AMA #12: Thoughts on Longevity Supplements (Resveratrol, NR, NMN, Etc.) & How to Improve Memory

1. Resveratrol doesn't appear to extend lifespan. Huberman considers the once-popular idea that resveratrol increases lifespan to be largely debunked; he is unaware of any modern, well-controlled human, non-human primate, or even mouse data supporting a longevity benefit.
2. Grapeseed extract for vascular health, not longevity. He takes 400–800 mg of grapeseed extract daily (usually with a meal) for its effects on vascular function and blood flow as a low-cost, low-risk insurance policy — but would not place it in his top 10 supplements.
3. NR and NMN for energy, taken in the morning. Huberman takes 500 mg of NR and 1–2 g of sublingual NMN each day before his first meal because, subjectively, it gives him sustained mental and physical energy that tapers off by evening — explicitly not to extend lifespan.
4. NAD infusions are effective-feeling but unpleasant. He has done NAD IV infusions (500–1000 mg) twice when feeling run down post-illness, finding them uncomfortable (nausea, chest and leg pressure for the first ~10 minutes) but reporting better sleep and vigor afterward; he'd do them at most a couple times a year.
5. No metformin, berberine, or rapamycin for him right now. Huberman avoids berberine (it gives him brutal headaches), metformin (insufficient human longevity data per his review with Peter Attia), and rapamycin (data don't justify the side-effect profile for longevity at this time) — though he'd reconsider as data evolve.
6. Supplements are supplements, not a foundation. He repeatedly stresses that light exposure, sleep, movement, nutrition, stress modulation, and social relationships must come first; supplementation only makes sense to consider after those are dialed in.
7. Sleep and exercise dwarf any longevity pill. No supplement or drug comes close to the longevity benefits of quality sleep and exercise — including 180–220 minutes of zone 2 cardio per week, weekly VO2 max work, and at least six sets per body part per week of resistance training to maintain nerve-to-muscle connectivity.
8. Always consult a physician. Any time you add or remove a supplement or prescription drug, you should consult a board-certified physician; safety for any individual must be determined personally.

Resveratrol and Grapeseed Extract

Responding to a listener question about whether resveratrol can extend lifespan, Huberman explains that resveratrol drew major attention years ago because it was believed to influence cellular pathways that might extend the lifespan not just of individual cells but of the whole organism. This put related compounds such as grapeseed extract — which contains a fair amount of resveratrol or can be converted into it — in the spotlight as well.

By 2023, however, Huberman considers most of that thinking debunked. While resveratrol may have some positive effects on cellular function, he says there is very little if any direct evidence that it increases lifespan, and he invites listeners to post links to any modern, highly controlled human, non-human primate, or mouse studies showing otherwise in the YouTube comments.

Despite rejecting the longevity claim, he does take 400–800 mg of grapeseed extract daily, usually with a meal, but specifically for its effects on vascular function and blood flow and a few other associated effects, where he considers the data reasonably strong. He frames it as a general insurance policy — a supplement that appears very safe at those dosages, may have positive cellular effects, and is low cost. He is careful to note he does not take it for resveratrol pathways or to extend lifespan, and would not rank grapeseed extract among his top five or even top 10 supplements. He mentions he plans to eventually do a full podcast episode listing all the supplements he takes, his rationale, how long he's taken them, and the effects observed subjectively and in blood work.

The NAD Pathway: NR, NMN, and NAD Infusions

Huberman explains that about four or five years ago, attention surged around NAD-related pathways for longevity. NAD is a pathway present in all cells across the entire lifespan but most active in young animals and humans; it relates to cellular energetics (energy production) and is tightly linked to mitochondrial function. Precursors in the pathway include NR and NMN. The argument, advanced by some prior podcast guests and others, was that increasing cellular NAD could potentially extend lifespan.

Three ways people raise NAD

He outlines the common methods people use to try to boost NAD, while noting the open question of whether raising NAD actually extends lifespan.

• NR supplementation — typically a capsule or powder, known to increase NAD levels.
• NMN supplementation — taken as a capsule or sublingual powder, though there is debate over whether NMN actually gets into cells and converts to NAD.
• Direct NAD — via intravenous infusion or, increasingly, oral administration in liquid or pill form.

His personal NR/NMN routine

Huberman has tried all three approaches. He takes 500 mg of NR daily and 1–2 g of sublingual NMN (which he describes as having a tangy flavor and dissolving under the tongue). He has at times taken them individually to compare subjective effects on energy and side effects, eventually settling on taking both together every day. He takes them within about one to two hours of waking and at least 30 minutes to two hours before his first meal, which usually arrives around 11 a.m.

He is emphatic that this is for NAD-related vitality, not lifespan extension. Subjectively — and he stresses this is purely anecdotal, not based on peer-reviewed studies — he finds that NR and NMN give him a lot of sustained mental and physical energy throughout the day that tapers nicely in the evening so he can still sleep. At 48, he wants to keep his naturally high energy as high as is reasonable. During periods when he stopped taking them, he noticed a decrement in energy, though not complete depletion.

He discloses he has zero financial relationship to any company that manufactures NR or NMN. He notes that in 2023 an FDA ruling, prompted by an NMN filing as an experimental drug in a clinical trial, made NMN technically unavailable as a supplement (since something listed as an experimental drug can't be sold as a supplement), though it can still be found on the open market and on Amazon — with purity left to the buyer to verify.

NAD infusions

Huberman has done direct NAD IV infusions twice, taking 500–1000 mg, at times when he felt particularly run down post-illness. He describes the experience as quite uncomfortable — so much so that many people take anti-nausea medication for it, which he chose not to do because he prefers to avoid extra medication. He had it administered as quickly as was safe (about 45 minutes to an hour). For roughly the first 10 minutes he felt nauseous and as if someone were stepping on his chest and legs, feeling generally awful, after which it passed and he felt fine. Afterward he felt terrific, with improved sleep and vigor coming off illness, and was still able to sleep that night, though he did it earlier in the day.

He notes there is no clinical trial he's aware of examining NAD infusion for vigor. It's generally assumed infusions raise cellular NAD more effectively than NR or NMN, though direct comparisons haven't been made, and there remains a general question of whether any of these get into cells and affect specific NAD levels. Given the expense, inconvenience, and discomfort, he doesn't see himself doing infusions often — maybe a couple times a year if feeling rundown or fatigued post-illness. He also notes growing numbers of oral NAD products (pills, tinctures) but says he's unaware of studies linking oral NAD to actual cellular NAD levels.

The ongoing expert debate

He references several experts — Dr. Charles Brenner, Dr. David Sinclair, and Dr. Matt Kaeberlein — who actively and heatedly debate these issues. The biggest debate is whether raising cellular NAD actually increases lifespan, along with whether NR is better than NMN and whether exploring any of this is premature. For the third time, Huberman restates that he does none of this for lifespan extension, only for the subjective vitality and energy effects.

Metformin, Berberine, and the mTOR Logic

Huberman states plainly that he does not take metformin, nor what some call the 'poor man's version of metformin,' berberine. Berberine gives him brutal headaches, which he attributes to its blood-glucose-lowering effect. Both compounds are explored for lowering blood glucose and affecting mTOR — mammalian target of rapamycin — which is abundant in developing and growing cells (including tumor cells) and tapers off across the lifespan.

He explains he has worked extensively on the mTOR pathway in his own laboratory in the context of regenerating the visual system, so he is very familiar with it. The longevity logic is that drugs or compounds reducing mTOR (and the related idea that fasting reduces mTOR) might extend lifespan — but he says there's no direct human evidence yet. He doesn't take metformin because expert colleagues, notably Dr. Peter Attia, reviewed the peer-reviewed metformin-and-lifespan data in a collaborative journal-club podcast, and his understanding is the data are not sufficient to justify taking it for longevity. He may revisit this if new data emerge.

Rapamycin

Huberman explains that mTOR is named for being a target of rapamycin, a drug used largely as an anti-cancer agent with other purposes. Rapamycin is under active scientific exploration by researchers like Dr. Matt Kaeberlein at the University of Washington, who runs a dog longevity project examining the drug across many species. Dr. Peter Attia has also discussed rapamycin extensively, including a recent podcast with Kaeberlein and a world expert on mTOR.

While there's substantial understanding of rapamycin and mTOR biology and clinicians like Attia are excited about its potential, Huberman does not currently take it. To his eye, present data don't justify it for lifespan extension, and although it can be taken safely under certain conditions, its side-effect profile is enough that he's not interested in taking it for longevity right now — a stance that could change with future data.

The Real Foundation of Longevity

Huberman repeatedly emphasizes that supplements are supplements — they sit on top of, not at the foundation of, mental and physical health and performance. He summarizes his own choices: he's happy to take grapeseed extract, NR, NMN, and the occasional NAD infusion, but stays away from metformin and rapamycin for now, with all of it subject to change.

Borrowing language from Peter Attia, he stresses that no supplement or drug for longevity comes close to the known health benefits of quality sleep and sufficient quality exercise. Insufficient sleep can reduce lifespan directly and indirectly (accidents, lower happiness and energy). On exercise, he prescribes a combination of cardiovascular work — a minimum of 180–220 minutes of zone 2 cardio per week (an intensity where you can still hold a conversation but would struggle to complete sentences if you pushed harder) — plus VO2 max work at least once per week to get the heart rate way up, and resistance training (weights, machines, or body weight) at a minimum of six sets per body part per week. Resistance training matters not only for muscle size and strength but for maintaining nerve-to-muscle connectivity, which correlates with cognitive function and other longevity metrics.

He rounds out the foundation with quality nutrition, quality social connection (eliminating toxic relationships and increasing enriching ones), stress modulation/control, and morning sunlight to set circadian rhythm — which he calls the anchor of everything. Only after getting all of these right should anyone consider adding a supplement or drug, and any addition or removal of a supplement or prescription should be done in consultation with a board-certified physician.

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