [22:45]; Satisfaction: one of the three macronutrients of happiness [30:45]; Sense of purpose: one of the three macronutrients of happiness [38:45]; Fame: one of the traps that hijack our happiness [46:30]; Success addiction, workaholism, and their detriment to happiness [49:15]; The reverse bucket list: one of Arthur's tools and practices he recommends for moving past the traps that hijack our happiness [59:15]; Metacognition: one of Arthur's tools and practices he recommends for moving past the traps that hijack our happiness [1:01:00]; Taking charge of your happiness: discipline, transcendent experiences, and other deliberate actions for "happier-ness" [1:11:30]; Tracking happiness: the biomarkers and micronutrients behind the macronutrients of happiness [1:22:45]; The value of minimizing the self and looking outward [1:30:45]; How Arthur surprised himself with his ability to improve his happiness [1:34:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View 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 tackles a wide-ranging set of listener questions spanning lifespan interventions, exercise, cardiovascular risk reduction, time-restricted eating, blood pressure management, hormone therapy, diagnostics, and more. Peter reveals the single most important lever for extending healthspan and lifespan, and explains how he motivates midlife patients using the Centenarian Decathlon framework. He discusses the importance of addressing high apoB and cholesterol even in metabolically healthy individuals with calcium scores of zero, how to manage high blood pressure, and how to accurately evaluate metabolic health beyond HbA1c. Additional topics include time-restricted eating, practical considerations around ultra-processed foods, nuanced approaches to HRT for women and TRT for men, and why early and expanded screening for chronic disease—colonoscopy, PSA, coronary imaging, low-dose CT—can be lifesaving. He also offers insights into treating prediabetes, crafting exercise programs for those short on time, and safely incorporating high-intensity training in older adults. 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 #78 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Introducing a wide-ranging AMA: practical perspectives on lifespan interventions, metabolic health, diet, hormones, diagnostics, and more [2:45]; Why exercise is the most powerful single intervention for lifespan and healthspan [4:15]; How Peter motivates midlife patients to prioritize exercise [6:00]; Why lifespan and healthspan should not be treated as competing priorities and how choosing sustainable interventions benefits both [9:30]; Why high apoB deserves treatment even in a metabolically healthy patient with a CAC score of zero [14:00]; Managing hypertension: ideal targets for blood pressure, lifestyle levers, and why early pharmacology matters [18:15]; Assessing metabolic health beyond HbA1c: fasting insulin, triglycerides, lactate, zone 2, and more [23:30]; How to avoid common self-sabotaging patterns by choosing sustainable habits over extreme health interventions [26:00]; Time-restricted eating: minimal effect beyond calorie control, implications for protein intake, and practical considerations for implementing it [28:00]; Ultra-processed foods: definitions, real-world risks, and practical guidelines for smarter consumption [30:30]; How women should prepare for menopause and think about hormone replacement therapy: early planning, symptom awareness, and guidance on HRT [36:45]; Testosterone replacement for aging men: indications, benefits, and safe clinical management [39:45]; Why Peter recommends earlier and more aggressive screening tests than guidelines suggest: colonoscopies, coronary imaging, PSA, Lp(a), and low-dose CT scans, and more [43:30]; Full-body MRI screening: benefits, limitations, potential false positives, and the importance of physician oversight [47:15]; Prediabetes: individualized treatment strategies using tailored combinations of nutrition, sleep, and training interventions [51:00]; Time-efficient training plans for people with only 30 minutes per day to exercise [53:00]; How to safely introduce high-intensity exercise for older adults [55:00]; Timed dead hangs and ripping phone books: a playful look at Peter's early attempts to impress his wife [57:15]; Peter's carve out: The Four Kings documentary about a golden era of boxing [1:01:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Dom D'Agostino is a neuroscientist and professor at the forefront of metabolic therapies, including ketogenic diets, exogenous ketones, and hyperbaric oxygen. In this episode, Dom breaks down nutritional versus supplemental ketosis, defines meaningful ketone thresholds, and outlines practical ways to achieve ketosis. He explains how a ketogenic diet can support metabolic health and weight loss, and advises on how to maintain adequate protein and avoid common mistakes. Dom surveys the growing landscape of exogenous ketones—from salts and esters to 1,3-butanediol—and effective pairings like caffeine, MCT oil, and alpha-GPC. He highlights the role of ketogenic therapy in cancer (particularly glioblastoma) and its promise for neurodegenerative diseases. The conversation also covers recommended hyperbaric oxygen protocols for brain injuries and cognitive function, situations where fasting or ketones offer cognitive and anti-inflammatory benefits, and touches on the carnivore diet as a ketogenic variant with potential relevance for autoimmune and metabolic conditions. We discuss: Dom and Peter's shared interest in ketosis, and Dom's scientific journey [2:30]; Dom's work for the Navy on oxygen toxicity [7:00]; Nutritional ketosis defined: physiology, biomarkers, and how fasting and diet generate therapeutic ketones [15:00]; The historical roots of ketogenic diets in epilepsy treatment, and evidence showing ketones reduce seizure activity and strengthen brain resilience [19:00]; Dom's personal experience on the ketogenic diet: tracking macros, getting enough protein, and monitoring ketone levels [24:15]; Using a ketogenic diet for weight loss: Dom's guidance on protein, fiber, calorie tracking, lipid monitoring, and more [31:00]; Protein on ketogenic diets: Dom's rationale for higher intake and muscle preservation [38:00]; Incorporating carbohydrates into keto: timing, high-fiber foods, and other considerations [41:30]; The carnivore diet: whether this diet induces ketosis, how it functions metabolically, and why it may help individuals with autoimmune conditions [44:15]; Early exogenous ketones: how 1,3-butanediol works, its liver toxicity risk, and why ketone esters replaced it [48:15]; The progression of exogenous ketones: why BHB monoesters and ketone salts emerged as better alternatives to 1,3-butanediol for ketone supplementation [59:30]; Ketone salts: easing the transition into ketosis, dosing, and how they compare to ketone esters [1:04:00]; The differences between D- and L-β-hydroxybutyrate, and how racemic mixtures may elevate ketones longer and offer unique biological effects [1:09:30]; How ketosis may boost NAD, and why NAD supplements have fallen short so far [1:16:30]; Emerging evidence for using a ketogenic diet to treat anorexia and other psychiatric disorders [1:20:30]; Potential cognitive and performance benefits of ketone supplementation, and why pushing ketones too high can be dangerous [1:23:45]; Applications for ketone esters, and why ketone salts or MCT-blended formulations may be safer and more practical for most people [1:29:15]; The role of a ketogenic diet in treating cancer [1:34:45]; The potential of a ketogenic diet for treating Alzheimer's disease [1:45:45]; Tools for cognitive enhancement: ketones, alpha-GPC, MCT, caffeine, strategic fasting, and more [1:53:45]; Hyperbaric oxygen therapy for concussion, TBI, PTSD, and cognitive function, including protocols and dosing approaches [1:55:30]; Peter's takeaways, recommended products, and additional resources to learn more [2:03:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of attempting to suppress them. The conversation also covers testosterone across the lifespan, the role of hormone therapy in both men and women, and Carole's own experience after surgical menopause, culminating in a broader discussion of masculinity, cultural narratives, and the consequences of denying biological sex differences. We discuss: How Carole became interested in exploring the biological and evolutionary roots of sex differences and the role of testosterone [2:30]; How testosterone and other hormones influence sex differences in aggression and behavior across species [9:45]; How chromosomes, the SRY gene, and early hormones direct embryonic sexual differentiation [12:15]; A stark contrast of male social bonding compared to females, and evolutionary parallels in chimpanzees [19:30]; How hormones like DHT shape sexual differentiation, and how 5⍺-reductase deficiency reveals the distinct roles of these hormones [22:45]; How sex chromosomes and prenatal testosterone shape early brain development and explain sex differences in childhood behavior [31:30]; How gamete differences shape reproductive strategies, energetic costs, and sex-specific behavior [42:30]; How evolutionary biology shapes sex differences in play, aggression, and conflict resolution (and how modern environments and cultural messaging can disrupt those patterns) [49:00]; Why males commit disproportionately more violent crime, and how cultural and environmental forces shape aggression [1:01:00]; Why females evolved different behavioral strategies: nurturing, risk aversion, and the cultural norms that override biology [1:04:00]; Whether male aggression is still necessary in modern society, why the underlying biological drives persist, and how modern society redirects these drives [1:06:30]; How testosterone levels naturally shift to support fatherhood and caregiving [1:13:30]; How testosterone shapes male mating strategies, and why long-term pair-bonding persists even when reproduction is no longer at stake [1:18:30]; The distinct roles of estrogen in male development, mood, libido, and muscle [1:25:00]; How evolution, health, lifestyle, and androgen receptor biology shape modern testosterone replacement therapy (TRT) [1:34:15]; Carole's experience with hormone replacement therapy (HRT), and the risks associated with TRT in younger men [1:45:15]; How Carole rebuilt after controversy: leaving academia and recommitting to scientific honesty [1:51:30,]; Carole's next book: examining masculinity, cultural narratives, and the cost of denying biological sex differences [1:57:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube