#276 ‒ Special episode: Peter answers questions on longevity, supplements, protein, fasting, apoB, statins, and more
Peter Attia, MD, discusses why extreme longevity claims are unrealistic, emphasizing healthspan over lifespan. He shares his individualized drug and supplement regimen, strategies for lowering ApoB, and insights into nutrition research, protein intake, and health-tracking wearables like CGMs.
Deep Dive Analysis
11 Topic Outline
Confidence in Living to 120 and Beyond
Importance of Acting for a 90-Year Lifespan
Future of mTOR Inhibition and Generational Longevity
Challenges of Geroprotective Interventions Without Biomarkers
Peter Attia's Personal Supplement Regimen
Pharmacologic Strategies for Lowering ApoB and ASCVD Risk
Misconceptions About 'Good' and 'Bad' Cholesterol
Difficulties in Nutrition Research and General Principles
Peter Attia's Approach to Optimizing Protein Intake
Favorite Health-Tracking Wearables and CGM Use
Future of Continuous Blood Pressure and Lactate Monitoring
6 Key Concepts
Geroprotection
This refers to targeting the underlying mechanisms of aging rather than specific diseases. It is challenging to study in humans due to the lack of reliable biomarkers to measure if interventions are working or to determine correct dosages.
ApoB
ApoB is a protein that is a key component of lipoproteins like LDL, which carry cholesterol. High ApoB levels are a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) because these lipoproteins traffic cholesterol into artery walls.
Pro-drug
A pro-drug is an inactive compound that becomes an active drug only after it has been metabolized within the body. This mechanism can allow for more targeted action, such as bempedoic acid only inhibiting cholesterol synthesis in the liver.
Energy Balance (Nutrition)
This is the most crucial parameter for determining metabolic health, representing the relationship between calories consumed and calories expended. Regardless of the specific diet, consuming calories in excess of energy balance will lead to poor metabolic health.
Antisense Oligonucleotide
This is a type of drug that works by disrupting the process of DNA making RNA, thereby interrupting the synthesis of a specific protein. An example is a drug in development that targets the synthesis of APO(a) to reduce Lp(a) levels.
Good/Bad Cholesterol Misnomer
The terms 'good' and 'bad' cholesterol are inaccurate because cholesterol is a single molecule. These terms actually refer to the lipoproteins (HDL and LDL) that transport cholesterol; LDL is considered 'bad' because it deposits cholesterol into artery walls, leading to atherosclerosis, while HDL does not.
9 Questions Answered
We lack the tools to address the underlying aspects of aging biology that relentlessly push us towards the end of our lives, and there is no real evidence that we can reverse or completely halt the diseases of aging or cellular processes.
Focusing on current tools for primary and secondary disease prevention and maximizing healthspan acts as a hedge against the low probability of dramatic breakthroughs for extreme longevity. The goal should be to compress the period of morbidity late in life, ensuring physical and cognitive robustness in the 'marginal decade'.
The lack of reliable biomarkers for aging means there is no way to measure if a geroprotective drug or supplement is working, or if the dosage is correct, making it difficult to understand what interventions are effective in humans.
Without pharmacology, dramatically reducing carbohydrates (to lower triglycerides) and cutting saturated fat (to upregulate LDL receptors) can lower ApoB. With pharmacology, drugs like PCSK9 inhibitors, bempedoic acid, and ezetimibe are used to achieve significant reductions.
Cholesterol is a single molecule; the terms refer to the lipoproteins (LDL and HDL) that transport cholesterol. LDL is considered 'bad' because it deposits cholesterol into artery walls, leading to atherosclerosis, while HDL does not.
The complexity of human biology and the intervention of eating make it difficult to conduct long-term, controlled studies. Most human nutrition data relies on epidemiology, which identifies patterns without randomization or direct experimentation.
Energy balance is paramount. Even a 'best diet' will lead to poor metabolic health if consumed in excess, causing accumulation of adipose tissue and metabolic dysfunction.
The data linking high protein to increased mortality in people under 50 is unconvincing and likely confounded by caloric excess. It is crucial for younger individuals to build and maintain muscle mass, as it becomes harder to do so after age 50, which is vital for preventing frailty in later life.
CGMs are valuable tools for understanding metabolic health, even in non-diabetics. Key metrics to monitor are average blood glucose and standard deviation, as lower values correlate with lower all-cause mortality, and less variability indicates better metabolic control.
30 Actionable Insights
1. Prioritize Energy Balance
Focus on achieving energy balance as the most important parameter for metabolic health, regardless of the specific diet chosen. Consuming even a ‘best’ diet in excess will lead to poor metabolic health.
2. Maximize Muscle Mass Pre-50
Prioritize putting on as much muscle mass as possible before entering middle age (over 50) to avoid a muscle deficit. This is crucial for physical robustness in the marginal decade, as muscle is harder to maintain and build later.
3. Compress Late-Life Morbidity
Fixate on reducing or compressing the period of physical and cognitive frailty in the last decade of life (the ‘marginal decade’). Aim for physical robustness as a centenarian, rather than just adding years to life.
4. Ultra-Primary ASCVD Prevention
Take dramatic steps early in life (e.g., in your 30s) to prevent ASCVD by ensuring ApoB never exceeds 30-40 mg/dL. Also, avoid even one year of mild hypertension and always maintain metabolic health.
5. Focus on Current Prevention
Be serious about using today’s tools for primary and secondary disease prevention and for optimizing lifespan and healthspan. This acts as a hedge against unlikely dramatic breakthroughs in extreme longevity.
6. Seek Biomarkers for Interventions
When using any intervention (nutrition, exercise, drugs, supplements), identify and use biomarkers to know if you are doing it correctly, taking the right amount, and if it’s working. Without measurable feedback, it’s a guessing game.
7. Apply Risk-Reward Matrix
Evaluate interventions (especially supplements) using a simple risk-reward matrix (low risk/high risk vs. low reward/high reward). Demand higher reward for higher risk interventions and be wary of high risk for no reward.
8. Target Low ApoB Pharmacologically
Aim for an ApoB target of 30-40 mg/dL, which often requires pharmacology, especially for those with genetic predisposition or high baseline ApoB. Consider a combination of drugs like PCSK9 inhibitors, bempedoic acid, and ezetimibe.
9. Utilize CGMs for Metabolic Insight
Use Continuous Glucose Monitors (CGMs) even as a non-diabetic to gain insights into metabolic health. Focus on lowering average blood glucose and reducing glucose variability (standard deviation), as these correlate with lower all-cause mortality.
10. Prioritize Dietary Sustainability
Choose a manageable and sustainable diet that can be adhered to indefinitely, even if it’s not ‘perfect,’ over a perfect diet that cannot be sustained long-term. A 7/10 diet sustained indefinitely is better than a 10/10 diet for three months.
11. Target High Daily Protein
Aim for a high daily protein intake (e.g., 150-180 grams for Peter) to support muscle mass. Spread this intake out into multiple ‘hits’ (e.g., four times a day).
12. Optimize Statin Use
If statins are necessary, aim for the lowest effective dose (e.g., 5mg Rosuvastatin for 85% efficacy) to minimize side effects. Monitor for side effects like muscle aches, elevated liver enzymes, and insulin resistance.
13. Individualize Supplement Regimen
Do not blindly follow someone else’s supplement list; understand the rationale, clinical history, and context. Regimens change over time based on new data and personal needs.
14. Lower ApoB via Nutrition
To lower ApoB without drugs, dramatically reduce carbohydrates (to lower triglycerides) and/or dramatically cut saturated fat (to upregulate LDL receptors). Acknowledge that this may not achieve optimal ApoB levels for everyone and sustainability is individual.
15. Use Accurate Cholesterol Terminology
Avoid using the terms ‘good’ or ‘bad’ cholesterol; instead, refer to LDL-C and HDL-C. Understand that LDL transports cholesterol into artery walls while HDL does not, reflecting a more accurate understanding.
16. Carbohydrate Restriction for Insulin Resistance
For patients with profound insulin resistance, carbohydrate restriction may be a more effective tool than general caloric or fat restriction to create a caloric deficit. This approach can help improve metabolic health.
17. Holistic View of Longevity
When studying long-lived populations, consider all contributing factors (activity, sleep, stress, social connections, environment) beyond just diet. Diet alone may not explain their longevity, as diverse diets exist among such groups.
18. Re-evaluate Fasting Protocols
If engaging in long fasting protocols, be aware of potential costs (e.g., muscle loss) and consider re-evaluating their utility in the absence of clear, biomarker-driven benefits. Peter stopped his long fasts due to lack of clear benefit and logistical challenges.
19. Anticipate Continuous Blood Pressure
Look forward to continuous blood pressure monitors (like the Actia device, available in Europe) becoming available in the US. These devices can provide frequent, objective blood pressure data to replace cumbersome ambulatory cuffs.
20. Anticipate LP(a) Drug Availability
For individuals with high LP(a), be aware of an antisense oligonucleotide drug in phase three trials that obliterates LP(a). While initially for secondary prevention, it may eventually be available for primary prevention (potentially off-label or with future insurance coverage).
21. Use Morpheus for Zone 2
Consider using a device like Morpheus to get a daily readiness score and heart rate training zones for zone two workouts. This can help approximate optimal training intensity, especially for those less attuned to RPE or unwilling to measure lactate.
22. Desire Continuous Lactate Monitoring
Express interest in continuous lactate monitoring during exercise to precisely understand metabolic breakdown and clearance during cardio and VO2 max training. This would offer a more accurate measure than heart rate or RPE.
23. Supplement Magnesium Daily
Aim for about 1 gram of total elemental magnesium daily, using forms like SlowMag, magnesium L-threonate (Magtein), and magnesium oxide for slow and complete absorption. Peter takes some of these at night.
24. Manage Homocysteine with B Vitamins
Consider taking methylfolate and methyl B12 (e.g., Gero brand, standard low dose) to keep homocysteine levels below 9. Adjust B6 intake (e.g., 50mg three times a week) to help with homocysteine while being careful not to overdo it due to neuropathy risk.
25. Target EPA/DHA Levels
Consider supplementing EPA and DHA (fish oil) to achieve a red blood cell membrane concentration of about 12%, using a blood test as a biomarker. Peter takes approximately 2g EPA and 1.5g DHA daily.
26. Supplement Vitamin D
Consider supplementing Vitamin D (e.g., 5,000 IU daily) due to its perceived insanely low risk, even if the exact reward is uncertain. Peter views it as potentially a $5 bill reward.
27. Consider Baby Aspirin
For younger individuals with low bleeding risk, a baby aspirin daily might be considered for potential cardiovascular benefits. Be aware the evidence is weak and benefits may be outweighed by bleeding risks in older individuals.
28. Ashwagandha for Nighttime
Consider taking 600mg of ashwagandha at night. Peter recently switched to the Solgar brand.
29. Glycine for Nighttime
Consider taking 2 grams of glycine at night. Peter uses the Thorn brand.
30. Phosphatidylserine for Travel
For long flights or significant time zone changes, consider taking phosphatidylserine (e.g., 400mg). Peter uses Gero’s 100mg gel caps.
5 Key Quotes
I haven't seen many examples where there's a bigger mismatch between what is actually happening scientifically and what is being talked about in the press, on social media, on podcasts. And that chasm is enormous.
Peter Attia
What I think people should fixate on is how do I not be really, really frail both physically and cognitively in the last decade of my life, what I call the marginal decade.
Peter Attia
Cholesterol is cholesterol is cholesterol. The same molecule of cholesterol inside the HDL is present inside the LDL.
Peter Attia
I always think people are majoring in the minor and minoring in the major on nutrition when they start to fight in dietary tribes on this stuff.
Peter Attia
It's better to have a seven out of 10 diet in terms of quality and perfection that you can sustain indefinitely than a 10 out of 10 diet that you can only sustain for three or six months.
Peter Attia
3 Protocols
Peter Attia's Daily Supplement Regimen
Peter Attia- Take ~2 grams of EPA and ~1.5 grams of DHA (fish oil, Carlson's Super EPA, highest EPA version).
- Take 5,000 IU of Vitamin D.
- Take ~1 gram of total elemental magnesium (SlowMag, magnesium L-threonate, magnesium oxide).
- Take methylfolate and methyl B12 (Gero brand, lower strength) to keep homocysteine below 9.
- Take 50 milligrams of B6 three times a week.
- Take a baby aspirin daily.
- Take 600 milligrams of ashwagandha (Solgar brand) at night.
- Take 2 grams of glycine (Thorn brand) at night.
- Take magnesium L-threonate (Magteen brand) at night.
- (Occasionally for travel) Take ~400 milligrams of phosphatidylserine (Gero brand gel caps).
- Take Athletic Greens (AG1) in the morning.
- Take two Pendulum Glucose Control probiotics in the morning with AG1.
Peter Attia's ApoB Lowering Protocol
Peter Attia- Consume a low carbohydrate and low saturated fat diet (nutritional intervention).
- Take a PCSK9 inhibitor (e.g., Repatha).
- Take a combination drug of bempedoic acid and ezetimibe (e.g., Nexlizet).
- Target an ApoB level of 30 to 40 milligrams per deciliter.
Peter Attia's Daily Protein Intake Strategy
Peter Attia- Target 150-180 grams of protein per day.
- Consume 5-10 venison jerky sticks (Maui Nui, ~10g protein each) as snacks.
- Obtain remaining protein from other food sources.
- (If necessary) Supplement with a high-quality whey protein shake.
- Spread protein intake across approximately four 'hits' throughout the day.