What are the different ways to increase NAD+ levels in the body?

Methods include direct intravenous infusions of NAD+, and oral supplementation with its precursors Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN). While each method aims to raise NAD+ levels in the blood, their specific bioavailability and effectiveness in different tissues are still under debate.

Does taking NR or NMN actually extend human lifespan?

Based on the most rigorous scientific tools like the Interventions Testing Program (ITP), there is no unambiguous evidence that NR or NMN supplementation extends lifespan in mice. Human studies have shown very few, clinically insignificant benefits, leading to a strong skepticism about their direct longevity effects in humans.

What is Rapamycin and why is it considered a promising geroprotective drug?

Rapamycin is a drug that targets mTOR, an important nutrient sensing system involved in cellular growth and aging. Experimental data, particularly in diverse model organisms (yeast, worms, fruit flies, mice), shows uniform life extension with rapamycin, making it one of only two interventions (the other being caloric restriction) to consistently achieve this.

What are the common side effects of Rapamycin and how is it typically dosed?

Peter Attia takes 8 milligrams of Rapamycin once a week. A common side effect is aphthous ulcers (canker sores), which paradoxically serve as a personal biomarker for him that the drug is active. Intermittent dosing (e.g., once a week) seems to improve immune function, while daily dosing may suppress it.

How accurate and reliable are biological aging tests?

Peter Attia expresses strong skepticism about current biological aging tests, arguing they apply a false level of precision. He emphasizes that chronological age is still a better predictor of remaining years of life. The measurements involved are often noisy, and the accuracy of underlying technologies like epigenome sequencing by commercial companies is questionable.

What are the most impactful levers for healthspan and lifespan beyond supplements?

Both Peter Attia and Andrew Huberman unequivocally state that foundational behaviors such as good sleep, regular exercise (including Zone 2 cardio and resistance training), proper nutrition, and emotional/mental health have a vastly greater impact on healthspan and lifespan than any single supplement.

What is the 'critical decade' and why is it important for longevity?

Peter Attia identifies the period from ages 50 to 70 as the 'critical decade' for building physiologic reserve. During this time, the body's resilience begins to decline, making it crucial to maximize muscle mass, strength, and overall fitness to set the stage for maintaining vitality in later decades, rather than trying to recover from setbacks.

What evidence supports the use of NR/NMN for anything other than lifespan extension?

One intriguing, albeit unreplicated, study suggested a 60-80% reduction in basal cell and squamous cell carcinomas (non-melanoma skin cancers) with NR/NMN supplementation. This might correlate with skin experiencing the greatest decline in NAD+ levels with age, though melanoma risk was not affected.

What are some of Andrew Huberman's core daily supplements?

Andrew Huberman takes AG1 (1-2 servings), high-quality fish oil (1-2 tablespoons, over 1g EPA), Vitamin D3 (3000-7000 IU), Tongkat Ali, green tea capsules, yerba mate, and Creatine Monohydrate (10g). He also occasionally takes NR/NMN but not religiously.

What are some of Peter Attia's core daily supplements (excluding prescription drugs)?

Peter Attia takes EPA and DHA (fish oil), Thymosin for cognitive function hypothesis, Vitamin D (5000 IU), Methylfolate and Methyl B12 for homocysteine reduction, Magnesium (L-Threonate, chloride, oxide) for sleep and muscle function, Momentous Electrolytes, Creatine Monohydrate (5g), AG1, and Pendulum probiotics (glucose control, polyphenol, Akkermansia).

How does exercise timing influence daily energy levels?

Andrew Huberman notes a self-observation that completing workouts before 9 AM, even if starting fatigued, leads to more energy throughout the day. Conversely, working out mid to late morning tends to cause afternoon fatigue. He hypothesizes this relates to daily body temperature changes and the body's response to exercise.

Why is the FDA moving to classify NMN as a drug rather than a supplement?

The FDA's decision stems from the initiation of clinical trials on NMN, which effectively classifies it as an investigational new drug. Historically, this has allowed the FDA to remove such compounds from the supplement market, as was also seen with N-acetylcysteine (NAC).

Key Moments

Supplements for Longevity & Their Efficacy | Dr. Peter Attia

Andrew Huberman

Science & Technology3 min read151 min video

Jul 29, 2024|357,409 views|6,821|731

andrew huberman huberman lab podcast huberman podcast dr. andrew huberman neuroscience huberman lab andrew huberman podcast the huberman lab podcast science podcast dr peter attia peter attia longevity

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Key Moments

TL;DR

Dr. Peter Attia and Dr. Huberman discuss NAD+ supplements and longevity, finding little evidence for their efficacy.

Key Insights

The NAD+ pathway is crucial for energy production and DNA repair, but its levels decline with age.

Current scientific evidence for NAD+ precursors (NR and NMN) significantly impacting human lifespan or healthspan is limited.

Rapamycin shows consistent lifespan extension in various organisms and targets aging pathways, though it has side effects.

Key longevity strategies remain foundational: exercise, sleep, nutrition, and mental health are more impactful than most supplements.

While some studies suggest potential benefits for NAD+ precursors in specific areas like skin cancer risk reduction and glucose disposal, these findings are often statistically significant but not clinically meaningful.

Biological age tests are currently too noisy and lack robust predictive power for remaining lifespan.

FRAMING LONGEVITY STRATEGIES

Dr. Peter Attia and Dr. Andrew Huberman frame longevity into three primary categories: essential behavioral practices (exercise, sleep, nutrition), exogenous molecules targeting specific disease processes (like cardiovascular or metabolic diseases), and exogenous molecules targeting the hallmarks and pathways of aging. Behavioral aspects are non-negotiable for healthspan and lifespan. Targeted molecular interventions aim to delay chronic diseases, while the third category explores compounds that may directly influence aging processes themselves. This framework helps contextualize the discussion around supplements and interventions.

THE NAD+ PATHWAY AND ITS ROLE

NAD+ is a ubiquitous co-actor essential for cellular energy production and serves as a substrate for critical enzymes like sirtuins involved in DNA repair. Its levels naturally decline with age, particularly in tissues like the skin. This decline has fueled interest in NAD+ supplementation, with precursors like NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) being popular. The core idea is that boosting NAD+ could counteract age-related declines and support cellular functions vital for healthspan and lifespan.

EVALUATING NAD+ PRECURSORS: NR AND NMN

Despite the theoretical rationale, robust evidence supporting NR and NMN for longevity in humans is scarce. While these compounds can increase NAD+ levels in the blood and potentially some tissues, the critical question of whether this translates to meaningful lifespan or healthspan improvements remains unanswered. Studies in humans have yielded mixed results, often showing statistically significant but clinically insignificant effects in areas like liver fat reduction or glucose disposal. Furthermore, the FDA's stance on NMN as a supplement has created regulatory complexity.

THE CASE FOR RAPAMYCIN

In contrast to NAD+ precursors, rapamycin has demonstrated consistent lifespan extension across multiple model organisms, including yeast, worms, flies, and mammals. It targets the mTOR pathway, a key nutrient-sensing pathway implicated in aging. While approved for other medical uses and having known side effects like mouth sores, its potential for geroprotection makes it a compelling area of research. Ongoing studies, like the dog aging study, are crucial for further evaluation in higher-order mammals.

SUPPLEMENT REGIMENS AND PRACTICAL CONSIDERATIONS

Both Dr. Attia and Dr. Huberman share their personal supplement regimens, highlighting a focus on foundational elements like omega-3 fatty acids (EPA/DHA), vitamin D, methylfolate, methyl B12, and magnesium. They emphasize that these are secondary to core lifestyle factors. While acknowledging some potential benefits of NR/NMN for specific, limited outcomes like hair growth or possibly reduced risk of certain skin cancers, they express skepticism about their broader longevity benefits. Intravenous NAD+ infusions were described as uncomfortable with uncertain benefits.

THE PRIMACY OF LIFESTYLE OVER SUPPLEMENTS

A strong consensus emerges: foundational lifestyle choices—consistent exercise (including Zone 2 and resistance training), quality sleep, optimal nutrition, and mental well-being—are vastly more impactful for healthspan and lifespan than any supplement. Supplements should be viewed as secondary, potentially offering marginal benefits or serving as an 'insurance policy' rather than a primary intervention. The time and resources invested in supplements could often be better spent on these core lifestyle pillars.

Mentioned in This Episode

●Supplements

●Products

●Software & Apps

●Tools

●Companies

●Organizations

●Books

●Studies Cited

●Concepts

●People Referenced

Common Questions

NAD+ is a ubiquitous molecule in the body, primarily functioning as a co-factor for electron shuttling in energy production pathways, especially in mitochondria. A small fraction is also used as a substrate by sirtuins for DNA repair. It's considered important for longevity due to its role in cellular energy and repair processes, which decline with age.

Topics

Health & Longevity Human Performance Mindset & Self-Improvement Mitochondrial Health Exercise Timing Caloric Restriction NAD+ Metabolism Longevity Pathways Supplement Efficacy Aging Science Biological Age Testing

Mentioned in this video

Organizations

Stanford University School of Medicine

The institution where Andrew Huberman is a professor and Peter Attia received some of his medical training.

FDA

The regulatory body that has deemed NMN not suitable for sale as a supplement because it is undergoing clinical trials as a drug.

NIH

Government body that initially pulled funding for the ongoing surveillance program related to the Dog Aging Study, which Peter Attia found inexplicable.

Johns Hopkins School of Medicine

The institution where Peter Attia received some of his medical training.

Interventions Testing Program

An NIH-funded program run out of three independent labs, considered the most robust scientific tool for testing exogenous molecules for lifespan extension in non-inbred mice; found no benefit for NR or resveratrol.

Supplements

Nicotinamide Mononucleotide

A precursor to NAD+, debated for its oral bioavailability and efficacy compared to NR.

PCSK9 Inhibitor

A medication taken by Peter Attia to directly impact cardiovascular disease processes.

AG1

A foundational nutritional supplement taken by Andrew Huberman daily for over 10 years, providing vitamins, minerals, probiotics, and adaptogens.

reactive oxygen species

Molecules that can impede mitochondrial function, targeted by some anti-aging approaches like red light therapy.

Rapamycin

A medication that targets mTOR, taken by Peter Attia for its geroprotective effects, demonstrating life extension in model organisms.

Bempedoic Acid

A medication taken by Peter Attia to directly impact cardiovascular disease processes.

NAD

A co-factor crucial for energy production and DNA repair, discussed as a potential longevity target.

Resveratrol

A famous sirtuin activator found in grape skin, initially thought to increase lifespan but found to have no consistent effect in rigorous ITP studies, except in a specific, bizarre mouse model.

Terastilbene

A ceran activator, believed to function like resveratrol, that was part of a commercial product (Basis) tested in human studies for fatty liver disease, showing no significant benefit.

N-Acetylcysteine

A mucolytic and precursor to glutathione, whose classification was changed from supplement to drug by the FDA, leading to lobbying efforts.

Nicotinamide Riboside

A precursor to NAD+, discussed alongside NMN and direct NAD+ infusions for increasing NAD+ levels.

SGLT2 inhibitor

A class of medication, including Canagliflozin, taken by Peter Attia and discussed for its broad geroprotective effects, particularly influencing glucose regulation.

EPA

An Omega-3 fatty acid, taken by both Andrew Huberman and Peter Attia in fish oil for overall health.

Methylfolate

Taken by Peter Attia to lower homocysteine levels, which are associated with negative vascular health outcomes.

Magnesium Oxide

A form of magnesium taken by Peter Attia.

Alpha-GPC

A supplement some people take (600-900mg) with coffee before a workout for a stimulant effect, but it can increase TMAO.

glutathione

An antioxidant whose levels are increased by N-acetylcysteine (NAC).

DHA

An Omega-3 fatty acid, taken by both Andrew Huberman and Peter Attia in fish oil for overall health.

Methyl B12

Taken by Peter Attia to lower homocysteine levels, which are associated with negative vascular health outcomes.

Ashwagandha

An herb taken by Peter Attia for sleep.

Inositol

Occasionally taken by Andrew Huberman (900mg) before sleep.

Thymosin

A supplement taken by Peter Attia, with reasonable evidence suggesting it improves cognitive function in MCI patients.

Tongkat Ali

A supplement taken by Andrew Huberman to lower sex hormone binding globulin and free up testosterone.

Green tea capsules

Taken by Andrew Huberman in the morning.

L-Theanine

A supplement taken by Andrew Huberman before sleep.

Magnesium L-Threonate

A form of magnesium taken by Peter Attia for sleep and by Andrew Huberman for sleep, with general positive effects noted for cognitive function and muscle cramps.

Creatine monohydrate

Taken by Peter Attia (5g/day) and Andrew Huberman (10g/day, occasionally missed) for muscle function and cognitive benefits.

Yerba mate

A caffeinated drink consumed by Andrew Huberman for its stimulatory effect.

Vitamin D

Supplemented by Peter Attia (5000 IU/day) and Andrew Huberman (3000-7000 IU/day) to maintain healthy levels, despite outdoor exposure.

SlowMag

A slow-release form of magnesium taken by Peter Attia.

Akkermansia muciniphila

An anaerobic bacteria that is a key component of Pendulum's probiotic products, working through the GLP-1 butyrate pathway.

Apigenin

A chamomile extract (50mg) taken by Andrew Huberman before sleep.

Tools & Products

Continuous Glucose Monitor

A device used by Levels to track blood glucose in real-time.

Levels

A program that uses continuous glucose monitoring (CGM) to provide real-time feedback on how foods impact blood glucose levels.

DEXA Scan

A scan that uses very low levels of radiation, less than a cross-country flight, for bone density measurement.

Studies & Research

Dog Aging Study

A research program led by Matt Kaeberlein, investigating the effects of rapamycin on longevity in companion dogs, with results expected in 2026.

Concepts

Sirtuin 2

A gene initially overexpressed in yeast experiments by Matt Kaeberlein, leading to increased lifespan.

mTOR

A molecule robustly expressed during development and associated with cellular growth; its activity is often targeted by longevity approaches like caloric restriction and rapamycin.

Klotho gene

A gene initially discovered in a mouse model for hypertension, found to be a longevity gene, where its knockout kills animals quickly and its overexpression extends lifespan significantly.

DNA repair

A cellular process that corrects damage to DNA, linked to longevity and the activity of sirtuins, which consume NAD+ as a substrate.

Sirtuin 6

A sirtuin homolog that, when overexpressed in a transgenic mouse model, extended the lifespan of male mice by 10-15%.

French paradox

The observation that French people, despite a high-fat diet, have lower rates of coronary heart disease, once attributed to resveratrol in wine but found to be incorrect.

Red Light Therapy

A therapy involving red and near-infrared light exposure, shown in studies to potentially spare vision processes in aged eyes by reducing reactive oxygen species.

Homocysteine

Elevated levels are associated with negative vascular and kidney health outcomes, and can be lowered by methylfolate and methyl B12.

Books

PNAS

A scientific journal that published a 2015 study on NAD+ and NADH levels in whole blood, demonstrating redox potential decline with age.

Outlive: The Science and Art of Longevity

Peter Attia's book that covers essential behavioral aspects for healthspan and lifespan.

People

Lloyd Klickstein

Researcher who published a paper in 2014 demonstrating that everolimus enhanced immunity.

Andrew Huberman

Host of the Huberman Lab podcast and Professor of Neurobiology and Ophthalmology at Stanford School of Medicine.

Joan Mannick

Researcher who published a paper in 2014 demonstrating that everolimus enhanced immunity.

Peter Attia

Medical doctor trained at Stanford University School of Medicine and Johns Hopkins School of Medicine, known for his work on healthspan and lifespan.

Brian Johnson

An individual known for his 'kitchen sink' approach to longevity, involving high doses of polyphenols, caloric restriction, red light therapy, and PRP.

Matt Kaeberlein

Researcher leading the Dog Aging Study, investigating the effects of rapamycin in higher-order mammals.

Dina Dubal

Professor from UCSF, discussed for her work on the Klotho gene and longevity.

Matt Conklin

Leading authority on rapamycin research, who, as a postdoc, first overexpressed Sirtuin 2 in yeast leading to extended lifespan.

Brian Kennedy

Collaborated with Matt Kaeberlein to demonstrate that sirtuin overexpression and caloric restriction are independent longevity pathways.

David Sabatini

Colleague of Matt Kaeberlein, mentioned in the context of early sirtuin research and a trip to Easter Island.

Glenn Jeffrey

Colleague at University College London, whose work on red light and near-infrared light for aged eyes is mentioned.

Charles Brenner

An expert in the NAD+ field who has pushed back against claims that NR increases cancer risk, and argues against linking NR/NMN to lifespan extension.

Rich Miller

Runs the Interventions Testing Program (ITP), consulted for insights on ITP experiments.

Jocko Willink

Fitness personality mentioned for his high vigor and early morning exercise routine.

Andy Galpin

Host of 'Perform with Dr. Andy Galpin,' a Human Performance expert and former fan-favorite on the Huberman Lab podcast.

Ben Barres

Late mutual friend of Andrew Huberman and Peter Attia, who questioned the reasons for energy decline with age.

Eddie Chang

Chair of neurosurgery at UCSF and an early morning exerciser with high energy levels.

Colleen Cutcliffe

CEO of Pendulum Therapeutics, described as a scientist doing fantastic interesting work.

Nassim Nicholas Taleb

Author or thinker, paraphrased for his quote about preferring action over mere opinion ('Don't tell me what you think, show me what's in your portfolio').

Products

Eight Sleep Pod Cover

A smart mattress cover with cooling, heating, and sleep tracking capabilities, used by Andrew Huberman to optimize sleep temperature.

Basis

A commercially available product containing NR and Terastilbene, tested in a human study for fatty liver disease.

Pendulum Polyphenol

One of three Pendulum products taken by Peter Attia.

Carlson's Fish Oil

A brand of liquid fish oil taken by Andrew Huberman.

Pendulum Glucose Control

One of three Pendulum products taken by Peter Attia.

Companies

LMNT

An electrolyte drink supplement containing sodium, magnesium, and potassium in correct ratios, without sugar, used by Andrew Huberman for hydration.

Pendulum Therapeutics

A supplement company specializing in anaerobic probiotics like Akkermansia, noted for its pharmaceutical-grade GMP conditions.

Drugs & Medications

Canagliflozin

An SGLT2 inhibitor that showed success in the Interventions Testing Program (ITP) for life extension.

Rapamune

The brand name drug for rapamycin, approved in 1999.

Metformin

A drug mentioned as a potential longevity intervention, but noted by Attia to have failed in ITP studies for lifespan extension.

Everolimus

An analogue of rapamycin, used in a 2014 study by Joan Mannick and Lloyd Klickstein that showed enhanced immunity in 65-year-olds in response to an influenza vaccine.

Sirolimus

The generic name for rapamycin, noted as surprisingly expensive despite being off-patent.