Summary
Andrew Huberman speaks with Dr. Peter Attia, a Stanford and Johns Hopkins-trained physician and host of The Drive podcast, about whether popular longevity supplements actually extend lifespan. They evaluate the NAD pathway in detail -- comparing NAD, NMN, and NR supplementation, different routes of administration, bioavailability, and safety profiles. Dr. Attia explains how sirtuins, caloric restriction, and the NAD pathway interact, and why results from yeast and mouse studies have not clearly translated to human longevity benefits. The Interventions Testing Program (ITP), which tests compounds in genetically diverse mice, provides the most rigorous animal data.
They discuss rapamycin as the most promising pharmacological longevity intervention based on ITP data, while noting human evidence remains limited. Resveratrol is largely dismissed based on failed replication of early sirtuin activation claims. Both share their personal supplement regimens -- Huberman takes NMN, NR, and various micronutrients, while Attia takes a more conservative approach. The central conclusion is that no supplement has demonstrated clear lifespan extension in humans, and the foundational behaviors -- exercise (especially resistance training and cardio), sleep, nutrition, and stress management -- remain far more impactful than any supplement for longevity. They also discuss biological age tests, radiation and cancer risk, and exercise timing for optimal energy.
Key Points
- No supplement has demonstrated clear lifespan extension in humans -- foundational behaviors (exercise, sleep, nutrition) remain far more impactful than any pill
- NAD, NMN, and NR supplementation increases circulating NAD levels but has not shown meaningful clinical longevity benefits in human trials
- Rapamycin shows the most consistent lifespan extension in the Interventions Testing Program (mice), but human longevity data remains limited
- Resveratrol's early promise was based on sirtuin activation claims that largely failed to replicate in subsequent studies
- NR supplementation shows a potential benefit for fatty liver disease (reducing liver inflammation markers) and nicotinamide may reduce skin cancer risk
- Biological age tests (epigenetic clocks) show correlation with chronological age but their ability to predict individual health trajectory or respond to interventions remains unproven
- Exercise -- particularly resistance training to maintain type 2 muscle fibers and cardiovascular training for VO2 max -- is the single most impactful intervention for healthy aging
Key Moments
Peter Attia on NAD and longevity supplements
Dr. Peter Attia reviews the NAD pathway as a longevity target, comparing NR, NMN, and direct NAD infusions.
"Dr. Atiyah is one of the world's most trusted voices on the topics of health span and lifespan. And with good reason, he is known to systematically review the research literature, the clinical trials, and he maintains an avid clinical practice. So when it comes to the topic of whether or not a particular molecule or supplement or prescription drug is indeed something that we should be thinking about and perhaps even taking in order to improve our health span and lifespan, Dr. Atiyah is the person that I choose to sit down with and discuss it. So today we are going to discuss the so-called NAD pathway. This is a pathway that's received a lot of attention in recent years as a potential target for improving lifespan, that is for living longer. Today, we discussed the various molecules in this pathway and the various approaches to increasing NAD, which is the end target goal of anyone that's trying to augment the NAD pathway, so to speak. So for instance, we talk about taking NR versus NMN versus direct infusions, or even orally taking NAD. And we compare them in terms of both what's known and what is not known about their ability to get into cells and any efficacy they may have for either longevity or health span."
Attia takes rapamycin weekly for longevity
Peter Attia takes 8mg rapamycin weekly for its geroprotective potential, tolerating mouth sores as a biomarker of drug activity.
"I take eight milligrams once a week for as long as I can tolerate it, but I usually have to take breaks. Why is that? I get these vicious apthous ulcers, little mouth sores. Canker sores. Yes. About 10% of people get them."
NAD is a cofactor in 500-600 body pathways
NAD is one of the most ubiquitous molecules in the body, tightly regulated like glucose and pH, serving hundreds of enzyme pathways.
"Right. So NAD is, again, one of the most ubiquitous molecules in the body. And most of what it does, and I mean most, meaning like somewhere between five and 600 pathways of it, utilize NAD as a cofactor, meaning that it's 99% of what NAD is doing in the body."
NAD boosting may fuel cancer cell growth
Since cancer cells depend on NAD for replication, boosting NAD could theoretically support tumor growth alongside healthy cells.
"Remember at the outset I said there's two big categories to think about NAD. Most of what NAD is doing is operating as a cofactor for electron shuttling."
Sirtuin activation drove the NAD supplement hype
The thesis that NAD precursors activate sirtuins to extend lifespan drove massive commercial interest, but mouse data is mixed.
"It would just break down in the gut into its constitutive products and then probably reform. But for the purpose of how people actually do this, they intravenously get NAD because it's not orally bioavailable. Or as you said, they orally take two precursors, NR and NMN."
NMN and NR human trials show weak results
Human trials of NMN and NR show statistically significant but clinically insignificant effects on glucose disposal.
"That's right. Because I asked a few folks that helped develop some of the NR supplements, like what are the data that support the use of NR for increasing NAD? And they say NR can cross the cell membrane directly. NMN cannot. Okay. But you can just cleave the phosphate group."
Early morning exercise boosts all-day energy
Forcing yourself to exercise early dramatically increases energy throughout the day, even if a brief nap is still needed.
"Yeah. I don't doubt it. I just have noticed that in the few times in my life where I've kicked my own butt to get out and start working out really early, I have more energy all day long. Sometimes I still require a brief nap, but it's a pretty striking effect as compared to, you know, the 10 AM workout effect. So I've started setting a standard of trying to get my workout done before 9 AM. So anyway, it's something for people to play with because the more energy to live in your waking hours, perhaps not longer, but certainly have more energy in terms of output, I think is a significant and undervalued parameter. So let's quickly return to supplements. We, I think, are converging on an answer about NR, NMN, and NAD, which is you don't take them."
Supplements are insurance, not essentials
Peter Attia compares supplements to the menu on the Titanic: exercise, sleep, nutrition, and mental health matter exponentially more.
"All this supplement bullshit that we just talked about is equivalent to were they serving lobster or were they serving steak? And was the band playing this song or that song? I'm not saying those things don't matter, but just put them in the context of the direction the Titanic is going."
