AMA
Pros and cons of GLP-1 weight loss drugs and metformin as a geroprotective agent
#246 – AMA #45: Pros and cons of GLP-1 weight loss drugs and metformin as a geroprotective agent
In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.”
- The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss [2:30];
- Overview of GLP-1 agonists and why these drugs are getting so much attention [6:15];
- Defining the term “geroprotective” [11:30];
- Semaglutide: background, brand names, indications, and more [15:15];
- Tirzepatide: background, brand names, indications, and more [19:15];
- How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics [23:45];
- Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide [29:00];
- What happens to body weight when a patient discontinues the medication? [34:45];
- Noteworthy side effects of GLP-1 agonists and similar classes of drugs [40:45];
- Increased resting heart rate and other concerning trends in patients using GLP-1 agonists [45:15];
- Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists [50:45];
- Possible reasons for the loss of lean muscle mass and tips for protecting lean mass [59:00];
- GLP-1 agonists and thyroid cancer [1:01:30];
- Who might be a candidate for GLP-1 agonists? [1:03:45];
- The large financial cost of this class of drugs [1:08:30];
- Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients [1:11:30];
- A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics [1:21:00];
- Peter’s current approach with metformin for his patients [1:25:15]; and
- More.
AMA
Peter’s historical changes in body composition with his evolving dietary, fasting, and training protocols
#242 – AMA #44: Peter’s historical changes in body composition with his evolving dietary, fasting, and training protocols
In this “Ask Me Anything” (AMA) episode, Peter reviews the last 12+ years of his DEXA scan results revealing the changes to his body composition, lean muscle mass, visceral adipose tissue, and more. He explains how his body composition and blood biomarkers were impacted by the various dietary approaches (ketosis, fasting, high protein, etc.) and training protocols (primarily endurance, primarily strength training, etc.) he has undertaken over the years. Furthermore, Peter explains his planned approach moving forward following his most recent DEXA scan in late 2022.
- DEXA scans and other methods for tracking body composition [2:30];
- Importance of tracking data over time to see trends [10:15];
- DEXA scans in 2011: swimming, lifting, and a carb-restricted diet [12:45];
- DEXA scans 2012-2014 during Peter’s time on a strict ketogenic diet [18:30];
- Blood biomarkers for evaluating metabolic health [25:15];
- DEXA scan in 2020 after several years of regularly engaging in time-restricted feeding and prolonged fasting protocols [28:45];
- DEXA scan in 2021: shifting focus to adding muscle, high-protein diet, and more strength training [40:00];
- DEXA scan in early 2022: eating additional calories and adding blood flow restriction (BFR) to his workouts [44:45];
- DEXA scan in late 2022: a dramatic change following shoulder surgery, and the impact of stress [48:30];
- Peter’s approach moving forward following his most recent DEXA scan [59:15];
- A rundown of the various nutritional methods of energy restriction [1:06:15];
- Current thoughts on fasting and key takeaways [1:09:45]; and
- More.
AMA
Understanding apoB, LDL-C, Lp(a), and insulin as risk factors for cardiovascular disease
#238 – AMA #43: Understanding apoB, LDL-C, Lp(a), and insulin as risk factors for cardiovascular disease
In this “Ask Me Anything” (AMA) episode, Peter answers questions related to the leading cause of death in both men and women—atherosclerotic cardiovascular disease (ASCVD). He highlights the most important risk factors for ASCVD, such as apoB, LDL, hyperinsulinemia, and Lp(a), and explains the mechanism by which they confer risk and how these factors are interrelated. Peter also dives deep into the data around apoB to try to answer the question of how much residual risk is conferred for ASCVD through metabolic dysfunction once you correct for apoB. He also looks at the data around lifetime risk reduction of ASCVD in the context of low apoB.
- A racecar analogy for understanding atherosclerotic cardiovascular disease [2:00];
- Defining and differentiating apoB and LDL-C [10:00];
- The interrelated nature of insulin levels, apoB, triglycerides, and ASCVD parameters [13:00];
- Another way that hyperinsulinemia plays a role in endothelial dysfunction [18:00];
- Why Peter uses the oral glucose tolerance test (OGTT) with all patients [20:15];
- Is there any evidence that hyperinsulinemia is an independent contributor to ASCVD? [23:00];
- Thinking through risk in the context of high-fat diets resulting in improved metabolic metrics but with an elevation of apoB/LDL-C [27:30];
- Thinking through risk in the context of low apoB but higher than normal triglyceride levels [32:15];
- The importance of lowering apoB for reducing ASCVD risk [38:15];
- Data on men and women with familial hypercholesterolemia that demonstrates the direct impact of high apoB and LDL-C on ASCVD risk [47:45];
- Importance of starting prevention early, calcium scores, and explaining causality [52:30];
- Defining Lp(a), its impact on ASCVD risk, and what you should know if you have high Lp(a) [56:30];
- Lp(a) and ethnic differences in risk [1:00:30];
- Why someone with elevated Lp(a) should consider being more aggressive with apoB lowering strategies [1:05:00];
- Addressing the common feeling of hesitancy to taking a pharmacologic approach to lower ASCVD risk [1:07:15];
- Peter’s take on the 2022 Formula 1 season and thoughts on 2023 [1:15:15]; and
- More.
AMA
Optimizing sleep - bedtime routine, molecule regimen, sleep trackers, sauna, & more
#233 – AMA #42: Optimizing sleep – bedtime routine, molecule regimen, sleep trackers, sauna, & more
In this “Ask Me Anything” (AMA) episode, Peter answers a number of questions on optimizing sleep. He describes his pre-bedtime routine, how he utilizes a sauna, and his current regimen of medicines and supplements for improving sleep time and quality. He goes in depth on each of the molecules that have shown promise in boosting sleep, including their mechanisms of action as well as any noteworthy contraindications. Peter also discusses sleep wearables, including both the positives and potential negatives of using such trackers, and much more.
- Peter’s current pre-bedtime routine [3:30];
- Sauna: Peter’s routine, sleep benefits, and tradeoffs [10:45];
- Importance of keeping an open mind as new information arrives [16:15];
- Importance of reducing stimulation leading up to bedtime [19:30];
- Medications that can enhance sleep: mechanisms of action, contraindications, risks, and Peter’s regimen [20:30];
- Why medications can enhance sleep, but should not replace good sleep habits [34:45];
- Sleep supplements: mechanisms of action, contraindications, and Peter’s regimen [37:30];
- Temperature during sleep, cooling devices, mattresses, and more [53:00];
- A tip to help avoid straining your back in the morning [59:15];
- Contrasting polysomnography with wearable sleep trackers [1:00:45];
- Sleep tracking wearables: interpreting metrics, and the pros and cons of trackers [1:04:30];
- Final takeaways on sleep [1:16:30]; and
- More.
AMA
Medicine 3.0, developments in the field of aging, healthy habits in times of stress, and more
#231 – AMA #41: Medicine 3.0, developments in the field of aging, healthy habits in times of stress, and more
In this “Ask Me Anything” (AMA) episode, Peter answers a wide variety of questions, starting with a discussion on the evolution of medicine and the hopeful transition to “Medicine 3.0.” Peter recounts his unique career path and explains how he assesses risk and utilizes frameworks for decision-making. He also describes how he prioritizes his health while navigating the stresses of life, and he reviews the most exciting developments in the aging and longevity space. He finishes with some rapid-fire questions on cold plunging, strategies for lowering apoB levels, designing an exercise program for beginners, and more.
- The evolution of medicine and the transition to “Medicine 3.0” [3:00];
- Peter’s unorthodox career arc and what led him to this point [11:45];
- What does Peter consider to be his superpowers? [22:15];
- How Peter thinks about risk and explains it to his patients when making medical decisions [26:45];
- The advantage of using frameworks for decision-making [37:00];
- What advice would Peter give his 30-year old self? [42:15];
- Why longevity is such a hard problem to solve [42:30];
- The most impactful developments in the field of longevity and aging in the last 5 to 10 years [46:15];
- What is Peter most excited to see develop in the health and longevity space in the next few years? [51:30];
- Prioritizing healthy habits while navigating the stresses of life and time constraints [53:45];
- How Peter navigates periods of high stress [58:00];
- What fitness watch did Peter recently purchase? [1:03:45];
- Potential benefits of cold plunging [1:05:15];
- Advice for someone beginning an exercise program [1:07:30];
- Strategies and tactics to lower apoB levels [1:09:00];
- Interesting studies and books Peter has recently read [1:11:30]; and
- More.
AMA
Body composition, protein, time-restricted feeding, fasting, DEXA scans, and more
#227 – AMA #40: Body composition, protein, time-restricted feeding, fasting, DEXA scans, and more
In this “Ask Me Anything” (AMA) episode, Peter discusses the importance of understanding body composition and explains how to interpret the most important metrics revealed by a DEXA scan, such as lean muscle tissue mass, visceral adiposity tissue mass, bone mineral density, and more. He discusses common concerning trends in these metrics as well as strategies to address them. He goes through DEXA scan results of both male and female patient case studies and explains the prescribed intervention for each patient. Additionally, Peter answers numerous questions about dietary protein including how much we need, when we need it, and how intake should be divided throughout the day to optimize muscle protein synthesis. Finally, Peter provides his updated point of view on time-restricted feeding and fasting and how his personal approach and recommendations for patients has evolved.
- Interpreting DEXA scans: important metrics, radiation levels, and more [2:15];
- DEXA metrics: Bone mineral density (BMD) [12:00];
- DEXA metrics: Visceral adipose tissue (VAT) [14:30];
- DEXA metrics on lean tissue: appendicular lean mass index (ALMI) and fat-free mass index (FFMI) [20:45];
- Concerning trends in BMD, VAT, & muscle mass revealed through DEXA scans [24:15];
- Muscle and lean tissue loss with age and how to overcome anabolic resistance [29:15];
- Female patient case studies: DEXA scan results and prescribed interventions [35:00];
- Male patient case studies: DEXA scan results and prescribed interventions [42:45];
- Protein consumption: recommended daily intake, Peter’s personal approach, timing around workouts, and more [48:15];
- What to look for with protein supplements [53:15];
- Protein intake: optimal timing and how it should be divided throughout the day [55:30];
- Time-restricted feeding (TRF): Peter’s updated perspective [57:45];
- Three strategies for reducing energy intake in over-nourished patients [1:03:15];
- Prolonged fasting: potential benefits and tradeoffs [1:07:15];
- A protein-supplemented version of time-restricted feeding (TRF) [1:09:30];
- Theories about time-restricted feeding (TRF) and its positive influence on sleep and circadian rhythm [1:12:00]; and
- More.
AMA
The Centenarian Decathlon, zone 2, VO2 max, and more
#223 – AMA #39: The Centenarian Decathlon, zone 2, VO2 max, and more
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.
- 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 VO2 max 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
- More.
AMA
Can you exercise too much?
#218 – AMA #38: Can you exercise too much?
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.
- How exercise reduces risk for all-cause mortality [2:30];
- Defining the metric called “MET” and how it’s useful for evaluating different exercises [7:45];
- The challenge in determining the optimal dose of exercise and the limitations of methods used to study the effect of exercise [13:30];
- Using VO2 max as a proxy for fitness to better predict mortality risk [19:00];
- Reviewing data which support the theory of a “J-curve” relationship between exercise and longevity [24:45];
- Importance of understanding p-values and statistical significance [33:30];
- Deconstructing the studies that show a J-curve: major limitations and how one could be misled [36:45];
- Peter’s takeaways on the theoretical “J-curve” relationship between exercise and longevity [51:15];
- Risk of sudden cardiac death from vigorous physical exertion [53:45];
- Atrial fibrillation associated with extreme levels of exercise [1:00:00];
- Parting thoughts: benefits of exercise far outweigh the risks [1:04:00]; and
- More.
AMA
Bone health—everything you need to know
#214 – AMA #37: Bone health—everything you need to know
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.
- 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) impacts 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
- More.
AMA
Fruits & vegetables—everything you need to know
#211 – AMA #36: Fruits & vegetables—everything you need to know
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.
- 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];
- Green powder supplements [1:11:15];
- Important takeaways [1:16:00]; and
- More.
AMA
"Anti-Aging" Drugs — NAD+, metformin, & rapamycin
#207 – AMA #35: “Anti-Aging” Drugs — NAD+, metformin, & rapamycin
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.
- 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
- More.
AMA
What Causes Heart Disease?
#203 – AMA #34: What Causes Heart Disease?
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.
- 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]
- Calcium scores: 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];
- Key takeaways regarding prevention [1:15:45];
- More.
AMA
Hydration—electrolytes, supplements, sports drinks, performance effects, and more
#200 – AMA #33: Hydration—electrolytes, supplements, sports drinks, performance effects, and more
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.
- 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];
- Key takeaways related to hydration [1:18:15]; and
- More.
AMA
Exercise, squats, deadlifts, BFR, and TRT
#196 – AMA #32: Exercise, squats, deadlifts, BFR, and TRT
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.
- 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
- More.
AMA
Heart rate variability (HRV), alcohol, sleep, and more
#193 – AMA #31: Heart rate variability (HRV), alcohol, sleep, and more
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.
- 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];
- Analysis of epidemiology studies suggesting moderate alcohol consumption lowers mortality risk [52:00];
- Alcohol consumption and Alzheimer’s disease [1:05:15];
- Heavy alcohol consumption and risk of dementia [1:08:30];
- Chronic effects of alcohol on the liver [1:17:45];
- The relationship between alcohol, sleep, and automotive deaths [1:20:45]; and
- More.
AMA
How to Read and Understand Scientific Studies
#188 – AMA #30: How to Read and Understand Scientific Studies
In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into all things related to studying studies to help one sift through all the noise to find the signal. They define the various types of studies, how a study progresses from idea to execution, and how to identify study strengths and limitations. They explain how clinical trials work, as well as the potential for bias and common pitfalls to watch out for. They dig into key factors that contribute to the rigor (or lack thereof) of an experiment, and they discuss how to measure effect size, differentiate relative risk from absolute risk, and what it really means when a study is statistically significant. Finally, Peter lays out his personal process when reading through scientific papers.
- 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.
AMA
GLP-1 Agonists - The Future of Treating Obesity?
#184 – AMA #29: GLP-1 Agonists – The Future of Treating Obesity?
In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss all things related to GLP-1 agonists—a class of drugs that are gaining popularity for the treatment of obesity. They cover the discovery of these peptides, their physiology, and what it is they do in their natural state. Next, Peter and Bob break down a recently published study which showed remarkable results for weight loss and other metabolic parameters using a once-weekly injection of the GLP-1 agonist drug semaglutide, also known as Ozempic, in overweight and obese patients. Finally, they compare results from the semaglutide study to results from various lifestyle interventions and give their take on the potential future of GLP-1 agonists.
- Remarkable results of a recent study in overweight adults [2:15];
- Key background on insulin, glucagon and the incretin effect to appreciate the effects of semaglutide [4:00];
- What is GLP-1 and how does it work? [16:30];
- 2021 semaglutide study: remarkable results, side effects, and open questions [30:00];
- Semaglutide vs. lifestyle interventions: comparing results with semaglutide vs. lifestyle interventions alone [44:00];
- Closing thoughts and open questions on the therapeutic potential of semaglutide [47:30]; and
- More.
AMA
All things testosterone and testosterone replacement therapy
#180 – AMA #28: All things testosterone and testosterone replacement therapy
In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss all things related to testosterone: what happens when testosterone levels are low, and the potential benefits and risks of testosterone replacement therapy (TRT). They explain the physiology of testosterone, how it works, and how its level changes over the course of a person’s life. They have a detailed discussion about existing literature, which reveals vast potential structural, functional, and metabolic benefits of testosterone replacement therapy. They also take a very close look at potential risks of this therapy, with a focus on the controversial effects on cardiovascular disease and prostate cancer.
- A primer on the hormone testosterone and how it influences gene expression [3:30];
- How the body naturally regulates testosterone levels [11:30];
- The defining threshold for “low testosterone,” how low T impacts men, and why free testosterone is the most important metric [16:15];
- When it makes sense to treat low testosterone [26:00];
- The structural and metabolic benefits of testosterone replacement therapy [29:15];
- Body composition changes with TRT [45:30];
- Changes in bone mineral density with TRT [48:15];
- The metabolic impact of TRT: glucose, insulin, triglycerides, and more [52:30];
- A study investigating testosterone replacement therapy for prevention or reversal of type 2 diabetes [59:30];
- The impact of TRT on metabolic parameters and body composition—A study comparing results from continuous vs. interrupted treatment [1:07:15];
- The controversy over TRT and cardiovascular disease [1:21:45];
- Two flawed studies that shaped perceptions of risks associated with TRT [1:44:15];
- The controversy over TRT and prostate cancer [1:56:45];
- Other potential risks with testosterone replacement therapy [2:02:15]; and
- More
AMA
The importance of muscle mass, strength, and cardiorespiratory fitness for longevity
#176 – AMA #27: The importance of muscle mass, strength, and cardiorespiratory fitness for longevity
In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss the longevity benefits from greater cardiorespiratory fitness (CRF) and greater muscle mass and strength. Conversely, they dive deep into the literature showing a rapid increase in morbidity and mortality risk as fitness levels decline with age. They also try to tease out the relative contributions of CRF, muscle mass, and strength. Additionally, they discuss the impact of fasting on muscle mass, the potential tradeoffs to consider, and finish by discussing why it’s critical to maximize your fitness level.
- VO2 max and its association with cardiorespiratory fitness [2:45];
- Changing mortality risk based on VO2 max and cardiorespiratory fitness [7:45];
- The profound impact of improving cardiorespiratory fitness [15:15];
- Muscle mass, function, and loss with aging: how it’s defined, measured, and the cutoff points for sarcopenia [25:00];
- Increasing mortality risk associated with declining muscle mass and strength [40:00];
- Muscle size vs. strength—which has the bigger impact on mortality risk? [58:00];
- Evaluating the cumulative impact of cardiorespiratory fitness and muscular strength on mortality risk when put together [1:03:30];
- Investigating the rising incidence in deaths from falls, and what role Alzheimer’s disease might play [1:09:00];
- The impact of fasting on muscle mass and the potential tradeoffs to consider [1:14:30];
- The critical importance of working to maintain muscle mass and strength as we age [1:20:30]; and
- More.
AMA
Continuous glucose monitors, zone 2 training, and a framework for interventions
#173 – AMA #26: Continuous glucose monitors, zone 2 training, and a framework for interventions
In this “Ask Me Anything” (AMA) episode, Peter and Bob answer numerous follow-up questions to recently discussed deep-dive topics such as the use of continuous glucose monitors and getting the most from zone 2 exercise. They also discuss the incredible feats of cyclists in the Tour de France through the lens of the amazing performance physiology required from these athletes. Additionally, Peter ties the conversation together by sharing his foundational framework when considering different interventions, even in the absence of data from a randomized controlled trial.
- Peter’s foundational framework when considering different interventions [1:30];
- Applying Peter’s framework to the idea of using a CGM [8:00];
- Why certain fruits have a bigger impact on glucose, and the limitations of a CGM can tell you [16:00];
- Importance of paying attention to insulin, and the prospects of a continuous monitor for insulin levels [20:00];
- How exercise impacts glucose and peak glucose numbers to stay under [24:15];
- Impact of anxiety on stress on glucose, and why it’s important to calibrate your CGM [26:30];
- The five main tools for managing blood glucose numbers [33:45];
- Benefits of moving or exercising after a meal, and where ingested carbohydrates get can be stored [37:15];
- How to make decisions about an action or intervention in the absence of data from a rigorous, randomized controlled trial [40:30];
- The incredible athletic feats of Tour de France cyclists [48:30];
- Different modalities for doing zone 2 exercise: running, rowing, cycling, and more [1:00:15];
- Proxies for knowing your in zone 2 short of using a lactate monitor [1:07:30];
- Monitoring lactate for zone 2 exercise [1:10:00]; and
- More.
AMA
Navigating the complexities and nuances of cancer screening
#170 – AMA #25: Navigating the complexities and nuances of cancer screening
In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into cancer screening, including why it’s important, what you need to know about a test, and Peter’s approach with patients. They specifically discuss various screening methods, explain important terms like sensitivity and specificity, and how layering and stacking different tests in tandem can improve predictive values. They conclude with a discussion on one of the more exciting screening tools, diffusion-weighted MRI, and how it’s changing the cancer screening landscape.
- The importance of cancer screening [1:15];
- Cancer screening terms: sensitivity, specificity, false positives, and false negatives [8:25];
- Cancer screening terms: positive and negative predictive value [17:00];
- Improving predictive value by layering tests, and the predictive values of mammograms [25:45];
- How smoking impacts the predictive value of cancer screening [30:45];
- Liquid biopsies for ruling out cancer and the blind spots of common cancer screening tests [33:00];
- The difference between cancer originating from inside versus outside the body [41:15];
- How diffusion-weighted MRI is changing cancer screening [45:15];
- Summary of Peter’s approach to cancer screening [53:45]; and
- More.
AMA
Deep dive into blood glucose: why it matters, important metrics to track, and superior insights from a CGM
#165 – AMA #24: Deep dive into blood glucose: why it matters, important metrics to track, and superior insights from a CGM
In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into blood glucose and why it matters so much with respect to metabolic health and longevity. They explain the need to pay close attention to metrics like average blood glucose, glucose variability, and peak glucose numbers. Additionally, Peter explains why he encourages all his patients, even nondiabetics, to utilize a continuous glucose monitor (CGM) which gives important insights that traditional lab testing and metrics consistently miss.
- The problem with traditional blood tests and metrics for determining metabolic health [1:10];
- The superior insights from a continuous glucose monitor [6:15];
- Why lower is better than higher: average glucose, glucose variability, and glucose peaks [12:00];
- Deep dive into average blood glucose and the importance of having the lowest average blood glucose possible [14:45];
- Deep dive into glucose variability and why less variability is better [33:15];
- Example of how HbA1c and traditional measures could catch metabolic issues too late [41:45];
- Postprandial dips in blood glucose as a predictor of subsequent hunger and energy intake [43:00];
- Exploring the idea that the suppression of fatty acids is actually causing hunger rather than a low blood glucose [49:45];
- Deep dive into peak glucose and why lower peaks is better [57:15];
- What the best rodent models tell us about the impact of peak glucose levels [1:06:25];
- Why Peter encourages all his patients to wear a CGM [1:14:30]; and
- More.
AMA
All Things Nicotine: deep dive into its cognitive and physical benefits, risks, and mechanisms of action
#161 – AMA #23: All Things Nicotine: deep dive into its cognitive and physical benefits, risks, and mechanisms of action
In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into nicotine, a complicated and interesting molecule that has effects on both the brain and the body. They analyze the results of the studies that describe nicotine’s cognitive benefits and potential for inducing weight loss. They talk about a smoking cessation technique called nicotine replacement therapy and give a full breakdown of the various routes of administration, dosing, and safety. Finally, they explore the fascinating and counterintuitive observation that cigarette smokers are less likely to get a severe case of COVID-19.
- How Peter first became interested in the potential benefits of nicotine [1:15];
- Untangling nicotine from tobacco [6:00];
- Nicotine replacement therapy (NRT) for quitting smoking: products, protocols, and a review of the literature [9:30];
- The cognitive benefits of nicotine: Overview of the literature [15:50];
- Where nicotine has the most positive impact on cognition [30:30];
- Possible mechanisms conferring the benefits of nicotine [37:00];
- How modafinil and other nootropics compare to nicotine [47:15];
- How nicotine may induce weight loss [54:00];
- Relationship between smoking and COVID-19: Analyzing the observation that smoking appears protective against COVID-19 [1:01:45];
- Breakdown of the various nicotine replacement therapies: route of administration, dosing, and safety [1:11:30];
- Concluding thoughts on nicotine: use cases, addictive properties, and more [1:19:45]; and
- More.
AMA
Losing fat and gaining fat: the lessons of fat flux
#157 – AMA #22: Losing fat and gaining fat: the lessons of fat flux
In this “Ask Me Anything” (AMA) episode, Peter and Bob take a deep dive into fat flux. They define the major players that impact the flow of fat entering and exiting a fat cell, which determines how much fat a person carries. They discuss the significant influence that insulin has on the net fat balance and explore common strategies, such as fasting and low-carb diets, that have efficacy in the liberation and oxidation of fat from fat cells. Additionally, Bob explains his research process and how he seeks answers to Peter’s challenging questions.
- The two main ways to reduce fat mass (1:30);
- Explaining fat flux—how fat enters and exits a fat cell (9:15);
- What fat balance looks like (21:15);
- What net fat influx looks like, and the impact of insulin in lipolysis (24:30);
- What net fat efflux looks like, and the benefits of fasting for breaking the hyperinsulinemic cycle (28:30);
- Exploring why most people with excess body fat will lose fat mass when reducing carbohydrates or eating a ketogenic diet (32:45);
- Why being in nutritional ketosis does not automatically translate to negative fat flux (fat loss) (42:40);
- Bob’s approach to scientific research (47:00);
- The importance of curiosity and a desire to learn (58:30);
- Bob’s tips and tricks for answering a scientific question in a time-crunch (1:00:00); and
- More.
