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#315 ‒ Life after near-death: a new perspective on living, dying, and the afterlife | Sebastian Junger
Sebastian Junger is an award-winning journalist, bestselling author, and previous guest on The Drive. In this episode, Sebastian returns to discuss his latest book, In My Time of Dying: How I Came Face to Face with the Idea of an Afterlife. This episode delves into Sebastian's profound near-death experience and how it became the catalyst for his exploration of mortality, the afterlife, and the mysteries of the universe. They discuss the secular meaning of what it means to be sacred, the intersection of physics and philosophy, and how our beliefs shape our approach to life and death. He also shares how this experience has profoundly changed him, giving him a renewed perspective on life—one filled with awe, gratitude, deeper emotional awareness, and a more engaged approach to living.
We discuss:
How Sebastian’s near-death experience shaped his thinking about mortality and gave him a reverence for life [3:00];
The aneurysm that led to Sebastian’s near-death experience [6:30];
Emergency room response, his subsequent reflections on the event, and the critical decisions made by the medical team [16:30];
Sebastian’s reaction to first learning he nearly died, and the extraordinary skill of the medical team that save his life [26:00];
Sebastian’s near-death experience [37:00];
The psychological impact of surviving against overwhelming odds [48:00];
Ignored warning signs: abdominal pain and a foreshadowing dream before the aneurysm rupture [54:30];
Sebastian's recovery, his exploration of near-death experiences, and the psychological turmoil he faced as he questioned the reality of his survival [58:15];
A transformative encounter with a nurse who encouraged Sebastian to view his near-death experience as sacred [1:03:30];
How Sebastian has changed: a journey toward emotional awareness and fully engaging with life [1:08:45];
The possibility of an afterlife, and how quantum mechanics challenges our understanding of existence [1:15:15];
Quantum paradoxes leading to philosophical questions about the nature of reality, existence after death, and whether complete knowledge could be destructive [1:26:00];
The sweet spot of uncertainty: exploring belief in God, post-death existence, and meaning in life [1:37:00];
The transformative power of experiencing life with awe and gratitude [1:53:00]; and
#314 ‒ Rethinking nutrition science: the evolving landscape of obesity treatment, GLP-1 agonists, protein, and the need for higher research standards | David Allison, Ph.D.
David Allison, a leading expert in obesity and nutrition, quantitative genetics, clinical trials, and research methodology, returns to The Drive to explore the evolving landscape of nutrition science and obesity treatment. In this episode, David begins by discussing the intricate relationship between nutrition, obesity, and body composition, emphasizing the multifaceted impacts of food beyond mere calorie intake. David provides a critical analysis of the complexities in nutrition research and their practical implications for tackling obesity. He critiques historical public health policies, addresses the trust issues plaguing nutrition science, and underscores the need for a paradigm shift to more effectively combat obesity. The conversation also delves into the rise of GLP-1 receptor agonists like Ozempic and Mounjaro, exploring their ethical and practical considerations in obesity treatment. The episode concludes with an in-depth look at protein intake recommendations and highlights the significant research gaps that remain in the field.
We discuss:
The complex relationship between nutrition, body weight, and body composition [2:30];
The slow progress in addressing obesity and public health despite substantial effort and investment [7:30];
The very limited success of public health initiatives in curbing obesity [17:15];
The evolving landscape of obesity research: public health initiatives and the impact of pharmacological success [26:30];
Rethinking obesity solutions: the need for a paradigm shift [32:45];
Understanding environmental triggers and embracing a balanced approach to addressing obesity that includes both pharmacological treatments and realistic lifestyle changes [41:45];
The need for higher standards in obesity research [51:45];
The rapid success of GLP-1 receptor agonists for weight loss: a discussion on the societal impact and controversy of their growing usage [1:02:15];
The ethical and practical considerations of obesity drugs: risks, benefits, and motivations for usage [1:11:30];
The use of GLP-1 agonists by athletes as performance enhancers [1:23:45];
Unanswered questions about protein intake and health [1:30:45];
Future research needed to understand basic questions around protein intake [1:45:00];
David’s weekly newsletter: “Obesity and Energetics Offerings” [1:50:45]; and
In this “Ask Me Anything” (AMA) episode, Peter provides insights on a broad range of important topics. He delves into the prevention of cognitive decline, the link between cardiovascular disease and Alzheimer's disease, and methods to lower blood glucose, insulin, and apoB. He also addresses nutrition-related queries, exploring the impact of dietary habits on weight loss and longevity, how a person can identify the best diet for themselves, and common nutrition myths. Additional discussions include optimal blood pressure, daily step goals, the benefits of standing versus sitting desks, and much more.
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 #60 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Overview of topics and episode format [1:40];
Preventing cognitive decline [5:00];
How to lower blood glucose and insulin [13:30];
The relationship between lipids, CVD, and Alzheimer’s disease, and whether statins can increase the risk of neurodegenerative disorders and AD [23:15];
Reducing apoB levels through exercise and diet [31:45];
Pharmacological options for lowering apoB [38:00];
How nutrition impacts longevity via metabolic health, muscle mass, BMD and more [40:15];
How can someone determine the best diet for themselves? [43:45];
Nutrition myth: All weight loss is good [46:45];
Nutrition myth: Metabolic rates are dramatically different among individuals based on genetics [49:00];
Nutrition myth: Losing weight after a brief period of overeating is impossible [53:45];
Nutrition myth: GLP-1 agonists are a replacement for a healthy lifestyle [57:45];
Nutrition myth: There is a single best diet for weight loss [1:03:00];
Nutrition oversimplification: All calories are created equal [1:05:45];
Daily step goals [1:06:45];
The benefits of standing versus sitting throughout the day [1:10:45];
How to identify the most impactful and easiest-to-implement ways to improve your health [1:12:30];
The critical importance of emotional health [1:14:30];
Why supplements should be considered as supportive aids rather than primary solutions in one’s strategy to improve longevity [1:18:00];
Strategies for reducing high blood pressure [1:20:45];
Peter’s biggest frustrations with "mainstream health advice" [1:28:00];
Peter’s chaotic, yet cherished, morning routine [1:31:00]; and
In this “Ask Me Anything” (AMA) episode, Peter describes what it means to exercise with the goal of longevity in mind, including his personal goals, exercise framework, and how he is optimizing for what he refers to as the “Centenarian Decathlon.” He explains the various types of cardiovascular training and how to partition your time between intensity levels (i.e., zone 2 training vs. zone 5 training) to optimize cardiorespiratory benefit. Additionally, Peter dives deep into questions around VO2 max, such as why it’s critical for longevity, how to improve it, and the value in starting VO2 max optimization early in life.
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 on our website at the AMA #39 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Exercise topics to be discussed [1:45];
Peter’s exercise goals, and the Centenarian Decathlon [4:00];
Peter’s exercise framework, and how he tracks his MET hours [8:30];
How to partition your time between low and high intensity exercise to optimize results [13:15];
Zone 2 exercise: ideal training methods and how to determine your zone 2 level [23:15];
Rucking as a versatile mode of exercise [31:45];
Zone 5 exercise: modalities of training, time per week, and other considerations [34:30];
The importance of knowing your VO2 max, and methods for estimating it [38:15];
Training methods for improving VO2 max, and realistic targets for improvement [46:00];
Relationship of VO2max with age and the required fitness levels for daily life activities and exercise [52:30];
The training necessary to maintain an elite VO2 max throughout life [58:45];
The value in starting early: the compounding nature of fitness [1:01:45]; and
Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan.
We discuss:
Challenges with understanding the effects of nutrition and studying interventions for aging [3:30];
How Peter’s and Matt’s convictions on nutrition and thoughts optimal health have evolved [8:15];
Calorie restriction for improving lifespan in animal models [16:15];
Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00];
Mutations and changes to the epigenome with aging [31:45];
Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15];
First potential applications of anti-aging therapies and tips for aging well [43:00];
Impact of calorie restriction on the immune system, muscle mass, and strength [47:00];
Insights from famous calorie restriction studies in rhesus macaques [55:00];
An evolutionary perspective of the human diet [1:03:45];
Antiaging diets: Separating fact from fiction—Matt’s 2021 review in Science [1:12:30];
Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30];
Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00];
Differing impact of calorie restriction when started later in life [1:31:00];
Lifespan extension with rapamycin in older mice [1:37:15];
Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30];
Impact of protein intake on mTOR, and why inhibition of mTOR doesn’t cause muscle loss [1:50:45];
Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30];
The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30];
Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45];
In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts with sleep expert Dr. Matthew Walker to help listeners understand this topic more deeply, as well as to identify which previous episodes featuring Matt may be of interest. In this episode, Matt gives an overview of why we sleep, the stages of sleep, and sleep chronotypes, and he provides tips to those looking to improve their total sleep and sleep efficiency. Additionally, Matt discusses the pros and cons of napping, and gives his current thinking on the effects of blue light and caffeine on sleep. Finally, Matt explains the dangers of sleeping pills and reveals what he believes are the most useful alternatives for someone struggling with sleep, such as those with insomnia.
We discuss:
Evolutionary reasons to sleep [2:15];
Stages of sleep, sleep cycles, and brainwaves [10:00];
Understanding sleep chronotypes and how knowing yours could help you [25:45];
Defining sleep efficiency and how to improve it [36:15];
Correcting insomnia: a counterintuitive approach [38:45];
Pros and cons of napping, and insights from the sleep habits of hunter-gatherer tribes [41:30];
Sleep hygiene, wind-down routine, and tips for better sleep [50:15];
The optimal room temperature and body temperature for the best sleep [59:30];
Blue light: how Matt shifted his thinking [1:08:30];
Caffeine: how Matt has adjusted his hypothesis [1:14:45];
The dangers of sleeping pills, useful alternatives, and cognitive behavioral therapy for insomnia [1:19:45];
Celia Morgan is a Professor of Psychopharmacology at the University of Exeter who has authored numerous publications on the potential therapeutic uses of ketamine in mental healthcare. In this episode, Celia dives deep into the neurobiology of ketamine, how it affects users, and how it differs from other, more classical psychedelics (LSD, MDMA, PCP, and psilocybin). She explains the potential promise of ketamine as a treatment for recalcitrant depression and addiction, and she details the results from her clinical trials in these areas. She discusses the importance of using ketamine in combination with psychotherapy to maximize its benefits, the potential risks associated with ketamine use, and advice for those interested in the therapeutic use of ketamine.
We discuss:
Celia’s training and interest in ketamine [2:15];
The history of ketamine, medical uses, and use as a party drug [3:30];
Neurobiology and pharmacology of ketamine [8:15];
Ketamine regulation and abuse, and how it compares with psychedelics and other molecules [18:15];
Ketamine as a therapeutic for depression [30:45];
The brain under the influence of ketamine and theoretical mechanisms for its anti-depressive effects [48:00];
Risks and concerns with overusing ketamine, and what an intermittent or maintenance dose might look for a patient [57:15];
Treating addiction with ketamine: Celia’s studies of alcohol dependance [1:04:00];
Advice for people considering the therapeutic use of ketamine [1:19:45];
Shireen Rizvi is a Professor of Clinical Psychology and Psychiatry at Rutgers University, where she is also the Director of the Dialectical Behavior Therapy Clinic. This episode focuses specifically on dialectical behavior therapy (DBT), a skills-based technique which was originally developed to treat borderline personality disorder (BPD) and has since been adapted to treat depression and other mental health conditions, as well as to help people who have difficulty with emotional regulation and self-destructive behaviors. Shireen explains the origins of DBT and how its creator, Dr. Marsha Linehan, came to find a need for something beyond cognitive behavioral therapy (CBT) when attempting to treat patients with suicidal behavior. From there, Shireen dives into how DBT works to resolve the apparent contradiction between self-acceptance and change to bring about positive changes in emotional regulation, interpersonal effectiveness, mindfulness, distress tolerance, and more. She also provides examples for how one can apply specific skills taught with DBT such as accessing the “wise mind,” applying radical acceptance, using the “DEAR MAN” technique, and utilizing an emotion regulation skill called “opposite action.” Finally, she explains how the tenets of DBT offer benefits to anyone, and she provides insights and resources for people wanting to further explore DBT.
We discuss:
The basics of dialectical behavior therapy (DBT) and how it differs from cognitive behavioral therapy (CBT) [3:00];
Treating depression with CBT: history, effectiveness, and how it laid the groundwork for DBT [8:15];
Marsha Linehan’s inspiration for developing DBT [16:00];
Explaining borderline personality disorder (and associated conditions) through the lens of DBT [20:00];
How work with suicidal patients led to the development of DBT—a dialectic between change and acceptance [35:30];
Details of DBT: defining the term “dialectical” and how to access the “wise mind” [44:30];
Practicing mindfulness and radical acceptance in the context of DBT [51:00];
Applying “radical acceptance” to tragic scenarios [1:02:00];
The five domains of skills taught in DBT [1:07:15];
Why Marsha chose borderline personality disorder as her focus when developing DBT [1:13:30];
Is there any benefit in doing DBT for someone without a pathological condition? [1:15:45];
The DEAR MAN skill of DBT [1:20:00];
Adapting DBT skills for adolescents and families [1:31:00];
Identifying vulnerability factors, increasing distress tolerance, and the impact of physical pain [1:33:45];
The DBT chain analysis: assessing problem behaviors and identifying vulnerability factors [1:44:30];
Why the regulation of emotions can be so challenging [1:50:30];
The importance of mindfulness skills in DBT [1:53:30];
Opposite action: an emotion regulation skill [1:57:00];
Advice for those wanting to explore DBT [2:03:15];
In this “Ask Me Anything” (AMA) episode, Peter dives deep into the question of whether there is such a thing as “too much exercise.” He explores the theoretical “J-curve” relationship between exercise and longevity, whereby mortality risk declines with increasing activity levels only to see an uptick above a certain exercise volume threshold. While Peter maintains that exercise is perhaps the single most important tool we have to live longer and live better, he explains the challenges involved in identifying an optimal dose. He takes a hard look at studies—many of which have contradictory results—to highlight major limitations in methodology and how readers could be misled. Additionally, he discusses the rare, but real, risks associated with extreme levels of physical activity and concludes by weighing the benefits against the risks of exercise.
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 #38 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
How exercise reduces risk for all-cause mortality [2:40];
Defining the metric called “MET” and how it’s useful for evaluating different exercises [8:00];
The challenge in determining the optimal exercise doses and the limitations of methods used to study the effect of exercise [13:45];
Using VO2 max as a proxy for fitness to better predict mortality risk [19:30];
Reviewing data which support the theory of a “J-curve” relationship between exercise and longevity [25:00];
Importance of understanding p-values and statistical significance [33:45];
Deconstructing the studies that show a J-curve: major limitations and how one could be misled [37:00];
Peter’s takeaways on the theoretical “J-curve” relationship between exercise and longevity [51:30];
Risk of sudden cardiac death from vigorous physical exertion [54:00];
Atrial fibrillation associated with extreme levels of exercise [1:00:15];
Parting thoughts: benefits of exercise far outweigh the risks [1:04:15]; and
Mike Joyner is a physician-researcher and one of the world’s leading experts on human performance and exercise physiology. In this episode, Mike discusses how to combat age-related declines in health and fitness levels by using various modes of exercise to improve lifespan and healthspan. Mike explains the impact of exercise on the autonomic nervous system, blood pressure, heart rate, heart rate variability, heart rate recovery, and max heart rate. He dives deep into VO2 max, including how it’s measured, what is driving it, and how to improve it. Mike provides training insights for the average person, including training volume and exercise intensity as well as simple metrics to track. Furthermore, he gives his take on the theoretical “J-curve” relationship between exercise and longevity, as well as whether possible health dangers may be associated with excessive exercise.
We discuss:
Mike’s training as an anesthesiologist and interest in exercise physiology [2:30];
How exercise increases longevity [7:00];
The impressive data on the benefits of exercise [9:45];
The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability [15:00];
The violent dropoff in strength and activity with age and how exercise preserves fitness in old age [19:00];
Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise [22:00];
How exercise benefits the autonomic nervous system and why this plays an important role in our health [26:30];
VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise [28:30];
Reduction in all-cause mortality with increased fitness levels and VO2 max [32:45];
Does the relationship between exercise and longevity follow a J-curve? [40:00];
Mitigating age-related decline in fitness by elevating your VO2 max at a young age [46:15];
Breaking down the variables that drive VO2 max [54:30];
Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics [1:00:15];
Health benefits of light exercise for the average person [1:09:00];
Simple training metrics to track, and Mike’s current exercise regimen [1:11:15];
How to boost your VO2 max, and the importance of form and tempo with interval training [1:18:15];
Training advice for the average person [1:25:15];
Why professional athletes have longer careers than they’ve had in the past [1:27:30];
Use of performance-enhancing drugs in professional sports [1:29:45];
Can the miracle of exercise be put in a pill? [1:36:00];
Mike’s current research and questions he’s most interested in answering [1:39:00];
Use of convalescent plasma to treat COVID-19 [1:41:15];
Parting thoughts on the current state of fitness and exercise in society [1:47:15];
Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment.
We discuss:
Josh’s background and unique path to becoming a research scientist at Princeton [3:30];
What sparked Josh’s early interest in metabolism [11:15];
Metabolomics 101: defining metabolites and how they are regulated [16:30];
Fluxomics: metabolism as a system in action [26:00];
The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30];
The important role of lactate as an alternate fuel [36:30];
Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00];
The beauty of the Krebs cycle and the role of NAD in energy production [53:15];
How the drug metformin acts on complex I of the electron transport chain [1:05:00];
The difference between NADH and NADPH [1:08:45];
NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45];
The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15];
Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30];
Cancer metabolism and the intersection with immunotherapy [1:39:00];
Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15];
The challenge of treating pancreatic cancer [1:50:30];
Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30];
Josh’s hopeful outlook on the future of cancer treatment [1:59:00];
Nutritional approaches to cancer attenuation [2:00:15];
What makes Princeton University special [2:06:15];
Mike Gershon is a Professor of Pathology and Cell Biology at Columbia University and has been at the forefront of studying neural control of the gut for the past 60 years. In this episode, Mike gives a tour de force on the pathways of gut-brain communication but first sets the stage with an overview of gastrointestinal tract development and anatomy. He then explains how the gut communicates with the brain and vice versa, from early observations in physiology and anatomy up to our present understanding of what makes the GI tract so unique and complex relative to other organs. He talks about how the gut responds to meals of different food qualities and how that affects satiety signaling to the brain. Additionally, he explains how antidepressants and other drugs impact digestion through effects on serotonin signaling, and he discusses the effects of antibiotics, and what’s really going on with “leaky gut.” Finally, Mike offers his thoughts on the utility—or lack thereof—of gut microbiome diagnostic tests, and wraps up the discussion by considering how diet, probiotics, and prebiotics impact the microbiome and GI tract.
We discuss:
The basics of the gastrointestinal (GI) system [3:45];
The very early development of the GI system [9:30];
The unique properties of the blood supply and portal system in the GI tract [12:45];
An overview of gut anatomy and innervation [16:30];
Turnover of the epithelial lining and why cancer rarely develops in the small intestine [26:45];
Nutrient and water absorption in the small and large intestine [30:30];
Ways in which the gut and brain communicate [34:30];
The gut's role in the regulation of appetite [43:30];
The impact of gastric bypass surgery on satiety signals [51:15];
How varicella-zoster virus (VZV) can infect neurons in the gut and create issues later in life [54:30];
The relationship between autism and gastrointestinal illness [1:02:45];
The important role of serotonin in the gut, and the impact of SSRIs on serotonin in the gut [1:09:45];
Defining “leaky gut” and its most common causes [1:16:45];
The gut microbiome [1:30:45];
Fecal transplants: use cases, limitations, and how they illustrate the importance of gut microbes [1:40:45];
Gut microbiome diagnostic tests: why they aren’t useful outside of special cases such as cancer detection [1:50:30];
Nutritional approaches to a maintain optimal flora in the gut [1:55:00];
Prebiotics and probiotics, and getting your GI system back on track after a course of antibiotics [2:02:30];
In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of bone health and explains why this is an important topic for everyone, from children to the elderly. He begins with an overview of bone mineral density, how it's measured, how it changes over the course of life, and the variability between sexes largely due to changes in estrogen levels. From there he provides insights into ways that one can improve bone health, from exercise to nutrition supplements to drugs. Additionally, Peter discusses what happens when one may be forced to be sedentary (e.g., bedrest) and how you can work to minimize the damage during these periods.
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 #37 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Overview of bone health topics to be discussed [1:45];
Bones 101: bone function, structure, and more [5:15];
Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [8:30];
The consequences of poor bone health [13:30];
The devastating nature of hip fractures: morbidity and mortality data [17:00];
Where fractures tend to occur in the body [23:00];
Defining osteopenia and osteoporosis [24:30];
Measuring BMD with DEXA and how to interpret scores [27:00];
Variability in BMD between sexes [34:15];
When should people have their first bone mineral density scan? [36:45];
How BMD changes throughout the life and how it differs between men and women [39:00];
How changes in estrogen levels (e.g., menopause) impact bone health [44:00];
Why HRT is not considered a standard of care for postmenopausal bone loss [47:30];
Factors determining who may be at higher risk of poor bone health [50:30];
Common drugs that can negatively impact BMD [54:15];
How children can optimize bone health and lay the foundation for the future [57:45];
Types of physical activity that can positively impact bone health [1:02:30];
How weight loss can negatively impact bone health and how exercise can counteract those effects [1:10:45];
Nutrition and supplements for bone health [1:14:15];
Pharmaceutical drugs prescribed for those with low BMD [1:17:15];
Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:22:00]; and
Joel Jamieson is a conditioning expert who developed Morpheus to give people a smarter way to build their conditioning regimen and improve their recovery. In this episode, Joel dives deep into the world of heart rate variability (HRV), explaining its scientific foundation, how it measures the balance between the sympathetic and parasympathetic nervous systems, the various methods of measurement, and how it can guide healthier lifestyle choices and improved training performance. He explores the nuances of HRV calculation, the impact of aging on HRV, and the roles of genetics, exercise, and other lifestyle factors in this process. He also covers Morpheus, the innovative training tool that won Peter over after his initial skepticism, highlighting its practicality and effectiveness in guiding training and optimizing fitness outcomes.
We discuss:
Heart rate variability (HRV): evolution, science, and practical applications of HRV in athletic training [4:00];
Methods of measuring HRV: EKG, wrist-based sensors, and more [11:30];
How HRV is calculated from the data [22:30];
The role of the autonomic nervous system (ANS) in regulating HRV [25:45];
The decline in HRV with age, and the mitigating effects of fitness and other lifestyle factors [33:30];
The role of genetics in HRV, the modifiability of HRV, and a comparison of VO2 max and HRV as predictors of mortality [37:00];
How aging affects HRV and sympathetic drive, and the importance of spontaneous movement and exercise in maintaining the body's adaptability [43:30];
How Morpheus measures HRV using RMSSD and normalizes it to a 100-point scale for easier interpretation [49:45];
The Morpheus system: development, integration with various metrics, and personalized daily training recommendations to optimize fitness and recovery [51:30];
The benefits of morning HRV readings for assessing daily readiness compared to overnight HRV measurements [1:03:00];
Why Morpheus recommends using a chest strap rather than an arm band [1:10:00];
The impact of consistent exercise, stress, alcohol, and other lifestyle factors on HRV [1:11:15];
Optimizing zone 2 training with Morpheus [1:18:15];
Using heart rate recovery (HRR) as an indicator of athletic conditioning and the balance between aerobic and anaerobic systems [1:22:45];
The importance of tracking HRV trends over time rather than focusing on data from a given day [1:29:00];
Effect of GLP-1 agonists on heart rate and HRV [1:34:45];
Where HRV belongs in the hierarchy of health metrics [1:42:00];
Max Diehn is a Professor of Radiation Oncology at Stanford and a clinical radiation oncologist specializing in lung cancer. Max’s research focuses on developing novel methods for detecting circulating tumor DNA in the blood of cancer patients and on elucidating the molecular pathways and genes associated with cancer. His interests also include uncovering biomarkers that can predict patient survival, responses to therapy, and disease recurrence. In this packed episode, Max discusses the history of blood-based cancer screening and the importance of understanding the predictive value of tests—sensitivity, specificity, negative predictive value, positive predictive value – and how these metrics play into cancer screening. Max then goes in depth on the topic of liquid biopsies, including the history, current landscape, and possible future of liquid biopsies as a cancer detection tool. He discusses how these non-invasive blood tests can detect DNA/RNA from tumor cells released into the blood as well as the different methods one can use to predict if a cancer is present. He gets granular on the topic of cell-free DNA/RNA signature, methylation patterns, and the importance of knowing mutation information, and he ends with a discussion on the exciting future of liquid biopsies and how we can possibly get to the panacea of cancer screening.
We discuss:
Max’s training that planted the seeds for development of liquid biopsies [4:30];
Max’s decision to specialize in radiation oncology [11:45];
A culture at Stanford that values research and physician scientists [17:00];
The motivation to develop liquid biopsies [19:15];
History of blood-based cancer screening and understanding the predictive value of tests [25:30];
Current state of lung cancer and the need for better screening [32:45];
Low-dose CT scans: an important tool for managing lung cancer but with limitations [42:00];
Using liquid biopsies to identify circulating tumor cells [47:00];
Liquid biopsy research moves from circulating tumor cells to cell-free DNA [1:03:00];
Zeroing-in on circulating tumor DNA in cell-free DNA [1:10:48];
Cell-free RNA and Max’s vision for cancer detection from a blood sample [1:22:00];
Methylation patterns and other informative signatures found in DNA [1:24:30];
Mutation-based methods of liquid biopsies [1:26:30];
Understanding the sensitivity and specificity of a diagnostic test [1:30:30];
Existing clinical liquid biopsy tests and their limitations [1:37:30];
The future of liquid biopsies [1:44:00];
How we get to the panacea of cancer screening [1:52:00];
In this episode, Ric Elias, founder of Red Ventures, opens up about the fateful day he knew for certain that he was going to die as a passenger on US Airways Flight 1549. Ric dives deep into how that day impacted his life, greatly changed his perspective, and improved his relationship with his family and the broader community. We also talk about his incredible role as CEO of an enormous company, his remarkable work in philanthropy, and all the wisdom he has acquired in his extraordinary life.
We discuss:
Ric’s life leading up to the day of the plane crash [2:15];
The plane crash—What it’s like knowing you’re about to die, feelings of regret and sadness [8:00];
The improbable plane landing in the Hudson River [15:45];
Emotions after the safe landing (and a story he’s never told before) [22:15];
A powerful story about Captain Sully [26:15];
Earning his second chance at life, and playing the “infinite game” [35:15];
Why time is the ultimate currency, and how (and why) to say “no” [43:00];
Raising kids in an achievement culture, Ric’s definition of life success, and what Ric wants to instill in his kids [49:45];
What Ric believes is actually worth getting upset about, and the organizations that are taking steps to help people [1:05:45];
The core principles of Red Ventures (Ric’s company) [1:16:00];
Ric’s tips for developing business acumen and negotiation skills [1:26:15];
What qualities does Ric look for in people he wants to work with? [1:29:15];
What is the next big problem that Ric wants to solve? [1:32:15];
What is the most challenging part of your business today? [1:34:15];
If Ric could go back and talk to himself in the morning before getting on that plane, what would he say? [1:36:00]; and
Stephan Guyenet is a neuroscientist focused on the neuroscience of obesity and energy homeostasis. He is the author of the book, The Hungry Brain and founder/director of Red Pen Reviews. In this episode, Stephan explains how obesity has changed phenotypically over the course of human history as well as what might explain the dramatic increase in prevalence of obesity in the last few decades. He talks in depth about the role of genetics, the brain, and hormones like leptin play in the regulation of fat mass. He dives deep into two common theories of obesity—the carbohydrate-insulin model and the energy balance model and provides his take on which theory has stronger evidence. Additionally, he provides insights on how we’re hard-wired to think about food and the consequences of modern foods designed for maximal pleasure. Finally, he goes through the factors that affect body weight, set points, and provides takeaways for people wanting to take advantage of what we know about the brain’s role in regulating our body weight.
We discuss:
Stephan’s neuroscience background and his focus on the nuances of obesity [2:15];
How obesity has changed for humans throughout history [8:00];
The association between obesity and adverse health outcomes, the “obesity paradox,” and confounders when relating BMI to longevity [14:00];
The sharp increase in obesity across demographics [23:30];
The hypothalamus and its role in obesity [30:00];
The role of the hormone leptin in obesity [40:00];
The genetic component of obesity [46:30];
Understanding the tendency of humans to store fat through an evolutionary lens [57:00];
The hedonic aspect of food, and how the brain reacts to modern, highly-rewarding foods [1:03:30];
How we are hard-wired to think about food [1:14:30];
A review of the “Carnivore diet” [1:21:45];
The energy balance model, carbohydrate-insulin model, and unifying the theories around adiposity [1:34:15];
Body weight set points: a hypothetical comparison of two individuals [1:41:45];
Takeaways for people who want to lose weight and keep it off [1:48:30];
Evidence that favors the energy balance model of weight gain [1:56:00];
The synergistic effect of fat and carbohydrates and observations that a low-fat diet or a low-carb diet can cause weight loss [2:04:30];
In this “Ask Me Anything” (AMA) episode, Peter discusses the nutritional profiles of various fruits and vegetables as a means of assessing their relative value. He explains the difference between eating them vs. drinking them, how processing fruits and vegetables can change their properties, and how one’s current state of health affects nutrition strategy when it comes to fruits and vegetable consumption. Additionally, Peter explains the potential benefits and negative effects of certain phytochemicals found in produce and concludes with a discussion of supplementing with green powders, multivitamins, and more.
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 #36 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
The limitations of nutritional data and challenges of making broad recommendations [2:00];
How one’s current state of health impacts their “optimal” diet [11:30];
Defining “metabolic health” [14:45];
The wide-ranging nutrition profiles of various fruits and vegetables [16:30];
The benefits of fiber [20:45];
Eating whole fruits vs. drinking fruit juice or smoothies [22:30];
Drinking alcohol: metabolic effects, calories in alcohol, and more [28:30];
Can excess fruit consumption lead to insulin resistance? [30:30];
Glycemic impact of different fruits, using CGM data to assist decision making, and how fruit is fundamentally different from what we evolved to eat [31:30];
Dietary approaches for people with a carbohydrate tolerance disorder (TD2, NAFLD, etc.), and when it makes sense to restrict fruit consumption [34:30];
Nutrition profile of select vegetables: sugar content, micronutrients, and more [40:00];
Phytochemicals in produce: potential positive health impacts on inflammation, cardiovascular (CV) risk, and cancer [44:30];
Phytochemicals with potential negative health impacts [50:45];
Nightshades and inflammation [53:15];
How important is it to eat organic foods? [56:00];
How necessary is it to wash fruits and vegetables? [1:00:45];
How does food preparation change the nutritional composition? [1:03:45];
Considerations when eating canned and frozen food, and paying attention to processed food additives [1:04:45];
Supplementing vitamins and nutrients as an alternative to eating whole fruits and vegetables [1:06:15];
Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it’s inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides.
We discuss:
How Benoît came to study Lp(a)—a new marker for cardiovascular risk [3:15];
The relationship between Lp(a) and CVD risk [6:45];
What genome-wide association studies (GWAS) revealed about Lp(a) [16:00];
Clinical tests to measure Lp(a) [22:00];
The biology of Lp(a) [25:45];
How statins lower LDL-cholesterol and why this doesn't work for an Lp(a) [29:15];
The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle [34:00];
The role of Lp(a) in aortic valve disease [42:45];
How greater numbers of Lp(a) particles are associated with increased risk of disease [48:00];
The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels [52:00];
Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk [1:00:45];
Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD [1:14:00];
The variability of disease in patients with high Lp(a) [1:19:00];
Diseases most associated with high Lp(a) [1:26:30];
The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9 [1:35:00];
The variability in PCSK9 inhibitors’ ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a) [1:50:30];
Peter’s approach to managing patients with high Lp(a), and Benoît’s personal approach to managing his risk [1:54:45];
Antisense oligonucleotides—a potential new therapeutic for Lp(a) [1:57:15]; and
Marty Makary is a surgeon, public policy researcher, and author of the New York times best-sellers Unaccountable and The Price We Pay. In this episode, Marty dives deep into the topic of patient safety. He describes the risk of medical errors that patients face when they walk into the hospital and how those errors take place, and he highlights what amounts to an epidemic of medical mistakes. He explains how the culture of patient safety has advanced in recent decades, the specific improvements driven by a patient safety movement, and what’s holding back further progress. The second half of this episode discusses the high-profile case of RaDonda Vaught, a nurse at Vanderbilt Hospital convicted of negligent homicide after she mistakenly gave a patient the wrong medication in 2017. He discusses the fallout from this case and how it has in some ways unraveled decades of progress in patient safety. Furthermore, Marty provides insights in how to advocate for a loved one in the hospital, details the changes needed to meaningfully reduce the death rate from medical errors, and provides a hopeful vision for future improvements to patient safety.
We discuss:
Brief history of patient safety, preventable medical mistakes, and catalysts for major changes to patient safety protocols [0:12];
Advancements in patient safety and the dramatic reduction in central line infections [14:55];
A surgical safety checklist—a major milestone in patient safety [23:03];
A tragic case stimulates a culture of speaking up about concerns among surgical teams [25:19];
Studies showing the ubiquitous nature of medical mistakes leading to patient death [29:42];
The medical mistake of over-prescribing of opioids [33:48];
Other types of errors—electronic medical records, nosocomial infections, and more [35:43];
Importance of honesty from physicians and what really drives malpractice claims [40:26];
A high-profile medical mistake case involving nurse RaDonda Vaught [47:31];
Investigations leading to the arrest of RaDonda Vaught [59:48];
Vaught’s trial—a charge of “negligent homicide” [1:05:16];
A guilty charge and an outpouring of support for Vaught [1:12:09];
Concerns from the nursing profession over the RaDonda Vaught conviction [1:18:09];
How to advocate for a friend or family member in the hospital [1:20:22];
Changes needed for meaningful reduction in the death rate from medical errors [1:26:42];
Blind spots in our current national funding mechanism and the need for more research into patient safety [1:31:42];
Parting thoughts—where do we go from here? [1:35:48];
Kelsey Chittick is the author of Second Half: Surviving Loss and Finding Magic in the Missing. In this episode, Kelsey describes her long healing process following the sudden death of her husband, former NFL player Nate Hobgood-Chittick. She describes her life with Nate before and after football, including her premonitions that something was off about Nate and the subsequent finding that he suffered from chronic traumatic encephalopathy (CTE). She speaks openly about how she handled his death with her children, the trauma and grief they faced in the aftermath, and how she’s found ways to be happy in her new life. She shares deep insights into her healing process, including her experience with psychedelics and how the concept of “radical acceptance” has helped her to find joy once again.
We discuss:
Kelsey’s childhood in Florida as an athlete [2:15];
Meeting Nate and early relationship with him [7:45];
Nate’s unbelievable work ethic and desire to play in the NFL [12:30];
Life with a professional football player, playing through pain, and head injuries related to football [17:00];
Nate’s final days of football and early retirement struggles [23:30];
The tough transition from the NFL to a “regular life” and how Nate found a way to serve others [28:45];
Nate’s struggle with his weight and overall health after retirement [34:45];
Kelsey’s anxiety and premonitions of Nate’s impending death, and Nate’s changing demeanor [37:30];
The traumatic experience of learning of Nate’s death during her own spiritual journey to Jamaica [45:30];
Breaking the news to her children of their father’s death [51:00];
The darkest days following Nate’s passing and how her children were handling grief [55:30];
A new relationship with death, finding happiness, and the duality of feelings [1:02:45];
Nate’s autopsy results showing evidence of CTE [1:07:00];
The grieving process [1:15:00];
Dealing with grief with kids and how children grieve differently [1:19:15];
Healing through her first psychedelic experience [1:23:00];
The therapeutic potential of psychedelics, meditation, and more [1:33:45];
The concept of “radical acceptance” and the peace that comes with it [1:42:30];
The up and down experience of writing her book [1:47:45];
In this “Ask Me Anything” (AMA) episode, Peter is joined by special guest, Dr. Matt Kaeberlein. Together they answer many questions around the field of aging with an emphasis on three specific molecules—NAD, metformin, and rapamycin—and their purported geroprotective qualities. They first discuss aging biomarkers and epigenetic clocks before breaking down the advantages and limitations of the most common experimental models being used today to study aging and pharmacological possibilities for extending lifespan. Next they dive deep into NAD and the much-hyped NAD precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). They compare data from NAD precursors to studies on metformin and rapamycin, assessing how they stack up against each other and using the comparison as an opportunity to illustrate how to make sense of new experimental data and make smart decisions about how to approach future research.
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 #35 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Logic behind comparing NAD precursors to rapamycin and metformin [3:40];
Aging biomarkers: current state, usefulness, and future promise [7:00];
Epigenetic clocks: definition, use case, and limitations [14:45];
Advantages and limitations of studying aging in non-humans and the strengths and weaknesses of different model systems [26:30];
Aging studies: importance of control lifespans and the problems with reproducibility [34:15];
Intro to NAD, potential role in aging, relationship to sirtuins, and more [48:15];
NAD precursors (NR and NMN): current data [1:10:00];
Human studies with NAD precursors [1:25:45];
Comparing NAD lifespan data to data from metformin and rapamycin [1:28:30];
Defining a “clean drug” and a “dirty drug” [1:38:00];
Reason for the lack of rapamycin studies in humans compared to NAD and metformin [1:41:00];
Ranking the geroprotective molecules in terms of risk and reward [1:48:00]; and
In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts about exercise to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter discusses his framework for exercise, what he’s really optimizing for, and how to train today to be prepared for a good life at age 100. He describes the importance of strength and stability, and why deadlifting is an important tool to consider for longevity. Additionally, he details why training in zone 2 and zone 5 is important, gives a primer on VO2 max, and describes the most effective ways to engage in those types of exercise. Finally, Peter reveals his current exercise routine.
We discuss:
What is Peter optimizing for with his exercise? [3:00];
Preparing for a good life at age 100: Training for the “Centenarian Olympics” [6:00];
The importance of preserving strength and muscle mass as we age [21:45];
The value of deadlifts for stability and longevity when done properly [27:30];
The importance of zone 2 aerobic training [35:45];
The most effective ways to engage in zone 2 exercise [40:00];
Zone 5 training and VO2 max [44:15];
A primer on VO2 max [52:00];
Stability—the cornerstone upon which all exercise and movement relies [1:03:00];
#304 – NEW: Introducing quarterly podcast summaries - Peter shares his biggest takeaways on muscle protein synthesis, VO2 max, toe strength, gut health, and more
In this quarterly podcast summary (QPS) episode, Peter introduces a new format aimed at summarizing his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from each episode, covering diverse topics such as protein and muscle building with Luc van Loon, toe strength with Courtney Conley, VO2 max with Olav Aleksander Bu, liquid biopsies for cancer with Alex Aravanis, gut health and probiotics with Colleen Cutcliffe, and road safety with Mark Rosekind. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions.
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 episode #304 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
How Peter keeps track of his takeaways from each podcast episode [5:15];
Luc van Loon episode: fat utilization, muscle protein synthesis, dietary protein, aging and inactivity, and more [8:45];
Behavioral changes that have come about from the conversation with Luc van Loon [23:45];
Courtney Conley episode: importance of toe strength and the impact of dedicated foot training [26:45];
Olav Aleksander Bu episode: the importance of VO2 max for lifespan, and the practicalities of measuring and improving VO2 max [36:45];
Behavioral changes that have come about from the conversation with Olav [56:00];
Alex Aravanis episode: liquid biopsies for cancer detection [1:01:30];
Colleen Cutcliffe episode: the importance of gut bacteria balance, and the potential therapeutic uses of probiotics, particularly Akkermansia [1:16:45];
Mark Rosekind: the significant issue of road fatalities and injuries, their causes, and practical safety measures to reduce risks [1:27:00]; and
Layne Norton holds a Ph.D. in nutritional sciences and is a physique coach, natural bodybuilder, and previous guest on The Drive. In the first half of this episode, Layne dives deep into the topic of energy balance, including the role that macronutrients and calories play in weight loss. He describes how many people struggle with tracking food and calories on their own across a variety of diets and how all of this can impact nutritional habits and behaviors. In the second half of the episode, Layne discusses the importance of protein and weightlifting for improving one’s body composition and increasing muscle mass. He explains how he would prescribe different training and nutrition programs for two hypothetical clients—a 50-year-old female who is entering menopause and wants to improve her health, and a 40-to-50-year-old male who wants to maximize muscle mass. Additionally, Layne discusses a number of supplements that could potentially benefit a training program including whey protein, branch chain amino acids, creatine, nitric oxide boosters, and more.
We discuss:
Defining energy balance and the role of calories [2:30];
Defining a calorie, whether they are all created equal, and how much energy you can extract from the food you eat [8:00];
Factors influencing total daily energy expenditure [12:15]:
The challenge of tracking energy expenditure accurately, and the thermic effect of different macronutrients [23:30];
Challenges of sustained weight loss: metabolic adaptation, set points, and more [34:45];
Weight loss strategies: tracking calories, cheat meals, snacks, fasting, exercise, and more [40:45];
Sitting in discomfort, focusing on habits, and other lessons Layne learned as a natural bodybuilder [52:15];
Commonalities in people who maintain long-term weight-loss [1:01:15];
Does a ketogenic diet result in greater energy expenditure? [1:03:15];
The metabolic benefits of exercise, muscle mass, and protein intake [1:15:00];
The impact of lean muscle and strength on lifespan and healthspan [1:20:00];
Hypothetical case study #1: Training program for 50-year-old female [1:27:45];
Muscle protein synthesis in a trained athlete vs. untrained individual following a resistance training program [1:31:30];
Protein and amino acids needed to build and maintain muscle mass [1:37:15];
Nutrition plan for the hypothetical 50-year-old woman starting to build lean muscle [1:42:45];
Dispelling myths that excess protein intake increases cancer risk through elevations in mTOR and IGF [1:55:30];
Hypothetical case study #2: Training program for a 50-year-old, trained male wanting to increase muscle mass [2:04:00];
Maximizing hypertrophy while minimizing fatigue—is it necessary to train to muscular failure? [2:11:30];
Ideal sets and reps for the hypothetical 50-year-old male interested in hypertrophy [2:16:15];
Maximizing hypertrophy by working a muscle at a long muscle length [2:22:15];
Recommended lower body exercise routines and tips about training frequency [2:24:00];
Nutrition plan for the hypothetical 50-year old male wanting to add muscle [2:29:00];
Cycling weight gain and weight loss when building lean muscle mass, and expectations for progress over time [2:33:30];
Supplements to aid in hypertrophy training [2:38:30];
Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent.
We discuss:
Insights from genetic studies of centenarians and twins [3:00];
Genes with protective variants that aid longevity [13:00];
The relationship between growth hormone and IGF-1 [22:45];
Use of growth hormone as a longevity tool [34:00];
Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45];
The correlation between high TSH and longevity [46:30];
Important pathways for longevity [52:00];
Insights from centenarian studies, nature vs. nurture, and more [59:00];
The contraction of morbidity that comes with improved healthspan [1:08:00];
Defining healthspan [1:13:13];
Unique perspectives and positive attitudes of centenarians [1:17:30];
Lessons to take away from centenarians [1:24:00];
Metformin overview: history, studies, and potential for gero-protection [1:28:45];
The TAME trial (Targeting Aging with Metformin) [1:39:00];
The challenge of studying metformin in animals models [1:46:45];
How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30];
The search for biomarkers to identify who can benefit from treatment [2:00:30];
The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30];
In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of atherosclerotic cardiovascular disease (ASCVD)—the number one killer in the developed world. Peter argues for the importance of paying attention to and understanding ASCVD given its ubiquity and inevitability. He goes into great detail about the development of atherosclerosis and how it can take hold at a very early age, the role of cholesterol, and the causal factors of ASCVD that determine prevention strategies. Additionally, he discusses the important metrics and biomarkers found in blood work, as well as diagnostic tests such as coronary artery calcium scores (CAC) and CT angiograms which help to determine the level of arterial damage present. Finally, Peter lays out the keys to understanding and interpreting calcium scores before wrapping up the conversation with his key takeaways regarding prevention.
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 #34 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
The importance of understanding atherosclerosis early in life [2:15];
Defining atherosclerotic cardiovascular disease (ASCVD), its causes, and the role of cholesterol [9:00];
The process of developing ASCVD, part 1 [15:00];
The process of developing ASCVD, part 2 [24:00];
The process of developing ASCVD, part 3 [32:45];
How early in life ASCVD can start to develop [40:30];
Case studies of atherosclerosis and figures showing real pathology [43:00];
Coronary artery lesions present in autopsies of different age groups [49:15];
The causal factors of ASCVD that determine prevention strategies [52:15];
Labs to identify biomarkers of ASCVD ]59:00];
Diagnostic tests to determine the level of arterial damage present—CAC, CTA, CIMT, and more [1:00:30]
Keys to understanding and interpreting a CAC score and/or CTA results [1:05:15];
Is there a risk from cholesterol levels being too low? [1:13:00];
In this second edition of the “Strong Convictions, Loosely Held” episode, Peter discusses topics on which his thoughts have evolved as a result of his interviews with podcast guests and other information he’s gained since episode 100. Peter covers topics including cancer therapy and screening, as well as prevention strategies for cardiovascular disease and Alzheimer’s disease. He also describes changes in his perspectives on time-restricted feeding and protein consumption and on the therapeutic use of psychedelics, and he discusses some sleep supplements with remarkable efficacy. He ends with a special discussion on all things Formula 1 racing.
We discuss:
The concept of “strong convictions, loosely held” [3:10];
Update on Peter’s upcoming book [8:30];
Cancer: the promise of immunotherapy [14:15];
Cancer: how aggressive screening for gastrointestinal cancers could save lives [24:30];
Cardiovascular disease: how early and aggressive lowering of apoB could change the course of ASCVD [31:30];
Alzheimer’s disease: genes that modify risk associated with the APOE4 variant [40:15];
Time-restricted feeding: where the benefit comes from, and when this practice can be problematic [44:00];
The common problem of protein underconsumption [51:45];
The tremendous impact of exercise on lifespan and healthspan [54:45];
Peter’s shoulder surgery [1:00:15];
An uninspiring viewpoint on NAD precursors as a longevity tool [1:06:15];
Psychedelics: a powerful therapeutic tool in the right setting [1:09:30];
Sleep: updated thoughts on blue light and a remarkable drug for aiding sleep quality [1:13:15];
Book recommendation from Peter [1:20:45];
Formula 1: the 5 variables that determine the winner [1:22:00];
Today’s episode of The Drive is a rebroadcast of the conversation with Sarah Hallberg (released on May 17th, 2021). It's with great sadness that we report that Sarah recently lost her battle with lung cancer, and as such we've decided to republish her episode to honor her amazing work in challenging the status quo in the treatment of metabolic disease.
Sarah Hallberg was the Medical Director at Virta Health and a physician who spent nearly two decades treating patients with obesity and type 2 diabetes. In the first half of this episode, Sarah discusses how she became a huge believer in the efficacy of carbohydrate restriction for the treatment of type 2 diabetes through her research and clinical experience. Sarah challenges the common beliefs about the role of dietary fat and carbohydrate on the plasma makeup of fatty acids and triglycerides. She also expresses the importance of understanding early predictors of metabolic illness—highlighting one particular fatty acid as the most important early predictor—before finishing with a discussion about how doctors might be able to personalize patients’ metabolic management in the future. In the second half of this episode, Sarah tells the personal story of her own lung cancer diagnosis. She talks about dealing with her grief, deciding to continue her work while prioritizing her family, and how she devised a plan to extend her survival as long as possible.
We discuss:
How Sarah discovered the profound impact of carbohydrate restriction for reversing obesity and type 2 diabetes [2:00];
Prediabetes and metabolic syndrome: prevalence, early signs, and the importance of treating early [14:45];
Overview of fatty acids, how they are metabolized, and understanding what you see in a standard blood panel [28:00];
The relationship between diet composition and metabolic markers [34:00];
Why palmitoleic acid is such an important biomarker [47:00];
The best early indicators of metabolic disease [58:45];
Personalized management of metabolic illness [1:05:45];
Sarah’s cancer diagnosis and the beginning of her journey [1:14:00];
The emotional impact of a devastating diagnosis [1:26:00];
Sarah’s plan to extend survival [1:35:30];
Sarah’s aggressive treatment plan [1:46:15];
Life-threatening complications and the return of her cancer [1:57:45];
Sarah’s reflections on her approach to life with chronic cancer and balancing her time [2:09:45]; and
Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU.
We discuss:
The amazing potential of cyclist Tadej Pogačar [3:00];
Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30];
The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [17:00];
Tadej Pogačar’s race strategy and mindset at the Tour de France [24:00];
Defining Zone 2, fat oxidation, and how they are measured [26:45];
Using fat and carbohydrate utilization to calculate mitochondrial function and metabolic flexibility [35:45];
Lactate levels and fat oxidation as it relates to Zone 2 exercise [40:00];
How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:45];
Bioenergetics of the cell and what is different in elite athletes [57:30];
How the level of carbohydrate in the diet affects fuel utilization and power output during exercise [1:08:30];
Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:15:00];
How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:21:00];
Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:25:00];
Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:41:15];
How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:51:15];
Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:45];
The effects of metformin, NAD, and supplements on mitochondrial function [2:05:15];
The role of lactate and exercise in cancer [2:13:30];
How assessing metabolic parameters in long COVID patients provides insights into this disease [2:19:00];
The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:45];
Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:45];
Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:39:15]; and
In this “Ask Me Anything” (AMA) episode, Peter discusses all things related to hydration, starting with how water is distributed in the body and the important concept of tonicity. He explains the difference between dehydration and volume depletion and their respective health consequences and implications. He describes the different conditions which affect our daily water needs, as well as the signs of dehydration and how it can affect performance. Next, he discusses all the ways in which we can rehydrate and when it makes sense to add electrolytes, glucose—or a combination of both—to rehydration fluids. Additionally, Peter gives his take on the plethora of sports drinks on the market and which ones stand out from the rest. Finally, he concludes with some key takeaways related to hydration.
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 #33 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Peter’s incident leading to a renewed interest in hydration [3:15];
Water in the human body: percentage, location, and implications [6:00];
Defining tonicity—isotonic, hypotonic, and hypertonic [11:45];
Defining dehydration and volume depletion [19:00];
The health consequences of dehydration and volume depletion [21:45];
How do we actually lose water? [25:30];
How much water do we need every day? [28:00];
Signs of dehydration during exercise and how it can affect performance [32:45];
Is it possible to be overhydrated? [43:15];
Electrolytes: benefits and when to include them in rehydration fluids [47:00];
Glucose: benefits and when to include it in rehydration fluids 51:15];
The ability of glucose to improve absorption of sodium [58:45];
The type of carbohydrates in drinks than actually impact performance [1:02:00];
Sodium during workouts: is there an optimal ratio of carbohydrate to sodium? [1:05:00];
Pros and cons of sports drinks and which ones stand out [1:09:15];
How much hydration comes from the food we eat? [1:14:30];
Is there a downside to drinking electrolytes throughout the day even without exercise? [1:15:15];
Ryan Hall is the fastest American ever to run the marathon (2:04:58) and half marathon (59:43) and is the author of the book Run the Mile You’re In. In this episode, Ryan discusses his amazing successes and epic failures during his remarkable running career and what he's learned through these experiences. Ryan explains not only the physical aspects of running - including his training routine, fueling regimen, and recovery process - but he also emphasizes the mental aspect of the sport. He discusses how accepting and reframing negative thoughts can empower you to take on challenges and reach your potential. Additionally, Ryan discusses the traits that make the best competitors, the keys to overcoming setbacks, and his amazing feat of 7 marathons in 7 days as a goodbye to the sport that gave him so much.
We discuss:
How Ryan got into running and his formative years of training [4:45];
The advantages of altitude—living high and training low [9:45];
Progressive overload, blood flow restriction, and switching up your workout routine [14:15];
Lessons learned from competing in the Beijing Olympics [16:45];
Importance of speed, power, and strength for runners [22:15];
The crazy idea that got Ryan hooked on running [35:15];
The mental aspect of training and the power of reframing negative thoughts [37:45];
The importance of fueling, and Ryan’s marathon diet [52:00];
Boosting performance with Tylenol and keeping core temperature down [59:00];
Ryan’s early struggles and later success at Stanford [1:09:45];
Keys to overcoming difficulty: faith, mindset, and being a better teammate [1:15:45];
Ryan’s professional running career and his discovery of his gift for marathon distances [1:22:00];
Reflections after breaking the American half marathon record, and challenges faced by retired athletes [1:32:45];
Ryan’s marathon training regimen at the Mammoth Track Club in 2010 [1:39:45];
Optimal body weight for competition and the pros and cons of going below your natural weight [1:48:45];
Training volume, importance of mixing up intensity level, and zone 2 and zone 5 for longevity [1:53:45];
The most impactful adjustments Ryan made to his training leading up the to 2011 Boston Marathon [1:58:15];
A new personal record at the 2011 Boston Marathon and lessons on maximizing your own potential [2:03:30];
Learning from failure and takeaways from his disappointing performance at the 2012 Olympics [2:12:30];
Utilizing cardio and strength training for overall health, and how Ryan uses blood flow restriction in his workouts [2:24:45];
Performance enhancing drugs (or lack thereof) in marathon runners [2:29:15];
Traits of the greatest marathon runners [2:32:30];
7 marathons in 7 days on 7 continents—saying goodbye to the sport [2:38:45];
Reflections on what running has given Ryan [2:49:30]; and
Steven Dell is an ophthalmologist, current Medical Director of Dell Laser Consultants, and a leader in refractive eye surgery with over 20 patents to his name. In this episode, Steven explains the anatomy and functional mechanics of the eye and how they relate to common variations in vision. He discusses changes in vision that occur with aging, the fundamentals of different types of vision loss, and provides an in-depth look into the various treatments and procedures available for corrective eye surgery. Additionally, Steven explains how one might protect the eyes and prevent vision loss—a topic particularly important for children in light of the epidemic of myopia.
We discuss:
Why Steven chose ophthalmology, and the crossovers to other medical disciplines [3:45];
Anatomy of the eye, common types of vision loss, and age-related vision changes [14:15];
Eye drops that can potentially improve vision [27:30];
The explanation for different eye colors [33:15];
Physiology of the eye and its connections to the brain [34:45];
Understanding human vision through an evolutionary lens [41:00];
Enhancing vision beyond 20/20 [47:00];
Astigmatism: definition, cause, and high prevalence [51:30];
Nearsightedness (myopia): causes, epidemic in children, and prevention strategies [54:15];
Cataracts: impact of aging and how they can be repaired [1:05:00];
Lens implants that can correct and improve vision [1:19:30];
Effects of eye trauma [1:26:45];
Corneal abrasion from ‘dry eye’: causes, treatment, and prevention strategies [1:29:00];
David Allison is an award-winning scientific writer who has been at the forefront of obesity research for the last 20 years. Currently the Dean of the Indiana University School of Public Health, he has also authored many publications on statistical and research methodology and how to improve research rigor and integrity. David’s focus on evidence and data brings forth an interesting discussion of what we know (and don’t know) about the science of obesity. He provides an insightful and unemotional explanation of the potential impact of nutritional epidemiology in public health while also explaining its many pitfalls and limitations. He offers his take on the path forward in addressing the obesity epidemic, and he closes with a lucid explanation for the evident lack of credibility in science and the steps we can take to change that.
We discuss:
David’s background, interest in obesity, and focus on evidence [5:00];
The moment when the obesity crisis was recognized, and the sloppy science that ensued [13:00];
What twins studies tell us about the genetics of obesity [20:30];
How doctors and scientists have historically approached obesity treatment [23:45];
Do surgical procedures for obesity prolong life? [32:00];
The ‘Obesity Paradox’ [36:00];
Interpreting BMI and mortality data and considering confounders [43:15];
How body composition and ethnicity factor into consideration of BMI data [50:30];
Superior tools for measuring obesity at the individual level [57:15];
Using BMI data for actionable steps to combat obesity [1:02:00];
Why maintaining weight loss is more challenging than losing weight [1:06:00];
Differing perspectives on the utility of nutritional epidemiology [1:16:30];
A mouse study illustrating the impossibility of fully controlling for confounds in observational studies [1:22:15];
Limitations of nutritional epidemiology and how it can improve [1:26:30];
Addressing the obesity epidemic—the path forward and obstacles to overcome [1:37:15];
What David believes to be the most promising interventions we could take to address obesity and improve public health [1:47:30];
Reproducibility in science, normative and non-normative errors explained [1:51:30];
Rebuilding trust in science and differentiating between science and advocacy [1:59:00];
#303 - A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer's disease | Dena Dubal, M.D., Ph.D.
Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.
Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease.
We discuss:
Dena’s fascination with aging and how she came to study klotho [3:30];
Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45];
Potential benefits of klotho on brain health [22:00];
The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45];
The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement [46:45];
Benefits of klotho observed in a mouse model of Parkinson’s disease [55:45];
Benefits of klotho observed in a mouse model of Alzheimer’s disease [1:03:00];
Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00];
Speculating why a single klotho injection has such long-lasting effects [1:25:30];
Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45];
The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease [1:34:45];
The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15];
Measuring klotho levels and determining an individual’s KL-VS status [1:52:15];
The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research [1:58:00]; and
In this “Ask Me Anything” (AMA) episode, Peter shares his current workout regimen and how he incorporates blood flow restriction (BFR). He walks through the mechanics and fundamentals of some of his favorite lifts including squats, deadlifts, and hip thrusters and stresses the relative importance of each in the context of longevity. He touches on the relative importance of muscle size vs. muscle strength and discusses the impact of fasting on muscle mass and the potential tradeoffs during aging. Peter then dives into the topic of testosterone replacement therapy (TRT) for both men and women, starting with a clinical discussion around how he actually replaces testosterone in patients. He explains the targets of this therapy as well as the risks and benefits, and he gives his interpretation of current data on the association between TRT and heart disease.
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#32 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
Peter’s current exercise routine [2:25];
How Peter incorporates blood flow restriction (BFR) into his workouts [5:45];
Relative importance of muscle size vs. muscle strength [16:45];
Comparing squats to deadlifts and why both are important [22:00];
Squatting technique and fundamentals [31:15];
Important cues to look for while lifting weights [38:30];
Proper mechanics of a deadlift [42:00];
Hip thrusters as an alternative to the squat or deadlift [44:00];
Split-leg work for simulating activities of daily living [47:00];
The impact of fasting/calorie restriction on muscle mass and the potential tradeoffs to consider [49:45];
Testosterone replacement therapy: considerations when contemplating TRT and Peter’s approach with patents [54:30];
Data on the association between TRT and heart disease [1:04:15];
TRT for women—risks and benefits [1:06:45];
Impact of fasting on testosterone levels [1:13:45]; and
Sebastian Junger is an award-winning journalist, documentary filmmaker, and New York Times best-selling author. In this wide-ranging discussion, Sebastian shares stories from his time as a war reporter and how it shaped his understanding of the psychological effects of combat, including the sacred bond of soldiers, the forces that unify a tribe, and the psychological mechanisms that protect humans from painful experiences. He draws upon his personal struggle with PTSD as he discusses trauma as an all-too-common consequence of war and the importance of community in the healing process. He explains his interest in viewing human behavior through an evolutionary lens, including how it influences his parenting style, and he voices concerns over society’s continuous shift away from our evolutionary roots. Sebastian also tells the story of his near-death experience and his new perspective on the possibility of an afterlife. Additionally, Sebastian shares his thoughts on the mental health implications of current events, such as the pandemic and the withdrawal of troops from Afghanistan, and contemplates what it really means to be “free” in modern society.
We discuss:
Sebastian’s upbringing and early lessons about the evil of fascism [3:20];
Sebastian’s search for a career, interest in writing, and what he loved about tree removal [11:30];
How Sebastian became a great writer [19:30];
Sebastian’s experience with his Achilles injuries [25:30];
Work as a war reporter and his experience in combat in Afghanistan [28:00];
Psychological effects of war and Sebastian’s own experience with PTSD [36:30];
The sacred bond of soldiers and what Sebastian learned from his time with troops in Afghanistan [48:30];
An evolutionary perspective on the forces that unify and bind tribes [1:00:00];
Hunter-gatherer societies, dealing with loss, and the ancestral connection to the spiritual realm [1:08:30];
Psychological mechanisms that protect humans from painful experiences and the power in giving thanks [1:13:15];
How parenting has changed Sebastian, and the incredible pain of losing a child [1:21:15];
PTSD and the influence of community on healing [1:32:15];
Isolation of modern society and the debate over young kids sleeping in bed with their parents [1:37:45];
Why Sebastian doesn’t own a smartphone [1:43:30];
Parenting through an evolutionary lens [1:50:00];
Sebastian’s near-death experience and new perspective on the possibility of an afterlife [1:54:00];
Sebastian’s experience with depression and anxiety [2:12:00];
The pandemic’s impact on mental health [2:16:45];
Sebastian’s thoughts on the withdrawal of troops from Afghanistan [2:22:00];
Sebastian’s latest book—Freedom, and knowing when to quit [2:27:00];
Rick Johnson, Professor of Nephrology at the University of Colorado and a previous guest on The Drive, returns for a follow-up about unique features of fructose metabolism, and how this system that aided the survival of human ancestors has become potentially hazardous based on our culture’s dietary norms. In this episode, Rick explains how the body can generate fructose from glucose and how circulating glucose and salt levels can activate this conversion. He discusses the decline in metabolic flexibility associated with aging, as well as how factors such as sugar intake or menopause-associated hormone changes can alter responses to sugar across a lifetime. In addition, Rick lays out strategies for combating the development of metabolic illness using dietary changes and pharmaceutical therapies, and he discusses the impact of fructose metabolism and uric acid on kidney function and blood pressure. He concludes with a discussion of vasopressin, a hormone that facilitates fructose’s effects on weight gain and insulin resistance.
We discuss:
Unique features of fructose metabolism and why it matters [2:45];
A primer on fructose metabolism and uric acid [10:30];
Endogenous fructose production, the polyol pathway, and the effect of non-fructose sugars [22:00];
Findings from animal studies of glucose and fructose consumption [29:00];
What calorie-controlled studies say about the claim that a “calorie is a calorie” [42:15];
Implications for aging and disease [51:15];
Impact of endogenous fructose production on obesity and metabolic syndrome [1:01:30];
Why vulnerability to the negative effects of sugar increases with age and menopause [1:04:30];
Dietary strategies to reduce the negative impact of fructose [1:16:30];
The role of hypertension in chronic disease and tips for lowering blood pressure [1:30:45];
The impact of fructose and uric acid on kidney function and blood pressure [1:39:45];
The potential role of sodium in hypertension, obesity, and metabolic syndrome [1:49:00];
The role of vasopressin in metabolic disease [1:54:00];
In this “Ask Me Anything” (AMA) episode, Peter and Bob first answer a variety of questions related to heart rate variability (HRV): what it means, why it matters, and how to measure, interpret, and potentially elevate it. Next, they dive deep into the topic of alcohol, beginning with a discussion on the negative impact that it can have on sleep. They then break down the confusing body of literature suggesting potential health benefits to moderate levels of drinking compared to complete abstinence and point out the limitations of these studies. Finally, they conclude by analyzing data on the impact of moderate and heavy drinking on the liver and on risk for Alzheimer’s disease and dementia.
Please note: this AMA is audio only. 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 #31 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.
We discuss:
What is heart rate variability (HRV), and why do we measure it? [2:10];
The association between low HRV and mortality risk [10:00];
What high and low HRV means and why athletes strive for a high HRV [15:30];
Factors that can raise or lower HRV [18:00];
How and when to measure HRV, and the best wearables [19:15];
Interpreting your personal HRV number and why there’s so much individual variation [23:15];
How Peter’s morning HRV reading impacts his decision to train [28:30];
Alcohol’s impact on sleep [31:30];
Metrics to track the impact of alcohol on your sleep [34:00];
Alcohol’s impact on the need to urinate during the night [39:00];
Alcoholic fatty liver disease (AFLD) [41:30];
Individual differences in the way people metabolize and react to alcohol consumption [44:15];
This episode is a follow-up to our recent COVID-19 podcast with Drs. Marty Makary and Zubin Damania (aka ZDoggMD). Here, we address many of the listener questions we received about our original discussion. In addition to Marty and ZDoggMD, we are also joined by Dr. Monica Gandhi, an infectious disease specialist and Professor of Medicine at the University of California, San Francisco. In this episode, we talk about new data on Omicron, long COVID, masks, kids and schools, vaccine mandates, policy questions, and treatments. We also discuss some of the most prevalent misinformation and spend time talking about claims made by Robert Malone. We end with a conversation about our exit strategy.
Please note: we recorded this episode on January 17, 2022, and in an effort to get it out as soon as possible, this won’t have full show notes or a video. Additionally, Monica was only able to join us for the first section of the podcast, so you’ll hear her drop off partway through.
We discuss:
Severity of infection from Omicron—reviewing the data [5:15];
Factors contributing to the relative mildness of Omicron infections [8:30];
Is SARS-CoV-2 evolving to cause less severe disease? [13:00];
Potential of Covaxin—an inactivated virus-based COVID-19 vaccine [17:45];
How B cells and T cells work together to defend against viruses [22:00];
Comparing COVID-19 vaccines, and the rationale for the time between doses [25:30];
Reviewing the purpose and effectiveness of boosters for reducing severity and transmission [32:30];
Debating vaccine mandates, and putting COVID’s mortality risk in perspective [41:00];
Why the topic of COVID has become so polarized [1:03:15]
Reviewing the data on masks for protecting oneself and protecting others [1:06:30];
The inconsistent logic used for mask mandates [1:16:00];
Long COVID and the potential for vaccines to reduce risk [1:21:45];
Risks for children and policies for schools [1:27:30];
Reviewing the outcomes from Sweden, where the government didn't impose lockdowns [1:31:00];
Draconian measures implemented in Canada [1:38:15];
Antiviral treatments for COVID and a common-sense approach [1:42:15];
Importance of ending tribalism and having rational discussions with humility [1:47:30];
Treating infection with monoclonal antibodies and convalescent sera [2:01:45];
Reviewing claims made by the controversial Dr. Robert Malone [2:11:15];
A potential exit strategy from the current situation [2:30:30];
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
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];
#189 - COVID-19: Current state of affairs, Omicron, and a search for the end game
03 Jan 2022
02:45:14
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];
Iñigo San Millán, Ph.D.: Zone 2 Training and Metabolic Health (Ep. #85 Rebroadcast)
27 Dec 2021
02:50:56
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;
#188 - AMA #30: How to Read and Understand Scientific Studies
20 Dec 2021
00:30:07
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.
#302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.
Julia Wattacheril is a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. In this episode, Julia delves deep into the complex world of liver health, beginning with a foundational overview of liver physiology. She provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. She provides a primer on the four major stages of liver disease, discussing risk and emphasizing the importance of early diagnosis. Julia highlights the role of liver disease in increasing the risk of cancer and cardiovascular disease and covers in detail the various strategies for diagnosing, treating, and preventing the progression of liver disease.
We discuss:
Julia’s training, the importance of liver health, and the challenges and innovations of hepatology [3:15];
The complex and crucial functionality of the liver, its four most essential functions, and more [8:45];
Liver injuries: historical and evolving understanding of causal factors, and the progression to liver diseases and cancer [13:15];
How the liver metabolizes nutrients and what happens in the presence of excess calories or alcohol [24:45];
Methods of diagnosing liver disease and how insights guide treatment and management strategies [33:30];
The poisonous nature of ethanol to the liver [40:30];
Varied responses to alcohol, damaging effects of alcohol beyond the liver, and the process of advising patients on their alcohol consumption [47:15];
Understanding liver enzymes AST and ALT—interpreting levels, lifestyle factors that affect them, and diagnostic approaches [58:30];
Interpreting liver function tests for fatty liver disease, and the challenges of diagnosing liver pathologies, particularly in children versus adults [1:13:15];
Comprehensive liver health assessments via imaging and various diagnostic tools to prevent overlooking potential liver pathologies [1:18:45];
Potential impact of recreational drugs, statins, and other medications on liver function test results [1:26:45];
Shifting nomenclature from NAFLD to MASLD to reflect accuracy in the underlying pathophysiology and understanding of liver diseases [1:30:30];
Pathophysiology of MASLD, the need for proactive screening, and the significance of liver fat percentage as an indicator of metabolic health [1:36:30];
The importance of screening for rare conditions alongside common metabolic diseases associated with fatty liver accumulation [1:42:45];
Practical strategies for managing MAFLD [1:45:30];
The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance [1:52:45];
The potential of GLP-1 agonists for the treatment of MASLD [1:57:45];
How the four stages of liver disease have evolved [2:00:30];
Increased cancer and heart disease risk associated with early-stage MAFLD [2:05:15];
Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD [2:12:15];
#187 - Sam Apple: The Warburg Effect—Otto Warburg’s cancer metabolism theory
13 Dec 2021
01:48:22
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];
#186 - Patrick Radden Keefe: The opioid crisis—origin, guilty parties, and the difficult path forward
06 Dec 2021
01:55:56
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];
#185 - Allan Sniderman, M.D.: Cardiovascular disease and why we should change the way we assess risk
29 Nov 2021
02:02:13
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];
Rick Johnson, M.D.: Metabolic Effects of Fructose (Ep. #87 Rebroadcast)
22 Nov 2021
01:49:48
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];