#404 ‒ Mental health beyond neurotransmitters: the role of hormones in psychiatry, why symptom reduction isn’t enough, and the future of psychedelic therapies | Linus Abrams, 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 In this episode, Peter sits down with Dr. Linus Abrams, a psychiatrist with nearly 35 years of clinical experience specializing in mood disorders and psychopharmacology, to explore how our understanding of mental health is evolving beyond the traditional neurotransmitter model. After decades in practice, Linus began questioning many of the assumptions underlying modern psychiatry, leading him to investigate how hormones, metabolism, inflammation, circadian biology, and the endocrine system shape mood and cognition. Together, Peter and Linus examine why psychiatric care should aim not only to reduce symptoms but also to restore the full human experience. They discuss how psychiatric medications work, where they fall short, and why distinguishing bipolar disorder from unipolar depression is essential for effective treatment. The conversation also explores the growing mental health burden of social isolationn associated with digital devices and social media, along with the biological factors—nutrition, exercise, sleep, and chronic stress—that influence resilience and distress tolerance. Linus explains the powerful roles of estrogen, progesterone, testosterone, and thyroid hormone in regulating mood and cognition across the lifespan. Finally, Peter and Linus review the promise and limitations of ketamine and psychedelic therapies, and why the future of psychiatry may lie in integrating neuroscience, endocrinology, and whole-body physiology to better understand, diagnose, and treat mental illness. We discuss: Linus’s passion for understanding his patients and going beyond traditional psychiatry [2:45]; A short primer on the different classes of drugs used in psychiatry [12:45]; Evaluation of a patient with bipolar disorder [26:00]; An evolutionary perspective on depression [33:30]; Changes in the modern world triggering mental health problems [41:00]; An evolutionary perspective on insomnia [48:15]; Peter’s window analogy to understand distress tolerance and irritability [49:45]; The impact of foundational biological factors on psychiatry: nutrition, exercise, sleep, and endocrinology [52:30]; The effect of estradiol on neurotransmitters in the brain [58:15]; Options for increasing testosterone in men, and why clomiphene is inferior to exogenous testosterone [1:11:00]; The rapid drop in progesterone is linked to both premenstrual dysphoric disorder (PMDD) and postpartum depression [1:14:30]; Treatment of postpartum depression [1:18:00]; Hypothyroidism presenting as depression: how Linus makes the diagnosis and what he uses for treatment [1:26:00]; The link between hyperarousal and chronically elevated cortisol [1:39:30]; A case where the menopause transition uncovers bipolar disorder [1:44:15]; Ketamine as a tool to treat recalcitrant depression, and concerns about its recreational use [1:49:15]; Case study: an Alzheimer’s patient who improved after psilocybin, and why Linus is cautious about drawing conclusions from it [1:55:15]; Peter’s experience with psychedelics, and the myth that estrogen is bad for men [2:00:30]; The therapeutic potential of psychedelics in psychiatry [2:11:00]; and More. Connect With Peter on Twitter, Instagram, Fa […]

#403 ‒ Peptides: separating scientific promise from marketing hypeView the Show Notes Page for This Episode Become a Member to Receive Exclusive Content […]

#403 ‒ Peptides: separating scientific promise from marketing hypeView the Show Notes Page for This Episode Become a Member to Receive Exclusive Content […]

#402 ‒ NMR blood analysis: how heart disease risk, insulin resistance, inflammation, and mortality risk can be assessed from a single blood sample | Jim Otvos, Ph.D.View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Jim Otvos is a biophysical chemist who pioneered the use of nuclear magnetic resonance (NMR) spectroscopy to measure lipoprotein particles and developed the first FDA-cleared method for directly quantifying LDL particle number (LDL-P), a technology that has since expanded to provide broader insights into metabolic health, inflammation, insulin resistance, and mortality risk. In this episode, Jim recounts the unlikely story of transforming a flawed cancer test into a new way of measuring lipoproteins, explains what standard cholesterol tests can miss and why LDL-P and apoB can inform treatment decisions beyond LDL cholesterol alone, and dispels the misconception that large, “fluffy” LDL particles are benign. He also explores how NMR can reveal insulin resistance before blood sugar rises, GlycA as a marker of chronic low-grade inflammation, and the metabolic vulnerability index (MVX) as a potential measure of frailty, resilience, and mortality risk across the lifespan. Finally, Jim explains why NMR diagnostics remain underused despite the wealth of information they can extract from a single blood test. We discuss: How investigating a flawed 1986 cancer test led to the development of NMR (nuclear magnetic resonance) lipoprotein testing [3:30]; How standard lipid panels measure cholesterol and triglycerides, and why LDL cholesterol is estimated rather than directly measured [15:15]; How NMR spectroscopy measures lipoprotein particle size and concentration [20:30]; Why LDL particle number matters more than particle size, and why large, “fluffy” LDL is not benign [28:45]; Discordance between LDL cholesterol and LDL particle number: which measure better reflects cardiovascular risk? [36:30]; How metabolic syndrome and lipid-lowering treatment contribute to the discordance between LDL-C and LDL-P, and the value of particle number for managing risk [45:30]; Using the NMR-derived LP-IR score to detect insulin resistance and predict type 2 diabetes before glucose rises [51:15]; The development, commercialization, and uncertain future of the Vantera NMR Analyzer and NMR-based diagnostics [1:04:45]; The analytical efficiency of NMR testing and the data-driven development of the Metabolic Vulnerability Index (MVX) [1:16:00]; GlycA as an NMR-derived marker of systemic inflammation: its discovery, biological basis, and advantages over hs-CRP [1:25:45]; Developing the Metabolic Vulnerability Index (MVX): biomarkers of inflammation, malnutrition, muscle wasting, and mortality risk [1:34:00]; What MVX can tell us about longevity and mortality [1:44:15]; How MVX may reveal metabolic frailty and predict premature mortality decades in advance in young, healthy adults [1:50:30]; Potential applications of MVX for predicting treatment response, surgical resilience, and clinical trial outcomes, and the barriers to broader use [2:00:00]; ApoB versus LDL-P: their clinical similarities, the additional information provided by NMR, and barriers to broader adoption [2:07:30]; Interpreting the effects of the CETP inhibitor, obicetrapib, on LDL-P, apoB, and small HDL particles [2:13:00]; The future of NMR diagnostics and MVX: translating scientific potential into broader clinical use [2:20:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTu […]

#402 ‒ NMR blood analysis: how heart disease risk, insulin resistance, inflammation, and mortality risk can be assessed from a single blood sample | Jim Otvos, Ph.D.View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Jim Otvos is a biophysical chemist who pioneered the use of nuclear magnetic resonance (NMR) spectroscopy to measure lipoprotein particles and developed the first FDA-cleared method for directly quantifying LDL particle number (LDL-P), a technology that has since expanded to provide broader insights into metabolic health, inflammation, insulin resistance, and mortality risk. In this episode, Jim recounts the unlikely story of transforming a flawed cancer test into a new way of measuring lipoproteins, explains what standard cholesterol tests can miss and why LDL-P and apoB can inform treatment decisions beyond LDL cholesterol alone, and dispels the misconception that large, “fluffy” LDL particles are benign. He also explores how NMR can reveal insulin resistance before blood sugar rises, GlycA as a marker of chronic low-grade inflammation, and the metabolic vulnerability index (MVX) as a potential measure of frailty, resilience, and mortality risk across the lifespan. Finally, Jim explains why NMR diagnostics remain underused despite the wealth of information they can extract from a single blood test. We discuss: How investigating a flawed 1986 cancer test led to the development of NMR (nuclear magnetic resonance) lipoprotein testing [3:30]; How standard lipid panels measure cholesterol and triglycerides, and why LDL cholesterol is estimated rather than directly measured [15:15]; How NMR spectroscopy measures lipoprotein particle size and concentration [20:30]; Why LDL particle number matters more than particle size, and why large, “fluffy” LDL is not benign [28:45]; Discordance between LDL cholesterol and LDL particle number: which measure better reflects cardiovascular risk? [36:30]; How metabolic syndrome and lipid-lowering treatment contribute to the discordance between LDL-C and LDL-P, and the value of particle number for managing risk [45:30]; Using the NMR-derived LP-IR score to detect insulin resistance and predict type 2 diabetes before glucose rises [51:15]; The development, commercialization, and uncertain future of the Vantera NMR Analyzer and NMR-based diagnostics [1:04:45]; The analytical efficiency of NMR testing and the data-driven development of the Metabolic Vulnerability Index (MVX) [1:16:00]; GlycA as an NMR-derived marker of systemic inflammation: its discovery, biological basis, and advantages over hs-CRP [1:25:45]; Developing the Metabolic Vulnerability Index (MVX): biomarkers of inflammation, malnutrition, muscle wasting, and mortality risk [1:34:00]; What MVX can tell us about longevity and mortality [1:44:15]; How MVX may reveal metabolic frailty and predict premature mortality decades in advance in young, healthy adults [1:50:30]; Potential applications of MVX for predicting treatment response, surgical resilience, and clinical trial outcomes, and the barriers to broader use [2:00:00]; ApoB versus LDL-P: their clinical similarities, the additional information provided by NMR, and barriers to broader adoption [2:07:30]; Interpreting the effects of the CETP inhibitor, obicetrapib, on LDL-P, apoB, and small HDL particles [2:13:00]; The future of NMR diagnostics and MVX: translating scientific potential into broader clinical use [2:20:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTu […]

#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcareView the Show Notes Page for This Episode Become a Member […]

#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcareView the Show Notes Page for This Episode Become a Member […]

#400 ‒ AMA #87: Environmental pollution and longevity: air pollution, noise, light, EMFs, and practical strategies to mitigate health risksView the Show Notes […]

#400 ‒ AMA #87: Environmental pollution and longevity: air pollution, noise, light, EMFs, and practical strategies to mitigate health risksView the Show Notes […]

#399 ‒ The evolution of Alzheimer’s disease and dementia care: how early detection, personalized treatment, new therapies, and a multimodal approach are changing the landscape | Gayatri Devi, 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 Gayatri Devi is a nationally recognized neurologist specializing in memory disorders, including Alzheimer’s disease and related dementias. In this episode, Gayatri explains how to think about dementia as a spectrum—including Alzheimer’s disease, vascular dementia, Lewy body dementia, and mixed presentations—while exploring the evolving biology of amyloid, tau, and neuroinflammation and why brain pathology does not always correlate with symptoms. She discusses her approach to detecting subtle cognitive decline in high-functioning individuals, the role of biomarkers and APOE4 testing in asymptomatic patients, the benefits and risks of anti-amyloid therapies such as lecanemab and donanemab, and strategies for minimizing treatment-related complications. Gayatri also examines why some patients may stabilize or even improve with individualized care, the overlap among different dementia syndromes, and the relationship between menopause, estrogen, and cognition—including her concept of menopause-related cognitive impairment. Finally, she discusses how advances in early detection, AI-assisted monitoring, targeted therapies, and precision medicine are reshaping the future of dementia care. We discuss: Gayatri’s training and clinical focus, why dementia is a spectrum disease, and how personalized treatment is changing Alzheimer’s care [3:45]; How Alzheimer’s disease fits within the broader spectrum of dementia: diagnosis, biomarkers, and early pathophysiology [7:15]; The emerging role of neuroinflammation and viral infections in Alzheimer’s disease [13:30]; Gayatri’s comprehensive approach to evaluating cognitive decline in high-functioning patients [17:45]; Why forgetting names is usually normal and when word-finding problems become concerning [29:00]; Why women are at higher risk for Alzheimer’s disease and how menopause influences cognition [33:45]; The promise and limitations of blood-based biomarkers for diagnosing Alzheimer’s disease [40:15]; When preclinical Alzheimer’s screening is appropriate and how to interpret positive biomarker results [45:00]; Case study: early Alzheimer’s prevention in a highly-functional woman in her 50s with two copies of APOE4 [47:15]; Anti-amyloid therapies: balancing clinical benefit with ARIA risk using slow titration [51:45]; The aducanumab controversy, why it was discontinued, and why Gayatri would still choose it [1:00:00]; How anti-amyloid therapies cause ARIA, strategies for detecting and managing these complications, and how future therapies may improve safety and accessibility [1:03:30]; Two patient examples of exceptional responses to anti-amyloid therapy [1:12:30]; A multimodal approach to Alzheimer’s treatment: combination therapy, MRI-guided TMS, GLP-1 receptor agonists, and more [1:15:00]; Vascular dementia, Lewy body dementia, and the overlap with Alzheimer’s disease [1:21:00]; Lewy body dementia and Parkinson’s disease: distinguishing two alpha-synuclein disorders [1:26:45]; Risk factors for Lewy body dementia and what remains unknown [1:36:15]; Treating menopause-related cognitive impairment: hormone therapy, brain rehabilitation, and balancing breast cancer risk [1:38:45]; How biomarkers changed Gayatri’s perspective on the potential for Alzheimer’s patients to improve [1:47:15]; The future of Alzheimer’s care: AI, precision medicine, and personalized treatment [1:49:30]; and More. Connect With Peter on Twitter, […]

#399 ‒ The evolution of Alzheimer’s disease and dementia care: how early detection, personalized treatment, new therapies, and a multimodal approach are changing the landscape | Gayatri Devi, 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 Gayatri Devi is a nationally recognized neurologist specializing in memory disorders, including Alzheimer’s disease and related dementias. In this episode, Gayatri explains how to think about dementia as a spectrum—including Alzheimer’s disease, vascular dementia, Lewy body dementia, and mixed presentations—while exploring the evolving biology of amyloid, tau, and neuroinflammation and why brain pathology does not always correlate with symptoms. She discusses her approach to detecting subtle cognitive decline in high-functioning individuals, the role of biomarkers and APOE4 testing in asymptomatic patients, the benefits and risks of anti-amyloid therapies such as lecanemab and donanemab, and strategies for minimizing treatment-related complications. Gayatri also examines why some patients may stabilize or even improve with individualized care, the overlap among different dementia syndromes, and the relationship between menopause, estrogen, and cognition—including her concept of menopause-related cognitive impairment. Finally, she discusses how advances in early detection, AI-assisted monitoring, targeted therapies, and precision medicine are reshaping the future of dementia care. We discuss: Gayatri’s training and clinical focus, why dementia is a spectrum disease, and how personalized treatment is changing Alzheimer’s care [3:45]; How Alzheimer’s disease fits within the broader spectrum of dementia: diagnosis, biomarkers, and early pathophysiology [7:15]; The emerging role of neuroinflammation and viral infections in Alzheimer’s disease [13:30]; Gayatri’s comprehensive approach to evaluating cognitive decline in high-functioning patients [17:45]; Why forgetting names is usually normal and when word-finding problems become concerning [29:00]; Why women are at higher risk for Alzheimer’s disease and how menopause influences cognition [33:45]; The promise and limitations of blood-based biomarkers for diagnosing Alzheimer’s disease [40:15]; When preclinical Alzheimer’s screening is appropriate and how to interpret positive biomarker results [45:00]; Case study: early Alzheimer’s prevention in a highly-functional woman in her 50s with two copies of APOE4 [47:15]; Anti-amyloid therapies: balancing clinical benefit with ARIA risk using slow titration [51:45]; The aducanumab controversy, why it was discontinued, and why Gayatri would still choose it [1:00:00]; How anti-amyloid therapies cause ARIA, strategies for detecting and managing these complications, and how future therapies may improve safety and accessibility [1:03:30]; Two patient examples of exceptional responses to anti-amyloid therapy [1:12:30]; A multimodal approach to Alzheimer’s treatment: combination therapy, MRI-guided TMS, GLP-1 receptor agonists, and more [1:15:00]; Vascular dementia, Lewy body dementia, and the overlap with Alzheimer’s disease [1:21:00]; Lewy body dementia and Parkinson’s disease: distinguishing two alpha-synuclein disorders [1:26:45]; Risk factors for Lewy body dementia and what remains unknown [1:36:15]; Treating menopause-related cognitive impairment: hormone therapy, brain rehabilitation, and balancing breast cancer risk [1:38:45]; How biomarkers changed Gayatri’s perspective on the potential for Alzheimer’s patients to improve [1:47:15]; The future of Alzheimer’s care: AI, precision medicine, and personalized treatment [1:49:30]; and More. Connect With Peter on Twitter, […]

Building strength and muscle mass: how to optimize training, nutrition, and more for longevity (AMA #71 rebroadcast)View the Show Notes Page for This Episode Become […]

Building strength and muscle mass: how to optimize training, nutrition, and more for longevity (AMA #71 rebroadcast)View the Show Notes Page for This Episode Become a […]

#398 ‒ AMA #86: GLP-1 RAs and muscle loss: new data, better questions, and how to preserve muscle during weight lossView the Show Notes Page for This Episode […]

#397 ‒ Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, and emerging treatments | Renato Tomioka, M.D., Ph.D.View the Show Notes Page for […]

#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 […]