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2022-08-31 - Interview Dr. David Sinclair - Optimize Longevity - Longevity Molecules and Supplements (view source)

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== Transcript ==
== Transcript ==
=== Kicking Off Episode Four: Longevity Molecules ===
=== Intro ===
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| - Welcome to the Lifespan podcast, where we discuss the science of aging and how to be healthier at any stage of life.
| we've met people that eat terrible diets and take a supplement thinking that that will replace a healthy diet and that's
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| I'm David Sinclair. I'm a professor at Harvard Medical School and Co-director of the Paul F. Glenn Center for Aging Research.
| not true what we have shown in my lab and others many others have shown is that
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| And I'm joined today by my lovely co-author and cohost, Matthew LaPlante.<br>- Hey, how are we doing?<br>- [David] Hey, welcome.
| you need to do both to get the biggest bang for the buck and you can't just expect supplements to replace a healthy
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| - Feeling good today.<br>- [Matthew] Back at it again.<br>- We are. We're here today to talk about how to live longer and better.
| diet [Music]
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| - As part of this podcast series, this deep dive into things that you can do to slow, stop, and reverse aging.
| hi hi serena how are you i'm great how are you doing i'm good so
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| - That is true and today is going to be a really interesting one.<br>- This is going to be the one that everybody,
| i didn't do a big intro on you today because i figure by now it's our fourth part in our series and everybody knows
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| I mean, this is the one that everybody's been begging for.<br>- That is true. We've been monitoring the responses to tweets
| who you are um and if they don't then they can go back and watch our other three episodes
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| and Instagram posts, and most of them are, David, just tell us what to take.
| and learn all the things um but there are so many questions and uh and it's
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| - [Matthew] The nice ones.<br>- Yeah.<br>- Some of those aren't very nice either, but yeah, please, please, please.
| and it's wonderful because i finally sort of had the chance to explain to everyone what these badges are that are
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| Should I take NR? Should I take NMN? What should I do with Metformin? We're going to be talking about all of that today.
| down here and my team was trying to get me to explain the last few episodes um but what i was telling everyone is
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| - We are, 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.
| you clearly are so busy you're on the road now you're on the road all the time you're tuning in and doing this live to
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| We're going to 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,
| answer questions as a q a to the podcast that you do every wednesday um and it's
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| especially with supplements.<br>- Yeah. We do need to say we usually take a moment
| just giving people an opportunity to ask questions and we we try to house all the questions we can all the hundreds of
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| to thank our sponsors, we're going to do that of course, but we also have to take a moment to say we are not medical doctors. We are not medical doctors.
| questions that come in every single week we do the best we can to answer them but it's so kind of you to do this and so
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| We are not medical doctors.<br>- What he said. I'm a PhD, I'm a researcher.
| kind of both of our teams put in their energies to make this happen but i was letting people know that these
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| I can read the literature. I've been doing it for the last 30 years. I distill that for everybody.
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| But of course, if you want to try supplement or even change your diet radically, please talk to your physician before you change anything.
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| 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.
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| And everybody's different.<br>- And what we want to do is give people the ability to have a more intelligent
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| and informed conversation with their physician.<br>- Exactly.<br>- Okay, with that out of the way, now we should thank our sponsors.
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| - Let's do that, because this podcast is free to anybody who wants to watch or listen.
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=== Thanking the Sponsors ===
=== What to expect in this longevity conversation ===
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| Our first sponsor is Levels. Levels is an app that syncs with a continuous glucose monitor, which they provide,
| badges that are down here is a way that they can show appreciation to the team and also if they want to
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| and it interprets your glucose data for you. I've been so impressed by Levels that I've recently joined them as an advisor.
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| Monitoring your blood glucose allows you to see how different foods impact you. I've used Levels to see what foods impact me.
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| I've learned that grapes spike my glucose, white rice, but actually potatoes aren't that bad.
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| It's not just interesting, it's also a lot of fun to see what's going on inside your body.
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| 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/sinclair.
| bring a really important question up and they want us to see it i guess the badges highlight them in some way
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| That's levels.link/sinclair. Today's podcast is also brought to us by Inside Tracker.
| uh so so that was something that i wanted to let everybody know and thank you for the
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| Inside Tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body
| people that have literally just sent in badges just as a thank you to the team and to dr sinclair so so that's it i
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| and reach your health goals. I've been using Inside Tracker for over a decade and also serve as chair of their advisory board.
| know use up three minutes and we're gonna go right into supplements so this past episode you talked about it's like
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| I really like Inside Tracker because they make it easy to get your blood test. Either someone can come to your home like they do for me, or we can go to a clinic.
| a burning question everybody has which are what supplements do
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| They then present the blood analysis in an easy to understand dashboard that provides recommendations for improving your health.
| or can we take for longevity what molecules are important and today we'll
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| Their InnerAge 2.0 test, which I helped develop using an AI algorithm, even shows your biological age.
| go over a handful of them that you talk about so often not just in the podcast drop the last podcast draft but um just
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| If you'd like to try Inside Tracker, you should go visit them at insidetracker.com/sinclair
| whenever you do talk so we're going to talk a little bit about mmn nr what those differences are nad
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| and you'll get 25% off every Inside Tracker plan. Use sinclair as the code at the checkout.
| uh the differences between those three things because most people don't really understand um respiratory we're going to
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| Today's episode is also brought to us by Athletic Greens, the all-in-one daily drink to support
| talk about some synalytics uh quercetin and the seton and did you want to talk about
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| better health and peak performance. Athletic Greens is a greens powder developed from a complex blend of 75 vitamins,
| the satanism if we have time we'll talk about that right yeah sounds good okay and then um i met foreman berberine
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| minerals, and whole foods sourced ingredients. It's filled with adaptogens for calvary, probiotics and digestive enzymes for gut health,
| spermidine and for those of you guys that don't know what spermadine is we're gonna get really clear on what spermadine is so
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:05
| as well as vitamin C and zinc citrate for immune support. I've been drinking Athletic Greens
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:11
| in the morning for many years and I do that because I don't often eat perfectly and I travel a lot
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| and I can rest assured that I'm getting all the nutrients I need for optimal health.
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:22
| So if you'd like to try Athletic Greens, you can go to athleticgreens.com/sinclair
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:27
| to claim a special offer. They're giving away five free travel packs, plus a year supply of vitamin D3 for immune support
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:34
| and vitamin K2 for keeping calcium out of your arteries and putting it where it's needed into your bones.
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 4:40
| Again, go to athletic greens.com/sinclair to claim this special offer.
|}
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=== An Additional Boost Beyond Adversity Mimetics ===
=== What is NAD? How do you increase levels of NAD in the body? ===
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| Okay, Matt, let's dive in. There's a lot to get through today and I know everyone's waiting to hear
| there's no confusion at all um and then probably some rapid myosin too so that's
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| what we have to say today.<br>- In the last episode, David, we talked about adversity mimetics. These are the things that we can do in our modern lives
| what we're planning on covering today if we don't cover everything then make a note of it and we'll cover the parts
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| to mirror the sorts of stresses we faced across our evolutionary history. But even if you're engaged in doing these things
| that we missed um in another episode so okay yeah
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| like we've talked about already, fasting and getting lots of exercise, getting out of your comfort zone,
| five dollars yeah we're gonna try to pack it all in
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| our modern lives are still designed around comfort and sedentariness, is that a word?
| all right i see lots of questions so let's start with that let's start with um the difference between nr enema and
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| - Sedentary lifestyles?<br>- [Matthew] Sedentary lifestyles. And that's not to mention the fact that even before modern times we aged, right?
| energy i'm just gonna let you kind of go uh while i scroll back and take a peek
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| So if we're going to combat aging we may need an additional boost.
| at some of these questions okay great um yeah so if you don't know nad is a
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| Do you believe we may need an additional boost?<br>- Well I do and I've been doing this since my early thirties.
| molecule that we need for life we have a lot of it in our bodies we make less as we get older and we destroy more as we get older we need to
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| We'll talk about my program at the end of this episode, but really what we want to do today
| raise that back up and so you typically if you're my age i'm 52 now i would have about half the levels that
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| is to talk about some of the major supplements and medicines that are thought and have the greatest
| i had when i was 20. so the idea is to supplement and to get those levels back up why because there are enzymes that
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| scientific evidence to be able to give you wellness now as well as long-term health in the future.<br>- Supplements and medicines,
| control longevity certains of the enzymes we work on and they need nad so
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=== Drugs vs. Supplements and Highlight Points ===
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| drugs and supplements, molecules and drugs. There are a lot of different terms that we're probably going to throw around
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| and we're going to use them fairly synonymously. But in fairness, let's define drug versus supplement, at least.
| do dna repair enzymes there's a protein called parp1 that needs nad and so what how do you raise an ad well
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| - Right, first of all, most drugs are chemicals, okay?
| you can uh fast you can exercise these are some ways but you can also
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| 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
| complement uh supplement that kind of a lifestyle with supplements and
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| and the FDA doesn't regulate them. They fall under what's called generally recognized as safe, or GRAS.
| well you know i'll be very careful to say when it's a mouse study versus a human study we do know from some human
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| And that's why you can pick up whole variety of molecules from the plant world, 'cause they're already in our food supply.
| studies and a lot of male studies that you can raise nad levels in the body so let me tell you how to do that
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| Therefore the government thinks, well, they're probably okay, even if they're a thousand times more
| well some people take nad now i don't think that's the best way given what i know about biology and cells because nad
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| concentrated than what you're eating.<br>- Which may or may not be the case, right?<br>- Right, and so that's why you always have to be careful.
| is a very big molecule relative to these other ones you've mentioned and it doesn't get taken up into cells very
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| You have to monitor yourself, like I have been with my blood work for many years to make sure that you're not hurting parts of your body.
| readily and probably what's happening in the body is if you have an iv of nad it's first broken down into its
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| Your liver particularly could be sensitive to some of these molecules, even if they are available freely at the pharmacy or the vitamin shop.
| constituents which are what we've talked about but it's the precursors and then rebuild
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:10
| A different story about drugs. Drugs are regulated molecules because they have the chance to actually cause damage.
| so if you're going to take it orally so take a pill uh it can be sublingual can be swallowed just as a powder or a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:16
| And many drugs actually do have serious side effects that need to be carefully monitored and discussed with the doctor.
| capsule i do the capsules every morning with some water what you want to do is is take a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:09
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:22
| Even those that are very safe. Like we'll talk about Metformin. These are regulated by the government
| precursor so how do you build nad what does the cell do it needs various components
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:14
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:27
| because they are not in the food supply. There are artificial molecules that could theoretically do damage.
| nad stands for nicotinamide adenine dinucleotide and those are three components that you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:19
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:34
| - And there are literally thousands of drugs and supplements that someone somewhere
| need so the nicotinamide part of it you can get as vitamin b3 but i don't recommend to raise an ad levels by
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:40
| will tell you we'll help you with health spans and lifespans. We're not going to talk about
| taking vitamin b3 also known as niacin or niacinamide or nicotinic acid this
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:45
| thousands of drugs and supplements today.<br>- No, maybe in future episodes we'll come back, but we want to hit the high points today.
| this is just one part of a big molecule we need to build so you want to give all the components so what
|}
=== How NMN raises levels of NAD ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:52
| are the other components there's the adenine which is a sugary molecule and then there's a phosphate which is
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:35
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:59
| - And so that's why today we're going to move through some of the most popular and some of the most promising. These are things that most people can have access to,
| phosphorus which is oxygen and phosphorus put together so nicotinamide is vitamin b3 the sugar
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:07
| or find a physician who, if the need exists, will prescribe.
| is the adenine now those two put together is nr nicotinamide riboside so you've got two
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:13
| - Right, and I get emails and I get all sorts of texts every day, DMs, what should I take?
| out of three out of three components but if you take an r you still need that phosphate so phosphate where do you get
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 7:56
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:19
| What about this? What about that? What's the dose. When should I take it? What should I take it with? Is it okay to take this drug with exercise or not?
| phosphate in the body well it's in your bones it's in your dna and your body needs to either take it
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:25
| That's what we're going to cover today. Your most pressing questions answered here today.
| from the outside or bring it from from your your bones or your dna so
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:30
| - And so we're going to talk about NAD boosters. We're going to talk about Metformin, berberine, rapamycin, spermidine, resveratrol,
| the the other molecule that you mentioned the one that i take is nmn nicotinamide
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:36
| fisetin and quercetin, and probably a few others. But those were sort of the highlight points.
| right vitamin b3 mononucleotide which has the sugar in the middle
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:42
| If you're only interested in one of these, or if you watch this whole episode need a reminder,
| it's called a ribose and then the phosphate is also on there and it's got the three main components to make an ad
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:48
| the show notes are going to be timestamped so that you can immediately go to berberine and find it and click on it.
| okay and so what we find in our experiments in mice and it seems true in humans
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:54
| - That's right, included in the show notes are the scientific references that we now have in front of us that we're going to talk about
| um though we do need some more research is that if you take nmn it raises nad
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:40
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:00
| so that people can do a deep dive, even deeper than what we're going to do here today.<br>- There's one more thing that we'll link
| more readily to higher levels because you've got all three of the components to build nad whereas with nr you only
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:07
| 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.
| have two out of the three and if you just take niacin or nicotinamide you've got one out of the three
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:53
| You're an entrepreneur, you're a researcher. You have I don't know how many patents.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 8:59
| 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,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:06
| they can go and look at your disclosures.<br>- I do disclose everything that I do. My lab has a website. You can Google Sinclair Lab.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:13
| And if you click through my bio, there's a link to all the work that I do outside of Harvard,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:18
| as well as what we do at Harvard, of course, but importantly, I've never sold any supplement in my life.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:24
| - And 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
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:31
| having not sold a supplement and having tried to sell a supplement and not sold a supplement.<br>- Right, I've actively kept myself away from the supplement industry because I want to be able
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:38
| to talk about things without any bias.<br>- Not for a lack of opportunity though,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:43
| there's plenty of people who would love to put your face on a package.<br>- Well, and they do, without my permission. You can see my face on the internet.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:49
| But if you see that, know that it's not with my permission and I do actively try to stop that.<br>- To get into this let's use some of the same framing
|}
|}
=== Longevity Molecules Target the Survival Circuit ===
=== Benefits of NMN ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 9:56
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:12
| that we've used for the other conversation. And that's these three longevity pathways, three longevity genes that we've been talking about.
| but it doesn't mean that if you take any of those it won't help i just take nmn because i think that it raises nad
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:18
| sirtuins, AMPK, and mTOR. Different drugs and supplements are thought
| levels the highest when you take it and some people say do you need iv do you need sublingual how should you take it well what i've
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:25
| to work on these different pathways in different ways. And we'll sort of like categorize them in those three buckets today.
| done and with my colleagues at harvard is test it in people and what happens is
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:14
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:30
| - Exactly, and the thing to also remember is that these three survival pathways we've talked about, and in episode one we talked a lot about,
| if you take nmn over a certain amount of time which is about two weeks it'll steadily rise up to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:20
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:36
| are responding to our environment. Whether you're exercising or fasting they'll turn on, but also appreciate that they talk to each other
| about two times the normal levels of what what i would have and so that's what i do but you don't
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:43
| and some drugs or supplements will activate one of these and talk to the other two. So it's a network and we're still
| need to do anything fancy you just swallow it and it seems to get in quite fine into the body and raise those
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:48
| trying to figure out exactly what the optimal combination for each individual might be. Whether to tweak it with this molecule
| energy levels and why do you do that because we think that the body's natural defenses against aging are heightened
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:40
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:54
| and then exercise here and then fast that day. We don't know all the answers, but we are going to present the cutting
| like we're young again and in mice there's lots of things that happen that are good we see that mice run further they have more activity they're better
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:00
| edge science here today.<br>- And I think it's been really interesting. I've been working with you for, what,
| metabolic control they're a bit leaner and we and others see that older mice are less frail now do we know this
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:51
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:06
| like about four years now. And in that time a lot of the molecules that we knew to be working on one of these pathways,
| happens in humans no we don't know but we are doing those trials and there are some studies already that show that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 10:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:12
| there's been further research that has said, oh, that's not just an AMPK effect. There's also an mTOR connection there.
| people have more endurance more oxygen capacity which is what we see in mice as well
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:17
| - Well they definitely talk to each other. Because if you're low on immuno acids and it'll turn on the mTOR protection pathway,
| so so thank you for that and that was really helpful i know that we've discussed it before and there are some
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:23
| that will then tell the other survival pathways to do their thing too.
| comments here about how we've talked about anime before but i think it's really important because this topic is
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:28
| It's like the Pentagon where there's centrally coordinated defenses and basically what we're trying to do
| about supplements and something that i actually wanted to ask you to address was what is the
|}
=== How much NMN Dr. Sinclair takes a day ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:34
| difference between drugs and supplements and and right before you go into that i'm just going to give our audience that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:41
| is to make 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,
| our amazing audience that's here we have over 2 000 people just a reminder that this is a this is a learning space and
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:29
| even though there's no immediate threat.<br>- I like that analogy. That's fun. Let's talk about the class of molecules
|}
|}
=== NAD Boosters ===
=== What is the difference between and drugs and supplements? ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:48
| that you've worked most extensively on in your lab. These are known as NAD boosters.
| it's a really kind space and for anyone on here at the din can we speak of that last episode
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:54
| Talk a little bit about why NAD is important in our bodies.
| that isn't that didn't hear me speak about this episode um we are going to remove any unkind commentary that's on
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:01
| It's really important, if it disappears, we're screwed, right?<br>- Well, we'd be dead in 30 seconds. We need it for energy but it was discovered
| here because it's very distracting to the rest of our learning audience so thank you so much and let's talk about
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 11:56
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:07
| about 100 years ago by Germans who were looking at extracts in yeast. And there was this component called NAD
| the difference between drugs and supplements right um i do want to mention before i say
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:02
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:12
| that was necessary for chemical reactions.<br>- We didn't say what that stands for, that's?
| that that i take a gram of nmn a lot of people ask me how much do i take it's a gram a day not every day sometimes i
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:18
| - So NAD stands for nicotinamide, which is vitamin B3, and adenine dinucleotide. This is a sugar and a phosphate.
| have a couple of days off we should talk about on off days and timing um okay but your question is drugs have
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:24
| The important part about it is that our cells use NAD to transfer hydrogen atoms
| supplements well actually they're the same thing it's just that one's regulated and one
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:19
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:29
| between proteins and even DNA. That is really important for life and without it
| isn't in a different way i mean they're both regulated but one is under the fda's control and needs a prescription
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:25
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:36
| we can't make chemical energy, which is in the form of ATP, which we'll talk about later
| in the u.s um and one doesn't and every country has different rules but in general um the drugs like metformin that we're
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:31
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:43
| because that's important for Metformin. NAD is found in abundance. There's many grams of it in the body.
| going to talk about later you do need a doctor's prescription and supplements fall into a different category which are
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:48
| It's probably, with the exception of ATP, the most abundant molecule we have in the body. It helps us make energy but it
| classified as food and food-like substances that you can buy over the counter and that's really the main
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:42
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:54
| also has this other function that's just as important that we worked on and just co-discovered in the 2000s.
| difference it's important to remember that a drug just because it's a drug doesn't mean it's any different
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:59
| It activates the sirtuins and the sirtuins are these defensive enzymes that, like the Pentagon, send out the troops.
| some drugs are directly from plants or just slight modifications metformin which requires a prescription is derived
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:53
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:06
| The problem is as we get older we make less NAD and we also destroy it more for reasons
| from a plant just slightly modified so you just have to remember it's more about regulation than actually
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 12:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:11
| 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.
| the substance itself um so that's clarity on that and then
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 13:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:16
| - And this is because NAD is a sensor for adversity.
| some people ask what a gram is a gram is a thousand milligrams so any time we kind of throw out uh measurements uh you
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 13:11
| - It is, if you exercise, it's known, and fast, it's known to raise NAD levels.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 13:16
| But even if you exercise and have the healthiest diet, you're still going to have lower NAD levels by the time,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 13:23
| you know, 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
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 13:31
| to where they were when you were young.<br>- Okay. So let's talk about the first NAD booster.
|}
|}
=== Nicotinamide Riboside ===
=== How to find trustworthy supplement brands ===
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| Probably the most well-known, it's definitely the most well studied of the NAD boosters, and probably the most taken used. That's NR.
| can always google to see what yeah how much that is uh for you in your metrics well there is
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| - Which stands for nicotinamide riboside. So that's the vitamin B3 plus the sugar.
| one more thing that i should mention that's really important yeah the the reason that the drugs are
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| Without the N part, which is a phosphate, we'll get to the phosphate, that's important later.
| also in a different category is that they've gone through more testing and that you can be less worried about
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| It may make a difference, but NR has been taken over the counter or through websites for, what, since 2014,
| side effects because they've been through so many uh tests and of course with a drug you get the listing of all
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| either solely just as a capsule or there's some companies that sell it in combination with other molecules.
| the side effects and you work with your doctor whereas the supplement world um you know for good or bad but you know
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| - And because it's been pretty well studied in humans, there've been plenty of human studies,
| mostly it's a concern is that some of these products are unregulated in terms of their
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| at least in the short term that show little to no side effects. This is a pretty safe molecule.
| their quality and this is a real problem that we can talk about which is what do you how do you know what's a good
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| - That's for sure. We know that if you take it as a supplement to swallow the pill, either 250 milligrams
| supplement right you trust what you're getting um and so what i would say is uh look
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| per day or a gram, there's no apparent negative side effects, and in fact, you will raise
| for a company that has a good reputation so a company that's been around for a decade often uh you can
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| NAD levels in blood tests.<br>- So I think this is an important distinction to make, though, like there's a difference between
| find these these companies that aren't just pop-up you know often
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| safe and effective, right? Just because we say something as safe, doesn't mean it's going to work enough. And in fact sometimes things that are the most safe
| unreputable companies destroy pitiful companies they they pop up for a couple of years then they get a bad name they
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| aren't going to work at all. That's why they're so safe is they don't have any effect. But we do know that NR is largely safe, you know,
| change their name so you don't want one of those the thing is as i mentioned in a previous live review
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| millions of people around the world take it. NRs have been well studied in animals as well.
| look for the letters gmp good manufacturing practices because that means that they're they've been certified to produce a product that
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| 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.
| genuinely has what they say is in there and there are no contaminants as well and um on that note you know we have so
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| - Well let's start with yeast. Go even further back.<br>- Okay, yeah.<br>- So that's where it was first discovered.
| many people asking about brands and i know this question is going to continue on throughout the course of our lives for
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| NR was a newly discovered molecule back in the early 2000s. It's found a little bit in milk and other food selves.
| each supplement that we're talking about so let's address brands you know we've talked about it
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| And if it was fed to yeast, they lived longer by turning on the yeast sirtuin pathway.<br>- Okay. How much longer were the yeast living?
| before and on this on the slide and just professionally we typically do not
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| - Generally yeast live about 30% longer when you give them these molecules, similar to choleric restriction.
| you know we can't really endorse a specific brand for various reasons david you have you
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| And that's what this was doing, mimicking choleric restriction, 'cause both activate the sirtuins and give increased genome stability
| have your reasons your associations your affiliations and um what we do offer is a guide of uh some
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| and epigenome stability that lengthens their life.<br>- And those kinds of findings make you really interested
| trusted resources that we like that is in our link in our bio
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| because you're really interested the sirtuin activation. And so you've been part of a group of scientists
| and we will speak specifically about some brands when it's appropriate but when it comes to nad
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| that have been looking at this.<br>- Yeah, one of the first things that we discovered, this is now, we're talking 2002, 2003 in my lab,
| and nmn as far as i understand there's really no specific brand that you endorse right uh
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=== Why Dr. Sinclair doesn't endorse supplement brands ===
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| though you may have spoken of some in the past so i just wanted some clarity on that because i know that people are
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| is that there's an NAD synthesis gene called PNC1. In our body it's called NAMPT.
| going to go online and they're going to google dr david st claire and nmn and all kinds of things will pop up so we
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| And it gets activated by these mild stressors. In a yeast cell it's low salt, it's low sugar, heat.
| just want to make sure it's really clear to our audience um where you stand on that
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| And that turns on the synthesis of NAD and we found that extended lifespan. And then a few years later it was shown
| yeah uh well so i need to be separated from from these brands and even though
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| you can mimic this effect with this NR.<br>- How does the NR turn into NAD?
| you might see my name on websites and often people just put my name or they link to a video or
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| - So NR has to go through an intermediate molecule. Let's start with the mouth. You swallow your NR, it'll go into the gut.
| my my research which you know my research is out there it's public information please know that i
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| Some of it will be metabolized by the gut bacteria, but most of it will go into the bloodstream
| don't endorse uh nad or supplements uh precursors to nad and if a company is
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| and then flow around and then get taken up into your muscle, into your brain and other cells, by transport that's called ENTs.
| doing that they're actually uh they're doing so without my permission why do i do that well
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| And there it's converted into NMN by what are called NRKs. And then you add the phosphate
| mainly it's because i want to have independent um objective status if i talk about the
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| and you've got this thing, NMN. What's NMN? Nicotinamide mononucleotide.
| science you know that i'm not uh biased in terms of well you know am i making
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| And then the cell puts two of those together to make NAD.<br>- And when we do this in laboratory animals,
| money from nr no no so then you know that what i have to say is totally just
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| you mentioned in yeast it extends life by 30%. What have we seen in mice,
| based on the science but that's my philosophy in general is try my best not to
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| which are a little closer to you and I than yeast is?<br>- Yeah, it's going back a number of years ago.
| be affiliated with a certain brand uh so that what i say you can trust is not contaminated by a conflict or at least a
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| It was found that NR, when given to mice, extends their lifespan by about 9%.
| perceived conflict of interest okay great yeah so so just to be clear
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=== Can you take NMN and NAD together? ===
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| with everyone on here um if you uh if you see
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| But it was given to them late in life at about 700 days, which is a pretty old mouse, that'd be like a 70 year old human, but it still worked.
| um dr sinclair if you see content out there that says he's endorsing a particular brand um
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| But they're also in improvements in health, they had more mitochondria, which is the energy. They had more athleticism, less inflammation.
| that's not the case you kind of heard it here from him directly which is important um people have questions about
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| And so that was the first real study that said, okay, maybe supplementing with these molecules
| whether or not they can take nmn and nad together at the same time not
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| like NR or NMN might have some long-term health benefits as well in humans.<br>- Among the other health benefits
| necessarily at the same time anyone sitting with the supplements but just some people do the shot some people do
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| that have been seen by researchers who have given NR to animals and lab enhanced oxidative metabolism.
| the trips and then they also want to take it uh the enemy orally so i would love for you to address that since there
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| Let's talk about that.<br>- So they burn more fat, they get thinner. And that also means that they're burning more oxygen and that's thought to be really good
| are a lot of people are actually doing that we've got quite a few questions about that specifically right uh well i
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| at staving off diabetes, type two diabetes, as well as improving lifespan.<br>- Let's carry this now into the human studies because what we don't have for reasons
| don't see any reason why that would be a problem um in fact i've been taking nmn for many years um and i've tried nad
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| that maybe are obvious, but I'm going to state it any way, which is that humans live a very long life. And it's really hard to put humans
| drips and i think that it's the there's no reason why they they cannot be mixed together just be aware
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| into a control group and a test group across a very long time, then control for every variable that's possible,
| or be aware uh that if you take nmn one day and at the same on the
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| is longitudinal studies that show increases in lifespan as a result of taking NR.
| same day have an nad drip you're probably gonna make your nad levels very high now
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| But we do have studies that have sought to show similar health benefits
| is there a problem with very high nad levels we don't know there hasn't been any evidence that
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| to what we've seen in rodents.<br>- Somewhat. I would say, NR,
| there's a downside that i'm aware of in people but i think in an abundance of caution
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| there've been a few positive results. Not a lot. Before we'd get to that I think
| we shouldn't push things too far until we know more and so i would say if it were me i don't make recommendations but
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| it's worth talking about why can't we just take vitamin B3, which is a precursor to NR.
| if it were me um i would not take my nmn or in our supplement the day that you're
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=== What is Resveratrol and what are the benefits? ===
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| having an nad trip that's um that's great that's a great uh
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| You can but it doesn't raise NAD levels anywhere near the level that NR does. NR doesn't seem to be as effective as NMN.
| i don't want to say piece of advice but that's a great share so thank you for letting us know that and hopefully
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| So the closer you get to NAD with your molecule, the better it seems. And that's probably because you need
| that's helpful for the people listening um we have so many questions about our
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| to bring in other components. So if you just take vitamin B3, you need a sugar and a phosphate. If you just take NR, you need the phosphate.
| spiritual which you've spoken of you've spoken on a lot but since you know in
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| Phosphate is pretty rare in the body. It's in your bones, it's in your DNA. And maybe when you take NR one of the issues
| the in the theme of our episode i think it's important to address that and then maybe we can even jump to metformin um and
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| is that you need to find a phosphate head on there before it becomes active.<br>- Okay, back to the human studies on NR.
| berberine after that before we dive into spermidine and a couple other things so we're going to try and get all the
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| We have sought to see, by we I mean the research community,
| topics today you guys yeah good well resveratrol is a core part of my life it's been i've been taking it
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| I don't mean necessarily you and me, we've sought to see the same sorts of effects
| since i was 34 and uh it's gone in and out of fashion you know
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| that have been seen in models, organism studies.
| the media old media likes to be swing this way extreme that way but
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| Sometimes that's happened. Sometimes it's not. Is that fair to say?
| the science has been pretty much direct on which is every week there's another study coming out either in cells or in
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| - That's very fair to say. With NR there've been a handful of studies in humans showing that low dose, 250 milligrams per day,
| animals and every few months in people um touting or showing that there are
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 19:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:30
| 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.
| benefits and there are no downsides that i'm aware of so what thousands of papers now have shown
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:38
| What we've also seen is, or others have seen, is lower inflammation as well as some other markers
| is that resveratrol enhances the body's ability to repair itself um it protects organs in animal studies
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:45
| such as minor changes in body composition. But these other things which are lower blood sugar,
| and even in human studies it's showing some benefits for example it lowers
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:50
| improvements in insulin sensitivity, increased mitochondria, those haven't been born out just yet
| blood sugar levels which is what we think is important for overall longevity and it has even shown some
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:56
| in these short term studies with NR.<br>- Sorry, so these are the things that were present
| uh benefits in alzheimer's patients you know an australian study that was done a few years ago and so i've been taking resveratrol at a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:03
| in the mice who also lived longer.<br>- Right, yeah. Now it could be that you need a longer
| gram a day with maybe a day off every couple of weeks just to give my liver a chance to rest but other
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:10
| term exposure of these people. These have been fairly short-term studies. Or that humans are not the same as mice.
| than that um it's been a staple and the other thing i want to mention is the resveratrol is one of the best known
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:17
| - So would you say, I mean, if somebody tells you, oh, David, I've been taking NR for so many times,
| molecules for uh preventing cancer uh in at least in animals we don't know in humans that's a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:23
| you're not rolling your eyes, but you're not convinced at this point. The jury's still out.
| longer study but i take it for all those reasons and it's a very safe molecule it's been
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 20:55
| - Well, it depends what you're asking. If it's to lower inflammation, yeah, it probably works. There's also a study that was put out by a group
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:02
| that combined NR with [indistinct], which is a resveratrol-like molecule, We'll talk about resveratrol next,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:09
| that found that in ALS patients, Lou Gehrig's disease, there was an improvement in their daily function.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:14
| So that is somewhat promising. I think that of course we need more studies. That's what we really need here to be able
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:21
| to make any sort of conclusion about what the long-term effects of taking this supplement are.<br>- It's fair to say that in the sirtuin
|}
|}
=== Nicotinamide Mononucleotide ===
=== What is the best way to take Resveratrol for the longevity benefits? ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:28
| activated compound research community, there's kind of team NR and then there's team NMN.
| in our diet for thousands of years so though not in the quantities that i'm taking of course i take a gram and if
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:35
| Your lab really focuses on NMN and I think if people were sort of like following
| you often people ask me would i get it from red wine the answer is yes but you need to have 200 300 glasses a day of
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:41
| what you said earlier about how NR turns into NAD,
| red wine which i do not recommend so that's really important for people to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:47
| they might go, oh, well, NR turns into NMN, NMN turns into NAD, so why don't we just
| know because i think that people are unaware of the amount of respiratory that they're getting from red wine
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 21:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:54
| take NMN to begin with anyway. And you had mentioned earlier phosphate, and that's an important component of this question.
| though you know a little bit of benefits are always great um in order to get the levels that dr sinclair is speaking of
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:01
| - Well, it is. NR is more popular because it's cheaper to make. It doesn't have that phosphate which can be expensive
| you would need like 200 glasses of wine well also don't forget as we've
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:07
| to put on the molecule through chemistry. And that's why most people started using NR first in humans and in mouse experiments.
| mentioned before to mix it with something oily or fatty or a lot of protein so a little bit of yogurt greek
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:12
| I didn't have a horse in the race. I didn't care which one. In fact, I'd prefer if both worked according to,
| yogurt is great it dissolves yeah so i just want to clarify you said a lot of protein i think you might a lot of fat
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:18
| you know, my theories, but what we found through empirical studies, basically,
| right just to dissolve it in either like a coconut yogurt or um or fat or did you
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:26
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:24
| we're looking at which ones work better, my lab and others, including Matt [indistinct], who's at Wash U,
| mean protein well so i'm not big on having a lot of protein as you know especially early in the morning but i
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:32
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:31
| who treated a mitochondrial disorder and we were treating regular mice on treadmills. We found that NMN just worked better at the same dose.
| know it does dissolve so in the case of a zero fat greek yogurt i do know from
|}
=== Sourcing quality supplements ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:36
| past experience that it does dissolve well in that if greek yogurt zero fat is your kind of thing okay great so thank
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:43
| We don't actually understand why it could be that this phosphate addition is one of the reasons, but, you know, just based on observations
| you for that clarification on that um but yes that's something that we've spoken of before just like making sure
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:48
| in our hands and in others, NMN works better than NR.<br>- When we supplement with NMN,
| that you dissolve it there's so many questions about the sourcing you've talked about the different colors of of
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:54
| when NMN is given to organisms in the lab, what's happening?
| how or spiritual should look like um and i know that sounds like almost like a silly simple guide but that's really one
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 22:58
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:01
| - Well, it's a little different, there's been an argument in the literature that NMN doesn't get into cells. And similarly, NAD is really a big molecule
| of your recommended guides in terms of your sourcing of that product because there's people here from all over the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:06
| because it's got multiple components. And that also has a real struggle to get it into cells.
| world and so that's another reason why it's really difficult to recommend a specific brand or source yeah well it's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:13
| Neurons take it up but other cells typically need to break it down into its various components and then re-uptake it.
| really important to look at the color of the molecules go online look at what color i kept this molecule should be
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:21
| And that's important because some people actually are giving themselves NAD through the IV route. When it comes to NMN what happens
| so some of them are yellow berberine and quercetin physique is they're generally yellow they should be bright yellow not
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:27
| is it was recently discovered by Shin Imai at Wash U, his team discovered that there's a specific transporter
| dirty yellow resveratrol is different residual is a light gray color and uh
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:33
| that takes NMN out of the liquid outside the cells inside the cell and its name is SLC128A.
| very fluffy it'll it won't dissolve in water this is why it mix it with food and if it comes out brown
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:40
| Still debated, a lot of things to figure out. But I think it's just best to say, okay,
| you can open up the capsule look at it i often open up capsule and put it into my food i don't swallow it with food i mix
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:43
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:46
| we know what's happening when you give it to animals, we are starting to learn what happens to people.
| it uh if it's not light gray or really close to white it's full of other stuff and some of the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:52
| We of course want to understand how it's working, but the fact that it does work is the most important point.
| that brown stuff that's in there causes diarrhea and and that's probably the least of the problems that could occur so
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 23:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:58
| - So when it comes to NMN, there's been a number of animals studies showing, for instance, similar to NR, restores NAD levels,
| i really look for really pure substances with my supplements i look for 98 99
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:04
| it enhances insulin sensitivity. One of the things that was surprising to me is that we don't have a study that shows
| pure supplements because it's this other you know thirty percent sometimes that is could be contaminants that could you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:10
| NMNs effect across analysis entire lifespan yet.<br>- Well, we have half a life span.
| could do long-term harm over decades of use sure no and that's a great that's a great point and to kind of piggyback off
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:18
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:17
| Shin Imai showed that it actually was pretty good at slowing down the effects of aging,
| of that i did see some comments here about japanese knotweed that's a source for a spiritual i there
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:24
| but he stopped the experiment because he ran out of NMN. It used to be rare stuff. Now you can buy it.
| are certain brands that do combine their resveratrol with say grape seed or you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:28
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:29
| But we took up the challenge and we've been doing these studies for the last few years in my lab. Now, preliminarily, these mice have less frailty.
| know there are other other ingredients in their particular blends
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:34
| We've reported that out in the scientific community. They seem to be younger, having better activity,
| and so that might be why it won't have that it won't be white but that's also because it's not pure so just to keep
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:42
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:41
| better mitochondrial function. They run further. The lifespan looks promising. We've done it once and they do live longer on NMN.
| that in mind that for those products and there are a few that i recommend to my clients that i won't name here but um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:48
| The doses are out 400mgs per kg.<br>- How much longer?<br>- At this point by recollections,
| but sometimes they're not completely white but that's because they have other ingredients that are blended into it so
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 24:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:54
| about 10 to 15%, but particularly strong in females.<br>- Okay, so not particularly, like, wholly different than what we saw
| just just to keep that in mind for those of you guys that are sourcing on your own yeah so for example there's a product on
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:00
| in the NR cases with the mice.<br>- Right, a little bit better than that, but certainly those mice are healthier
| our product there's a there's a substance called foti fot i do know that one and that has a lot of resveratrol in
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:05
| and more active and are more youthful.<br>- And you said it was more pronounced in the females,
| it now that's been used for thousands of years uh in china and and that i think
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:11
| or at least according to the first phase of this it's more pronounced in the females.<br>- Right, well we had fewer females
| is is you know an example of you can choose to have a biological
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:19
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:16
| so we have to repeat that. So we've now got a larger cohort of mice. We're repeating the whole thing. We'll see how it goes.
| product that's been taken uh by people for thousands of years but it's this the products that are trying to
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:25
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:23
| But right now with the small number of females, yeah. They did do better than the male.<br>- And even though mice live pretty short lives,
| pretend to be pure that are not pure that i avoid yeah and so that's really that's really
|-
|}
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:31
=== What time of the day is better for taking supplements ===
| what we have to understand here is that there's still live two, three years on average. Right, and so in order to see lifespan extension,
{| style="padding-top: 1em;"
|-
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:29
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:38
| the note to make it's just that if something if a product claims to have purity and it's uh in its ingredients in
| especially if they live much longer, it takes some time to do these studies.<br>- Yeah, it's quite painful actually,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:45
| because you think about this, an average experiment takes three years and then you have to repeat it. So that's now six years.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:52
| Then to analyze the data and publish it is another three or four. That's a decades worth of work for one experiment.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 25:59
| And, you know, your career only goes for about five of those times. So, five experiments?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:04
| - Well, that's how careers used to go. But we're going to change that, right?<br>- We're going to live a lot longer.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:09
| We run things in parallel as well. That's important. But we can also mimic things, not just in animals,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:15
| but growing tissues in the dish will be the subject of a later episode.<br>- So, so far what I'm hearing is in animals,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:24
| NR and NMN both have some similar effects, right? Lengthening lifespan, restoring mitochondrial activity,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:33
| restoring NAD levels, enhancing insulin sensitivity. But in NR the human studies haven't always
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:36
| confirmed that that's the exact same thing that's happening in humans. What are we seeing in the human studies for NMN?
| it you'll be able to tell by the notes that dr sinclair gave us and how to discern between that so um okay so so
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:44
| - I know a fair bit about the effect of NAD boosters in humans because I'm helping a group that is actually
| maybe we should shift a little bit and talk about um well let's talk about time of day
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 26:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:49
| doing clinical trials at Harvard Medical School and they've been giving a molecule that's similar to NMN to subjects for many years now.
| because there are questions about that time of day to take these supplements so with the resveratrol i can see scrolling
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:56
| First of all, importantly, there's been no evidence of any negative side effects. That's important.
| um is there a specific time of day that you recommend for the max amount of the maximum benefits
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:03
| We're about to learn whether it actually does anything that's similar to the mice. We don't have results in yet, but hopefully by 2022,
| yeah so the the molecules that we're talking about here are activating sirtuins
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:14
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:08
| we'll actually know if people have more energy, more mitochondrial function, better blood flow, more endurance, which is what we saw in those mice.
| and they so resveratrol acts like the accelerator pedal nad is the gas
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:13
| - There's been a little bit less human research on NMN then in NR,
| or the petrol if you're in a different uh country and together they they rip off the stratus so why is that important because
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:26
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:19
| but we're starting to see just in the last couple of years, especially sort of a flood of studies
| the saturn's and nad ramp up in activity in the morning
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:32
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:24
| being published, early results, for instance, from Yoshino et al. in 2021 showed increase
| it's part of the circadian rhythm the daily diurnal cycle as it's called and you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:29
| insulin stimulated glucose disposal. We talked about this a little bit when this study came out,
| want your body to be in sync with itself otherwise you have jet lag you get tired and so i take these molecules um almost
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:37
| you were pretty excited about it. Tell me why.<br>- It's one of the real first proofs that NMN does something in humans
| without exception in the morning and i feel this boost of energy because of it and if i take them late at night often i
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:51
| the way it works in mice. So this was a 10 week study. It's well done, it's randomized, placebo controlled.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 27:56
| It was 250 milligrams, which is a relatively low dose. Remember, I'm taking in my clinical trials,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:02
| a gram and two grams, this is 250 milligrams. Nevertheless, it improved what you said,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:07
| insulin stimulated glucose disposal. That's basically insulin sensitivity. And that's a hallmark of longevity.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:13
| Keeping the glucose out of the bloodstream, keeping it low levels is a hallmark of wellness and ultimately longer life.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:20
| So that's the beginning but we have a lot more to figure out. We need to figure out if that increased endurance that we see in my lab with NMN
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:26
| treated mice is true for humans. We also want to note, are organs protected? Other labs, not mine, but other labs have shown that NMN
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:33
| protects the organs when they're damaged. Kidney and heart, the two main ones. Even increased wound healing.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:39
| I'd love to know if NMN does that in humans. That'd be a big deal. Kidney injury is huge.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:44
| And particularly, I don't know if you know this, but most surgeries on the heart end up
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:49
| damaging the kidneys and there's not much you can do about it. So ultimately we've seen a glimpse with Yoshino et al.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 28:56
| My studies that I'm involved with at Harvard Medical School are looking promising, we'll know more next year,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:01
| but yeah, there's a lot more in the works. And there are other NAD boosting molecules that have been made that are even better than NMN.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:09
| So-called NCEs called, new chemical entities. And those I'm aware of probably in the next year
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:14
| will go into the first human study.<br>- I mean, that can be a whole episode of this podcast in and of itself, yeah.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:21
| - We should do it.<br>- Yeah, okay. Why don't we just give NAD directly?
|}
|}
=== NAD Intravenous Drips ===
=== What is metformin and how it affects longevity? ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:43
| We're talking about like NAD boosters. NR creates NMN, NMN creates NAD, that boosts NAD.
| don't sleep well so that's very important there are other supplements such as metformin vitamin d k2
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:32
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:50
| Or NMN boosts NAD, but it all gets us to NAD. So why don't we just, you know, set up the drip line and get it going?
| fish oil that i know or at least i the science says they don't affect sleep
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:42
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 22:56
| - Well, we don't, but others do. There's a lot of activity going on in Florida and LA,
| wake cycle so i take those ignition instead okay great so you just mentioned it
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:01
| particularly, of having large drips, long drips of over an hour of NAD.
| let's let's kind of segue into metformin and berberine and then maybe we can
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 29:53
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:07
| - These are not in a study settings. This is not in a research setting. This are like people trying this out.
| adjust bermadine after that uh since we're at yeah we're about the 30 minute mark so we've got maybe about
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:14
| - Well, they're done under medical supervision, but I haven't yet seen a placebo-controlled trial
| 20 more minutes left i'm trying to break it up here you guys i'm gonna get better about the pacing
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:19
| that would tell us for sure if it's just wishful thinking or not. I don't think so given how many people
| all right so let's go quickly so metformin is a drug for type 2 diabetes it's used around the world people
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:26
| have been now treated and there's a serious amount of anecdotal data on this, better mood,
| who have diabetes typically take one to two grams a day it's a lot um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:32
| better energy, but you know, you cannot conclude anything unless you actually have one of these placebo-controlled trials.
| and you want high purity but you'll need to talk to your doctor or or go online and have a doctor prescribe it for you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:38
| I'd love to be involved if anybody's going to do one, I'd love to help. But I'm asked this probably every day.
| if you're in the united states or europe or another english-speaking country other parts of the world you can
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:43
| NAD IVs, do they work? My answer has to be we don't know yet.<br>- What do we think they might be doing?
| actually get it like aspirin over the counter but not here in the us now it's it's a molecule that has been shown in
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:35
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:49
| I mean, what are people trying them for?<br>- Well they're used for various things. It's been used for many years are to treat addiction,
| tens of thousands of people to not just prevent and treat type 2 diabetes which is high
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 23:55
| whether it's drug or alcohol, it's also used for depression, and also increasingly for hangovers.
| blood sugar brings it down again in most people but also just by looking retroactively at these people that take
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:01
| - Is it as good as the Australian hangover cure that you've given me a few times?<br>- Oh, the raw egg and the Vegemite?
| it they are relatively long-lived compared to people that don't take metformin and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 30:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:07
| I hope it's better than that.<br>- Because the truth is that doesn't work. I just pretend it works because it makes you happy.
| we don't even have type 2 diabetes and the reason is it looks like that those people who are susceptible to heart
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:02
| - That's true and you're one of the few people that eat my Vegemite. But the reason that it probably works
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:07
| is there's an enzyme that detoxifies alcohol called alcohol dehydrogenase, and a lot of Asians are susceptible
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:14
| to high levels of alcohol because they lack a lot of this enzyme. Alcohol dehydrogenase needs NAD.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:20
| And so what's probably happening is when you wake up with a hangover, you lack NAD, your liver is depleted,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:26
| and if you take NMN or NR, you can raise those levels back up, get your liver working again,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:31
| and get rid of the excess alcohol.<br>- So you think chances are that is actually,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:37
| it's not just like a placebo effect. That there's a chance that, like, it makes sense that that would work.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:43
| - I think makes sense is the right words to use, you know, I'm a Harvard professor. I'm not going to say something works
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:48
| unless I've seen hardcore proof. And I hope that'll come in the next year or so.<br>- Just so I'm clear on this though,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 31:55
| 'cause it's still a little fuzzy to me. I can understand why we might want to use NAD.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:03
| I'm not understanding why we're not starting, for instance, all the research with NAD and then
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:09
| moving backwards to NMN and then moving backwards to NR.<br>- It all started in yeast when I was at Harvard early 2000s.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:16
| Even in yeast if you give them NAD it doesn't work because it's too big, it doesn't get taken up into the cells.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:22
| So what we want to do is back off in size. So the next smaller molecule behind NAD is NMN
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:28
| and there we know there's a transporter protein that sucks it into cells and NR is even smaller and it gets taken up even better into cells.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:36
| And so that's the reason why it may be that NMN is at the sweet spot of the right size,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:42
| but also has the right components to make just the right amount of NAD.<br>- It feels like a good time to talk about bioavailability and making things
|}
|}
=== Bioavailability of NAD Boosters ===
=== What is an alternative for metformin? ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:12
| available to our body's machinery. How do we make NR and NMN most bioavailable?
| disease cancer frailty and even alzheimer's disease dementia are protected somewhat by this
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 32:56
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:18
| - Just swallowing it is enough in our studies to raise NAD by two to three fold.<br>- So if you buy the, for instance,
| drug and that's remarkable that to me says very likely that there's a drug on the market that happens to be for type 2
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:02
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:25
| the capsules, they're often sold in capsules, just swallowing. That's going to be?<br>- Or the powder, just drink it.
| diabetes by the fda but it's actually slowing down aging um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:30
| We make tablets and give it to the patients that way, the subjects, but there were others, there was a sublingual version.
| and so that that's one of the reasons that i take metformin most days of the week i don't take it typically if i'm
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:35
| I have heard there's evidence that works. I haven't yet seen it. It makes sense that it would be
| going to do a lot of exercise the next day because there is about a five percent difference in muscle growth taking metformin versus
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:20
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:42
| absorbed under the tongue, or you can inject it.<br>- In terms of the research right now,
| not and it probably is because it interferes with your body's production of energy slightly it interferes with your mitochondria that make the energy
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:49
| it doesn't seem like there's a huge advantage one way or another?<br>- No, I haven't seen any reason for saying that you need to put it onto your tongue versus swallow it.
| atp molecule now often people say well my doctor won't give me that vomit i'm young or i
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 24:54
| What I can say for sure is that I've seen so much data on swallowing it that it definitely works to raise NAD levels.
| don't have type 2 diabetes and there's an alternative which is there's a berber what's called berberine
|}
=== NAD and Cancer ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:40
| - There has been some concern around the use of NAD boosters
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:00
| when it comes to the potential that it might stimulate cancer growth.
| from the burger plant it's it's yellow um and it's an extract
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:05
| And obviously that's something that we don't want to be dismissive of. It does you no good to be boosting your NADs
| what's great about berberine is that uh it works very similarly it boosts the mitochondria uh it inhibits it but then
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 33:58
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:11
| and extending your lifespan if you're just giving yourself cancer. What's the latest research on that
| is in in reaction to that and it also reduces blood sugar levels like pet hormone does and that's been shown in a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:04
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:18
| and how concerned should people be?<br>- Well, so most of these studies, actually, there's only two main studies have been done in mice.
| number of human clinical trials and so you can get berberine online now talk
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:24
| So here's what they are. There was one, again, out of Washington University by a different group that found
| to your doctor because playing with your metabolism is no small thing make sure your doctor knows you're taking supplements that's always the case you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:32
| that knocking down the levels of NAD in brain tumors slowed the growth of the tumor.
| need especially if you're taking other medicines you want your doctor needs to know what you're taking um and then some there's been a study
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:20
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:37
| And unfortunately the news story ended up being, oh, NAD causes cancer, which is not the same, right? That's the complete opposite.
| that shows that the combination of net form and berberine together has additive effects and can actually help metformin
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:43
| So that study, I wouldn't put a lot of stock into, but there is one other study that came out in 2019
| lower blood sugar even better than not taking birth yeah and so um and i just want to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:32
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:48
| by [indistinct] and they found that NAMPT, this NAD boosting gene,
| address and thank you so much for that so much great information i just want to address some of the questions that have come up here yes this will be recorded
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 25:56
| it increases the number of senescent cells and makes them more inflammatory, giving out these SAS proteins as they're called,
| and we release uh we the replays go up usually within three or four days but if
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:02
| the senescence associated secretory phenotype is the word, but also there were mice that were predisposed
| you sign up to the link in our bio both dr sinclair and i have links in our bios
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 34:51
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:07
| to pancreatic cancer and when given NMN they developed more precancerous and cancerous growths
| for a list that you can go on and you get those replays sent straight to your email along with along with the notes
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:14
| when they consumed this NMN. Exactly how it works we're not sure, but it might be because it was down-regulating
| about the topics we covered and often we also share links as well so some of these studies that dr sinclair is
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:20
| a tumor suppressor gene called P53.<br>- And this was a subgroup of mice that were already predisposed.
| referring to we will have those in those emails and so i highly suggest that you do that and i'm sure you already follow
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:09
| They had a gene that made them more likely to get cancer.<br>- Right, but remember we fed NMN to mice,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:14
| but normal mice, not predisposed, and if anything they lived longer and healthier. So it's a question whether it's this
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:20
| predisposition that's the difference.<br>- Something to watch for and to think about and to work into anyone's calculations
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:27
| if they're going to be considering an NAD booster in any case.<br>- For sure and another reason to consult your physician.
|}
|}
=== Resveratrol ===
=== The dosage of metformin and what to pay attention to when taking supplements ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:27
| - Absolutely. Okay. Now there are other NAD boosters,
| us both but if you don't you do that and put no post notifications on because then you'll know when we come up here
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:32
| sirtuin inactivating compounds. One of the ones that you've been really interested in that I think a lot of people are interested
| and then you also know when the replays are ready because we always share so just a quick note on that um and i also
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:39
| in, probably really widely used, is resveratrol. You started working with resveratrol
| wanted to share because i don't often in these talks that i am very much in the same protocols as dr sinclair very
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:45
| back when you were trying to understand sirtuin inactivation in yeast.
| slightly uh obviously because i'm female and built differently than dr
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 35:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:51
| - Right. I was just a kid. I was in my early thirties and I'd just come out of MIT with Lenny Guarente where
| sinclair and i also have some herbal supplements that i also take that we
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 26:56
| we'd found that up-regulating the sirtuin gene in yeast extends their lifespan.
| won't talk about in this episode but we can we're planning on doing on another episode to kind of address adaptogens
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:01
| But of course we can't up-regulate genes easily in our body. We're not going to genetically modify ourselves anytime soon.
| and other supplements and there are questions about dosage for metformin and that's really something that you should
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:08
| - Not anytime soon.<br>- We can but we're not going to. IT's easier to find a safe, natural molecule that does the same thing.
| talk to your practitioner about along to echo what dr sinclair said all things
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:13
| And so our goal back in the early 2000s at Harvard was to look for any molecule that we could find
| that you're putting into your body what we share here is not advice or recommendation so much as is what we've
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:20
| that was safe that would activate the protein, not the gene, but the protein, it's an enzyme that controls other proteins, remember.
| done for ourselves um obviously there's scientific findings on things maybe things that we've uh that we've shared
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:27
| And so he set up an essay that looks for what's called Sirt-1 activation. Sirt-1 is the first out of seven of them in the body,
| with our clients but to each your own you need to know your own biomarkers and you always want to speak with your own
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:33
| and Conrad Howards, my collaborator, and I were using an essay in a test tube that would fluoresce when you had more activity.
| practitioner about what you're taking whether it's a supplement or a prescription medication so i would say for metformin
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 36:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:40
| And so we added these chemicals, we added a dozen. Then we added thousands and eventually tens of thousands
| you really want to talk to your doctor about that and you may titrate up so whatever
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:45
| to Sirt-1 and found which ones raised the level of fluorescence.
| amount you end up at you might start lower and then kind of move up over the course of a month or three months so
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 27:52
| - And you've found a bunch of them. There were like 20 of them that did.<br>- We published 20. Yeah, in Nature 2003. The one that was the best at the time,
| keep that in mind and also sometimes there's some digestive side effects from taking something like metformin uh and
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:00
| which activated 13 fold Sirt-1 activity was resveratrol. And there were others, of course, [indistinct],
| for myself that was the case and so options for that is uh asking your
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:18
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:05
| which are actually now used by others for longevity. But resveratrol got most of the attention
| practitioner for a compounded version of it so it's a little bit cleaner it does it won't upset your tummy quite as much
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:12
| because it's found in red wine.<br>- And you've told me this a bunch of times, red wine stock went out the roof, right?
| um for any any of you who do find that it may give you digestive discomfort so just little notes that you guys can take
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:18
| Like people started buying red wine like crazy.<br>- 30% Sales, and they've stayed up ever since. And I've started drinking more red wine as a result as well.
| with you to your doctors yeah and i have mine with food a little bit of food because it kind of lines the stomach i
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:23
| - The truth is though, how much red wine would you actually need to drink in order to increase your levels of resveratrol
| also have this problem with the stomach there's a lot of references to scientific papers including all that
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:28
| and get an actual effect out of this?<br>- You know, you can't drink enough red wine to get the kind of doses that are efficacious.
| metformin that you can share with your doctor in my book and so that's lifespan if you haven't
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 37:51
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:35
| - You can't.<br>- Well you can try, but I don't recommend it. You'd need hundreds of glasses of red wine a day,
| come across it it's packed with lots of information about ampk about
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:40
| which I don't recommend. Even if your doctor says so, not recommended.<br>- That's not going to extend your life.
| sirtuins mtor which we'll talk about in a minute about brephomycin that is a that's the handbook for what
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:04
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:46
| - Probably not, no. But what you can do is you can purify it out of grapevines or polygonum cuspidatum,
| we're talking about today yes and so and so and for those of you if you don't actually have dr sinclair's
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:53
| which is an herb, a plant mostly grown in Asia.<br>- When you say that, can you just take your pen?
| book then you need to get it or you need to at least go and download it onto your
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 28:58
| All right, now say that word again and go like this when you do it.<br>- Polygonum cuspidatum.
| audible or your kindle or whatever it is because what we're doing here as we sort of
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:03
| - Okay. Thank you. I appreciate that.<br>- This is magic I think. Harry Potter?<br>- How much resveratrol do we actually need to see an effect?
| unpack all this information it comes from his book and it comes from his podcast which drops every wednesday if
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:09
| - There are a lot of human studies now. The minimum that I've seen is 250 milligrams a day.
| you haven't already tuned in and downloaded his new podcast episode dropped today because it's wednesday and
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:15
| And some people take 1000 or 2000 milligrams a day.<br>- This is a Sirt activator like the other
| our follow-up q a is usually on mondays today is a wednesday but it's usually on a monday after his podcast drops so for
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:22
| NAD boosters we've been talking about, works a little bit differently, but like you said,
| anyone that jumped on late jumped on after the first 10 or 15 minutes or you're new to this community then get
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:29
| really well studied and for almost 20 years now. What's happening when we put resveratrol,
| the book download it share it gift it um and make sure you go and you follow you
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 38:53
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:35
| let's start with the animal studies. What do we know?<br>- Well, we know, first of all,
| rate and review the podcast which you can find anywhere oh i've got a surprise for everybody ooh
|-
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| if you just give it to them in their water supply, it's not going to work. You can't just swallow it and expect it to get in easily.
| uh right now you can get the ebook 4.99 wow
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 39:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:48
| - Why not?<br>- Well, resveratrol is the equivalent of brick dust, it's really insoluble. If you put it in a glass of water
| yeah there's an ebook are they crazy the publisher i think accidentally
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:53
| it will fall to the bottom. So what you need to do is we found in both mice and humans, mix it with some food.
| uh timed this with the podcast so you can get really cheap so this isn't very well widely known but anyone who's
|}
=== What is Spermidine? What are the benefits? How it is extracted? ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 29:59
| listening go go get it it's basically free right now but okay so you guys um load up get it send it
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:06
| You can use yogurt, you can use that kind of olive oil, that kind of oily food, and it will dissolve. It's hydrophobic. This is the problem, it's scared of water.
| and you know what there might be a surprise if someone actually does these things screenshots in it dm
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 39:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:13
| - And this is actually why you suggested that maybe some resveratrol studies that have shown that it doesn't work
| maybe we'll have a surprise for or someone who doesn't in the audience because we love it when you take notes and we love it when you engage and you
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 39:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:19
| as well as other studies show, those studies may have involved people who were feeding mice resveratrol
| love it when you share um your thoughts with us on here okay so before we jump into mtor and
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:27
| without that additional fat.<br>- Yeah, that's the case.
| raphaemyson let's spend a little bit of time on spermidine so
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:32
| Some of these studies didn't include food. We found that early on in the mid-2000s that if we gave it with a meal,
| so i want to make sure that as we start talking about spermadine and i actually
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:37
| the levels in the blood went way up.<br>- There have been a number of animal studies
| have a bottle of it because i take it oh wait oh that glare is no good can we see it no we can't okay so
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:45
| on resveratrol going back almost 20 years. Now we're seeing extended replicative lifespan in yeast.
| well you know what if you guys go to the link in our bios spermadine is one of our trusted resources and we're going to
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:51
| We're seeing activation of AMPK in rodents.
| dive into it a little bit now and you'll you'll be able to see it better because you can go to the link all right that's
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 30:57
| What are these things telling you?<br>- Well, they're similar to what we expected from the sirtuins.
| that's a fail i'm sorry it's spermidine and you'll be able to see it when you go to the link in our bio but let's talk a
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 40:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:04
| They defend the body. They raise the metabolic rate. They protect against free radicals.
| little bit about that even like let's and explain people first of all what spermatidine is and then and then the
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:11
| And when we see research given to these rodents, what the biggest surprise was was that they were protected
| benefits yeah uh so spermatidine is a is found throughout life it is found in sperm but
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:18
| against a high-fat so-called Western diet. Those mice on resveratrol, even though they were really obese
| it's also found in plants it's found in you know in our bodies and it's called a
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:23
| on this really chunky meal, they lived as long as the lean mice that we had as the control group.
| polyamine it's a really small molecule that is actually very protective against
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:29
| And that was really, as far as I know, the first study of any that showed that you could mimic caloric restriction with a molecule and be fat
| things like oxidative stress and one of the things that it's been found to do mostly is to induce autophagy the ability of
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:35
| but live as healthy as a lean animal.<br>- Have those findings translated over
| the body to recycle all proteins and make proteins back into amino acids to build new proteins which is very
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:41
| as we've moved resveratrol into human studies?<br>- Yeah, somewhat.
| important for longevity and frank madeo who certainly you know and i know he's a
|-
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:48
| Not all studies have worked, but there are a number of them that have. And for instance, resveratrol has been shown
| scientist from austria has done about 15 years of really high quality research looking at starting with yeast
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 31:54
| to reduce fasting glucose and significantly increase insulin sensitivity. This was a study in 2019, and then again, in 2020,
| cells where there's spermatidine but also in worms and flies and mice and increasingly some studies in humans that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:01
| Battista and George et al. showed that a randomized control study of 25 individuals
| we're aware of that is not yet published but we're going to share that with you this molecule extends the lifespan of
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:07
| ranging from 30 to 60 year olds with a slightly high BMI of 30 were able to lower their cholesterol levels,
| all those species and that's really amazing there are very few molecules that i'm aware of that that does that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:12
| their urea levels, which is important for kidney function, as well as raise their good cholesterol, the HDL.
| um so i've recently started taking spermatine as well because we we want to induce autophagy
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:18
| - Well, once again, we don't know long-term what this is going to do but the trajectory seems good when we consider it
| and that would help induce what fasting would normally do or it could help accentuate the benefits of fasting
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:25
| in the context of what we've seen in animals and what we are seeing in these early human studies.
| yeah yeah it's really i have uh i've been taking the product now for several
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:31
| - Yeah I think so. Even before I worked on resveratrol, it was known to be an agent that suppressed cancer.
| months um and i i it's so funny we're already seeing comments about the name um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 41:57
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:38
| If you put a carcinogen on the skin of mice and then rub resveratrol on it, a 1999 science paper showed that those cancers
| but it really is and and something that what doctors think they were saying about that it's about
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:04
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:44
| are much smaller in those treated mice. So the anticancer activity of resveratrol
| poly polyamine is how you pronounce right um it's it's really difficult to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:49
| has been known before I came along. And since then we've seen effects on body composition, on metabolic rate,
| extract it naturally where it can be safe and stable for human consumption
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 32:54
| mitochondrial boosting, glucose levels. The list goes on, there's probably 1000 papers now
| so so when you when you get the bottle when you see what it is there's different uh
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:01
| showing at least the benefits in animals and a dozen in humans. Cardiovascular disease I haven't mentioned,
| there's some confusion about grams versus milligrams and so the product that's on the market that we use it's
|}
=== Red Wine and The French Paradox ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:28
| but that's a big one. May help explain the French paradox. The French can eat high-fat foods
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:08
| and with this glass or two of red wine every day, it helps mitigate the effects.<br>- I mean like, but what you've just said,
| got um it contains one milligram of spermidine per 800 milligrams of the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:14
| like you actually have to drink so much red wine in order to get this effect, but then we're thinking maybe the French
| wheat germ extract because that's where they get it from so so i just want to give the audience a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:19
| who don't drink that much red wine, even though they do drink a lot of red wine, but they don't drink that much red wine.
| little bit of clarity on that because the numbers may seem confusing when people make recommendations about
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:25
| - There's two considerations here. One is that drinking red wine over 30 years
| how much to take and again it's one of those products like everything else where you have to sort of take what is a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 42:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:31
| could have a cumulative effect and a buildup in the body. And the second is that red wine
| tune for your body um and work with your practitioner on that so the recommend the recommended dosages are two capsules
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:38
| has more than resveratrol and it has some of these other xenohermetic polyphenols that we talked about in earlier episodes
| which is 800 milligrams of of the wheat germ extract and that's one
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:44
| that could give a combination effect.<br>- Okay. The two other molecules I wanted to mention, you mentioned them earlier actually by name,
| milligram of spermatine so that's what it is on the bottle but you know dr st
|}
|}
=== Fisetin and Quercetin ===
=== Supplements vs a healthy diet ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:49
| these were part of the group molecules that were identified in those early experiments
| clary may take a little bit more than that more or less i may take more or less so so clarity on that and um and as we're
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:18
| with the yeast that identified resveratrol as a potential sirtuin activating compound,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:26
| these are fisetin and quercetin. And both in addition to being serotonin activators
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:33
| potentially also seemed to have this other property to them that is making them sort of like a hot number now.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:39
| - Right, they are what are called senolytic. Kill senescent cells.<br>- Senescent cells.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:45
| - Are zombie-like cells. The ones that accumulate over time in your body probably because their epigenome gets screwed up.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:52
| But what they do is they shut down, they stop dividing and they start secreting inflammatory factors and also factors that cause cancer.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 43:59
| - Yeah, and so getting rid of those would be presumably a good thing. And that's what fisetin and quercetin appear to do.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:07
| - They do in the dish and in mice and there even some human studies now that show that killing off these senescent cells
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:14
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 33:57
| in the body can improve health. And ultimately, we think, could extend lifespan.<br>- And these have been shown,
| talking about spermatine and uh and how it's extracting and again
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:19
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:02
| in the case of fisetin at least, to extend lifespans in some model organisms.
| a lot of these supplements as doctors and saying come from whole plants and foods and that's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:25
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:08
| - Like fruit flies?<br>- Yeah.<br>- And even in mice recently. I was particularly impressed by the mouse studies.
| something to really remind ourselves as because even though we're talking about supplements they aren't meant to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:31
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:15
| Couple of colleagues out at the University of Minnesota were able to show that fisetin put in either in the food of the mouse when it's young
| replace you know eating a healthy diet and i would love for dr sinclair to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:21
| or even late in life after 700 days, which is like a 75 year old human, was able to extend lifespan quite dramatically,
| speak more about that because he's really the go-to expert about supplements but we want to remind people that um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:27
| up to 30%, including improving their health. And that's extensively because both
| there's nothing better than having a really whole nutrition nutrient dense
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 44:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:32
| it's removing those senescent cells and activating the Sirt-1 defenses.<br>- And there's been human studies in both of these as well.
| uh plant forward if it's not plant-based diet oh boy yeah you've been teaching me a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:38
| I know we kind of talk about these in a group because they were discovered as sirtuin activators and now they're being seen also as potential senolytics
| lot about that um i i didn't really know i was uh existing on a cheese and red wine diet um but yeah i switched to the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:07
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:45
| but maybe we can differentiate a little.<br>- Well, a lot more is known about quercetin.
| much more plant-focused and feel the benefits and see the benefits of my blood work which i do fairly regularly
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:14
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:52
| That was discovered first as a senolytic by Jim Kirkland at the Mayo Clinic who combined it with a drug called dasatinib
| uh but it's taking supplements even though we've shown in animals and others have shown in people that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:20
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 34:57
| and together those two molecules are potent killers of senescent cells. And those have been put into mice and into humans
| can mimic exercise can mimic fasting this it's not an excuse to sit on the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:26
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:02
| where they are showing really remarkable effects in treating age-related diseases.
| couch and just pop pills we've met you and i were talking earlier today we've met people that eat terrible diets and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:31
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:08
| - And we've had some randomized controlled trials with humans and quercetin. The effects are?<br>- Reduces liver steatosis, or fatty liver,
| take a supplement thinking that that will replace a healthy diet and that's not true what we have shown in my lab
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:40
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:14
| as well as other effects like inflammation in the body. You can actually see that the number
| and others many others have shown is that you need to do both to get the biggest bang for the buck and you can't just
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:20
| of senescent cells in the body goes away when you treat with quercetin and dasatinib.<br>- Dasatinib is a drug that's used to treat leukemia.
| expect supplements to replace a healthy diet yeah and and that's just like a reminder
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 45:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:26
| It's got a lot of promise as a senolytic too, it seems. As of right now you can really only
| and i think it's a great award we're a little bit past midway but a great you know sort of midway point to remind
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:00
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:32
| get it for treatment for leukemia.<br>- That's right. You can only get it if you're part of a clinical trial,
| people even though we're talking about these supplements and all the amazing things that can help you that it can do
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:38
| you can't just go buy it on the internet. It's a regulated drug as well as another drug that's senolytic which is called [indistinct].
| for your body and help you in terms of your health your immunity um obviously your longevity it's most important that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:45
| These are being tested. They're not ready for prime time at all. But fisetin is the interesting one. That one is a plant molecule, it's found in grapes.
| you are using them supplementally you know that they in no way replace high
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:20
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:51
| It's found in apples. Relatively high levels in strawberries. You can now buy that relatively cheaply on the internet.
| quality nutrient-dense whole foods uh so i just want to circle back because there
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 35:57
| - So if people are like, man, I really like want to get into senolytics, the gateway right now,
| are some questions about spermadine um it is from austria it's not from china and there is no sperm in it it's from
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:04
| the most accessible place for people is fisetin.<br>- Well, it is, but it's early days. There's not a lot of data compared to,
| wheat germ um i know that if you just jumped on it might sound confusing but this is uh
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:10
| quercetin and dasatinib. Really we know that it reduces inflammation.
| derived from wheat germ it's a wheat germ extract and even if you are someone that has a pollutant intolerance um it's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:17
| That's about it in humans. I think we still have to wait to see whether it's really truly safe before people rush out and try this.
| absolutely something that you can use uh again if you are celiac or if you
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:24
| I'm excited about this affirm light study by Jim Kirkland with fisetin. He's got a number of patients are on 20 milligrams
| have a really severe allergy then you might want to work with a practitioner i
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 46:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:29
| per kilogram of body weight and this, over the next year or so, should tell us whether fisetin is truly a senolytic
| always recommend working with a practitioner and kind of starting slow titrating in
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:07
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:34
| in humans and can have some health benefits too.<br>- Okay, so there's a third class
| seeing if it's attuned to your system and your body but as far as the studies have shown people with gluten
|}
|}
=== Rapamycin and Rapalogs ===
=== A Carnivore vs a vegan diet when it comes to regulating mTOR ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:12
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:40
| of drugs we want to talk about today. We're not going to spend too much time with them because, broadly speaking,
| intolerances and even allergies can take spermidine with no issues whatsoever
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:17
| they're not available for purchase or even prescription right now, except for very, very narrow instances.
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:46
| I'm talking about rapamycin and these drugs, rapalogs, drugs are supposed to mimic
| uh okay so i'm gonna go through and i'm going to remove some people from the live because
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:31
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 36:52
| the effects of rapamycin perhaps without all the toxicity. These drugs have a really interesting history.
| there's been commentary from our audience that there's some comments that aren't kind so as i do that i'm going to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:00
| - Well, they do, these are drugs that inhibit mTOR, which is mimicking fasting. They were discovered a number of years ago on Easter Island.
| let dr sinclair talk about recognizing and then maybe we can we can talk about
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:46
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:05
| Rapanui, which is why it's called rapamycin. On the back of a statue, I believe, somebody found.
| some analytics before we wrap up good idea okay um and i also sort of question
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:51
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:10
| - [Matthew] Yeah, there's like the mold and they are some fungus and they scraped it off and lo and behold,
| uh what about the carnivore diet yeah and yeah i talk a lot about this um the summary is that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 47:57
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:17
| we have a drug that actually has been used for other purposes.<br>- Immune suppression.<br>- Yeah.<br>- Cancer.
| you know there's a big debate there's the carnivores and there's the vegans and they're seemingly opposed
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:03
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:23
| - Like, really, I mean, this is a life saving drug. We just don't know yet if it's a life extending drug
| now in the in the short run both have been shown to have benefits you know it's there's no argument that you can
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:09
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:29
| that's going to be useful in humans.<br>- I'd put good money on it. The reason is that it's extended the life span of every organism it's been given to in low doses,
| see that there are benefits but the question is what about long-term health and there the science speaks volumes and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:36
| not immune suppressing doses. In humans it's considered around 10 milligrams per week,
| i would i would love for a carnivore diet to be associated with long life i wish that were true
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:42
| but you definitely don't want to suppress your immune system. But even from yeast to worms to flies and mice,
| because i love meat but it's not it's just not the case you know speaking as a scientist if you look at
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:47
| if you give it late in life it still extends lifespan. It's really quite potent.
| people who eat certain diets the people that live longest are those that don't eat a lot don't eat three big meals a
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 37:54
| The only downside is that it could be toxic. So you have to be extremely careful and right now it's not available.
| day they eat less than that and they are mostly plant focused they don't eat meat
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:00
| - And rapamycin works by inhibiting mTOR.<br>- Yeah, actually, TOR stands for Target Of Rapamycin.
| all the time especially processed meat we know that of course that is the worst but even large amounts of meat what
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:05
| So that's how mTOR was discovered. And when you give animals rapamycin, you're mimicking low protein intake.
| happens uh is that you're you can be in two different states there's the abundance
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:53
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:11
| - You're mimicking this adversity that we've been talking about throughout this entire series.<br>- Right, so your body says, oh my goodness,
| state what i call the abundance abundance medics mimicking an abundance state or the adversity state the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 48:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:16
| I'm running out of protein. I need to scavenge protein from within. And so the body starts recycling old proteins
| adversity state is when the body thinks well times are taught i could starve i could get into trouble i need
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:23
| in this process we talked about earlier called autophagy.<br>- And that brings us to another drug, spermidine,
| to run away from a saber-toothed tiger that's the adversity we also call this hormesis if anyone's listened to us
|}
=== Spermidine ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:16
| which is also working on this autophagy process.
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:28
| - It does. So, spermidine is more recent. You've only recently been able to get it on the internet. It has an interesting history.
| before hormesis is what doesn't kill you makes you live longer and both diets
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:33
| Anton van Leeuwenhoek, the inventor, basically, of microscopy, was looking at his sperm.
| will have an impact either on one or the other of course the carnivore diet is the abundant state your body times
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:40
| No one believed him that there were these swimming things down there, but he started to get crystals in the sperm,
| lots of amino acids build muscle uh grow heal uh wounds that's what that state is and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:47
| and that was spermidine, hence the name.<br>- Kids, if you want to get into science. And what do we know about spermidine now?
| it'll actually be very good in the short run there's really no question you will build up muscle uh probably you know
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 38:53
| Because this is really old. I mean, this has got an old history, but like really new research that's showing potentially extensions of lifespan.
| slightly faster certainly uh more fast than if you're only on plant-based but the problem is that if
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 49:56
| Well, we know it extends lifespan of yeast and flies and worms.<br>- And even mice.<br>- And mice.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:02
| - There's a new study that was really compelling. If you give spermidine to mice, either when they're young or even late in life,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:08
| they live longer and they have better heart function or other youthful capacities. There are two ways that spermidine
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:14
| is known to work in mammalian cells. One is it stimulates autophagy, just like rapamycin does in the mTOR pathway.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:21
| There's another really interesting property that seems to be true which is it also stabilizes changes to the epigenome, which as you know,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:29
| is one of the major causes of aging.<br>- There have been a number of human studies on spermidine, particularly revolving around enhancing memory
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:38
| and dealing with memory loss in older Americans.<br>- That's true. We don't know a lot about aging itself
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:43
| but cognition has greatly improved in a number of studies. The one that stands out for me is the one by Schwartz et al., 2018.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:50
| They were giving people 1.2 grams per day over three months and there was significant enhancement of memory.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 50:55
| - I want to go back to the history of this stuff. You mentioned earlier the Antony van Leeuwenhoek
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:01
| discovered the crystalline structures that led us to spermidine by examining his own sperm,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:07
| presumably his own sperm, in a microscope. Is that still where we're getting spermidine?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:15
| - No, not that I know of.<br>- Where are we getting it from?<br>- We're getting it from wheat germ. It's a lot easier. It's much more abundant.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:22
| You can also find it in soy products.<br>- That makes me feel better about it. All right. We've talked about sirtuin activators.
|}
|}
=== Metformin ===
=== Rapamycin ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:00
| We've talked about mTOR inhibitors, but really one of the most exciting classes of drugs
| you stay with that for decades the science says that it's not going to be as healthy in the long run as being
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:07
| is also sort of actually kind of the most boring because it's been around for so very long,
| on a plant-based diet now you can have a really nutritious um plant-based diet really you've been
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:45
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:13
| an AMPK activator called metformin,
| educating me on this that will be as good as the meat-based diet for
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:20
| which hundreds of millions of people around the world already take for diabetes.
| for physical and mental capabilities but in the long run we'll be turning on these defense pathways that in large
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 51:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:27
| - Yeah, it's been used since the 1950s as the frontline medicine to bring down glucose levels in type two diabetics.
| part are controlled by m little m capital t o r which stands for
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:02
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:33
| And it is relatively safe as a drug goes. Half the world it's available over counter at pharmacies.
| mammalian target of rapamycin so we get to this drug rapamycin
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:07
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:39
| Here in the US and in Europe, and UK, Australia, you need a prescription.<br>- And we know that Metformin works by activating AMPK.
| rapamycin is a drug that was discovered on the island easter island rappanui and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:44
| Do we know how that process kind of unveils itself?<br>- Well, there are a lot of theories
| hence the rapa name and it's used in high doses to tone down the immune system so it doesn't the body doesn't
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:51
| and it's been debated for over 50 years. One thought is that the microbiome changes, but a leading school of thought that most scientists agree
| reject organs but it was also shown to inhibit this mtor enzyme that senses
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 39:56
| on is that it activates a protein complex called complex one which is involved
| amino acids and meat consumption particularly leucine and serine these are abundant in need not so much
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:35
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:02
| in making energy in mitochondria. And what it does is it lowers the amount of energy that the cell has in the form of ATP,
| available in plants so the the summary is that if you eat a lot of meat
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:07
| this chemical that we use for energy. And then you get mitohormesis, mitochondrial hormesis, what doesn't kill the cell makes it stronger.
| your mtor defenses will not be as active against aging
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:13
| And the reaction is two fold. One is to make more mitochondria, so you get more energy a few days later,
| as if you're on a plant-based diet but you can mimic a plant-based diet and fasting by taking rapamycin in the drug
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 52:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:20
| but also by inhibiting mTOR it'll improve what's called insulin signaling so that the blood sugar
| but not in high doses of course you don't want to down-regulate your immune system you want to just inhibit it a little bit
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:26
| that's in your blood, and if you're a type two diabetic, it's too high, it gets sucked out of the bloodstream and utilized,
| so that it's as though you're not eating a lot of meat and then you'll turn on this autophagy recycling proteins that's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:08
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:32
| which is why it's used to treat type two diabetes.<br>- And this is another one of those cases where there
| very good fail um but you should know you can't just go out and buy rapamycin you do need to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:39
| is a perceived diversity and then not just one of these pathways but multiple
| talk to your doctor it's actually not that easy to get so that's why i typically just skip
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:18
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:45
| pathways in this case are impacted.<br>- Yeah, similarly to all of these factors
| meals it has a very similar effect um yes so thank you for this um and i i
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:52
| which are talking to each other, this is a good example. Metformin will lower energy, inhibit mTOR. It will activate AMPK, obviously,
| there haven't been as many questions about wrapping myself but i thought it was really important to bring to the conversation because there have been
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 40:58
| we talked about that's what it's mainly doing, but it also raises NAD levels, which as we all know will activate the sirtuin.
| enough um and people are so curious about it but again it's just one tool and a whole toolbox
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:38
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:05
| So Metformin is a remarkable molecule, comes from the plant world, is very simple.
| of things that you can do to support yourself to help you know trigger all the things um
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:11
| The French hellebore or lilac plant produces what's called guanidines,
| that help your system um with longevity so one of the things
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:49
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:17
| and these have been known to treat diabetes for many years, in fact, over a century, and then chemists have put methyls on them,
| that we want to talk about and and thank you for the question about c60 we have uh
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 53:56
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:22
| chemically modified it so that it's more stable. And we call this Metformin and that's what we have as the drug today.
| dr sinclair as you know i do another live series uh with another scientist and mitchell and he's got some
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:29
| - And we've given this drug to animals. In worms it's extended lifespans, 30 to 40 days,
| incredible uh products that he's created in his lab
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:10
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:35
| which is no small amount of extension for a worm.<br>- Yeah I was involved in the mouse study
| that are that are also really helpful and so for those of you who have questions again i
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:40
| with Rafael de Cabo down at the NIH and we found that the mice were healthier and longer lived on Metformin.
| encourage you to go to the link in our bios and there is a trusted resources a trusted library um and i can at least
|-
|}
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:21
=== Senolytics and longevity- Quercetin and Fisetin ===
| - And what are the other things, 'cause again, what we want to look for if we want to know if Metformin is working in humans
{| style="padding-top: 1em;"
|-
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:47
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:27
| speak of the things that i use um there are some brands that i share there uh
| like it works in animals, you know, we're not necessarily just going to look at the lifespan extension 'cause that takes a long time.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:33
| What are sort of the intermediary things that we're seeing with Metformin?<br>- In humans, you mean?<br>- Well in animals and that we can look for in humans?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:41
| - Well, the main one of course is glucose lowering, but we also see more energy, more mitochondria, less inflammation, and muscle switching.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:48
| We haven't talked much about muscle type switching, but muscles, as you get older, become more glycolytic.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:53
| They start to use more anaerobic mechanisms and you can see that switch back when you give them Metformin.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 54:59
| Like they're more like an athlete.<br>- And we're seeing all of these things in animals and also in humans.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:05
| - Right, and this is where we can speak to a lot of data. Because millions of people have taken Metformin.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:11
| And one of the most interesting things about it is you can do a retrospective study of tens of thousands of elderly people
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:18
| on Metformin and ask, okay, their type two diabetes may be reduced and slowed down,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:23
| but what about other diseases that they're susceptible to? Cancer, heart disease, Alzheimer's, frailty. And the answer that's quite remarkable
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:30
| is that Metformin lowers the risk of all those other diseases.<br>- So when we control for everything else
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:36
| what we see is that the people who were on Metformin are living longer.<br>- Than people who don't have type two diabetes.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:43
| It's a remarkable fact.<br>- So now the question becomes, okay, take the type two diabetes part of the equation out,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:50
| will we still see an effect? And that is something that's being investigated in this really large study that's underway. The tame study.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 55:59
| - Yeah, you're right. The targeting of aging by Metformin study run by [indistinct] down at Albert Einstein College of Medicine,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:05
| this is a very large study over many different institutes and hospitals. It's costing tens of millions of dollars.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:11
| It's taken a while to raise that money. But ultimately the goal is to show to the American FDA
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:17
| that you can target aging with a drug and slow it down. The ultimate goal being having aging
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:22
| a treatable medical condition.<br>- Why is it taking so long to raise money for this? Because this is really, I mean,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:28
| everybody I know in the aging space is excited about this and yet the money's hard to come by because?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:36
| - Well, this is where capitalism has a little bit of a downside, which is that Metformin is very cheap.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:41
| It costs a few cents and it's off patent.<br>- Which means anybody can make it. There's no profit motive for making this drug right now.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:50
| - Right, so [indistinct] has relied on the government and they've given half the money and the rest of the half
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 56:55
| he's relying on donors and he's still raising that money, but he's getting started. Fortunately he's off to the races and we should know in the next few years
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:01
| if he's seeing signs of slowing aging and he's looking at a number of things, not just diseases, but also things like stability, ability to walk,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:11
| strength, these kinds of things, mental acuity, these are things that would indicate that aging itself is being slowed down.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:17
| And he's even now able to measure the human biological clock with accuracy. And that should also be slowed down
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:22
| if this is truly an anti-aging medicine.<br>- We're seeing a lot of doctors get a lot more comfortable
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:53
| with the idea of prescribing Metformin off-label. Just a few years ago, you know,
| and you can go there and take a look there's a lot of information um on there and uh it's just really
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 41:58
| the constraints of what Metformin was actually approved for was keeping it out of the hands of a lot of people
| helpful as you navigate these conversations and the different questions that come up are answered in previous
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:04
| who thought that it might be good for them in their efforts to slow their aging. There's starting to be a little bit of a shift there.
| episodes um in the notes in the bullet points that we share and the links that we share there too so um okay so we have
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:48
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:12
| - Well, yeah, I'm seeing a lot more people taking Metformin with the approval of their physician.
| a few more minutes what do you think we should focus on let's do something
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:54
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:17
| And part of it is education. Typically when a doctor sees the evidence
| yeah okay let's let's i'm gonna let you dive into synthetics um all right so if you don't know
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 57:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:23
| and there's extensive literature, and sometimes it's the patient takes the information to the doctor or our book.
| senescent cells or old cells that stop dividing and put out inflammatory molecules called cytokines and they've
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:29
| The doctor in most cases is convinced that this is worth the risk. Now, it's not risk-free.
| been shown in animals and some studies in humans but if you get rid of them kill them off the body recovers and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:35
| We should mention that Metformin has some downsides. One is that it can cause lactic acidosis,
| heals and becomes more youthful and that includes treating metabolic
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:40
| which is quite a severe condition. It can be fatal. You have to be very careful there,
| disease and high blood sugar as well and jim kirkland who's at the mayo clinic is the world's expert in this and he's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:46
| but most people are fine on Metformin. The biggest thing that happens to them is that they have an upset stomach, lack of hunger,
| running human clinical trials so he's a friend of mine so we were up to speed on that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:29
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:52
| which can actually be a good thing if you want to lose weight as well.<br>- But doctors now are saying, okay,
| and what he's shown is that there are plant molecules and some drugs that work to kill those senescent cells and not so
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:36
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 42:59
| they're advising their patients as to these potential side effects and also saying, yeah,
| much normal cells of course you you don't want to touch the normal cells now there are drugs there's no veda
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:42
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:04
| either because that doctor is sold on the idea that there's a potential aging benefit here,
| clocks there's the satniv but the ones that are available to the regular consumer are quercetin
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:10
| or anti-aging benefit here, or one of the other things you and I have talked about before is doctors are increasingly getting sick
| which is again a plant polyphenol similar in shape to resveratrol and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 58:58
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:16
| of waiting until patients are full-blown sick to prescribe the medications and they're prescribing it to pre-diabetic people and pre,
| another one you mentioned earlier serena physique terminal yeah yeah i call it physical hesitant and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:22
| what we might call pre-pre-diabetic people.<br>- Well, there's a shift in medicine and the way doctors are looking at their patients.
| it's also a plant molecule and these two are shown to either prevent the senescent cells from
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:29
| More and more doctors are saying, okay, let's not wait until the patient is so sick that we have to treat them. Let's get ahead of that.
| secreting those inflammatory molecules that's called a cinnomorphic or in the case of physique it's actually can kill
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:36
| And let's start treating them earlier.<br>- The one other thing that people should talk to the doctors about if they're considering trying to get on Metformin
| those senescent cells and there's a group at uh university of minnesota uh laura nieto hofer uh and paul robbins
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:26
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:44
| is the concerns about the connection between Metformin and muscle loss.
| have shown that if you give physitin to mice they actually live longer by about 10 by my recollection
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:52
| - Right, particularly in the elderly this is an issue, but actually if you look at the data and there's been a couple of human studies,
| but what's interesting about it it also works if you give it to the mice midway through their lifespan to extend their
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:40
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 43:57
| Metformin doesn't make a big difference to muscle size. It probably makes a difference if you're trying to win Mr. Universe.
| lifespan and um and the other thing it's not very well known but because it goes back a number of years but in 2003 my
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:04
| But other than that the difference is really slight. If you look at the graphs it's only a 5% difference, and actually 5% difference,
| lab published a nature paper that showed that resveratrol activates certain one these are two and enzymes but in that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:53
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:10
| I'll give up 5% body size for longevity any day. But the other important thing is that those muscles
| group was also quercetin and physique and so those three are ones that i take regularly not just
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 59:59
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:17
| on Metformin were just as strong as the others and had less inflammation. So there's other benefits to that.
| to to work on senescent cells but they also activate uh cert one so you get this
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:22
| What some people are doing just in an abundance of caution is taking Metformin on days that they don't exercise. And if you're wondering, why does it affect exercise?
| double potential double benefit but overall i i think that's analytics are really interesting um and can be
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:12
| Well, really it's pretty obvious. It reduces the body's ability to make energy. And so you don't feel as strong on the days
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:19
| that you take Metformin so you do less reps, fewer reps. And so what you could really do is just put a little bit of extra effort in and probably make up that 5% difference.
|}
=== Berberine ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:27
| - If people are interested in the effects of Metformin, but are not able to work with a doctor
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:29
| to get a prescription for it, or if they've tried out Metformin and it just doesn't sit well with them,
| really useful to prevent that type of uh aging which is called caused by inflammation yeah and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:36
| which is the case with about 20% of people, there's another alternative that works on some of the same pathways activating AMPK.
| again that's such a good reminder about inflammation and how that does cause aging there's so many things that we can do to lower our
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:43
| That's berberine.<br>- That's right. This is a molecule from the plant world bark and roots.
| inflammation levels and we're just giving you a handful of tools now but in past episodes and just in lifestyle
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:52
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:50
| You can find it's a yellow substance. Again, it's fairly insoluble. So if you want to take it, take it with some food.
| and other topics that i've talked about not necessarily on this series that can really lower inflammation uh including
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00:58
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 44:56
| Yogurt, olive oil, all this kind of stuff, but it's been remarkable what's been found in animals. And even in people that it can mimic
| meditation which we'll talk about another time um there have been a lot of comments about the difference between men and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:05
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:03
| the effects of Metformin. Specifically what it does, is it, again, it binds to this complex one and reduces
| women taking these supplements and for those of you that are really interested in that
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:11
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:09
| chemical energy in the body. And in reaction this mitohormesis is to amplify up mitochondria and make the body
| uh dr sinclair's podcast that drops today covers hormones
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:17
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:15
| more sensitive to insulin and lower the blood glucose. We've seen this in my lab in mice and human studies
| and there may be questions that you have that are already going to be answered in
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:20
| have actually validated this as well. The doses are high, one to two grams per day,
| that podcast episode so i highly encourage you to go download it listen to it um review it
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:28
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:27
| but it does seem to work.<br>- And when you say it does seem to work, you mean not just showing, you know,
| and if you have questions that aren't answered in that episode then bring them next week and we'll address them and
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:33
| the activation of AMPK and increased mitochondrial energy, but we actually in mice have seen increases,
| anything that we don't specifically address we might just create an episode around so so i'm not going to dive into that here
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:41
| pretty substantial increases, in lifespan.<br>- Actually, it's really interesting. In mice berberine will extend the lifespan
| since there are a lot of questions about fertility about male and female hormones
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:46
| of mice treated with chemotherapy and have a pretty big lifespan extension of normally aged mice. That's also true in fruit flies.
| about how these different supplements affect um affect you if you are in that fertility
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:01:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:52
| So it seems to be a common mechanism that you lower the energy in an animal and it responds by living longer.
| process when we do do that i will share that i have been through ivf myself and so i'm
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 45:58
| - And I think you said you got to take quite a bit of this stuff, though.<br>- Yeah, the clinical studies, it's at least a gram,
| well versed in the process in terms of food and supplements with fertility and enhancing fertility so i'm happy to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:06
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:04
| there's one that worked with two grams, but it does seem to work just like Metformin in improving the body's sensitivity
| share that with you guys when we do that episode um go ahead yeah no we should definitely do that because my love is
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:12
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:10
| to insulin and lowering the blood glucose levels, which is a good sign that it's going to have future health benefits.
| one of the few in the world at least in all in animal studies can reverse female infertility she talked about the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:18
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:16
| - Any concerns about side effects with berberine?<br>- I'm unaware of any downside of berberine.
| potential of that yeah i think that would be a really great focus because i have seen just throughout the course of
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:23
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:22
| - We should say berberine does have some of the similar side effects of Metformin. We don't know in different groups of people
| this of the episodes we've done that there is a lot of questions about fertility so i think it'd be great to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:28
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:28
| might be different, but you're looking at diarrhea, constipation, gas, potentially upset stomach.
| just focus a whole episode on that and we can dive into some of the different recommend um let's see recommendations
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:33
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:34
| - Right. Yeah, no molecule's perfect. But this one's really interesting because it's a natural and commonly available one that you can try at home.
| some of the supplements we've talked about um and how that can help and i'd also like to address some of the
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:41
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:39
| Of course, talk to your doctor first though.<br>- All right. Well, that kind of brings us to try at home.
| comments about food i know that we've talked a little bit about food it was so broad and there's so many things to
|}
|}
=== Dr. Sinclair’s Protocol for Longevity Molecules ===
=== C 60 ===
{| style="padding-top: 1em;"
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:47
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:45
| And again, with the caveat that we're not telling anybody what to do, we're not giving them medical advice. You're not a doctor.
| cover that we will likely focus an episode that's specifically about food um the
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02:55
| I know you have been really open about what you do. That has changed over the years,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:03
| but let's just sort of take it through the things that you started doing, you know, 20 years ago, 10 years ago,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:10
| five years ago, just start from sort of a chronology. When you started investigating resveratrol,
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:16
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:51
| you also started taking resveratrol. How did you know how much to take though?
| foods you can eat where some of these products are derived from you know procedure from cherries
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:22
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 46:56
| Because you were giving resveratrol to yeast and eventually to mice.<br>- It's not a one-to-one,
| and i have to see some strawberries so there are foods that you can just add to your diet on a regular basis that may
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:28
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:02
| it's not like you should take 3000 times as much as the mouse had.<br>- If you were 3000 times bigger than the mouse is.
| not be in the quantities that you need to have this kind of effect your body but at least you're kind of it's just
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:34
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:08
| - Right, it's not just proportional. It's actually more related to our surface area and how much the drug can get into
| there you know it's part of your daily practice um it's not going to hurt you to add a few more strawberries and cherries to your diet and it has
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:39
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:15
| our bodies versus the mouse and the calculation for a mouse, which is called the allometric scaling, is about 12.
| benefits so you're not even yet aware of so until now yeah oh uh serena somebody
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:44
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:20
| So you multiply it, let's say, if the mouse has 100 milligrams, 1.2 grams for a human.
| asked just now uh about c60 and what do i come down all right
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:25
| For a rat it's 3, for a mini pig it's 1 to 1. Turns out we have about the same
| i'm taking c60 and so far so good um and you're using um the same product
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:03:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:32
| surface area as a mini pig.<br>- And so you take about a gram of resveratrol every day.
| right aren't we using the same product uh maybe okay so so this is um where i'm getting
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:39
| - I do and I've been taking that since about 2004. But like I said, you can't just
| i'm getting messages about the time stamp here so we're gonna have to wrap this up in just a couple of minutes but
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:07
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:45
| put it in water and drink it.<br>- You have to add some fat to it.<br>- Yeah, so I typically have some yogurt,
| uh dr st claire uses c60 i obviously do as well and there are i think the replays
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:13
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 47:53
| a couple of spoonfuls, not a lot because I'm trying to fast until dinner, but I could mix it with olive oil. Olive oil, recently, as we mentioned
| actually the replays on the discussions we've had not you and i but i've had about c60 is already up uh
|-
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| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:18
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:00
| earlier in a previous episode, seems to be really good for activating sirtuins, but also you can dissolve resveratrol in it.
| i would say go to youtube and subscribe it's just random hoon if you haven't
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:24
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:05
| - So you get a twofer.<br>- You do. I don't have a lot of it. There's a lot of calories in olive oil. I don't want to break the fast severely, but you know,
| subscribed on our list please do because we send that information out and we definitely dive into c60 um in a couple
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:30
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:12
| mix it with bit of vinegar and basil leaves and it doesn't taste too bad.<br>- Okay, so resveratrol,
| of those episodes on my series with iron mitchell and if you want to talk about this we can david in a different episode
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:37
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:19
| you're taking about a gram a day in the morning, Also in the morning you take NMN.
| but i feel like it's it's it's been covered yeah i know this stuff yeah yeah
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:43
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:25
| - I do, and there you don't have to worry about food. It's dissolved easily. You can put it in water or swallow it, put it under your tongue. And so I do that.
| so okay you guys well i'm wrapping up i it's been amazing to share space with
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:50
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:31
| That's my main combo in the morning.<br>- How much NMN are you taking?<br>- Again, it's a gram, but that's not a guess.
| you guys today thank you for all the support we have a great audience thank you david for being here again weekly uh
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04:55
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:38
| That's actually based on the human studies that we've done that show that a gram over 10 days raises your NAD levels about two-fold.
| you're amazing for creating this space and time and um is there anything that you want to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:02
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:44
| - And that's sort of the dosing amount that we're seeing in a lot of the human studies now. Both the past studies and the current studies.
| i guess let people know oh people are asking about your special the ebook or is it an ebook or is it is it
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:09
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:51
| - I take one gram of NMN every morning along with my resveratrol. The reason is in humans we know that
| the kindle or the yeah you can get it on kindle right okay so david's book lifespan you can get it on kindle for
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 48:59
| that doubles NAD levels which is important because someone my age has half the levels of NAD than I did when I was 20.
| 1.99 right now and i don't know how long that's going to last but i would highly recommend you get it if you haven't if
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:21
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:06
| But you can go as high as two grams and triple the amount. It's important to mention that I take these
| you already have the book get the kindle anyway um so you have it in different formats and make sure you go to
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:27
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:13
| at a certain time of day based on science as well. I take these in the morning because that's when the natural rise in NAD and Sirt-1 activity should happen.
| apple podcast or anchor anywhere and download and listen to dr sinclair's
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:35
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:18
| And we actually know this, that the Sirt-1 NAD cycle is part of our body's natural 24-hour clock.
| episode that draws today lots of information and make sure you have your questions ready for next week
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:41
| Sirt-1 regulates a protein called BML that controls the genes that tell us whether it's night or day, should we be hungry or not?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:47
| Whether we have jet lag or not. And I do find anecdotally that NMN is remarkably good at preventing jet lag as well.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:05:56
| I can reset my body's clock ostensibly through the Sirt-1 BML pathway.<br>- You're also taking Metformin.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:02
| - Yes.<br>- How much? When?<br>- I take 800 milligrams at night.<br>- Okay, and you take that at night because?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:09
| - Well, because doctors tell me that it's a good time simulate a fast. I take it with my dinner, just after.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:16
| And then through the night, I'm presumably having low levels of glucose and my body has all the benefits
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:22
| of stimulating those repair pathways, those survival genes.<br>- And that's the most recent thing that you've added to your regimen?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:28
| - It is. Actually what happened was I had terrible blood biochemistry. I was eating badly, I gained weight.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:34
| I wasn't sleeping. I was stressed. And those numbers just went through the roof. And I said, I got to do something. So I went on NMN and things were somewhat rectified.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:42
| And then I added Metformin and they really got back to my optimal.<br>- We mentioned earlier some concerns about exercise,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:51
| Metformin, your practices, where that's concerned?<br>- Yeah, I pause Metformin.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:06:57
| It doesn't sit well in my stomach anyway. So on days where I know next day I'm going to exercise and lift weights,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:02
| I might skip Metformin that night before.<br>- And then there's also spermidine.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:07
| - There is. You can buy it now. There's a company that makes it in pure from very low levels of gluten.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:13
| And just the last few months I've added that to my protocol and we'll have to see how my numbers look on Inside Tracker.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:19
| - Okay, so that's not something you've adopted and you're like, I'm definitely taken with it. This is I'm adopted and I'm testing
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:25
| it out to see how it works.<br>- I am. And actually, I advise that company. The first supplement company I am advising
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:30
| and I did that because I wanted to look at the human clinical trials and they look really promising as well.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:36
| - How much of that are you taking?<br>- A gram as well.<br>- [Matthew] Okay. You are also periodically taking fisetin,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:44
| quercetin, aimed at senescent cells.<br>- There are clinical trials being run out of the Mayo Clinic
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:52
| for fisetin and for quercetin. These are high doses. They're typically two grams taken one day a week for a matter of months,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07:59
| Myself, I'm on a maintenance dose. I take about half a gram of each every day.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:04
| - Let's take this morning through night just really quickly. Resveratrol, one gram.<br>- In the morning with yogurt or olive oil.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:10
| - NMN as well.<br>- A gram, yep.<br>- Fisetin and quercetin.<br>- Half a gram in the yogurt.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:16
| - Spermidine.<br>- Definitely spermidine in the morning, about a gram.<br>- And then in the evenings,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:21
| if you're not working out the next day, Metformin. How much?<br>- 800 milligrams.<br>- Okay.<br>- That's it.<br>- That's it.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:28
| Now, you're not most people. A lot of other people are going to be different. You don't advise people,
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:34
| but it might be a good place for people to start their conversation with their doctor though, yeah?
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:39
| - Well, I think so. Most doctors are open to looking at, say, Inside Tracker data and hearing about the latest science.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:47
| It's very difficult for them to keep up with it. It's one of the reasons we're doing this podcast in the first place.<br>- So David, this has been a really
|}
=== Wrap-up and Next Week’s Episode: Interventions on the Cutting Edge ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08:53
| comprehensive conversation. Even still we could have gone deeper on any one of these drugs or supplements.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:00
| Maybe we'll do that in future episodes, in a future season of Lifespan podcast.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:06
| But what we're trying to do today is really give people an opportunity
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:11
| to really start thinking about whether this might be something that they want to bring into their lives.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:17
| And if so, how, of course, again, in consultation with their physician.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:24
| - And monitoring, this is important. You don't know if you're doing good or harm to your body unless you measure it, particularly your liver.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:30
| You can measure what's called ASTALT. I do that routinely just to make sure nothing's going wrong in that regard.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:36
| - Our next episode is?<br>- Things that are not supplements things. Maybe you could regard them as being on more
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:42
| on the cutting edge, things like testosterone, growth hormone, exosomes, peptides. We're going to dive deep into those as well.
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:48
| - All right.<br>- Sounds like fun?<br>- Yeah.<br>- Let's do it. If you're enjoying this podcast and would like to support us, please subscribe on YouTube,
|}
=== Options for Subscription and Support ===
{| style="padding-top: 1em;"
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:09:56
| Apple Podcasts and Spotify. On Apple you have the opportunity to leave us up to a five-star review.
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:10:01
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:23
| Also check out the sponsors that we mentioned at the start of the episode. That's probably the best way to support the show.
| uh and i think that's it thank you guys so much thank you so much david and i will see you guys really
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:10:07
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:29
| We also have a Patreon account. That's patreon.com/davidsinclair. And there you can support the show at any level you'd like.
| soon bye [Music]
|-
|-
| style="min-width:4em; color: blue; text-align: right; padding-right: 1em; vertical-align: top;" | 1:10:15
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 49:53
| Thanks again for joining us on this episode of the Lifespan podcast.
| you
|}
|}
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