The Peter Attia Drive

In this episode, Francisco Gonzalez-Lima, a Professor of Neuroscience and Pharmacology & Toxicology, explains the vascular hypothesis of Alzheimer's disease which says the central problem is a progressive neuronal energy crisis of impaired blood flow to the brain and impaired mitochondrial respiration. He walks us through the ways we can intervene in this process and also shares details of the exciting future of Alzheimer's treatment and prevention.

We discuss:

• Background and interest in the brain [5:15];
• The unique nature of the human brain [9:15];
• Why we've made so little progress in Alzheimer's research [23:00];
• The amyloid beta hypothesis [28:30];
• Hypometabolism in the brain leading to cognitive decline [39:30];
• Early signs of AD, and deciphering between age-related decline versus something pathologic [47:45];
• The vascular hypothesis of Alzheimer's disease [54:00];
• The relationship between mitochondria, cytochrome c oxidase, and Alzheimer's disease [1:08:00];
• Chronic inhibition of cytochrome c oxidase leads to chronic neurodegenerative disease [1:22:45];
• Major risk factors for AD, head trauma, and other forms of dementia [1:33:45];
• Methylene blue for treating and preventing neurodegeneration [1:38:15];
• Current standard of care for AD, and the reasons for a lack of advancement [2:01:45];
• Near infrared light as a targeted treatment for cognitive decline [2:05:30];
• The ketogenic diet as a treatment and preventative measure [2:13:15];
• Exciting future research coming from Francisco [2:23:00];
• Methylene blue for traumatic brain injuries [2:25:15]; and
• More.

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In this episode, Zubin Damania, a.k.a. Zdogg MD, a Stanford trained physician and founder of Turntable Health, discusses his evolution from disillusioned doctor suffering burnout to leading the charge for a radical shift in how we practice medicine. We also go down the rabbit hole on all sorts of juicy topics from meditation to nutrition to the nature of consciousness itself.

• Med school antics [7:00];
• Hierarchies in healthcare, physician burnout, and a broken system [20:15];
• Why Zubin left medicine, and what lead to the ZdoggMD persona [31:30];
• Peter's tough decision to leave medicine [44:00];
• Benefits and challenges of meditation [54:15];
• Zdogg's theory of consciousness [1:11:30];
• Nutrition: Peter's current strategy with patients [1:31:00];
• The anti-vaccine dispute [1:38:15]
• The common thread of all "diets", the obesity epidemic, and Peter's dream experiment [1:44:30];
• Do we have free will? And how do we make better decisions and learn from our mistakes? [1:55:15];
• Peter's current obsessions: fasting and rapamycin, measuring autophagy, and becoming a kickass 100-year-old [2:03:15];
• Reforming the healthcare payment model [2:14:45];
• How to find doctors like Peter and Zubin in your area [2:28:15];
• Zdogg's amazing videos [2:31:15]; and
• More.

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In this episode, Dr. Eric Chehab, orthopedic surgeon and sports medicine specialist, explains the measures we can take to live better and maintain our physical health through exercise and the avoidance of common injuries that prove to be the downfall for many. He also provides valuable insight for those weighing their treatment options from physical therapy to surgery to stem cells.

We discuss:

• Favorite bands, musicians, and concerts [3:30];
• Eric's upbringing, biggest influences, college life, and teaching overseas [12:45];
• Eric's training, fellowship with the New York Giants, and the risk vs. reward of playing football [39:15];
• The knee joint: common injuries, knee replacements, and proper exercise [1:00:00];
• Best exercise for orthopedic health and bone density [1:10:00];
• Most common injuries: knee, hip, shoulder, elbow, ankle, foot [1:20:45];
• Physical therapy vs. surgery, and the meniscus surgery controversy [1:28:30];
• PRP, stem cells, sham surgeries, and the placebo effect [1:41:00];
• Back injuries: when does surgery make sense? [1:54:15];
• How to find the right orthopedic surgeon for you [2:01:45];
• How to cope with complications and maintain quality of life through adaptation [2:09:15];
• Dr. Bukk Teef [2:26:45]; and
• More.

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In this episode, Nir Barzilai, director of the Institute for Aging Research and expert in the genetics of longevity, discusses the evidence that metformin and rapamycin have anti-aging properties and how his TAME study aims to support this hypothesis in humans. Additionally, he describes the role of genetics in lifespan/healthspan and how it might affect important pathways such as IGF and insulin sensitivity.

We discuss:

• Nir's background and interest in aging and endocrinology [3:30];
• History of metformin, and understanding the mechanism [11:15];
• Attempting to define insulin resistance [21:15];
• Metformin as a possible anti-aging drug [48:45];
• The TAME trial: Targeting Aging with MEtformin [57:45];
• Why Nir believes metformin can slow aging [1:16:30];
• The genetic gift of centenarians [1:28:00];
• IGF/GH and its impact on aging and chronic diseases [1:34:15];
• Genetics/epigenetics of centenarians, gene sequencing, CETP-VV, Lp(a) [1:49:15];
• Should you be taking HGH? [2:05:30];
• NAD and NAD precursors (NR and NMN) [2:30:00];
• Parting thoughts on metformin [2:36:15];
• Possible blind spots in Nir and Peter's thinking? [2:43:00]; and
• More.

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In this episode, Sam Harris, neuroscientist, author, and host of the Waking Up Podcast, walks us through the profound, yet practical, ways that meditation can transform our lives. Additionally, he helps to define the types of meditation and clarifies potential misconceptions with terms like happiness, pain, and suffering.

We discuss:

• The transformative moment that led to Peter reaching out to Sam [3:45];
• Comparing the two broad types of meditation, and Peter's favorite meditation apps [7:45];
• The pleasure of a concentrated mind, meditating with pain, and the difference between pain and suffering [13:15];
• What it means to be happy, and how to break out of our default state [23:15];
• The disease of distraction, why humans suffer, the limitation of happiness, and letting go of anger with mindfulness [31:00];
• The challenge of learning mindfulness, the benefit of silent retreats, and Sam's first experience in solitude as a teenager [54:15];
• Sam's life-altering experience with MDMA [1:03:00];
• Mettā meditation a.k.a. loving-kindness, and the concept of 'moral luck' [1:14:00];
• Overcoming grief and dread with meditation [1:34:45];
• The wrong way to practice mindfulness, and the difference between Vipassana and Dzogchen [1:44:45];
• Sam's commitment to never lie, honesty in politics, and Sam's viewpoint on the Trump phenomenon [2:06:00];
• Teaching kids to be more mindful [2:18:30];
• Sam's current book projects, the consequences of a politically correct environment, and the potential of neuroscience to cure psychopathy [2:25:30];
• How you can follow Sam's work [2:39:00]; and
• More.

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In this episode, Dr. Rudy Leibel, an expert in Clinical Molecular Genetics and Genomics at Columbia University, discusses his role in the remarkable scientific story of discovering leptin. He also gets into the genetics of obesity, as well as a broader discussion of the causes and effects of obesity, energy expenditure, and metabolism.

We discuss:

• Rudy's background, interest in obesity, and trying to understand the role and impact of adipose tissue [4:15];
• Finding the first evidence of leptin by studying obese mice [23:30];
• Zucker rats, and the push/pull theories of obesity [34:45];
• A breakthrough in obesity research, and closing in on leptin [45:45];
• Understanding leptin in humans [1:03:30];
• What Prader–Willi syndrome teaches us about body weight regulation [1:09:45];
• Leptin and the broad condition of obesity, metabolic consequences of weight reduction, and Peter's self-experiments [1:18:00];
• How is appetite being regulated? [1:29:45];
• Are there epigenetic consequences of being obese? [1:37:00];
• What makes low-carb diets so effective at obesity reduction? [1:46:15];
• What did Rudy believe 10 years ago that he no longer believes to be true? [1:55:15];
• Rudy's dream study of the FTO gene [1:57:15];
• What the hell does insulin resistance actually mean? [2:08:30]; and
• More.

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In this episode, Siddhartha Mukherjee, oncologist, researcher, and author of the Pulitzer Prize-winning book "The Emperor of All Maladies: A Biography of Cancer," discusses his writing process, his thoughts about medicine, cancer, immunotherapy, and his recent collaboration on a study combining a ketogenic diet with a drug in mice that provided remarkable and encouraging results.

We discuss:

• Sid's background [5:00];
• How Sid and Peter met [6:00];
• Sid's Pulitzer Prize-winning book: The Emperor of All Maladies [8:00];
• Sid's writing process: the tenets of writing [12:30];
• Our struggle to find preventable, human, chemical carcinogens of substantial impact [23:30];
• The three laws of medicine — Law #1: A strong intuition is much more powerful than a weak test [26:30];
• Law #2 of medicine: "Normals" teach us rules; "outliers" teach us laws [32:00];
• Law #3 of medicine: For every perfect medical experiment, there is a perfect human bias [35:00];
• The excitement around immunotherapy [38:15];
• The story of Gleevec [46:00];
• How does the body's metabolic state affect cancer? [49:30];
• Can a nutritional state be exploited and/or a drug sensitivity be exploited through a nutritional intervention? [52:00];
• How does Sid balance his family, writing, research, laboratory, and patients? [1:00:30]; and
• More.

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In this episode, Nav Chandel, a professor of medicine and cell and molecular biology at Northwestern University, discusses the role of mitochondria and metabolism in health and disease. Nav also provides insights into the mitochondria as signaling organelles, antioxidants, and metformin's multifaceted effects on human health, among many topics related to well-being.

We discuss:

• What got Nav interested in mitochondria [5:00];
• Reactive oxygen species (ROS) [16:00];
• Antioxidants: helpful or harmful? [20:00];
• Mitochondria as signaling organelles [22:00];
• Hydrogen peroxide (H2O2) [25:00];
• Mitochondrial DNA [28:00];
• Mitochondria and aging [45:00];
• Metformin [52:45];
• Metformin and the gut microbiome [54:00];
• Metformin as complex I inhibitor and the importance of the NADH/NAD ratio [1:01:00];
• Anticancer benefits of metformin [1:07:45];
• Mitochondrial function is necessary for tumorigenesis [1:15:00];
• Are somatic mutations the result of mitochondrial dysfunction? [1:31:30];
• Vitamins and antioxidants [1:37:00];
• Targeting inflammation in disease [1:43:00];
• NAD precursors [1:45:45];
• MitoQ [1:52:00];
• Metabolite toxicity [1:56:30];
• Cortisol and healthy aging [2:02:00];
• Nav turns the tables and asks Peter how he deals with the "So what should I eat?" question during social encounters [2:09:00]; and
• More.

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In this episode, Thomas Seyfried, a cancer researcher and professor of biology at Boston College, discusses a controversial view of cancer as a mitochondrial metabolic disease. Many topics related to the causes, treatments, and prevention of cancer are covered in this in-depth conversation.

We discuss:

• How Tom got interested in cancer research [9:00];
• Calorie-restricted ketogenic diets, fasting, and epileptic seizures [18:30];
• Otto Warburg and the Warburg effect [30:45];
• Germline mutations, somatic mutations, and no mutations [42:00];
• Mitochondrial substrate level phosphorylation: Warburg's missing link [51:30];
• What is the structural defect in the mitochondria in cancer? [1:02:00];
• Peter's near-death experience with the insulin suppression test while in ketosis [1:06:30];
• Insulin potentiation therapy and glutamine inhibition [1:13:15];
• The macrophage fusion-hybrid theory of metastasis [1:39:30];
• How are cancer cells growth dysregulated without a mutation? [1:47:00];
• What is the dream clinical trial to test the hypothesis that we can reduce the death rates of cancer by 50%? [2:03:15];
• How can the hypothesis be tested rigorously that structural abnormalities in the mitochondria impair respiration and lead to compensatory fermentation? [2:26:30];
• Case studies of GBM survivors [2:32:45]; and
• More.

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In this episode, 8-time Olympic medalist, Apolo Ohno, discusses the lessons he's learned from his remarkable career in speed skating and the extreme physical and mental training — and determination — required to reach greatness.

We discuss:

• Apolo's childhood with his single dad, early success in sports, and falling in love with skating [7:30];
• The differences between inline and ice skating, and short- & long-track speed-skating, and the evolution of the clap skate [21:00];
• The mental game and the physical game: intense training and mindset [29:30];
• Apolo's early success in short-track that led to an amazing opportunity and his reluctance to go for it [40:15];
• Early days at Lake Placid, first experience on the world stage, and a little self-sabotage [56:45];
• Tough love parenting, making a commitment, training like Rocky, and developing the mindset of a fighter [1:17:30];
• 2002 Olympics, winning his first medal, and rising above the sport [1:32:45];
• Apolo's evolving training and body composition throughout his Olympic career [2:05:15];
• Going into the Lion's Den to learn from Korean skaters and making a radical and risky change that led to his most successful Olympic games [2:12:45];
• Apolo's tumultuous relationship with South Korea, from hatred to respect to admiration [2:29:00];
• Applying lessons learned through training, adjusting to life after skating, and the struggles many athletes face transitioning to retirement [2:46:30];
• The final years of Apolo's career: intense focus, crazy training, mental fortitude, and resiliency [2:57:30];
• Officially retiring and contemplating a comeback [3:16:15];
• Where does Apolo want to be in 10 years? [3:22:45];
• The pursuit of perfection and flow states [3:29:30];
• Where you can follow Apolo [3:35:00]; and
• More.

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