#202 - Peter on nutrition, disease prevention, sleep, and more — looking back on the last 100 episodes
In this "Strong Convictions, Loosely Held" episode, Peter Attia, joined by Nick Stenson, updates his views on cancer, cardiovascular disease, Alzheimer's genetics, nutrition (fasting, protein), psychedelics, and sleep. He also shares insights on Formula 1 racing.
Deep Dive Analysis
18 Topic Outline
The Concept of Strong Convictions, Loosely Held
Peter's Book Writing Process and Challenges
The Promise of Cancer Immunotherapy and Adaptive Cell Therapy
Aggressive Screening for Gastrointestinal Cancers
Early and Aggressive ApoB Reduction for ASCVD Prevention
Alzheimer's Disease: Genetic Modifiers Beyond APOE4
Time-Restricted Feeding: Caloric Restriction and Muscle Loss
Addressing Protein Underconsumption in Adults
Profound Impact of Exercise on Lifespan and Healthspan
Uninspiring Outlook on NAD Precursors for Longevity
Psychedelics as Adjuncts to Therapeutic Work
Updated Views on Sleep Aids and Blue Light Exposure
Book Recommendation: The Comfort Crisis
Formula 1: Key Variables for Race Victory
Formula 1: Tire Strategy and Pit Stops
Formula 1: Engine, Chassis, and 2022 Rule Changes
Formula 1: Importance of Qualifying and Race Strategy
Formula 1: 2022 Season Outlook and Predictions
6 Key Concepts
Strong Convictions, Loosely Held
An investment philosophy applied to science and medicine, emphasizing the need to base decisions on strong beliefs while remaining open to updating assumptions with new information. Peter Atiyah attributes this concept to his friend John Griffin.
Neoantigens
Unique proteins found on cancer cells that are recognized by the immune system, making them targets for immunotherapy. Peter Atiyah notes that 80% of patients have these, offering significant hope for future cancer treatments.
ApoB (Apolipoprotein B)
A single number that captures the total concentration of all lipoproteins (LDL, IDL, VLDL, Lp(a)) that contribute to atherosclerotic cardiovascular disease (ASCVD). It is considered a better predictor of ASCVD risk than LDL cholesterol.
Time-Restricted Feeding (TRF)
A dietary pattern where all daily food intake is consumed within a specific window of hours. Peter Atiyah believes most of its benefits, particularly for weight loss and insulin resistance, come from reduced caloric intake rather than a magical effect of the timing itself.
Sleep Architecture
The cyclical pattern of sleep stages (light sleep, deep sleep/slow-wave sleep, REM sleep). Effective sleep medications should preserve or improve this architecture, not just induce unconsciousness, to ensure restorative sleep.
Downforce (Formula 1)
An aerodynamic force that pushes a Formula 1 car down onto the track, increasing grip and allowing for higher speeds through corners. F1 cars generate so much downforce that they could theoretically drive upside down at speeds above 50-60 mph.
12 Questions Answered
It's an approach to knowledge and decision-making where one holds firm beliefs but is always ready to re-evaluate and change them based on new evidence, rather than digging in one's heels.
He is now far more optimistic, believing that designer-based immunotherapies will eradicate most solid organ metastatic cancers within 10 years, based on the high percentage of patients with neoantigens recognized by their immune system.
Peter Atiyah advocates for much more aggressive screening, suggesting colonoscopies every 1 to 3 years starting around age 40, rather than the standard 5-10 years, to prevent colon, esophageal, and stomach cancers.
Peter Atiyah suggests an ApoB ceiling of 60 mg/dL, ideally aiming for levels in the 20-30 mg/dL range (infantile levels) to effectively eliminate death from atherosclerotic causes.
Beyond APOE4, genes like TOM40 and certain mitochondrial haplotypes can amplify risk, while a specific KLVS subtype of the clotho gene appears to erase the downside of APOE4, returning risk to baseline.
Peter Atiyah believes most of the benefit from TRF comes from caloric restriction, as a narrower eating window naturally makes it harder to consume excessive calories, rather than any magical effect of the timing itself.
Peter Atiyah suggests that the current RDA of 0.8 grams per kilogram of body weight is insufficient for thriving, and optimal intake is closer to 2 grams per kilogram or about 1 gram per pound of body weight.
Exercise has an unbelievable impact on lifespan and healthspan, likely greater than any other intervention, with improvements in cardiorespiratory fitness (VO2 max) and strength significantly reducing all-cause mortality.
He remains uninspired and pessimistic about NAD precursors (NR, NMN) as a longevity tool, as he believes there's no clear evidence of phenotypic benefit in normal aging individuals, despite their ability to increase NAD levels.
Psychedelics like psilocybin and MDMA are powerful tools to create vulnerability and an environment for deep therapeutic work, but they should be used as adjuncts to psychotherapy rather than as standalone solutions.
Trazodone, an old antidepressant, is recommended at low doses (25-100 mg nightly) for most people, as it produces remarkable sleep while preserving sleep architecture and avoiding the dependency or memory issues of other sleep drugs.
The five variables are the driver's skill, the tires (grip and degradation), the engine (power generation), the chassis (aerodynamics and power transmission), and the overall race strategy.
20 Actionable Insights
1. Embrace Multimodal Exercise
Engage in a broad range of exercise types, as it has an “unbelievable impact” on lifespan and healthspan, likely more than any other intervention, and is accessible to everyone.
2. Aggressive GI Cancer Screening
Be aggressive with screening for gastrointestinal cancers, including colonoscopies and upper endoscopies, as early detection of polyps can prevent colon cancer deaths. Consider colonoscopies every 1-3 years starting around age 40, and advocate for this with your doctor.
3. Aggressively Lower ApoB Early
Aim to lower ApoB levels aggressively and early, ideally to a ceiling of 60 mg/dL (or below the 5th percentile) by your late 30s or early 40s, to significantly reduce the risk of atherosclerotic cardiovascular disease.
4. Increase Daily Protein Intake
Consume more protein than the recommended daily allowance, aiming for closer to two grams per kilogram or about a gram per pound of body weight, as current RDAs are insufficient for thriving and muscle maintenance.
5. Use DEXA for Body Composition
Utilize DEXA scans to accurately track body composition, including fat-free mass index (FFMI), appendicular lean mass index (ALMI), and visceral adipose tissue (VAT), to make informed decisions about diet and exercise.
6. Boost Cardio Fitness & Strength
Prioritize improving cardiorespiratory fitness (VO2 max) and overall strength, as these metrics are strong drivers of mortality reduction and contribute significantly to lifespan and healthspan.
7. Update Beliefs with New Information
Constantly update your assumptions and beliefs with new information, rather than digging your heels in, as this approach is crucial for evolving understanding in science and medicine.
8. Psychedelics: Tools for Therapy
View psychedelics like psilocybin and MDMA as powerful tools to create vulnerability for deep therapeutic work, rather than standalone cure-alls, and pair them with hard work before and after to achieve lasting benefits.
9. Consider Trazodone for Sleep
Discuss Trazodone (typically 25 to 100 milligrams nightly) with your doctor as a potential sleep aid, as it can produce remarkable sleep quality and duration while preserving sleep architecture, unlike some other medications.
10. Skepticism on NAD Precursors
Remain uninspired by NAD precursors (NR, NMN) for general longevity, as current data does not clearly demonstrate phenotypic benefits in normal aging outside of very pathological states.
11. “Kill Your Babies” in Work
Apply the principle of “killing your babies” in creative or scientific work by relentlessly cutting content that, while interesting, is not essential to the broader point, to improve clarity and impact.
12. Prioritize Mental Calm for Sleep
Focus on reducing mental stimulation from electronics before bed, rather than solely blocking blue light, as the content consumed (e.g., social media vs. relaxing videos) may be a greater disruptor of sleep.
13. Incorporate Intentional Discomfort
Seek appropriate doses of discomfort in your comfortable modern life to recoup benefits for mental and physical health, as constant comfort can have negative outcomes.
14. Train Grip Strength Regularly
Improve grip strength by regularly picking up heavy things and performing dead hangs, as it is a great proxy for overall body strength, muscle mass, and longevity.
15. Request ApoB Blood Test
Ask your doctor to include an ApoB test in your lab work, as it provides a single number for total ApoB concentration and is a better indicator of cardiovascular risk than standard LDL cholesterol.
16. Avoid Ambien for Sleep
Do not use Ambien for sleep, as it renders you unconscious but reduces slow-wave/deep sleep, trading quality sleep for low-quality sleep and potentially causing memory alterations.
17. Use BFR & Isometrics for Recovery
In the context of recovery from injury or surgery, consider using blood flow restriction (BFR) training and isometric exercises to get muscles to work without putting stress on the joint.
18. Provide Podcast Feedback
Send a message to the podcast team if you have strong opinions on topics like Peter reading the audiobook, as feedback helps shape future content.
19. Watch “Drive to Survive” (F1)
Start watching the Netflix series “Drive to Survive” (seasons 1 or 3 recommended) to gain an understanding of Formula One, its teams, drivers, and dynamics.
20. Read “The Comfort Crisis”
Read Michael Easter’s book “The Comfort Crisis” to explore how modern comfort negatively impacts mental and physical health and how to strategically reintroduce discomfort.
8 Key Quotes
You have to invest based on strong convictions, but they need to be loosely held. And so you have to constantly update your assumptions with new information.
Peter Atiyah
I really think that in 10 years, we're going to basically be using designer-based immunotherapies to eradicate most solid organ metastatic cancers.
Peter Atiyah
Nobody should ever die from colon cancer.
Peter Atiyah
I just don't see a reason to have an ApoB ever north of 60 milligrams per deciliter.
Peter Atiyah
The drawback is it's the hardest, I think. It takes the most time, that's for sure. And it's the most uncomfortable.
Peter Atiyah
I remain quite uninspired by the entire NAD stratosphere.
Peter Atiyah
Psychotherapy is probably the most powerful tool in different forms.
Peter Atiyah
It might not be your phone per se that is killing you. It might be what you're doing on your phone.
Peter Atiyah
3 Protocols
Aggressive Gastrointestinal Cancer Screening Protocol
Peter Atiyah- Start colonoscopy screening around age 40, even without a history of colon cancer.
- Perform colonoscopies every 1 to 3 years, more frequently than standard guidelines.
- Include upper endoscopy (EGD) as part of the screening to examine the esophagus and stomach.
Pharmacological ApoB Reduction Protocol
Peter Atiyah- By the time a person is in their late 30s or early 40s, measure their ApoB levels.
- If ApoB is even north of the 20th percentile, initiate lipid-lowering therapy.
- Target an ApoB ceiling of 60 mg/dL, ideally aiming for levels in the 20-30 mg/dL range.
- Utilize available therapeutic choices (statins, ezetimibe, bempedoic acid, PCSK9 inhibitors) to achieve target levels while minimizing side effects.
Trazodone Sleep Aid Protocol
Peter Atiyah- Consult a doctor to obtain a prescription for Trazodone.
- Start with a low dose, typically 25 milligrams nightly.
- Adjust the dose as needed, usually between 25 and 100 milligrams, to find the effective amount that produces remarkable sleep without next-day grogginess.