AMA #12: Thoughts on Longevity Supplements (Resveratrol, NR, NMN, Etc.) & How to Improve Memory
Dr. Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford, discusses the efficacy of longevity supplements like resveratrol, NAD precursors (NR/NMN), metformin, and rapamycin, emphasizing foundational health practices over supplementation for lifespan extension.
Deep Dive Analysis
8 Topic Outline
Introduction to Ask Me Anything and Premium Channel Purpose
Resveratrol and Longevity Supplementation Efficacy
Grapeseed Extract for Vascular Function
NAD Pathway Supplements (NR, NMN) for Energy
NAD Infusions for Vigor and Recovery
Metformin and Berberine for Longevity and mTOR Pathway
Rapamycin and its Role in Lifespan Extension
Foundational Pillars of Health for Longevity
3 Key Concepts
Resveratrol
A compound once believed to extend lifespan by influencing certain cellular pathways, but current evidence suggests it does not directly increase human lifespan. It may, however, have other health benefits such as supporting vascular function.
NAD Pathway
A cellular pathway crucial for energy production and mitochondrial function, which is highly active in younger organisms. Precursors like NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), or direct NAD infusions, are used to increase its levels, primarily for subjective energy and vitality, though its direct impact on human lifespan is currently unproven.
mTOR (mammalian target of rapamycin)
A cellular pathway abundant in developing cells and active during any cellular growth, including tumor growth. Some drugs and compounds, such as metformin and berberine, are thought to impact or reduce mTOR levels, with the hypothesis that this could increase lifespan.
5 Questions Answered
While resveratrol may have some positive effects on cell functioning, there is very little, if any, direct evidence from modern, highly controlled human or primate studies that it can increase lifespan.
At present, it is unclear and seems somewhat unlikely that increasing NAD levels through these methods will increase human lifespan, though some animal data exist. Many individuals use them for subjective increases in mental and physical energy.
Current peer-reviewed data do not sufficiently support taking metformin for increasing lifespan. Berberine, often considered a 'poor man's metformin,' can cause uncomfortable side effects like brutal headaches for some individuals.
Rapamycin is under active scientific exploration for its ability to extend lifespan in various species, but the current data do not justify taking it for this purpose due to its potential side effect profile.
The most impactful strategies are getting sufficient quality sleep, engaging in regular quality exercise (cardiovascular and resistance training), maintaining good nutrition, fostering quality social connections, effectively modulating stress, and getting morning sunlight exposure to set circadian rhythms.
24 Actionable Insights
1. Consult Physician for Regimen
Always consult your board-certified physician before adding or removing any supplement or prescription drug from your regimen to ensure safety and appropriateness for your individual health.
2. Prioritize Foundational Health Basics
Before considering any supplements or drugs, ensure you have the basics of sleep, morning sunlight, quality nutrition, sufficient movement (exercise), stress control, and quality social relationships correctly established. These foundational elements have a ‘huge outsized effect’ on mental health, physical health, and performance compared to anything taken in pill or infusion form.
3. Ensure Quality Sleep
Get sufficient amounts of quality sleep each night. This is considered the most fundamental and important basic for a quality and long life, as not doing so can reduce lifespan and lead to less happiness and energy during the day.
4. Perform Zone 2 Cardio
Engage in a minimum of 180 to 220 minutes of Zone 2 cardiovascular exercise per week. This type of cardio allows you to maintain a conversation but would make it hard to complete sentences if intensity increased, and it leads to known improvements in health metrics related to longevity.
5. Incorporate VO2 Max Work
Perform high-intensity VO2 max work, getting your heart rate way up, at least once per week. This is another form of exercise that contributes to known improvements in health metrics related to longevity.
6. Implement Resistance Training
Do resistance training (with weights, machines, or bodyweight) at sufficient intensity, with a minimum of six sets per body part per week. This maintains muscular size, strength, and nerve-to-muscle connectivity, which correlates with cognitive function and other important longevity metrics.
7. Focus on Quality Nutrition
Prioritize and maintain a regimen of quality nutrition. This is a fundamental component of a quality and long life, contributing to overall mental and physical health.
8. Cultivate Quality Social Connections
Actively eliminate toxic social connections and increase interactions with people you genuinely like, enjoy spending time with, and feel enriched by. Quality social connection is a key basic for a quality and long life.
9. Practice Stress Modulation
Develop and practice effective strategies for stress modulation or control. This is identified as a fundamental basic for maintaining mental and physical health and performance.
10. Get Morning Sunlight Exposure
Expose yourself to morning sunlight. This practice is crucial for setting your circadian rhythm, which anchors all other foundational health elements.
11. Understand Supplement’s Role
View supplements as enhancements, not replacements, for foundational health practices. They can potentially enhance mental and physical health if they fit within your safety and economic frameworks, but they are not the foundation.
12. Take Grapeseed Extract
Consider taking 400 to 800 milligrams of grapeseed extract daily, usually with a meal. This is taken as a general insurance policy for vascular function and blood flow, among other potential benefits, due to reasonably strong data and low downsides.
13. Prioritize Supplements Over Grapeseed
If you have a limited budget or are looking for top-tier benefits, prioritize other supplements over grapeseed extract. It is not considered a top five or even top ten supplement recommendation.
14. Take NR Supplement Daily
Take 500 milligrams of an NR (nicotinamide riboside) supplement every day. This is done to increase NAD levels, which subjectively provides sustained mental and physical energy throughout the day.
15. Take NMN Supplement Daily
Take 1 to 2 grams of NMN (nicotinamide mononucleotide) as a sublingual powder daily. This is also taken to increase NAD levels, which subjectively provides sustained mental and physical energy throughout the day.
16. Combine NR and NMN
Consider combining NR and NMN supplementation daily. This protocol aims to increase NAD levels for sustained mental and physical energy throughout the day.
17. Time NR/NMN Intake
Take NR and NMN supplements in the morning, typically within one to two hours of waking and at least 30 minutes to two hours before your first meal. This timing is intended to provide sustained energy throughout the day that tapers off nicely by evening, allowing for sleep.
18. Do Not Expect Longevity from NR/NMN
Do not take NR and NMN with the expectation that they will increase your lifespan. At present, the data do not sufficiently substantiate a direct link between increased NAD levels and extended human lifespan.
19. Consider NAD Infusions for Vigor
Consider NAD infusions (500-1000mg intravenously) when feeling particularly run down or post-illness. Subjectively, this has led to improved sleep and vigor, though it is described as ‘pretty darn uncomfortable’.
20. Adjust NAD Infusion Rate
If undergoing an NAD infusion, request the administrator to adjust the drip rate to be slower. This can make the infusion more tolerable and reduce discomfort.
21. Schedule NAD Infusions Early
Schedule NAD infusions earlier in the day. Anecdotal evidence suggests that infusions later in the day may lead to challenges with sleep.
22. Avoid Metformin for Longevity
Do not take metformin with the goal of increasing lifespan. Current peer-reviewed data do not sufficiently support its efficacy for this purpose in humans.
23. Be Aware of Berberine Side Effects
Be aware that berberine, sometimes called ’the poor man’s metformin,’ can cause brutal headaches. This side effect is likely due to its blood glucose-lowering effects.
24. Avoid Rapamycin for Longevity
Do not take rapamycin with the goal of increasing lifespan at this time. The current data do not justify its use for longevity, and it has a significant side effect profile.
5 Key Quotes
It is very, very clear that at present there is no supplement or drug for increasing longevity that even comes close to the known improvements in health metrics that relate to longevity that come from getting quality sleep and especially from getting sufficient amounts of quality exercise.
Andrew Huberman
I do see supplements as indeed supplements. I think only by getting your light exposure, sunshine, movement, nutrition, stress modulation, social relationships, et cetera, correct, should you even begin to consider supplementation.
Andrew Huberman
My current line of thinking is that resveratrol, while it may have certain health benefits, does not seem to increase lifespan.
Andrew Huberman
I do not take NR and NMN in order to increase my lifespan. In fact, at this point in history, it's unclear and seems somewhat unlikely that increasing NAD is going to increase lifespan.
Andrew Huberman
I do not take metformin. And I also don't take what some people call the poor man's version of metformin, which is berberine.
Andrew Huberman