Supplements for Longevity & Their Efficacy | Dr. Peter Attia
Dr. Peter Attia, M.D., a Stanford and Johns Hopkins-trained physician and host of The Drive podcast, joins to discuss the NAD pathway's link to aging. They evaluate NAD, NMN, and NR supplementation for lifespan and healthspan, comparing them to critical behaviors like sleep, nutrition, and exercise, and share their personal supplement regimens.
Deep Dive Analysis
19 Topic Outline
Framework for Longevity Approaches
Peter Attia's Supplement Regimen and Rapamycin Research
NAD Pathway: Energy, DNA Repair, and Aging
Yeast, Sirtuins, Caloric Restriction, and Lifespan
Sirtuins, Transgenic Mice, and Sex-Specific Lifespan Effects
DNA Repair, Sirtuins, Cancer, and Resveratrol
NAD & NADH: Roles in Energy and Mitochondrial Health
NAD, NR, NMN Supplementation: Routes, Doses, and Efficacy
Interventions Testing Program (ITP) Results for Longevity
Human Studies on NR/NMN: Fatty Liver and Glucose Disposal
Safety, FDA Status, and Potential Benefits of NMN/NR
Rapamycin's Impact on Immune Function
Biological Aging Tests vs. Chronological Age and Vigor
Radiation Exposure and Cancer Risk
Importance of Self-Care and Physiological Reserve in Middle Age
Exercise Timing and Energy Levels
Andrew Huberman's Supplement Regimen
Supplement Use vs. Foundational Behaviors for Longevity
Final Stance on NAD Pathway Supplementation for Lifespan
7 Key Concepts
mTOR (Mammalian Target of Rapamycin)
mTOR is a molecule robustly expressed during development, tapering off across the lifespan. It is associated with cellular growth, and its activity is targeted by approaches like caloric restriction or drugs such as rapamycin to slow cellular growth and potentially aging.
Sirtuins
Sirtuins are a class of proteins that consume NAD as a substrate in the process of DNA repair. Overexpression of sirtuins in some yeast strains and one transgenic mouse model has been shown to extend lifespan, suggesting a role in longevity, independent of caloric restriction.
Clotho Gene
Clotho is a gene initially discovered when its knockout in mice led to rapid death and neurodegenerative disease. Conversely, overexpressing the Clotho gene in mice resulted in a 15-20% increase in lifespan, indicating it is both necessary and sufficient for extended life.
NAD (Nicotinamide Adenine Dinucleotide)
NAD is a ubiquitous molecule in the body, primarily acting as a cofactor for electron shuttling in metabolic pathways, essential for energy liberation. A small fraction of NAD is consumed as a substrate by sirtuins for DNA repair, and its levels decline with age, particularly in skin.
Redox Potential
Redox potential refers to the ability of the body's systems, particularly mitochondria, to facilitate the transfer of electrons between molecules like NAD and NADH. A decline in redox potential with aging suggests that mitochondria become less efficient, rather than just a simple reduction in total NAD/NADH.
Interventions Testing Program (ITP)
The ITP is an NIA-funded, highly rigorous program that tests exogenous molecules for their ability to extend lifespan in non-inbred mice. Experiments are conducted in triplicate across three independent labs, making it a gold standard for lifespan intervention research in mammals.
Statistical vs. Clinical Significance
Statistical significance indicates that a measured effect is unlikely due to chance, but clinical significance refers to whether that effect is meaningful or impactful in a real-world, practical sense. An effect can be statistically significant but clinically insignificant if its magnitude is too small to alter the course of a disease or life.
9 Questions Answered
Longevity approaches can be categorized into essential behavioral things (eating, sleeping, moving correctly), exogenous molecules targeting specific disease processes (e.g., for cardiovascular or metabolic disease), and exogenous molecules targeting hallmarks of aging (gyroprotective, like rapamycin).
Rapamycin is one of only two interventions (the other being caloric restriction) that has uniformly extended life across four categories of eukaryotes: yeast, worms, fruit flies, and mammals (mice), showing consistent life extension in experimental data.
No, detailed experimental evidence in yeast, including studies by Matt Caberlin and Brian Kennedy, indicates that sirtuin overexpression and caloric restriction extend lifespan independently and additively, suggesting they are parallel, not overlapping, pathways.
NAD's primary role (99%) is as a cofactor for electron shuttling in hundreds of metabolic pathways, facilitating the conversion of chemical energy from food into electrical energy. A smaller fraction of NAD is consumed as a substrate by sirtuins for DNA repair.
Based on current evidence, including the rigorous Interventions Testing Program (ITP) in mice which found no lifespan extension with NR, there is no unambiguous scientific evidence that NAD, NMN, or NR supplementation extends human lifespan.
Human studies on NR and NMN have shown limited and often clinically insignificant results, such as a modest increase in glucose disposal with NMN or a statistically significant but clinically minor reduction in liver fat in a subset of fatty liver patients with NR. The most promising, though unreplicated, finding is a 60-80% reduction in basal and squamous cell carcinomas with supplementation.
Currently, biological aging tests are not considered reliable predictors of remaining lifespan. Chronological age remains a better actuarial predictor, and these tests often have high biological noise and lack robust evidence that a 'younger' biological age translates to a proportionally longer life expectancy.
No, normal radiation exposure from sources like airport scanners or even frequent flights (including across poles for pilots) is unlikely to significantly increase cancer risk. The annual recommended limit for radiation exposure is 50 millisieverts, and common exposures are well below this, with even higher occupational exposures not consistently showing increased cancer risk.
The most critical factors for improving healthspan and lifespan are foundational behavioral elements: consistent good sleep, regular and appropriate exercise, optimal nutrition, and maintaining good emotional and mental health.
19 Actionable Insights
1. Prioritize Foundational Health Behaviors
Engage in essential behavioral practices correctly, including moving appropriately and often (zone two cardio, resistance training, maintaining nerve-to-muscle connection), eating right, and understanding your genetics. These foundational behaviors are vastly more impactful for healthspan and lifespan than any supplement.
2. Prioritize Emotional Health & Well-being
Focus on emotional health, happiness, and overall well-being, as this directly impacts longevity and makes it significantly easier to adhere to other foundational health behaviors like diet and exercise.
3. Delay Chronic Disease Onset
To extend lifespan, concentrate on delaying the onset of major chronic diseases such as cardiovascular disease, cerebrovascular disease, cancer, neurodegenerative diseases, and metabolic diseases.
4. Build Physiologic Reserve in Midlife
Actively build and maintain as much physiologic reserve as possible, especially muscle mass and strength, during your 50s and 60s, as it becomes substantially more challenging to gain these later in life.
5. Avoid Injury and Prolonged Inactivity
Prevent injuries and extended periods of inactivity, particularly in midlife and beyond, because recovery from such setbacks becomes significantly more difficult and time-consuming with age.
6. Manage Blood Glucose Levels
Strive to keep blood glucose levels steady to maintain optimal energy and focus, avoiding significant spikes or crashes. Tight glycemic control, independent of body weight, is associated with longevity benefits.
7. Use a Continuous Glucose Monitor (CGM)
Utilize a CGM (like Levels) to gain real-time feedback on how different foods affect your blood glucose levels. This information can help optimize food choices, timing of meals around workouts, and improve sleep quality by stabilizing blood sugar throughout the night.
8. Control Sleep Environment Temperature
Regulate the temperature of your sleeping environment (e.g., using a smart mattress cover) to facilitate the natural body temperature drop required for deep sleep and the subsequent increase needed for refreshed waking.
9. Ensure Proper Electrolyte Hydration
To maintain optimal cognitive and physical performance, ensure proper hydration and electrolyte balance. Andrew Huberman’s protocol involves dissolving one packet of Element in 16-32 ounces of water first thing in the morning, and another packet later in the day, potentially a third if exercising or sweating heavily.
10. Optimize Exercise Timing for Energy
Experiment with the timing of your workouts; completing exercise before 9 AM may lead to increased energy throughout the day compared to mid-to-late morning workouts, potentially due to body temperature regulation.
11. Incorporate Sauna and Cold Exposure
Integrate practices like sauna and cold exposure into your weekly routine (e.g., once a week) as part of a comprehensive health and wellness strategy.
12. Consider Geroprotective Molecules (Rapamycin)
Explore exogenous molecules that target hallmarks of aging, such as rapamycin, which is the only molecule besides caloric restriction that has shown uniform life extension across various eukaryotes in experimental data.
13. Rapamycin Dosing (Peter Attia’s Protocol)
If prescribed rapamycin for geroprotection, Peter Attia’s personal protocol involves taking 8mg once a week for two months, followed by a one-month break, to manage potential side effects like canker sores.
14. Consider Disease-Targeting Molecules (Prescription)
Consult with a medical professional about taking prescription exogenous molecules like metformin, SGLT2 inhibitors, GLP-1 agonists, PCSK9 inhibitors, statins, or bempedoic acid to directly impact and delay the onset of specific chronic diseases.
15. Avoid Resveratrol for Longevity
Do not take resveratrol with the expectation of extending lifespan, as rigorous testing in the Interventions Testing Program (ITP) found no such effect in relevant animal models.
16. Avoid NAD/NMN/NR for Longevity
Do not take NAD, NMN, or NR supplements with the primary expectation of lifespan extension, as there is currently insufficient scientific basis to support their efficacy for this purpose.
17. Consider NR/NMN for Skin Cancer Risk
If you are an individual at high risk for basal cell and squamous cell carcinomas (non-melanoma skin cancers), consider NR or NMN supplementation, as one study showed a 60-80% reduction in risk for these specific cancers.
18. Alpha-GPC as Pre-Workout
Consider taking 600-900mg of Alpha-GPC with a double espresso prior to a workout for a stimulatory effect. Peter Attia notes he does not believe TMAO, which Alpha-GPC can increase, is a significant health concern.
19. Supplements as Augments, Not Necessities
View supplements as an insurance policy or an augmentation to mental and physical health, rather than necessary components. Prioritize foundational behavioral practices over supplement use, as they have a far greater impact.
5 Key Quotes
People enjoy the comfort of opinion without the discomfort of thought.
Peter Attia (paraphrasing JFK)
Everything we have talked about on this podcast today, whether it be NR, NAD, NMN, Theracumin, Magnesium, this supplement, that supplement, all of that stuff, while potentially mattering, I would put in the category of, was the Titanic serving lobster or steak? I like steak more than lobster. That's a relative discussion. Exercise, sleep, nutrition, emotional health, is the question of what was the heading of the Titanic?
Peter Attia
If you have to resort to really interesting statistical machinations to see something, there probably isn't something very interesting there.
Peter Attia
The fact that something feels so awful shouldn't be used as an explanation for why it's doing good physiologically.
Peter Attia
I will reserve the right to change my mind for the rest of my life in the presence of new data.
Peter Attia
3 Protocols
Peter Attia's Supplement Regimen
Peter Attia- Take EPA and DHA (fish oil) in capsule form.
- Take Theracumin for cognitive function.
- Take Vitamin D (5,000 IU) to maintain levels around 50-ish.
- Take Methylfolate and Methyl B12 to lower homocysteine.
- Take Magnesium L-Threonate, Magnesium Chloride (Slow Mag), and Magnesium Oxide for sleep and general health.
- Consume electrolytes (e.g., Element).
- Take Creatine Monohydrate (5 grams a day).
- Take AG1 (Athletic Greens) most mornings.
- Take Pendulum probiotics (Glucose Control, Polyphenol, Ackermansia) for gut health.
Andrew Huberman's Supplement Regimen
Andrew Huberman- Take AG1 (Athletic Greens) one to two servings daily, sometimes three when traveling, typically in the morning or evening.
- Take a quality fish oil (e.g., AG or Carlson's liquid) to get above 1 gram of EPA per day.
- Take Vitamin D3 (3,000-7,000 IU) daily via dropper, adjusting based on blood levels.
- Take Methyl B12.
- Take Tongkat Ali (one capsule) in the early part of the day to lower sex hormone binding globulin.
- Take a couple of green tea capsules in the morning.
- Consume Yerba Mate for stimulatory effects.
- Take NMN (powdered, sublingual) and sometimes NR, though not with strict adherence.
- Use Element as an electrolyte.
- Take Creatine Monohydrate (10 grams per day), adjusting for missed days.
- Before sleep, take Magnesium Threonate, Apigenin (50 milligrams), and Theanine. Occasionally take 900 milligrams of Inositol as an alternative or addition.
- Use a quality whey protein as a protein replacement.
Exercise Timing for Increased Daytime Energy
Andrew Huberman- Complete workouts before 9 AM, even if starting fatigued.
- Observe if this timing leads to more energy throughout the day compared to mid-to-late morning workouts.
- Consider that early morning exercise (e.g., 4:30 AM) may leverage the body's circadian temperature rhythm to drive increased energy.