#02 - Rhonda Patrick, Ph.D.: the performance and longevity paradox of IGF-1, ketogenic diets and genetics, the health benefits of sauna, NAD+, and more
Dr. Rhonda Patrick joins Peter Attia to discuss evolving scientific beliefs, the IGF-1 paradox, PPARs, and genetic responses to ketogenic diets. They also explore the health benefits of heat and cold exposure, and the role of NAD+ in longevity.
Deep Dive Analysis
11 Topic Outline
Rhonda's Evolving Beliefs on Longevity Modalities
Rethinking Caloric Restriction and IGF-1
Ketogenic Diets: Long-term Benefits and Challenges
Genetic Factors Influencing Ketogenic Diet Response
The Paradox of IGF-1 in Human Health and Longevity
Prolonged Fasting for Autoimmune Disease and Cancer
Exercise as a Primary Driver of Brain Health
The Health Benefits of Sauna and Heat Exposure
The Benefits of Cold Exposure and Mitochondrial Biogenesis
Understanding NAD+ Decline and Supplementation
Unanswered Questions: Optimal Fasting and Rapamycin Dosing
7 Key Concepts
IGF-1 Paradox
While low IGF-1 levels are linked to increased longevity in some simple organisms and can be beneficial during fasting, it is also crucial for muscle repair, neurogenesis, and stem cell proliferation during refeeding, suggesting that chronically low levels may not always be optimal for human health.
PPAR-alpha
A nuclear hormone receptor transcription factor primarily found in the liver, which plays a critical role in fatty acid catabolism and the production of ketone bodies. Genetic variations in PPAR-alpha can influence an individual's ability to generate ketones and metabolize fats.
PPAR-gamma
A nuclear hormone receptor transcription factor highly expressed in adipose tissue, involved in the uptake of fatty acids into fat cells. Genetic variations in PPAR-gamma can affect lipid metabolism, potentially leading to higher free fatty acids and impacting insulin sensitivity.
Fasting Mimicking Diet (FMD)
A periodic, low-calorie, low-protein dietary regimen designed to induce the cellular and systemic effects of prolonged water-only fasting, such as cellular rejuvenation, stem cell activation, and potential benefits for autoimmune diseases and cancer.
Heat Shock Proteins
A family of proteins produced by cells in response to various stressors, particularly heat. They play a crucial role in maintaining protein homeostasis, cellular protection, and are implicated in preventing neurodegenerative diseases.
NAD+ (Nicotinamide Adenine Dinucleotide)
A vital co-factor involved in numerous metabolic processes, including mitochondrial energy production and DNA repair. Its levels naturally decline with age, potentially due to increased consumption by DNA repair enzymes (PARPs) and inflammation.
PARP (Poly ADP-ribose Polymerase)
A family of enzymes that play a key role in DNA repair, consuming NAD+ as a substrate. Increased DNA damage and inflammation with aging can lead to higher PARP activation, contributing to the age-related decline in NAD+ levels.
7 Questions Answered
Rhonda now believes that chronic caloric restriction and low IGF-1 may not be the optimal path for health span, and she is more convinced of the long-term benefits of ketogenic diets, especially when combined with calorie restriction or cycling.
A subset of people, potentially due to genetic variations in genes like PPAR-alpha and PPAR-gamma, may respond poorly to high saturated fat ketogenic diets, leading to increased cholesterol biosynthesis, inflammation, and elevated LDL particle numbers.
These dietary interventions can induce cellular rejuvenation by promoting apoptosis of dysfunctional cells and activating stem cells during the refeeding phase, leading to the repopulation of tissues with healthy new cells, with potential benefits for autoimmune diseases and cancer.
Regular sauna use, particularly 4-7 times per week, is linked to a 50% lower risk of cardiovascular-related mortality, a 40% lower risk of all-cause mortality, and a 20% lower risk of dementia and Alzheimer's disease, alongside improvements in arterial compliance and blood pressure.
Cold exposure can increase norepinephrine levels in the brain, which may improve focus and reduce anxiety, and it has also been shown to boost biomarkers of mitochondrial biogenesis in muscle and adipose tissue.
NAD+ levels decline with age primarily due to increased consumption by DNA repair enzymes (PARPs) in response to DNA damage and inflammation, as well as potential issues in the NAD+ salvage pathway. Animal studies suggest NAD+ precursors can improve health span and mitochondrial function.
Rhonda is most interested in determining the optimal frequency and duration of prolonged fasting in humans to maximize stem cell production, eliminate dysfunctional cells, and achieve a robust rejuvenation effect to delay age-related diseases.
19 Actionable Insights
1. Prioritize Daily Exercise for Brain Health
Prioritize daily physical activity for brain health, as it is considered a highly effective strategy for preserving cognitive function, improving executive function, and managing anxiety levels.
2. Incorporate Periodic Prolonged Fasts
Consider incorporating periodic prolonged fasts (e.g., a few days, a couple of times a year) to activate stem cells, clear dysfunctional cells, and promote cellular rejuvenation, potentially delaying age-related diseases and improving health span.
3. Regular Sauna Use for Longevity
Incorporate frequent sauna sessions (4-7 times per week, 20 minutes at 175-179°F in a dry sauna) to significantly reduce cardiovascular-related and all-cause mortality, and improve arterial compliance.
4. Maintain Muscle & Aerobic Performance
Focus on maintaining muscle mass and peak aerobic performance through regular exercise to dramatically improve your healthy years of life (median health span).
5. Suppress Chronic Inflammation
To promote longevity and cognitive function, prioritize strategies that suppress chronic inflammation, as low inflammation has been shown to be a key predictor of healthy aging and survival in centenarians.
6. Combine Ketogenic Diet with Time-Restricted Feeding
If considering a ketogenic diet for long-term health benefits, combine it with calorie restriction or time-restricted feeding (e.g., eating within an 8-9 hour window) to manage calorie intake and enhance benefits like increased health span and improved cognitive function.
7. Optimize Ketogenic Fat Burning
To optimize fat burning on a ketogenic diet and prevent fat storage, avoid constant fat intake and ensure periods of rest from eating, allowing for efficient fatty acid catabolism.
8. Sauna for Enhanced Sleep
To improve sleep quality, try a routine of sauna use before bed, followed by a cold shower, then sleeping in a cold environment, as this rapid temperature drop can enhance sleep onset and duration.
9. Sauna for Mood Improvement
Utilize sauna sessions to potentially improve mood and reduce depressive symptoms, as the heat stress induces IL-6 and beta-endorphin release, which are linked to antidepressant effects.
10. Choose Dry Saunas for Benefits
For optimal benefits from sauna use, prioritize traditional dry saunas that reach temperatures of 175-179°F, and aim for sessions of approximately 20 minutes.
11. Cold Showers for Focus
To enhance focus and reduce anxiety, consider taking cold showers, as this practice is associated with increased norepinephrine levels.
12. Cold Exposure for Mitochondria
To potentially increase mitochondrial biogenesis in adipose and muscle tissue, incorporate cold exposure into your routine.
13. Timing Cold Post-Strength Training
Avoid immediate cold exposure (within an hour) after strength training if your goal is muscle hypertrophy, as it may dampen the muscle growth response by interfering with the post-exercise inflammatory and repair processes.
14. Use Exogenous Ketones for Focus
To potentially enhance focus, reduce anxiety, or improve endurance performance, consider experimenting with exogenous ketones (e.g., BHB ester).
15. Exogenous Ketones Lower Glucose
To significantly lower blood glucose levels, even after a high-carbohydrate meal, consider taking a BHB ester, as it has been shown to cause substantial drops in blood glucose.
16. NAD Precursor Supplementation
To potentially combat age-related NAD decline and support mitochondrial function, consider supplementing with NAD precursors like nicotinamide riboside, which has shown benefits in animal models for muscle and brain health and increases NAD levels in humans.
17. Acarbose for High-Carb Meals
If you plan to indulge in high-carbohydrate meals, consider taking 100mg of Acarbose beforehand to significantly reduce or flatline your blood glucose response.
18. Explore Rapamycin for Longevity
Explore the potential of rapamycin for longevity and improving age-related conditions like cardiomyopathy, as it has shown life-extending effects across species and can improve cardiac function by targeting senescent cells.
19. Utilize Rhonda’s Video Podcasts
If you want to deeply understand complex scientific topics discussed on Rhonda Patrick’s podcast, watch her video podcasts for enhanced learning with on-screen explanations and definitions.
5 Key Quotes
Virtually all facts have a half-life and our knowledge is constantly evolving.
Peter Attia
The main reason I exercise is for my brain. It's certainly just not only for, you know, preventing neurogenetic disease and atrophy and all that, but just because it affects my executive function and affects my anxiety levels.
Rhonda Patrick
I think today I feel I am much more convinced by a lot of the data you've described, certainly the central stuff... if you took a completely unbiased approach and look at the literature, what was the single most compelling thing you could do to generate or preserve brain health? And we came away thinking that it was actually exercise.
Peter Attia
Fasting is not fun. I wish I could tell you that, you know, not eating is fun, but like, I just love eating. So anytime I'm not eating, I'm sort of like, there's a discipline that's required to do it.
Peter Attia
It's not hard to kill a cancer cell with a chemical that's trivial. It's hard to kill a cancer cell and not a normal cell.
Peter Attia
2 Protocols
Sauna Use for Cardiovascular & All-Cause Mortality Reduction
Rhonda Patrick (referencing Dr. Jari Laukkanen's work)- Use a dry sauna (or one where water can be thrown on rocks).
- Ensure temperature reaches 175-179 degrees Fahrenheit.
- Stay in the sauna for approximately 20 minutes per session.
- Repeat 4 to 7 times per week.
Acute Glucose Flatlining Protocol
Peter Attia- Take 100 milligrams of Acrobose.
- Consume immediately before a high-carbohydrate meal.