The Peter Attia Drive podcast

The Peter Attia Drive

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View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Episode Description: Karl Deisseroth is a world-renowned clinical psychiatrist, neuroscientist, and author of Projections: A Story of Human Emotions. In the episode, Karl explains his unique career path that led to the development of optogenetics—a revolutionary technique that uses specialized light-sensitive ion channels to precisely control the activity of select populations of neurons. Karl provides a concise overview of how optogenetics works and how it can be used to better understand mental illness, to identify the neurons responsible for specific behaviors, and to guide development of new treatments. Karl uses his experience as a practicing psychiatrist to provide deep insights into depression, anxiety, autism, and personality disorders and explains the role of optogenetics in mapping out brain regions responsible for common mental health afflictions. We discuss: Karl’s journey through medical school and interest in the brain [5:00]; A profound medical school experience that changed Karl’s career path to psychiatry [17:30]; Karl’s commitment to research and challenges overcome early in his career [27:00]; The state of psychiatry and mental health therapies when Karl started his lab in 2004 [33:15]; Neuroscience 101: fundamentals of neuroanatomy and neurophysiology [38:15]; Traditional techniques for identifying the brain regions involved in specific behaviors [47:15];   Intro to optogenetics and how to get a gene into a neuron [51:15]; How viruses helped make optogenetics possible [1:01:45];   How optogenetics was used to investigate the effects of dopamine neurons [1:15:45]; Appreciating the power of optogenetics [1:22:00]; Investigating and treating anxiety with optogenetics [1:26:45]; Autism and autism-related anxiety, and the potential of optogenetics in treating autism [1:38:00]; Optogenetics as a powerful tool for the discovery and creation of medical treatments [1:45:00]; Karl’s inspiration to write his book, Projections [1:48:00]; Mania and bipolar disorder: evolutionary basis, symptoms, and the high prevalence in North America [1:52:45]; Depression: evolutionary basis and insights from optogenetics [2:03:15]; The effects of trauma early in life [2:18:45]; and More. Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

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The Peter Attia Drive Podcast Episodes

#191 - Revolutionizing our understanding of mental illness with optogenetics | Karl Deisseroth M.D., Ph.D.

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Episode Description: Karl Deisseroth is a world-renowned clinical psychiatrist, neuroscientist, and author of Projections: A Story of Human Emotions. In the episode, Karl explains his unique career path that led to the development of optogenetics—a revolutionary technique that uses specialized light-sensitive ion channels to precisely control the activity of select populations of neurons. Karl provides a concise overview of how optogenetics works and how it can be used to better understand mental illness, to identify the neurons responsible for specific behaviors, and to guide development of new treatments. Karl uses his experience as a practicing psychiatrist to provide deep insights into depression, anxiety, autism, and personality disorders and explains the role of optogenetics in mapping out brain regions responsible for common mental health afflictions. We discuss: Karl’s journey through medical school and interest in the brain [5:00]; A profound medical school experience that changed Karl’s career path to psychiatry [17:30]; Karl’s commitment to research and challenges overcome early in his career [27:00]; The state of psychiatry and mental health therapies when Karl started his lab in 2004 [33:15]; Neuroscience 101: fundamentals of neuroanatomy and neurophysiology [38:15]; Traditional techniques for identifying the brain regions involved in specific behaviors [47:15];   Intro to optogenetics and how to get a gene into a neuron [51:15]; How viruses helped make optogenetics possible [1:01:45];   How optogenetics was used to investigate the effects of dopamine neurons [1:15:45]; Appreciating the power of optogenetics [1:22:00]; Investigating and treating anxiety with optogenetics [1:26:45]; Autism and autism-related anxiety, and the potential of optogenetics in treating autism [1:38:00]; Optogenetics as a powerful tool for the discovery and creation of medical treatments [1:45:00]; Karl’s inspiration to write his book, Projections [1:48:00]; Mania and bipolar disorder: evolutionary basis, symptoms, and the high prevalence in North America [1:52:45]; Depression: evolutionary basis and insights from optogenetics [2:03:15]; The effects of trauma early in life [2:18:45]; and More. Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

#190 - Paul Conti, M.D.: How to heal from trauma and break the cycle of shame

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Episode Description: Paul Conti, a returning guest on The Drive, is a practicing psychiatrist and recent author of Trauma: The Invisible Epidemic: How Trauma Works and How We Can Heal From It, in which he offers valuable insights on healing from trauma. In this episode, Paul explains how his personal experience with trauma and his many years seeing patients have shaped his understanding of trauma’s impact on the brain, its common patterns and manifestations, and how often people don't recognize the implications of trauma in their own life. He discusses major challenges in recognizing trauma, including the lack of biomarkers in psychiatry and psychology, as well as the misguidance of the mental health system in targeting symptoms as opposed to root problems. He talks about shame as the biggest impediment to healing from trauma and offers solutions to how, as a society, we can start to change the stigma of mental health and allow more people to receive help. Finally, he concludes with a discussion about the potential role of psychedelics like psilocybin and MDMA in treating trauma. We discuss: Paul’s background and unique path to psychiatry [2:30]; A personal tragedy that shaped Paul’s understanding of trauma and resulting feelings of shame and guilt [5:30]; The current state of psychiatry training and need for improvement [20:15]; The over-reliance on outdated metrics and lack of attention to past trauma as impediments to patient care [28:30]; Defining trauma: various types, heterogeneity, and effects on the brain [34:30]; Importance of finding the roots of trauma and understanding the “why” [47:00]; The major challenge of recognizing trauma in patients [55:15]; How shame and guilt are barriers to treatment and healing [1:06:00]; How treating trauma compares to treating an abscess—a powerful analogy [1:11:30]; How evolutionary survival instincts create problems in modern society [1:15:15]; First step toward healing: overcoming the fear of talking about past trauma [1:19:00]; Shame: the biggest impediment to healing [1:25:15]; The antidote to shame and the need for discourse and understanding [1:34:15]; The emotional health component of healthspan [1:41:15]; How to reframe the conversation about mental health for a better future [1:52:00]; The growing impact of trauma on our society and the need for compassion [1:58:45]; Society’s antiquated way of treating manifestations of trauma rather than root issues [2:04:15]; Potential role of psychedelics like psilocybin and MDMA in treating trauma [2:11:15]; Parting thoughts and resources for getting help [2:16:30]; More. Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

#189 - COVID-19: Current state of affairs, Omicron, and a search for the end game

In this episode, Peter sits down with Drs. Marty Makary and Zubin Damania (aka ZDoggMD), both previous guests on The Drive. Marty is a Johns Hopkins professor and public health researcher and ZDoggMD is a UCSF/Stanford trained internist and the founder of Turntable Health. This episode, recorded on December 27, 2021, was in part inspired by some of the shoddy science and even worse messaging coming from top officials regarding COVID-19. In this discussion, Marty and ZDoggMD discuss what is known about the omicron variant, the risks and benefits of vaccines for all age groups, and the taboo subject of natural immunity and the protection it offers against infection and severe disease. Furthermore, they discuss at length the poor messaging coming from our public officials, the justification (and lack thereof) for certain mandates and policies in light of the current evidence, and the problems caused by the highly politicized and polarized nature of the subject. Themes throughout the conversation include the difference between science and advocacy, the messaging which is sowing mistrust in science despite major progress, and a search for what a possible “end” to this situation might look like.  NOTE: Since this episode was recorded over the holiday and published ASAP, this is an audio-only episode with limited show notes.  We discuss: Comparing omicron to delta and other variants [4:15]; Measuring immunity and protection from severe disease—circulating antibodies, B cells, and T cells [13:15]; Policy questions: what is the end game and how does the world go back to 2019? [18:45]; A policy-minded framework for viewing COVID and the problem of groupthink [24:00]; The difference between science and advocacy [39:00]; Natural immunity from COVID after infection [46:00]; The unfortunate erosion of trust in science despite impressive progress [57:15]; Do the current mandates and policies make sense in light of existing data? [1:02:30]; Risks associated with vaccines, and the risk of being labeled an anti-vaxxer when questioning them [1:18:15]; Data on incidence of myocarditis after vaccination with the Pfizer and Moderna vaccines [1:26:15]; Outstanding questions about myocarditis as a side effect of mRNA vaccination and the benefit of boosters [1:35:00]; The risk-reward of boosters and recommendations being ignored by policy makers in the US [1:40:30]; Sowing distrust: lack of honesty and humility from top officials and policy makers [1:43:30]; Thoughts on testing: does it make sense to push widespread testing for COVID? [1:52:15]; What is the endpoint to all of this? [1:58:45]; Downstream consequences of lockdowns and draconian policy measures [2:05:30]; The polarized nature of COVID—tribalism, skeptics, and demonization of ideas [2:10:30]; Looking back at past pandemics for perspective and the potential for another pandemic in the future [2:20:00]; What parents can do if their kids are subject to unreasonable policies [2:25:00]; Voices of reason in this space [2:28:45]; Strong convictions, loosely held: the value in questioning your own beliefs [2:32:15]; More.   View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Learn More About Peter Attia Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

Iñigo San Millán, Ph.D.: Zone 2 Training and Metabolic Health (Ep. #85 Rebroadcast)

Today’s episode of The Drive is a rebroadcast of the conversation with Iñigo San Millán, (released on December 23rd, 2019). This episode with Iñigo was one of the most popular discussions to date and is a prelude to an upcoming follow-up discussion in 2022. In this episode, Dr. Iñigo San Millán, Assistant Professor at the University of Colorado School of Medicine, explains the crucial role of mitochondrial function in everything from metabolic health to elite exercise performance. Iñigo provides a masterclass into the many different energy system pathways, the various fuel sources (including the misunderstood lactate), the six zones of exercise training, and the parameters he uses to measure metabolic health. Additionally, he highlights the power of zone 2 training as both an effective diagnostic tool and, perhaps more importantly, as a treatment for mitochondrial and metabolic dysfunction. We discuss: Iñigo’s background in sports and decision to focus on education [3:45]; The various energy systems and fuels used during exercise [11:15]; Iñigo’s qualification of energy systems into six training zones [19:30]; Lactate as an important fuel source [29:30]; Zone 2 training—physiologic characteristics, fuel sources, lactate, and the transition into zone 3 [37:00]; Using blood lactate levels (and zone-2 threshold) to assess mitochondrial function [43:30]; Accessing mitochondrial function by testing one’s ability to utilize fat as fuel [51:30]; Athletes vs. metabolically ill patients—mitochondria, fat oxidation, muscle glycogen capacity, “fat droplets”, and more [56:30]; Physiologic characteristics of zone 3, zone 4, and the lactate threshold [1:16:30]; Fueling exercise—dietary implications on glycolytic function [1:27:00]; Relationship between exercise and insulin sensitivity (and what we can learn from studying patients with type 1 diabetes) [1:43:00]; Metformin’s impact on mitochondrial function, lactate production, and how this affects the benefits of exercise [2:00:45]; Raising awareness of the risk of “double diabetes” [2:11:30]; How to dose zone 2 training, and balancing exercise with nutrition [2:14:30]; Proposed explanation of the Warburg Effect: Role of lactate in carcinogenesis [2:23:30]; Doping in cycling, and the trend towards altitude training [2:35:45] and; More. View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Learn More About Peter Attia Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

#188 - AMA #30: How to Read and Understand Scientific Studies

In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into all things related to studying studies to help one sift through all the noise to find the signal. They define the various types of studies, how a study progresses from idea to execution, and how to identify study strengths and limitations. They explain how clinical trials work, as well as the potential for bias and common pitfalls to watch out for. They dig into key factors that contribute to the rigor (or lack thereof) of an experiment, and they discuss how to measure effect size, differentiate relative risk from absolute risk, and what it really means when a study is statistically significant. Finally, Peter lays out his personal process when reading through scientific papers. If you’re not a subscriber and 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 on our website at the AMA #30 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The ever changing landscape of scientific literature [2:15]; The process for a study to progress from idea to design to execution [4:15]; The various types of studies and how they differ [7:30]; The different phases of a clinical trial [19:15]; Observational studies and the potential for bias [26:30]; Experimental studies: Randomization, blinding, and other factors that make or break a study [44:00]; Power, p-values, and statistical significance [56:15]; Measuring effect size: Relative risk vs. absolute risk, hazard ratios, and “Number Needed to Treat” [1:07:45]; How to interpret confidence intervals [1:17:30]; Why a study might be stopped before its completion [1:23:45]; Why only a fraction of studies are ever published and how to combat publication bias [1:31:30]; Why certain journals are more respected than others [1:40:30]; Peter’s process when reading a scientific paper [1:43:45]; and More.

#187 - Sam Apple: The Warburg Effect—Otto Warburg’s cancer metabolism theory

Sam Apple is the author of the book Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection, published in May 2021. In this episode, Sam describes the fascinating life story of Otto Warburg, a Nobel Prize-winning scientist who, despite being both Jewish and gay, survived Nazi Germany because of his valuable research on cellular metabolism and cancer. Sam describes Warburg’s observation that cancer cells consume large amounts of glucose anaerobically – a phenomenon subsequently known as the “Warburg Effect” – and relates how Warburg’s seminal work on this topic was largely forgotten after the discovery of oncogenes, only to regain relevance decades later within the field of cancer biology. Sam sheds light on the current debate around Warburg’s interpretation of the causes of cancer, and Peter gives his personal take on the matter. Finally, Peter and Sam tie it all together with a discussion about cancer prevention, the role of hyperinsulinemia, and the link between dietary sugar and cancer. We discuss: Sam’s interest in Otto Warburg and work as a writer [2:30]; Otto Warburg’s dedication to science and his complicated life in Germany [14:00]; Warburg’s interest in cancer and early discoveries about cellular consumption of oxygen [23:00]; The role models who fueled Warburg’s desire to make a great discovery [34:15]; How Warburg described the primary and secondary causes of cancer [42:15]; Warburg’s Nobel Prize in 1931 [45:45]; Warburg’s life and work during WWII in Nazi Germany [46:30]; Warburg’s research in hydrogen transfers and coenzymes—his best science? [59:45]; Warburg’s decision to stay in Germany after WWII [1:03:30]; Discovery of oncogenes in the 1970s and the decline in interest in Warburg’s ideas [1:07:30]; The renaissance of Warburg’s ideas on cancer metabolism and a new explanation for the Warburg Effect [1:13:45]; The argument against the Warburg Effect as a primary cause of cancer and the potential role hyperinsulinemia [1:21:15]; Identifying primary and secondary causes of cancer for the purpose of prevention [1:27:00]; The link between sugar, fructose, and cancer [1:35:30]; Sam’s reflections on the work that went into Ravenous [1:39:45]; More View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Learn More About Peter Attia Sign Up to Receive Peter’s Weekly Newsletter Connect With Peter on Twitter, Instagram, Facebook & YouTube

#186 - Patrick Radden Keefe: The opioid crisis—origin, guilty parties, and the difficult path forward

Patrick Radden Keefe is an award-winning staff writer at The New Yorker and the bestselling author of Empire of Pain: The Secret History of the Sackler Dynasty. In this episode, Patrick tells the story of the Sackler family and Purdue Pharma - makers of the pain management drug OxyContin, providing the backdrop for the ensuing opioid epidemic and public health crisis. He reveals the implicit and sometimes explicit corruption of all parties involved in the development, approval, and marketing of OxyContin, leading to a cascade of unintended consequences including addiction and death. He explains the unfortunate lack of accountability for the current crisis, as well as what it all means for those with legitimate pain management needs. Finally, he examines the difficult path ahead towards finding a solution. We discuss: Patrick’s investigation into distribution and use of drugs in our society [3:55]; The scale of the opioid crisis [9:15]; The Sackler brothers: family life, career in the pharmaceutical industry, and role in the current crisis [11:45]; Purdue Pharma: origins, early years, and move towards pain management drugs [17:30]; The development of OxyContin: its conception, marketing, and the controversy around the FDA approval process [25:30]; Early reports of OxyContin addiction and unintended consequences and how Purdue Pharma sidestepped responsibility [40:45]; The many paths to addiction and abuse of OxyContin and the ensuing downfall of Purdue Pharma [47:15]; Peter’s personal experience with OxyContin [57:00]; Pain—the “fifth vital sign,” how doctors are trained in pain management, and the influence of money [1:08:00]; Other players that helped facilitate the eventual opioid crisis [1:16:15]; Lack of accountability following the investigation and prosecution of Purdue and the Sackler family [1:23:30]; Legacy of the Sackler family and their disconnect from reality [1:34:45]; Patrick’s views on the regulation and use of pain management drugs [1:42:15]; The difficult path forward [1:44:45]; and More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/PatrickRaddenKeefe  Subscribe to receive exclusive subscriber-only content:  https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#185 - Allan Sniderman, M.D.: Cardiovascular disease and why we should change the way we assess risk

Allan Sniderman is a highly acclaimed Professor of Cardiology and Medicine at McGill University and a foremost expert in cardiovascular disease (CVD). In this episode, Allan explains the many risk factors used to predict atherosclerosis, including triglycerides, cholesterol, and lipoproteins, and he makes the case for apoB as a superior metric that is currently being underutilized. Allan expresses his frustration with the current scientific climate and its emphasis on consensus and unanimity over encouraging multiple viewpoints, thus holding back the advancement of metrics like apoB for assessing CVD risk, treatment, and prevention strategies. Finally, Allan illuminates his research that led to his 30-year causal model of risk and explains the potentially life-saving advantages of early intervention for the prevention of future disease. We discuss: Problems with the current 10-year risk assessment of cardiovascular disease (CVD) and the implications for prevention [4:30]; A primer on cholesterol, apoB, and plasma lipoproteins [16:30]; Pathophysiology of CVD and the impact of particle cholesterol concentration vs. number of particles [23:45]; Limitations of standard blood panels [29:00]; Remnant type III hyperlipoproteinemia—high cholesterol, low Apo B, high triglyceride [32:15]; Using apoB to estimate risk of CVD [37:30]; How Mendelian randomization is bolstering the case for ApoB as the superior metric for risk prediction [40:45]; Hypertension and CVD risk [49:15]; Factors influencing the decision to begin preventative intervention for CVD [58:30]; Using the coronary artery calcium (CAC) score as a predictive tool [1:03:15]; The challenge of motivating individuals to take early interventions [1:12:30]; How medical advancement is hindered by the lack of critical thinking once a “consensus” is reached [1:15:15]; PSK9 inhibitors and familial hypercholesterolemia: two examples of complex topics with differing interpretations of the science [1:20:45]; Defining risk and uncertainty in the guidelines [1:26:00]; Making clinical decisions in the face of uncertainty [1:31:00]; How the emphasis on consensus and unanimity has become a crucial weakness for science and medicine [1:35:45]; Factors holding back the advancement of apoB for assessing CVD risk, treatment, and prevention strategies [1:41:45]; Advantages of a 30-year risk assessment and early intervention [1:50:30]; More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/AllanSniderman  Subscribe to receive exclusive subscriber-only content:  https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Rick Johnson, M.D.: Metabolic Effects of Fructose (Ep. #87 Rebroadcast)

Today’s episode of The Drive is a rebroadcast of the conversation with Rick Johnson (originally released January 6th, 2020). This episode was one of the most popular discussions to-date and is a prelude to an upcoming follow-up discussion which will be coming out in February 2022 along with the release of Rick’s new book. In this episode, Rick Johnson, professor of nephrology at the University of Colorado, explains how his research into the causes of blood pressure resulted in a change of research direction to focus more on how fructose has such profound metabolic effects. Rick begins by talking about the relationship between salt and high blood pressure, then provides a masterclass into uric acid, and then expertly reveals the mechanisms and pathways by which sugar (specifically fructose) can profoundly impact metabolic health. From there, he explains how he applies this information to real life patients as well as touches on some of the most promising ideas around pharmacotherapy that are being developed in response to the epidemics of fatty liver, insulin resistance, diabetes, and obesity. Furthermore, Rick gives his take on artificial sweeteners compared to real sugar, discusses cancer’s affinity for fructose, and much more. We discuss: The connection between blood pressure and fructose that shifted Rick’s professional focus [3:00]; The relationship between salt and blood pressure (and the role of sugar) [4:45]; Defining fructose, glucose, and sugar [18:30]; An ancient mutation in apes that explains why humans turn fructose into fat so easily [22:00]; The problems with elevated uric acid levels, and what it tells us about how sugar causes disease [30:30]; How sugar causes obesity—explaining the difference in glucose vs. fructose metabolism and the critical pathway induced by fructose [39:00]; Why drinking sugar is worse than eating it [49:00]; Unique ability of sugar to drive oxidative stress to the mitochondria, insulin resistance, and diabetes [53:00]; Why cancer loves fructose [59:20]; The many areas of the body that can use fructose [1:04:00]; Fructokinase inhibitors—a potential blockbuster? [1:06:15]; Treating high uric acid levels—Rick’s approach with patients [1:09:00]; Salt intake—what advice does Rick give his patients? [1:15:30]; How excess glucose (i.e., high carb diets) can cause problems even in the absence of fructose [1:20:00]; Artificial sweeteners vs. real sugar—which is better? [1:28:15]; Umami, MSG, alcohol, beer—do these have a role in metabolic illness? [1:32:45]; Fructose consumption—Is any amount acceptable? Is fruit okay? Where does Rick draw a hard line? [1:37:45] How does Rick manage the sugar intake of his young kids? [1:42:00]; and More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/rickjohnson/  Subscribe to receive exclusive subscriber-only content:  https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

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