- The Lifespan Podcast discusses the science of aging and how to be healthier at any stage of life.
- The hosts are David Sinclair, a professor at Harvard Medical School, and Matthew LaPlante.
- They discuss how to live longer and better, focusing on supplements and medicines that can slow, stop, and reverse aging.
- They emphasize the importance of consulting with a physician before making any changes to your diet or taking supplements.
- The podcast is sponsored by Levels, InsideTracker, and Athletic Greens, who offer products related to health and wellness.
- They define drugs and supplements and discuss the regulation and potential risks associated with each.
- They mention several popular and promising supplements and drugs, including NAD boosters, metformin, berberine, rapamycin, spermidine, resveratrol, phizodin, and quercetin.
- Show notes and scientific references are provided for further information.
- David Sinclair discloses his involvement in various companies and emphasizes that he has never sold any supplements.
- They discuss the three longevity pathways: Sirtuins, AMPK, and mTOR.

- The video discusses three longevity pathways: Sirtuins, AMPK, and mTOR.
- Different drugs and supplements target these pathways in different ways.
- The pathways communicate with each other, and some drugs/supplements activate one pathway and talk to the other two.
- NAD boosters, such as nicotinamide riboside (NR), are important for energy production and activating sirtuins.
- NR has been well-studied in animals and has been shown to extend lifespan, improve health, and enhance oxidative metabolism.
- Human studies on NR have shown mixed results, but it is generally safe and can raise NAD levels.

- Studies have shown that low doses of NR and NMN can raise NAD levels in humans, but other effects like lower inflammation and improved body composition have not been consistently observed.
- NR is more popular because it is cheaper to make, while NMN has shown to work better in terms of restoring NAD levels and improving overall health in animal studies.
- NMN has been found to enhance insulin sensitivity and may have potential benefits for ALS patients.
- Human studies on NMN are still ongoing, but early results have shown increased insulin sensitivity and improved glucose disposal.
- NMN may have potential benefits for organ protection and wound healing, but more research is needed.
- Other NAD boosting molecules, called NCEs, may be even more effective and are expected to enter human studies soon.
- Some clinics offer NAD drips, but the effectiveness and safety of this method are still being studied.

- NAD IV drips are being used by people in Florida and LA, but there is no placebo-controlled trial to confirm their effectiveness.
- NAD is used to treat addiction, depression, and hangovers.
- NMN and NR are smaller molecules that can be used to raise NAD levels.
- NMN is considered the sweet spot in terms of size and effectiveness.
- Swallowing NMN capsules or powder is enough to raise NAD levels.
- Concerns about NAD boosters potentially stimulating cancer growth have been raised, but research is limited and inconclusive.
- Resveratrol is a widely used SIRT activator, but drinking red wine is not enough to get effective doses.
- Resveratrol needs to be mixed with fatty foods to dissolve and be absorbed properly.
- Some studies on resveratrol may have been flawed by not including food in the administration.

- Resveratrol has shown benefits in animal studies, including extended lifespan and protection against a high-fat diet.
- Human studies on resveratrol have shown reductions in fasting glucose, increased insulin sensitivity, and improvements in cholesterol levels.
- Resveratrol has also shown anti-cancer activity.
- Fisidin and curcumin are potential senolytic compounds that can kill senescent cells and potentially extend lifespan.
- Quercetin and dasatinib have shown promising effects in treating age-related diseases by reducing liver steatosis and inflammation.
- Rapamycin and rapalogs, which inhibit mTOR, have extended lifespan in various organisms but can be toxic and are not currently available for widespread use.
- Spermidine, which works on autophagy, has more recent availability and is also being studied for its potential benefits.

- Spermidine has shown potential in extending lifespan and improving heart function in mice
- Spermidine stimulates autophagy and stabilizes changes to the epigenome
- Human studies on spermidine have shown enhanced memory and cognition
- Metformin, an AMPK activator, has been used for diabetes and has shown positive effects on lifespan and various health markers in animals and humans
- Metformin lowers the risk of diseases such as cancer, heart disease, Alzheimer's, and frailty
- The TAME study is investigating the effects of metformin on aging
- Metformin is cheap and off-patent, making it challenging to raise money for research
- Doctors are becoming more comfortable with prescribing metformin off-label for anti-aging purposes
- Metformin has some downsides, including the risk of lactic acidosis, but most people tolerate it well
- Doctors are shifting towards treating patients earlier to prevent illness
- Concerns about muscle loss with metformin may not be significant based on available data.

- The difference in muscle size between taking metformin and not taking it is only around 5%
- Metformin has other benefits such as reducing inflammation and improving muscle strength
- Some people take metformin on days they don't exercise to counteract its effects on energy levels
- Berberine is an alternative to metformin that works on similar pathways and has shown similar benefits
- Berberine can be taken in doses of 1-2 grams per day and has been shown to increase lifespan in animals
- Side effects of berberine may include diarrhea, constipation, gas, and upset stomach
- Resveratrol and NMN are also taken in the morning, with resveratrol requiring a fat source for absorption
- Metformin is taken at night to simulate a fast and stimulate repair pathways
- Spermidine and quercetin are taken daily in lower doses for maintenance
- Fasodin and quercetin can be taken in higher doses once a week for a certain period of time
- It is important to consult with a doctor and monitor liver health when taking these supplements
- The next episode will cover other non-supplement options like testosterone, growth hormone, exosomes, and peptides.

- The Lifespan Podcast discusses the science of aging and how to be healthier at any stage of life, focusing on supplements and medicines that can slow, stop, and reverse aging.
- Hosted by David Sinclair and Matthew LaPlante, the podcast emphasizes the importance of consulting with a physician before making any changes to your diet or taking supplements.
- The podcast is sponsored by Levels, InsideTracker, and Athletic Greens.
- They define drugs and supplements, discuss their regulation and potential risks, and mention several popular ones, including NAD boosters, metformin, berberine, rapamycin, spermidine, resveratrol, phizodin, and quercetin.
- They discuss the three longevity pathways: Sirtuins, AMPK, and mTOR, and how different drugs and supplements target these pathways.
- NAD boosters, such as nicotinamide riboside (NR) and NMN, have been studied for their potential to extend lifespan and improve health.
- Resveratrol, fisidin, curcumin, quercetin, and dasatinib have shown promising effects in treating age-related diseases.
- Rapamycin and rapalogs have extended lifespan in various organisms, but they are not currently available for widespread use.
- Metformin, berberine, and spermidine have shown positive effects on lifespan and various health markers.
- The TAME study is investigating the effects of metformin on aging.
- It is important to consult with a doctor and monitor liver health when taking these supplements.

The speaker discusses various substances such as testosterone, growth hormone, exosomes, and peptides. They ask for support through subscribing and leaving reviews on YouTube, Apple Podcasts, and Spotify. They also mention sponsors and a Patreon account for supporting the show.

- The speaker discusses substances like testosterone, growth hormone, exosomes, and peptides.
- They ask for support through subscribing and leaving reviews on YouTube, Apple Podcasts, and Spotify.
- Sponsors and a Patreon account are mentioned for supporting the show.

In this week’s episode, Dr. David Sinclair and co-host Matthew LaPlante zero in on drugs and supplements that have been reported to combat aspects of aging. They share the latest experimental and clinical data for NAD boosters (these being NR, NMN, NAD IV drips and shots), resveratrol, fisetin, quercetin, rapamycin, spermidine, metformin, and berberine. Given the abundance of data available, a special focus is placed on the NAD precursors nicotinamide riboside and nicotinamide mononucleotide. Known mechanisms, limitations, and/or side effects associated with these molecules are additionally highlighted. 

Correction and clarification: At time point 1:07:37, Dr. Sinclair says he takes 1 gram of Spermidine, but the active ingredient in the capsules is 1-2 milligrams. We apologize for the confusion. 

#DavidSinclair #Longevity #Lifespan

Thank you to our sponsors:
Levels - https://levels.link/sinclair
InsideTracker - https://insidetracker.com/sinclair
Athletic Greens - https://athleticgreens.com/sinclair

Our Patreon page:
https://www.patreon.com/davidsinclair

Lifespan book: 
https://amzn.to/3sUqurT

Dr. David Sinclair Social:
Instagram - https://www.instagram.com/davidsinclairphd
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Facebook - https://www.facebook.com/davidsinclairphd

Matthew LaPlante's Social:
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Timestamps:
00:00:00 Kicking Off Episode Four: Longevity Molecules
00:02:15 Thanking the Sponsors
00:04:46 An Additional Boost Beyond Adversity Mimetics
00:05:52 Drugs vs. Supplements and Highlight Points
00:09:54 Longevity Molecules Target the Survival Circuit
00:11:33 NAD Boosters
00:13:32 Nicotinamide Riboside
00:21:26 Nicotinamide Mononucleotide
00:29:22 NAD Intravenous Drips
00:32:45 Bioavailability of NAD Boosters
00:33:40 NAD and Cancer
00:35:33 Resveratrol
00:42:26 Red Wine and The French Paradox
00:43:08 Fisetin and Quercetin
00:47:09 Rapamycin and Rapalogs
00:49:10 Spermidine
00:51:27 Metformin
01:00:27 Berberine
01:02:43 Dr. Sinclair’s Protocol for Longevity Molecules
01:08:51 Wrap-up and Next Week’s Episode: Interventions on the Cutting Edge 
01:09:52 Options for Subscription and Support

Links:
The Sinclair Lab website: https://sinclair.hms.harvard.edu/
Nicotinamide riboside is well-tolerated in humans: https://go.nature.com/3G1blbb
Nicotinamide riboside is a sirtuin-activator: https://bit.ly/3FUWWxa
Mice treated with nicotinamide riboside are longer-lived: https://bit.ly/3KD5L2h
Nicotinamide riboside protects mice against obesity: https://bit.ly/345E4hF
An inflammatory signature is attenuated by nicotinamide riboside: https://bit.ly/3Aum78I
Nicotinamide riboside, pterostilbene, and ALS: https://bit.ly/3nYdxK6
Nicotinamide mononucleotide combats diabetes in mice: https://bit.ly/3AwakXx
Aging is slowed by nicotinamide mononucleotide: https://bit.ly/344jGgW
Nicotinamide mononucleotide in prediabetic women: https://bit.ly/3H1vv6b
NAD and cancer in mice: https://go.nature.com/32xl1wp
Resveratrol protects mice against a high-calorie diet: https://go.nature.com/3G2pZyE
Resveratrol in patients with type 2 diabetes: https://rsc.li/3Aupk8h
Supplementing resveratrol in metabolic syndrome patients: https://bit.ly/3IE6C0Q
Fisetin enhances longevity in mice: https://bit.ly/3o10hom
Quercetin and fatty liver disease: https://bit.ly/3H4KWdF
Dasatinib and quercetin decrease senescent cell burden: https://bit.ly/35pCHuY
Mice fed rapamycin late in life live longer: https://go.nature.com/3F0yud3
Spermidine induces life extension and cardioprotection in mice: https://go.nature.com/3fXL5nn
Spermidine and older subjects with cognitive decline: https://bit.ly/3IG0MMy
Healthspan and lifespan in mice are improved by metformin: https://go.nature.com/3JSRZbs
Metformin, age-related diseases, and mortality: https://bit.ly/3KG0iaS
Targeting aging with metformin (TAME) trial: https://bit.ly/3eU9ABk
Treating mice with berberine extends lifespan: https://bit.ly/3AwkO9l
Lifespan in fruit flies is prolonged by berberine: https://bit.ly/3nYpwYt
Berberine and metabolic disorders: https://bit.ly/3KUpwCC

Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed.

Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

Welcome to the Lifespan Podcast, where we discuss the science of aging and how to be healthier at any stage of life.

I'm a professor at Harvard Medical School and co-director of the Paul F.

And I'm joined today by my lovely co-author and co-host, Matthew LaPlante.

We're here today to talk about how to live longer and better.

dive into the things that you can do to slow stop and reverse aging.

And today is going to be a really interesting 1.

This is going to be the 1 that everybody, I mean, this is the 1 that everybody's been begging for.

We've been monitoring the responses to tweets and Instagram posts.

And most of them are, David, just tell us what to take.

Some of those aren't very nice either, but yeah.

Please, please, please, should I take NR, should I take NMN?

And our research team has been spending weeks on this.

And if you can't see, I'm actually sitting in front of many pages of notes here.

We're gonna go deep dive into what is fact and what is not fact, what is known, what is not known, because there's so much misinformation out there, especially with supplements.

Yeah, we do need to say, we usually take a moment to thank our sponsors.

We're gonna do that of course, but we also have to take a moment to say, we are not medical doctors.

I've been doing it for the last 30 years.

But of course, if you want to try a supplement or even change your diet radically, please talk to your physician before you change anything.

Because some of the things we'll talk about today can affect your body in hopefully many good ways, but sometimes can be dangerous depending on the person and everybody's different.

And what we wanna do is give people the ability to have a more intelligent and informed conversation with their physician.

Okay, with that out of the way, now we should thank our sponsors.

Let's do that because this podcast is free to anybody who wants to watch or listen.

Levels is an app that syncs with a continuous glucose monitor, which they provide, and it interprets your glucose data for you.

I've been so impressed by Levels that I've recently joined them as an advisor.

Monitoring your blood glucose allows you to see how different foods impact you.

I've used levels to see what foods impact me.

I've learned that grapes spike my glucose, white rice, but actually potatoes aren't that bad.

It's not just interesting, it's also a lot of fun to see what's going on inside your body.

So if you'd like to try levels, you can skip the 150,000 person wait list and you can join today by going to levels.link slash Sinclair.

Today's podcast is also brought to us by InsideTracker.

InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and reach your health goals.

I've been using InsideTracker for over a decade and also serve as chair of their advisory board.

I really like InsideTracker because they make it easy to get your blood test.

Either someone can come to your home like they do for me, or you can go to a clinic.

They then present the blood analysis in an easy-to-understand dashboard that provides recommendations for improving your health.

Their InnerAge 2.0 test, which I helped develop using an AI algorithm, even shows your biological age.

If you'd like to try InsideTracker, you should go visit them at insidetracker.com slash Sinclair, and you'll get 25% off every InsideTracker plan.

Use Sinclair as the code at the checkout.

Today's episode is also brought to us by Athletic Greens, the all-in-one daily drink to support better health and peak performance.

Athletic Greens is a greens powder developed from a complex blend of 75 vitamins, minerals, and whole food sourced ingredients.

It's filled with adaptogens for recovery, probiotics and digestive enzymes for gut health, as well as vitamin C and zinc citrate for immune support.

I've been drinking Athletic Greens in the morning for many years.

And I do that because I don't often eat perfectly and I travel a lot.

And I can rest assured that I'm getting all the nutrients I need for optimal health.

So if you'd like to try Athletic Greens, you can go to athleticgreens.com slash Sinclair to claim a special offer.

They're giving away 5 free travel packs, plus a year supply of vitamin D3 for immune support and vitamin K2 for keeping calcium out of your arteries and putting it where it's needed into your bones.

Again, go to athleticgreens.com slash Sinclair to claim this special offer.

There's a lot to get through today, and I know everyone's waiting to hear what we have to say today.

In the last episode, David, we talked about adversity mimetics.

These are the things that we can do in our modern lives to mirror the sorts of stresses we faced across our evolutionary history.

But even if you're engaged in doing these things like we've talked about already, fasting, getting lots of exercise, getting out of your comfort zone, our modern lives are still designed around comfort and sedentary-ness, sedentary, is that a word?

And that's not to mention the fact that even before modern times, we aged, right?

So if we're gonna combat aging, we may need an additional boost.

You believe we may need an additional boost.

And I've been doing this since my early 30s.

We'll talk about my program at the end of this episode.

But really what we want to do today is to talk about some of the major supplements and medicines that are thought and have the greatest scientific evidence to be able to give you wellness now as well as long-term health in the future.

Supplements and medicines, drugs and supplements, molecules and drugs, there are a lot of different terms that we're probably gonna throw around and we're gonna use them fairly synonymously, but in fairness, let's define drug versus supplement at least.

Well, first of all, most drugs are chemicals, okay?

But some are naturally occurring and some are freely available over the counter OTC.

And that's because they've been in our food supply before and the FDA doesn't regulate them.

They fall under what's called generally recognized as safe or grass.

And that's why you can pick up whole variety of molecules from the plant world because they're already in our food supply.

Therefore the government thinks, well, they're probably okay even if they're a thousand times more concentrated than what you're eating.

And so that's why you always have to be careful.

Like I have been with my blood work for many years to make sure that you're not hurting parts of your body, your liver particularly could be sensitive to some of these molecules, even if they are available freely at the pharmacy or the vitamin shop.

Drugs are regulated molecules because they have the chance to actually cause damage.

And many drugs actually do have serious side effects that need to be carefully monitored and discussed with a doctor.

Even those that are very safe, like we'll talk about metformin, these are regulated by the government because they are not in the food supply.

They are artificial molecules that could theoretically do damage.

And there are literally thousands of drugs and supplements that someone somewhere will tell you will help you with health spans and long life spans.

We're not going to talk about thousands of drugs and supplements today.

No, maybe in future episodes we'll come back, but we wanna hit the high points today.

And so that's why today we're gonna move through some of the most popular and some of the most promising.

These are things that most people can have access to or find a physician who, if the need exists, will prescribe.

Right, and I get emails and I get all sorts of texts every day, DMs, what should I take?

Is it okay to take this drug with exercise or not?

Your most pressing questions answered here today.

And so we're gonna talk about NAD boosters.

We're gonna talk about metformin, berberine, rapamycin, spermidine, resveratrol, phizodin and quercetin and probably a few others.

But those are sort of the highlight points.

If you're only interested in 1 of these, or if you watch this whole episode and need a reminder, the show notes are gonna be timestamped so you can immediately go to Burberine and find it and click on it.

That's right, included in the show notes are the scientific references that we now have in front of us that we're gonna talk about so that people can do a deep dive, even deeper than what we're gonna do here today.

There's 1 more thing that we'll link to in the show notes that's on your website that I think is valuable for people to know about.

You're involved in a lot of different companies.

You're an entrepreneur, you're a researcher, you have I don't know how many patents.

There are plenty of people who would say, oh, this guy's just trying to sell stuff.

If they suspect that you might have a conflict of interest, they can go and look at your disclosures.

My lab has a website, you can Google Sinclair Lab.

And if you click through my bio, there's a link to all the work that I do outside of Harvard, as well as what we do at Harvard, of course.

But importantly, I've never sold any supplement in my lifetime.

that's not because you're a bad salesman, it's because you haven't actually tried to sell.

I mean, there's a difference between having not sold a supplement and having tried to sell a supplement and not sold a supplement.

Right, I've actively kept myself away from the supplement industry because I wanna be able to talk about things without any bias.

There's plenty of people who would love to put your face on a package.

You can see my face on the internet, but if you see that, know that it's not with my permission.

To get into this, let's use some of the same framing that we've used for the other conversation.

And that's these 3 longevity pathways, 3 longevity genes that we've been talking about, Sirtuins, AMPK, and mTOR.

Different drugs and supplements are thought to work on these different pathways in different ways.

And we'll sort of like categorize them in those 3 buckets today.

Exactly, and the thing to also remember is that these 3 survival pathways that we've talked about, and in episode 1, we talked a lot about, are responding to our environment, whether you're exercising or fasting, they'll turn on, but also appreciate that they talk to each other and some drugs or supplements will activate 1 of these and talk to the other 2.

So it's a network and we're still trying to figure out exactly what the optimal combination for each individual might be, whether to tweak it with this molecule and then exercise here and then fast that day.

We don't know all the answers, but we are gonna present the cutting edge science here today.

Well, and I think it's been really interesting.

I've been working with you for what, like about 4 years now.

And in that time, a lot of the molecules that we knew to be working on 1 of these pathways, there's been further research that have said, oh, that's not just an AMPK effect, there's also an mTOR connection there.

Well, they definitely talk to each other and because if you're low on amino acids and it'll turn on the mTOR protection pathway, that will then tell the other survival pathways to do their thing too.

It's like the Pentagon, where there's centrally coordinated defenses.

And basically what we're trying to do is to make a prank phone call to the Pentagon to say there's an emergency and they'll send out the troops in various ways and protect the body, even though there's no immediate threat.

Let's talk about the class of molecules that you've worked most extensively on in your lab.

Talk a little bit about why NAD is important in our bodies.

But it was discovered about a hundred years ago by Germans who were looking at extracts in yeast.

And there was this component called NAD that was necessary for chemical reaction.

So NAD stands for nicotinamide, which is vitamin B3 and adenine dinucleotide, this is a sugar and a phosphate.

The important part about it is that the cells, our cells use NAD to transfer hydrogen atoms between proteins and even DNA.

And without it, we can't make chemical energy which is in the form of ATP, which we'll talk about later because that's important for metformin.

It's probably, with the exception of ATP, the most abundant molecule we have in the body.

It helps us make energy, but it also has this other function that's just as important that we worked on and co-discovered in the 2000s.

It activates the sirtuins, and the sirtuins are these defensive enzymes that, like the Pentagon, send out the troops.

The problem is, as we get older, we make less NAD, and we also destroy it more, for reasons that we don't fully understand, but it leads to a decline in our ability to fight off aging and the diseases that it causes.

And this is because NAD is a sensor for adversity.

It is if you exercise, it's known and fast, it's known to raise NAD levels.

But even though, even if you exercise and have the healthiest diet, you're still gonna have lower NAD levels by the time you're in the latter half of your life.

So that's why these supplements are thought to help because they'll boost up those older levels of NAD to where they were when you were young.

Okay, so let's talk about the first NAD booster, probably the most well-known.

It's definitely the most well-studied of the NAD boosters and probably the most taken, used.

So that's the vitamin B3 plus the sugar without the N part, which is a phosphate.

But NR has been taken over the counter or through websites for what, since 2014, either solely just as a capsule, or there's some companies that sell it in combination with other molecules.

And because it's been pretty well studied in humans, there's been plenty of human studies, at least in the short term, that show little to no side effects.

And we know that if you take it as a supplement, just swallow the pill, either 250 milligrams per day or a gram, there's no apparent negative side effects.

And in fact, you will raise NAD levels in blood tests.

So I think this is an important distinction to make though, like there's a difference between safe and effective, right?

Just because we say something is safe doesn't mean it's gonna work enough.

And in fact, sometimes things that are the most safe aren't gonna work at all.

That's why they're so safe is they don't have any effect.

You know, millions of people around the world take it.

NR has been well studied in animals as well.

And let's start with that because we actually know more about what NR does in the bodies of animals than we do in the bodies of humans.

Let's start with yeast, go even further back.

NR was a newly discovered molecule back in the early 2000s.

It's found a little bit in milk and other foodstuffs.

And if it was fed to yeast, they lived longer by turning on the yeast sirtuin pathway.

Okay, how much longer were the yeast living?

Generally, yeast live about 30% longer when you give them these molecules, similar to caloric restriction.

And that's what this was doing, mimicking caloric restriction, because both activate the sirtuins and give increased genome stability and epigenome stability that lengthens their life.

And those kinds of findings make you really interested because you're really interested in the sirtuin activation.

And so you've been part of a group of scientists that have been looking at this.

Yeah, 1 of the first things that we discovered, this is now we're talking 2002, 2003 in my lab was that there's an NAD synthesis gene called PNC1.

In our body, it's called NAMPT and it gets activated by these mild stresses.

In a yeast cell, it's low salt, it's low sugar, heat, and that turns on the synthesis of NAD, and we found that extended lifespan.

And then a few years later, it was shown that you can mimic this effect with this NR.

So NR has to go through an intermediate molecule.

You swallow your NR, it'll go into the gut.

Some of it will be metabolized by the gut bacteria, but most of it will go into the bloodstream and then flow around and then get taken up into your muscle and to your brain and other cells that by transport is called ENTs.

And there it's converted into NMN by what are called NRKs.

And then you add the phosphate and you've got this thing NMN.

And when we do this in laboratory animals, you mentioned in yeast it extends life by 30%.

What have we seen in mice, which are a little closer to you and I than your yeast is?

Yeah, it's going back a number of years ago, it was found that NR, when given to mice, extends their lifespan by about 9%, but it was given to them late in life at about 700 days, which is a pretty old mouse.

This has been like a 70-year-old human, but it still worked.

But there were also improvements in health.

They had more mitochondria, which is the energy.

They had more athleticism, less inflammation.

And so that was the first real study that said, okay, maybe supplementing with these molecules like NR or NMN might have some long-term health benefits as well in humans.

Among the other health benefits that have been seen by researchers who have given NR to animals in the lab, enhanced oxidative metabolism.

And that also means that they're burning more oxygen.

And that's thought to be really good at staving off diabetes, type 2 diabetes, as well as improving lifespan.

Let's carry this now into the human studies because what we don't have for reasons that maybe are obvious, but I'm going to state anyway, which is that humans live a very long life and it's really hard to put humans into a control group and a test group across a very long time, then control for every variable that's possible, is longitudinal studies that show increases in lifespan as a result of taking NR.

But we do have studies that have sought to show similar health benefits to what we've seen in rodents?

I would say NR, there have been a few positive results, not a lot.

Before we get to that, I think it's worth talking about why can't we just take vitamin B3, which is a precursor to NR.

And you can, but it doesn't raise NAD levels anywhere near the level that NR does.

And NR doesn't seem to be as effective as NMN.

So the closer you get to NAD with your molecule, the better it seems.

And that's probably because you need to bring in other components.

So if you just take vitamin B3, you need a sugar and the phosphate.

If you just take NR, you need the phosphate and phosphate is pretty rare in the body.

And maybe when you take NR, 1 of the issues is that you need to find the phosphate to add on there before it becomes active.

We have sought to see it, by we I mean the research community, I don't mean necessarily you and me.

We've sought to see the same sorts of effects that have been seen in models, organism studies.

Sometimes that's happened, sometimes it is not.

With NR there have been a handful of studies in humans showing that low dose, 250 mg per day, up to a pretty large dose, a gram a day, does raise NAD levels.

But it takes about 9 to 10 days to get to those peak levels.

What we've also seen is, or others have seen is lower inflammation, as well as some other markers such as minor changes in body composition.

But these other things, which are lower blood sugar, improvements in insulin sensitivity, increased mitochondria, those haven't been borne out just yet in these short-term studies with NR.

the things that were present in the mice who also lived longer.

Now it could be that you need a longer term exposure of these people.

These have been fairly short term studies or that humans are not the same as mice.

So would you say, I mean, if somebody tells you, oh, David, I've been taking NR for so many times, you're not rolling your eyes, but you're not convinced at this point, the jury's still out.

If it's to lower inflammation, yeah, it probably works.

See all David Sinclair transcripts on Youtube

NMN, NR, Resveratrol, Metformin & Other Longevity Molecules | Lifespan with Dr. David Sinclair #4