Longevity Supplements: Resveratrol, NR, NMN, and Beyond
Summary
Andrew Huberman reviews the most commonly discussed longevity supplements—resveratrol, NR, NMN, NAD infusions, metformin, berberine, and rapamycin—sharing both the current scientific evidence and his personal protocols. He concludes that while some of these compounds may support energy and vitality, none have sufficient evidence to justify taking them specifically for lifespan extension. Foundational lifestyle behaviors remain far more impactful than any supplement or drug.
Key Takeaways
- Resveratrol has been largely debunked as a lifespan-extending supplement; current evidence does not support it extending human longevity.
- Grape seed extract (400–800 mg/day with a meal) may support vascular function and blood flow, but is not a top-tier supplement recommendation.
- NR and NMN can increase NAD levels and may improve subjective energy and vitality, but do not yet have strong evidence for extending lifespan.
- NAD infusions (500–1,000 mg IV) produce notable but uncomfortable side effects during administration, and are best done earlier in the day to avoid sleep disruption.
- Metformin, berberine, and rapamycin are not currently part of Huberman’s regimen due to insufficient lifespan evidence and/or personal side effects.
- No supplement or drug comes close to the longevity benefits of quality sleep and consistent exercise.
- The basics must come first: sleep, sunlight, nutrition, movement, stress modulation, and social connection should all be optimized before considering supplementation.
Detailed Notes
Resveratrol
- Received significant attention for potential to activate cellular pathways linked to lifespan extension.
- Grape seed extract contains or can be converted into resveratrol; was popular for similar reasons.
- As of 2023, evidence that resveratrol extends lifespan has largely been debunked.
- Huberman’s personal use: 400–800 mg grape seed extract daily with a meal, taken for vascular and blood flow benefits—not longevity.
- Would not rank grape seed extract in his top 10 supplement recommendations.
NR and NMN (NAD Precursors)
- NAD (nicotinamide adenine dinucleotide) is central to cellular energetics and mitochondrial function; naturally declines with age.
- NR and NMN are precursors that can raise intracellular NAD levels.
- Debate exists around whether NMN is effectively absorbed and converted to NAD in cells.
- Huberman’s personal protocol:
- 500 mg NR daily
- 1–2 grams sublingual NMN daily (placed under the tongue)
- Taken in the morning, typically 30 minutes to 2 hours before the first meal (~11 a.m.)
- Subjective effects reported: Sustained mental and physical energy throughout the day, without disrupting sleep.
- He does not take NR/NMN for lifespan extension—only for subjective vitality benefits.
- Regulatory note: As of 2023, NMN was filed as an experimental drug in a clinical trial, making it technically unavailable as a commercial supplement (though still findable on the open market).
NAD Infusions
- Direct intravenous infusion of NAD; assumed to be more effective at raising cellular NAD than oral supplements.
- Huberman has done this twice, at doses of 500–1,000 mg IV.
- Used post-illness or when feeling run-down.
- Side effects during infusion: Nausea, chest pressure, leg discomfort—typically resolving within ~10 minutes.
- Slowing the drip rate can reduce discomfort.
- Post-infusion effects: improved sleep, increased vigor, faster recovery.
- Best performed earlier in the day to avoid sleep disruption.
- Oral NAD products exist but lack direct evidence linking them to increased cellular NAD levels.
- Considered expensive, inconvenient, and uncomfortable; Huberman estimates using them only a few times per year if needed.
Metformin and Berberine
- Both are associated with lowering blood glucose and reducing mTOR (mammalian Target of Rapamycin) activity.
- mTOR is highly active during cellular growth and development; reducing it is theorized to support longevity.
- Berberine: Huberman does not take it—causes him severe headaches, likely due to blood glucose lowering.
- Metformin: Huberman does not take it; cites a review with Dr. Peter Attia concluding insufficient peer-reviewed data to support metformin for lifespan extension.
Rapamycin
- Named for its role as the mammalian Target of Rapamycin; primarily used as an anticancer drug.
- Under active research by Dr. Matt Kaeberlein (University of Washington) for longevity, including a dog longevity project.
- Huberman does not currently take rapamycin.
- Reason: insufficient evidence to justify its side effect profile for lifespan purposes at this time.
- Notes that clinicians like Peter Attia are more enthusiastic about its potential.
Foundational Longevity Behaviors (Non-Supplement)
Huberman emphasizes these carry far greater impact than any supplement:
- Sleep: Sufficient, quality sleep nightly; sleep deprivation directly and indirectly shortens lifespan.
- Exercise:
- Zone 2 cardio: Minimum 180–220 minutes/week (conversational pace)
- VO2 max work: High-intensity cardio at least once/week
- Resistance training: Minimum 6 sets per muscle group per week to preserve muscle, strength, and nerve-to-muscle connectivity (linked to cognitive function)
- Morning sunlight: Sets circadian rhythm, anchoring all other health behaviors
- Nutrition: Quality food intake
- Stress modulation
- Social connection: Reducing toxic relationships and increasing enriching ones