The Peter Attia Drive

Latest Episodes:

#117 - Stanley Perlman, M.D., Ph.D.: Insights from a coronavirus expert on COVID-19 Jun 29, 2020

Show notes

In this episode, Stanley Perlman shares insights from his impressive career studying coronaviruses—both the common and more deadly ones, like MERS and SARS. In comparing preceding coronaviruses with SARS-CoV-2, Stanley discusses how other coronaviruses can aid our current understanding of, and be used to infer about, COVID-19. He also gives his thoughts on durable immunity, therapeutic strategies, and future outbreak preparedness. We discuss:

His background and early work with coronaviruses [2:45];
The coronavirus family—various types, common traits, and scientific understanding [9:00];
The origin of viruses, animal to human transmission, R_0, immunity, and more [17:45];
Insights from the 2002 SARS outbreak [28:30];
Insights from the 2012 MERS outbreak [35:00];
Comparing SARS-CoV-2 to MERS, SARS, and other coronaviruses [42:00];
COVID-19 survivor potential for long-term damage [53:30];
Using the current pandemic for lessons on future preparedness [57:00];
Genetic drift and the potential for long-term immunity to COVID-19 [1:07:00];
Prevention and treatment strategies for COVID-19 and future diseases [1:22:30];
Alternative hypothesis to the origin of SARS-CoV-2 [1:32:30];
Determining durable immunity to COVID-19 and what a successful vaccine looks like [1:34:30]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/stanleyperlman Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#116 - AMA with Dom D'Agostino, Ph.D., Part I of II: Ketogenic diet, exogenous ketones, and exercise Jun 22, 2020

Show notes

Back by very popular demand for a special AMA episode, ketosis expert Dom D'Agostino joins Bob Kaplan, Peter's Head of Research, to address many lingering questions about the ketogenic diet, exogenous ketones, and exercise for overall health. Dom also shares valuable insights from his personal experience with training, supplements, intermittent fasting, and other nutritional strategies to optimize his own health and performance. 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 the website show notes page.

We discuss:

Dom's recent and ongoing projects [3:00];
Benefits of a ketogenic diet for an otherwise healthy person [7:00];
Book recommendations to become more knowledgeable about a ketogenic diet [11:30];
Best devices for measuring ketones [13:45];
Genetic factors that influence how someone responds to the ketogenic diet [24:45];
Ketogenic diet for those with the APOE e4 allele [28:15];
Impact of long-term ketogenic diets on thyroid function [34:25];
Low-carb and ketogenic diets for appetite control and weight management [39:00];
Ketogenic diet and the microbiome [43:00];
Comparing monounsaturated fat versus saturated fat on the ketogenic diet [45:55];
Implications of long-term genetic and epigenetic adaptations to a ketogenic diet [47:45];
Why some people see a rise in LDL-C and LDL-P when on a ketogenic diet and what they can do about it [50:15];
Should someone with familial hypercholesterolemia consider a ketogenic diet? [55:00];
Exogenous ketones—benefits, therapeutic uses, and ketone supplements that Dom has tested [56:45];
Ketogenic protocols for management of traumatic brain injuries [1:06:00];
Comparing the benefits and therapeutic uses of various medium-chain fatty acids—caprylic acid (C8), capric acid (C10), MCT oil, and coconut oil [1:08:45];
Nootropics, caffeine, and other stimulants [1:16:15];
Supplemental use of testosterone, DHEA, and creatine for muscle growth and performance [1:23:45];
Impact of fasted-state training on strength and performance [1:30:15];
Stacking exogenous ketones with MCTs for optimal effectiveness [1:33:30];
BCAA supplements during a fast for muscle preservation [1:35:45];
What app is Dom using to track his macros? [1:42:00];
Getting enough micronutrients while on a ketogenic diet [1:47:15];
Ideal macros and getting enough protein for strength training in ketosis [1:48:15];
Pros, cons, and ideal macros of one meal a day [1:51:15];
Dom's take on "carb backloading" [1:54:45];
Dom's take on "carb up" days for ketogenic dieters [2:01:00];
Dom's thoughts on the carnivore diet and the paleolithic ketogenic diet [2:05:30];
Advantages of the ketogenic diet for extreme endurance athletes [2:10:30];
Impact on strength, power, and performance during the adaptation period of the ketogenic diet [2:14:00];
Fasted-state elevation in growth hormone and its impact on training [2:17:45];
Is it possible to build muscle on a ketogenic diet? [2:23:30];
Why Dom took a year off from weight training [2:28:00];
What does Dom do for cardio exercise? [2:30:45];
Protocols for hard training recovery [2:33:15];
Dom's personal approach to fasting, time-restricted eating, and sleep [2:35:45];
People, books, and other resources that shaped Dom's training and nutrition [2:38:45]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/domdagostinoama01 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#115 - David Watkins, Ph.D.: A masterclass in immunology, monoclonal antibodies, and vaccine strategies for COVID-19 Jun 15, 2020

Show notes

In this episode, David Watkins, professor of pathology at George Washington University, shares how insights from his HIV and Zika virus research could apply to SARS-CoV-2 protection strategies. David introduces monoclonal antibodies as an intervention to prevent and treat COVID-19 infection, and also discusses how they could be used as a hedge to vaccine development. Additionally, David's immunology tutorial explains the innate and adaptive immune systems and their differentiated responses to viral infection.

We discuss:

Background and current interest in immunology [4:30];
Immunology 101—The innate and adaptive immune system [10:15];
Defining antibodies, importance of neutralizing antibodies, and serology testing for COVID-19 [19:00];
B cells—How they fight viruses, create antibodies, and fit into the vaccine strategy [25:00];
T cells—Role in the adaptive immune system and ability to kill infected cells to prevent viral spread [36:15];
Valuable lessons from HIV applied to SARS-CoV-2 [51:00];
Lessons taken from the hepatitis C success story [1:01:30];
Monoclonal antibodies, vaccines, and the most promising strategies for preventing and treating COVID-19 infection [1:04:45];
COVID-19 vaccines in development [1:19:00];
How David's work with Zika virus informs his thinking on SARS-CoV-2 [1:25:20];
Why a vaccine for COVID-19 doesn't need to be perfect to be effective [1:27:45]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/davidwatkins Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#114 - Eileen White, Ph.D.: Autophagy, fasting, and promising new cancer therapies Jun 08, 2020

Show notes

In this episode, Eileen White, Chief Scientific Officer at the Rutgers Cancer Institute, describes the fundamental role of autophagy in the maintenance of health and prevention of neurodegeneration, cancer, and other diseases. She also goes into detail about the paradoxical finding that autophagy may benefit an existing cancer cell and help it to survive—a discovery leading to new possibilities in cancer therapy. We also discuss fasting (and molecules that induce autophagy) and the critical need to decode the proper fasting "dose" in order to improve human health.

We discuss:

Eileen's discovery that a specific oncogene blocks apoptosis [3:40];
Defining apoptosis and its role in cancer prevention [10:00];
How cancer cells use the autophagy pathway to survive [17:20];
Stressors that induce autophagy [29:15];
The importance of autophagy in the brain and liver [32:45];
The mechanisms that can trigger autophagy to support longevity [40:00];
Evidence for cancer treatment by blocking autophagy [42:30];
Types of cancer that are most autophagy-dependent [46:45];
The autophagy paradox [52:40];
Finding a molecular signal for autophagy [59:15];
Current knowledge gaps around fasting as a tool for longevity [1:13:00];
Rapamycin, metformin, and other molecules that may induce autophagy [1:22:15];
How to study fasting and exercise as longevity tools [1:32:50];
The Nobel Prize for autophagy research [1:36:45];
Eileen's future areas of research [1:38:25];
A fasting strategy for Alzheimer's Disease prevention[1:49:25];
Future study of metabolism and autophagy [1:51:30]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/eileenwhite Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#113: Normative errors—a conversation with my daughter about current events Jun 03, 2020

Show notes

In this episode, I sit down with my daughter to discuss the brutal death of George Floyd, and the aftermath we are watching unfold. Though I have no expertise in race relations, law enforcement, or police brutality, I do have some knowledge in the training of physicians, and it is that training of doctors that I've been thinking about lately as it may offer one small insight into this crisis. In this very short discussion, we speak about three types of errors in medicine (and medical training), how to distinguish between the two variants that are acceptable, and the one that is unacceptable. My question, ultimately, is if such a framework can be applied to law enforcement?

Learn more: https://peterattiamd.com/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#112 - Ned David, Ph.D.: How cellular senescence influences aging, and what we can do about it Jun 01, 2020

Show notes

Ned David is the co-founder of Unity Biotechnology, a company developing senolytic medicines—molecules that target and destroy senescent cells in the human body. In this episode, Ned explains the science of cellular senescence and how it impacts the aging process. Ned discusses how senolytics may delay, prevent, treat, or even reverse age-related diseases, including cancer, cardiovascular disease, and neurodegenerative disease. As a serial entrepreneur, Ned also provides advice on how to transform a simple idea into the creation of a company.

We discuss:

Defining longevity and the principles of aging [2:50];
The control knobs of aging and how we can turn them [15:10];
Role of cellular senescence in aging and cancer [27:00];
History of senescence in scientific study [40:30];
The cellular senescence paradox [46:00];
Developing medicines that target cellular senescence [52:15];
Ned's lessons on risk analysis in business [1:05:15];
The search for a molecule that could eliminate senescent cells [1:15:15];
Senescent cell elimination example in osteoarthritic knees [1:30:30];
Extending lifespan by removing senescent cells [1:45:00];
Senolytic molecule example in macular degeneration reversal [1:52:30];
The future of senescent cell targeting [1:58:30];
The role of cellular senescence and metabolic syndrome [2:01:30];
The role of cellular senescence and brain health [2:03:30]
What prepared Ned to start Unity Biotechnology [2:05:45];
Advice for someone deciding between business and academics [2:08:50]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/neddavid Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#111 - AMA #14: What lab tests can (and cannot) inform us about our overall objective of longevity May 18, 2020

Show notes

In this "Ask Me Anything" (AMA) episode, Peter explains his framework for understanding what lab tests can (and cannot) inform us as it pertains to overall longevity, with a specific focus on atherosclerosis, cancer, Alzheimer's disease, and the physical body. Additionally, Peter shares details into two patient case studies around cardiovascular disease, including how the lab results influenced his diagnosis and treatment plan for the patients. Once again, Bob Kaplan, Peter's head of research, will be asking the questions. 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 #14 show notes page.

We discuss:

Important lab tests and reference ranges [2:35];
How lab testing fits into the overall objective of longevity [4:25];
A healthcare system set up to react to a disease rather than prevent it [8:00];
The four pillars of chronic disease, and the three components of healthspan [14:30];
Atherosclerosis—How much can labs tell us about risk? [18:00];
Coronary calcium score (CAC)—Interpreting results based on your age [24:15];
Cancer—What lab work can tell you, and the future of liquid biopsies [28:00];
Alzheimer's disease—What's driving Alzheimer's disease, and what labs can tell you about your risk [33:15];
Healthspan and the physical body—Where lab testing fits, the endocrine system, and zone 2 testing [39:00];
Summarizing the usefulness of lab testing—Where it gives great, reasonable, or lousy insight [43:15];
Patient case study—Elevated Lp(a): Understanding ApoB, and how cholesterol levels get reduced [45:30];
Patient case study—Familial hypercholesterolemia [59:30];
Coming up on a future AMA [1:10:30]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/ama14 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#110 - Lew Cantley, Ph.D.: Cancer metabolism, cancer therapies, and the discovery of PI3K May 11, 2020

Show notes

In this episode, Lew Cantley, Professor of cancer biology and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College in NYC, walks us through his amazing discovery of phosphoinositide 3-kinase (PI3K) and the implications for the care of patients with cancer. He explains various combinations of therapies being tested and used, including the possibility of pairing prescriptive nutritional therapies to increase the efficacy of drugs like PI3K inhibitors. Lew also explains the metabolic nature of cancer through the lens of his research into the connection between sugar consumption, insulin resistance, and tumor growth. Additionally, Lew provides some details about his exciting new clinical trial that is just now enrolling patients with stage 4 breast cancer and endometrial cancer.

We discuss:

Teaching science through the lens of discovery—A better approach to learning science [5:15];
The metabolic nature of cancer, mitochondria, and a more nuanced explanation of the Warburg Effect [8:30];
The observation that convinced Lew to stop eating sugar [20:15];
The connection between obesity, insulin resistance, and cancer [25:30];
Sugar consumption and tumor growth—What did Lew's 2019 paper find? [32:00];
Natural sugar vs. HFCS, fruit vs. fruit juice, insulin response and cancer growth [43:00];
Increasing efficacy of PI3K inhibitors with ketogenic diets, SGLT2 inhibitors, and metformin [53:30];
Lew's clinical trial enrolling stage 4 breast cancer and endometrial cancer patients [1:07:30];
Pairing diet with drug could be the future of cancer treatment [1:09:30];
PI3K inhibitors on the market, alpha vs. delta isoform, and the possibility of pairing them with a food prescription [1:16:15];
What questions will Lew be focused on in the next chapter of his career? [1:22:15];
Lew's early work that ultimately led to the discovery of PI3K [1:27:30];
Studying the mechanism by which mitochondria make ATP [1:30:45];
How understanding the mechanism by which insulin drove glucose uptake into a cell got Lew closer to finding PI3K [1:38:15];
How Lew knew PI3K was important in driving the growth of cancer cells [1:55:00];
Lew's unlikely observation of phosphorylation at the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate [1:59:00]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/lewcantley/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#109 - John Dudley: The beauty in archery, the love of practice, and a model system for life May 04, 2020

Show notes

In this episode, professional archer, John Dudley, shares the many insights he's gleaned through the process of not only becoming an elite competitor of archery but also an exceptional teacher. John describes how his desire for improvement has cultivated a sheer love of practice, and how pursuing mastery helped put into context how archery is an amazing model system for life. Additionally, John discusses the often misunderstood nature of hunting, but also makes the case as to why one should consider trying archery even if there is no desire to hunt. We discuss:

Why John loves archery, and what it means to be a professional archer [4:50];
How John's love of practice and training led to archery [10:45];
How an intense desire to improve drove John to quit football and pursue archery [22:00];
A traumatic childhood event that changed John's course from troublemaker to committed athlete [34:15];
The nuts and bolts of archery—Competitive events, types of bows, hunting, etc. [45:30];
The blissful nature of archery, and the uselessness of anger [57:15];
Hyper-focus and flow states—Did John's ADD and task-driven personality give him an advantage? [1:07:15];
The common traits found in the most successful people [1:12:45];
The keys to maintaining credibility as a salesman—Integrity, honesty, and straightforwardness [1:18:45];
The coaching technique that makes John a great teacher [1:28:30];
Why you should consider trying archery (even if you never want to hunt) [1:36:15];
Hunting discussion—The morality argument, hunting vs. commercial farming, managing overpopulation, and the unique emotional connection [1:45:00];
Resources for those interested in taking up archery [2:12:00]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/johndudley Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

#108 - AMA #13: 3-day fasting, exogenous ketones, autophagy, and exercise for longevity Apr 21, 2020

Show notes

In this "Ask Me Anything" (AMA) episode, Peter explains some observations he's noticed since switching to a 3-day fasting cycle from the longer fasts, the various things he's measuring, and some helpful tips for getting through a prolonged fast. He also discusses the role of exogenous ketones in fasting and ketogenic diets as well as their impact on autophagy, specifically. Finally, Peter provides some practical advice for those looking to fit exercise for longevity into their busy life. Once again, Bob Kaplan, Peter's head of research, will be asking the questions. 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 #13 show notes page. If you are not a subscriber, you'll be able to listen to a sneak peak of this episode.

We discuss:

Peter's observations since switching from a 7-day to a 3-day fasting regimen [1:25];
Ketone measuring devices—blood and breath [7:40];
Can zero-calorie sweeteners affect ketone production? [10:40];
Will there be a continuous insulin monitor anytime soon? [11:55];
Exogenous ketones—Role in fasting and ketogenic diets and their effect on insulin, blood glucose, and autophagy [14:10];
5 tips to help you get through a multi-day fast [25:55];
Relationship between BHB levels, glucose levels, and autophagy—Are high levels of ketones enough to produce autophagy? [34:10];
Why is measuring blood insulin so much harder than blood glucose? [36:55];
Advice and resources for people wanting to stay up to date on developments related to health and longevity (and how to quickly sift through all the bad science) [40:10];
Advice for those looking to fit exercise for longevity into their busy life [51:10]; and
More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/ama13 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

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