Welcome to the huberman Lab podcast where we discuss science and science based tools for everyday life. I'm Andrew huberman, and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. My guest today is dr. Peter a TIA. Dr. Peter. A TIA is a medical doctor who did his training at Stanford University School of Medicine and Johns Hopkins school of medicine. Dr. Arati is one of the world's most trusted voices on the topics of Health span and lifespan.
And with good reason he is known to systematically review the research literature the clinical trials and he maintains an avid clinical practice. So when it comes to the topic of whether or not a particular molecule or supplement or prescription drug is indeed something that we should be thinking about and perhaps even taking in order to improve our health span and lifespan. Dr. Atia is the person that I choose to sit down with and discuss it. So today we are going to discuss the so-called NAD pathway. This is a pathway that's received a lot of attention and
And here's as a potential Target for improving life span that is for living longer today. We discussed the various molecules in this pathway and the various approaches to increasing NAD, which is the end Target goal of anyone that's trying to augment the NAD pathway so to speak. So for instance, we talked about taking an R versus nmn versus direct infusions or even orally taking NAD and we compare them in terms of both. What's known
Known and what is not known about their ability to get into cells and any efficacy they may have for either longevity or health span, dr. Arati and I compare and contrast the literature on this again both research and clinical literature and we discuss whether or not he or I take NAD nmn or an r and if so, or if not the reasons for that. We also each go through our own supplement regimen which of course reflects what we do believe can potentially have an effect on health span.
And or lifespan, so by the end of today's episode you'll learn a lot about NAD you learn a lot about the biological pathway. You'll learn a lot about the delivery routes the various supplements and why people think they may be useful While others perhaps even dr. Etienne myself think they may not be useful for longevity. You have to listen to find out what the answer is there. I should also mention that we give somewhat of an overview or a framework for thinking about approaches to longevity. So if you're interested in things like rapamycin metformin and whether or not fasting can improve longevity we
Get into that as well before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's podcast. Our first sponsor is element element is an electrolyte drink that has everything you need and nothing you don't that means the electrolytes sodium magnesium and potassium in the correct ratios, but no sugar no proper hydration.
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And that's eight sleep.com hubermann. And now for my discussion about NAD and Longevity with dr. Peter Atia Peter Oto welcome. How are you?
Great to see you again. Great to be here again.
Should we parse this NAD thing?
I think we should
do you mind if I set up a little bit of a framework?
Great. So for people that want to live as long as possible, I figured there are at least four categories of approaches broadly speaking.
The first I'll just call the do's and don'ts you've talked a lot about these your book out live beautifully covered these and I tend to regurgitate some of what you say on this podcast namely you want to move appropriately and often enough get enough Zone to cardio. Do your resistance training keep nerve to muscle connection strong.
Avoid the sorts of things that would lead to falling and being immobile.
Eat right there's a whole category of things there. We're not going to talk about today. Although we might touch on a bit and know your genetics and make some good decisions on the basis of your genetics. So the do's and don'ts
The second category I would put under the umbrella of calories glucose insulin Etc that all kind of funnel in at least in my mind to mtor. Mammalian Target of rapamycin.
A molecule that's robustly expressed during development and essentially all cells of the body and then across the lifespan tapers off.
During puberty, especially well, let's say infancy through puberty cells are expressing so much mtor, and they're growing like crazy and we often associate that early stage of life as youth not aging because we think of it as a kind of a timestamp as opposed to the verb, but I would argue as a developmental neurobiologist by training that it's one of the most rapid phases of Aging of our entire lifespan.
Look at a picture of you when you were five. Look at a picture of you when you were 8 verses 15, you look very different and your sizes robustly different. By the way. I just did this exercise because my daughter her birth her 16th birthday is around the corner and we take a picture of her every single year at the minute of her birth. So we have a picture of her every single year holding a clock that says 356 at 3:56 p.m. Because that's when she was born and I just went through and
Pulled each of the last 16 of them from the day. She was born all the way up and you're right. The biggest changes are actually in about the first ten years, you know, the difference between being 13 and 14 14 and 15 15 and 16 becomes incrementally less and less and less whereas going from 2 to 3 and 3 to 4 and 4 to 5 are ridiculous changes. Yeah. I mean the brain the same brain has to learn an entirely new body every year in turn out how to move it limb length Etc.
So a lot of the so called anti aging or longevity approaches that fall under this umbrella relate to things like caloric restriction or taking drugs such as rapamycin. And of course mammalian Target of rapamycin is the target of rapamycin duh in an effort to essentially remove excess insulin blood glucose and thereby.
Reduce mtor activity. So essentially slow cellular growth and all that fits nicely into the logic that mtor is associated not just with development but with aging because development is aging and then I would say there's a third category and it's the one we were going to talk about today, which is targeting specific cellular Pathways that some people have deemed potentially interesting for longevity and the pathway that we're going to spend some time on is the so-called NAD
way and are nmn and AD being the major players and we'll talk about some of the biochemical and enzymatic steps in between and then I suppose there's a fourth category which we could say is, you know, the do everything even the most esoteric of things category. This is a rarer category. There are folks like Brian Johnson who spend a lot of time in this category specifically, you know, taking very high doses of polyphenols limiting their caloric intake to just early part of the day. I think he
is dinner at 11:00 a.m. I don't know if it still qualifies as dinner at 11 a.m. But his final bite of calories is I believe at 11 a.m. Doing everything from red light to PRP platelet platelet-rich plasma scuse me, and essentially the kitchen sink approach to longevity and agent did I miss any categories?
So II I would frame it slightly differently because I like categories to be more me see mutually exclusive collectively exhaustive. So so I don't I don't know that I would formulate it that way right? I might say look category one are sort of the essential behavioral things that you have no choice but to engage in whether you want to or not, right? So you have to eat you have to sleep.you have to move.
Move you just have a choice in do you want to do those things correctly or not correctly, or do you want to do those things in a manner that promotes health or a roads Health, right. So again, there's nobody listening to us who doesn't eat but again, you can choose how much you eat and what you eat and when you eat there's nobody who's alive who isn't moving because Locomotion is life in the absence of life is the absence of locomotion, but you can certainly choose to move very little you can choose to move a lot. You can choose to decide on how you move you alluded.
All right, you can you can move in a certain way that puts your Aerobic System in a zone that maximizes fat oxidation. We call that zone 2. You can move at a level where you consume incredible amounts of oxygen at your maximum aerobic level. You can choose to move in a manner that uses resistance and and gravity against you and all those sorts of things. Similarly. We all have to sleep right Matt Walker would probably tell us the number of days you could go with sleep without sleep before you would literally Parish. But again, you have a lot of choices and how you do it. So anyway, I agree that's kind.
A category one, but that's kind of the way I would frame it and then I would put in category two sort of what are the molecules that you would exotic Janice Lee take to try to impact any of those systems and maybe and again I'm not saying my framework is correct in yours is and I'm just saying this is the way I think about it. I would then say what are the molecules that I could take that specifically Target disease processes, so I kind of think of like if you want to live.
Longer and I describe this I think in chapter 4 about live there is a that's that turns out to be mathematically equivalent in the modern society to delaying the onset of chronic disease and I wasn't true 100 years ago 100 years ago. If you wanted to live longer a few things had to be true you couldn't die during childbirth and that because that was a huge hit on mortality and then you had to not get an infection or succumb to trauma and then
Maybe 150 years ago that was the case. But today most of those things are taken care of by antibiotics sanitation and you know the modern Miracle of childbirth in the in this era. So now for you and I to live longer we basically have to delay the onset of cardiovascular disease cerebrovascular disease cancer, neurodegenerative disease dementing diseases and metabolic diseases. We have to delay the onset of those things the longer we delay the onset the longer we will live. So,
You can use everything that you talked about in the first category plays into that. But you also have this other category of where you can take molecules that specifically Target those things you can take Metformin or in sglt2 Inhibitors or a glp-1 agonists and you will directly impact those things. You can take a pcsk9 inhibitor or a Statin or been Potomac acid, you will directly impact those disease processes. You will delay the onset of those diseases and you will reduce the mortality associated with them.
Then I'ma go to a third category that says are there eggs, ah genus molecules that you can take that don't Target a disease per se specifically, but we're going to put them in a category called gyro protective, which is they target Hallmarks and Pathways of Aging that you've described. So we talked about all of these things that occur in an aging phenotype where we see more inflammation. We see a greater abundance of senescent cells. We see reduced.
Nutrient sensing capacity of mtor which you described as the probably the most important nutrient sensing system in our body. So we have you know, these somewhere between 9 and 14 the number just keeps changing arbitrarily, but it doesn't really matter. We have these Central things that everybody would agree Define what an aging phenotype is and can we use exoticness molecules to Target those specifically you gave one example, which I would argue is the single best example, which is rapamycin.
Ison so rapamycin targets a very specific Hallmark of aging and we can talk about what the experimental evidence is to suggest that that makes you live longer. So I would sort of say those are the big three categories and then basically the fourth category you could just say is like how do you put them all together? And how aggressive do you want to be in culminating those of course, none of this touches on another area that I want to talk about that we won't talk about today which is like how does all that factor into kind of emotional health and happiness and well-being.
Where you know none of this other stuff matters if you're kind of unhappy and so you have to and you've done so many podcasts on that topic, right? You've had Paul Conte on where you kind of go through the understanding of ourselves and our minds and why that's also a very important part of it because it actually does impact how long you live because if that piece isn't working. It's very difficult to regulate the first bucket because the first bucket takes so much work. So if you can't regulate yourself, it's very difficult to regulate the the do's and don'ts
bones, but even absent just length of Life stuff. It impacts quality of life, which is this idea of healthspan as well. So I guess that's just my slightly different way to frame it, but it's a little bit more me see in that, you know, we talked about the behaviors the exoticness molecules that Target diseases the exoticness molecules that Target aging
Aside from food what exoticness molecules do you take I take a few right? So I take some that are disease-specific. Right? So take a pcsk9 inhibitor. I take bump adoha kascid. I take an sglt2 Inhibitors. And then I take at least one that is purely just based on the belief of its capacity injury protection, which is rapamycin and and also the SGS the sglt2 Inhibitors, I think.
Probably just broadly gyro protective and we can even talk about that a little bit in terms of the success of one of those molecules called kanaga Flows In in the interventions testing program the ITP which I am sure will talk about in the context of NAD as well.
What dosage of rapamycin do you
take I take eight milligrams once a week for as long as I can tolerate it, but that I usually have to take breaks. Why is that I get these vicious apps to Salters little
mouth sores canker sores. Yes about 10% of people get them. Hmm. It's paradoxically the only biomarker we probably have so I I secretly rejoice in knowing that at least I'm getting a good batch of rapamycin by
virtue of this is a virtue of these miserable side
effects, but it's so so in reality what it works out to is I'm probably on it for two months and then off it for a month on it for two months off it for a month or thereabouts.
And the idea there is that you're limiting mtor.
Or you're causing your cells to grow less mature slower. And in that sense slowing down aging something idea.
Yeah, I mean, you know, and this will be an important theme today, right? It's like we can talk all day long about mechanisms and theoretical Arguments for why it would work and I think my conviction around taking rapamycin is less about
Sort of looking at the molecular explanation for why rapid Works, although I find that to be quite convincing and why does the inhibition of mtor stimulate a toffee? Gee, why would that suppress senescent cells? But truthfully my conviction around mtor is far more based on the experimental data something that is actually sorely lacking in the NAD story which will discuss so the experimental data are far more convincing right, which is when you look at the
Ation of rapamycin or its analogs for example everolimus when you look at the administration of these molecules to organisms that are as close as possible to the species of Interest where the species of Interest so looking at mammals such as mice and small primates looking at fruit flies looking at worms and even looking at least although that's so far from us that you would argue. That's the least important. You see something that you
you don't see for a single other molecule, which is uniform life extension.
No other molecule has done this. It's very important to understand. There are only two interventions. That have ever extended life across those four categories of eukaryotes caloric restriction and rapamycin.
Very important point right?
How do you feel when you're on rapamycin aside from the canker
sores? Yeah. I wish fortunately aren't that frequent. You died. I don't feel anything and the very few of my patients who take it because I maybe ten percent of my patients also take it. I've never heard actually, that's not true. Everybody heard two people say they feel better on it. But you know, I don't know what to make of that. Maybe they do and maybe that's just a placebo effect.
Does it synergize with caloric restriction or collide with caloric excess meaning if you're
taking rapamycin, but you're slightly over your caloric needs. Maybe you're trying to add a little bit of body weight and happen to overeat a little bit just because is it going to collide with rapamycin potential positive impact on slowing aging?
Yeah. That's a good question. I don't I don't
know. I don't think we know
we do know that there's one other really important readout we're waiting for which is Matt K. Berlin's dog aging study, which is
Is going to be an exciting read out in 2026. We're also waiting for another read out of the University of San Antonio looking at another another trial in mammals. And again, I think those two will be really interesting right because we have a ton of we've just overabundance of mouse data that are so reproducible and reproducible in really good Mouse models, you know, as you know, I'm sure from your work the model you choose matters, right?
And and sort of you, you know in an Ideal World you want to use a mouse model that is you know, not in bread that is more closely related to the what we care about which is ourselves. And and so when you see many Labs getting the same result over and over again regardless of how they do it you really start to believe there's a signal there. So now to be able to see this in a higher order mammal and ultimately in companion dogs, which is where Matt K Berlin is looking I think that's
That's going to be really exciting and I've often said to my patients look in 2026. I'm either going to feel a lot more conviction about taking rapamycin and prescribing it to some of my patients the again not most or I'm going to you know have a second look at this and say, you know, maybe maybe we just shouldn't be taking this right because I do think that the dog study is going to be more telling but again what the wait and see what that shows
without going off track too much my understanding. Is that the dog study
Has halted because of a lack of federal funding. Is it
continuing it is going to go on there's there's yeah there it's so initially there was kind of insufficient funding to do this study in an adequate way and then it turned out there was a shortfall of about two and a half million dollars to do the study that Matt really wanted to do and then actually a group of us raise that money format and did that so great me and a few of my patients and a couple of other folks came together and put them
The end to close the gap but yes, there has been what's what did get pulled back by the NIH inexplicably and in my view totally incorrectly was the ongoing surveillance program the funding for the ongoing surveillance program that would allow this type of work to continue and to allow greater follow up on this. So yes, unfortunately until we can get more funding we're not going to be able to maybe do as much as we like to do and understand.
This which again when you look at some of the things that are funded it's hard to believe that there's not a more interesting question right now in biology than this drug that seems so promising why we wouldn't want to know, you know, if this is something we should all be taking is kind of a mystery to me.
Yeah. I was on NIH study sections for many years reviewing grants. I've rotated off as a regular member a little over a year ago and I can tell you that the whole process is designed to be as targeted to the
Best and most exciting work possible but there's a number of features now that make it such that it's largely the work that's already mostly completed. They gets funded you can even go all like how does that work? But anyway, we could have a whole other Journal Club discussion about funding but I had to ask I was curious. So hopefully that that study will get completed and thanks for raising those funds. Let's talk about NAD. Yes. It's in essentially every cell of the body except red blood cells,
correct, you know.
No, I don't even know if it's in red blood cells. My intuition is I I've never looked to be honest with you, but given that red blood cells have a different metabolic pathway right where they're purely glycolytic I do they wouldn't have the need for it in the way that others would but they might write because they still undergo redox potential. So it's possible NAD is in every single cell
and it's generally thought to be associated with energy production and mitochondrial Pathways in every single cell.
Right? So NAD is again one of the
most ubiquitous molecules in the body and most of what it does.
And I mean most meaning like somewhere between five and six hundred Pathways of it utilize NAD as a cofactor meaning that it's not consumed in a chemical reaction, but rather it serves as an electron shuttle. So NAD and nadh basically play catch with electrons. And that's 99% of what NAD is doing in the body. And for that reason NAD is
so tightly regulated in the body the levels of NAD in the cell are really tightly regulated and that shouldn't be surprising just as glucose really tightly regulated pH or hydrogen ion concentration really tightly regulated. We as a species cannot survive outside of a very narrow band of pH, right if it's below 7 or above 7.8 on a zero to 14 scale we die.
Stop. So similarly NAD is managed across all ages and across all physiologic conditions in a super type and there's another place where NAD shows up and that shows up as a substrate. Right? So cofactor means used coenzyme used but not consumed recycled. That's 99% of it a small fraction of it is used and it's used by these things called sirtuins that
consume an add as an actual substrate in the process of DNA repair and maybe we can go into this but this is really where the story picks up. It's also as I recall where the story began that's exactly right. It was some experiments where the sirtuins were mutated in One Direction or the other meaning gain of function or loss of function these days people here gain-of-function and they immediately think to pandemic related themes but gain of function as a way of changing.
Jeans typically to augment a function increase its robustness or in some cases to rescue a phenotype where you have a knockout mouse that lacks a gene. So that's loss of function or a strain of yeast that lacks a gene and then you do the gain-of-function rescue experiment you re re introduce the gene of interest. It's an important would even call it a control. It's an important experiment in any case because loss of function will tell you a lot.
But gained a function and loss of function assuming that the results jibe tells you much much more. This is one of the major areas. I think this is very important to highlight where human genetics really struggles because you can get humans with a mutation in a particular pathway like the Sonic Hedgehog pathway there somebody has hypo morphic for Sonic Hedgehog and they might actually lack a major tooth up middle because the role of Sonic hedgehog at the midline and
It's okay. Well loss of function here. Here's the role of Sonic Hedgehog. But the ideal experiment is to put the genie back in and then rescue that phenotype because as any logical mind can tell there could be many things Downstream of Sonic Hedgehog that could create the phenotype that you observe. But if you put Sonic Hedgehog back in yes, that's still true, but you get more reassurance that that's the gene of Interest. So with respect to sirtuins. I recall they deleted the
sirtuins. Yes, and let's use another example of what the gold.
Standard is here or what a great example is so I recently did a podcast with Dina do ball from UCSF on clotho, which is an amazing scientific story and it's a great story because it shows how accidents can lead to great discoveries, right? So there was a researcher in Japan who is really interested in understanding hypertension high blood pressure and they had created a mouse model where they were trying to knock out certain sodium channels to see if they could perturb blood pressure and then there was this one strain of mouse with this one.
Out that died really really quickly and it developed like devastating neurogenic disease and design died very quickly and you know like a good scientist. He didn't say well that sucks. I'm going to discard that one because it didn't give me what I wanted which is the blood pressure change and he kind of went and figured out what was going on and he figured out that there was a certain Gene that he had hit that wasn't a sodium transporter and instead was this other Gene. He named it cloth. Oh, so so you had this one piece of evidence right now, which was if you knock out that Gene, you kill an animal very quickly.
Now that doesn't mean it's a longevity Gene. You have to do the other experiment to your point. You have to overexpress that Gene and ask the question. Do you live longer and sure enough when they over Express that same gene that they had just knocked out and killed the mouse. The thing was living 15 to 20% longer.
So it's both necessary and
sufficient for extended life and say well that's a longevity Gene
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Huberman to claim a special offer they'll give you five free travel packs with your order plus a year supply of vitamin D3 K to again. That's drink AG one.com hubermann. So let's go to the sirtuin story. So it goes back to the late 90s Matt K Berlin again. This is amazing. Right? So you have this guy who's like the leading Authority or one of the leading authorities on the work going on today with rapamycin along with one of his colleagues David sabatini and a few others, but when Matt was a postdoc he didn't
Experiment in a strain of mice. Pardon me strain of yeast I think is the W 303 strain of yeast and he overexpressed sir to and lo and behold the yeast lived longer now a year later someone else in the same lab took a different strain of yeast and calorically restricted them and they also live longer.
I forget the name of that. I forget what that strain was. It was something 316 was it was a different strain of used at that moment. Again, this is about 25 years ago hypothesis emerged which was we have two different strains of yeast and in one of them when you overexpress sir to this gene, they live longer and another strain if you calorically restrict them, they live longer the understandable hypothesis was
like restriction, which we had known was life-extending is working through sirtuins that hypothesis sort of fell apart about four years later when Matt K Berlin again this time with Brian Kennedy did another experiment in a different yet a third strain of yeast that allowed them to test a hypothesis because there was a problem with the story. I just told when you took the 303 strain, this is the strain
That when overexpressing sir to lived longer if you took that strain and you calorically calorically restricted them no change that's odd even more odd is when you took the 316 strain and this is the strain that lived longer with CR if you overexpress sir to no change. So right off the bat the story didn't make sense, but it was further solidified that story didn't make sense when Brian and Matt published in 2004 in yet a difference.
Strain got I'm blanking on the name. It's like BBY 4742 like these don't matter if you calorically restricted them. They lived longer. If you overexpress sir to they live longer if you did both they lived even longer. It was additive again further suggesting that overexpression of Sir to and caloric restriction independently and separately extended lifespan.
These are parallel Pathways. They're parallel.
Pathways for reasons that honestly Escape me Andrew, there are still people who maintain that the benefit of sirtuin overexpression is through the caloric restriction pathway and vice versa
and that's wrong.
My reading of the literature in addition to every person I have talked to on this who works in the space including Matt K. Berlin who has done the most research on this is that there is no evidence that caloric restriction and sirtuins operate through the same pathway. And in that sense, I think.
There's there's relatively uniform agreement that caloric restriction extends life across the model systems. We discussed what about in humans? What about it specifically does orchestration are sir? Well that experiments never been done and never will be done the joke. I was trying to set up for is the one I'll make now which is no one wants to be in the control experiment that said nobody what are you? Nobody wants to be in the treatments permit either and got me beat me to the punch. No one wants to be in the treatment group either because it requires eating so little
You know it just the the
joke is hear a joke is you probably will live longer and it will feel even worse like it's just it's yeah caloric restriction which by the way, there are real debates about whether it will extend life in humans because it will clearly I shouldn't say clearly. I think it would be a very safe bet that severe caloric restriction will absolutely reduce the risk of most chronic diseases. Meaning I have I think there's very good reason to believe
believe that if an individual constitutive Lee consumed 25% fewer calories than they were meant to eat their risk of cardiovascular disease cancer. Alzheimer's disease would go down. The problem is what things go up. What does that do to your immune system? What does that do with respect to sarcopenia? What does that do to your risk of falling but the Frailty? Yeah, exactly. Yeah, so you trade one set of diseases for another it's not at all clear that life span goes up. And by the way when you
Even look at some of the wild like that some of the animal literature where they're using different strains of mice that are not in bread and they don't put them in hermetically sealed situations. They don't live longer. So it's not always the case that caloric restriction extends life and therefore while it's safe to say caloric restriction probably reduces the onset of chronic disease that might not translate to an all-cause mortality benefit based on those downsides, but all of that said,
I think the holster to in story got off to an incorrect start where it basically locked onto the see our story which was hey, we've got this thing CR that we've known since orchestras right clerk thinking we've got this thing which you know for 50 years. We've known has a signal that really says, it's life-extending and we've got this yeast where it works and this other yeast worser to inactivation work so it's got to be sore. But again if you if you go through the story in detail as I just did there's no evidence whatsoever.
Ever that sirtuins have anything to do with caloric restriction and
vice versa.
It's incredibly interesting because I think when you look at cell biology and you see these parallel Pathways, when you see these effects of experiments, we're changing sirtuins or changing caloric restriction independently increase lifespan combine the two you get this what appears to be a synergistic effect, but it's as you pointed out and additive effect like a pretty straightforward experiment to do you could just do an occlusion, right you could court and put back in the sirtuin.
Or adjust calories and see whether or not you get the effectively whether the math is corrected, you know, so
now none of this gets to the question you raised yet. That's just all that's all prologue. Right? That's like where did this story come up? But then the question becomes will if you believe that sirtuins are truly a factor that drives longevity, how can you activate them? Right? How do you activate a sirtuin?
So we have to now simultaneously start to hold things true in parallel that may or may not be true. So we want to then ask the question. Do we believe that what we saw in yeast which I think is the only reproducible finding I can draw meaning this is a reproducible finding in many but not all strains of yeast if you overexpress sirtuins, the yeast will live longer. So let's park that in the parking lot as a very likely
A statement you would then say well if it does it in yeast does it do it in flies? Does it do it in worms? Does it do it in mammals? You want to be able to check those three boxes because again that's a billion years of evolution. So if something works across a billion years, we be much more confident. It works in
US. Yeah, making a fly mutant drosophila mutant that over expresses sirtuins a worm C elegans mutant that over expresses sirtuins. That's a pretty quick experiment to do because of this short generation time of those species.
Right now the
mouse it's a longer experiment but I'm guessing all of those experiments have been
done. Yeah, and the only one that I can find that has demonstrated a survival Advantage is one particular transgenic Mouse experiment that overexpressed cert 6 and it did indeed for the male mice increase lifespan by ten to fifteen percent. So this is one.
Transgenic Mouse model that overexpressed cert six and those mice the male mice lived ten to fifteen percent longer the female. Mice did not we should probably clarify. What a transgenic Mouse is. I talked about knockout mice. That's when a gene or genes in some cases. It's deleted from The genome. So it's null does not express that Gene. The gain of function would be to put back that Gene in that would be a knock in Mouse. So in that case, you still get some normal expression of the gene.
The endogenous genome but now you have a transgene that's inserted there and there are all sorts of important intricacies that relate to this for instance where the transgene is inserted. If it's you know Downstream of of an enhancer that's muscle specific, then you can get a mouse that it over expresses sirtuins just in muscle you can get it ubiquitously expressed their number of different ways that this can happen. I'm assuming this was ubiquitous expression of you said cert six cert six. So every cell in the body that normally wouldn't
Express cert six would Express more
sort of six don't remember Andrew to be honest that if you go back and look at the paper, I don't know if it was muscle specific or whole body
specific. I'm guessing unless they made it clear that it was tissue-specific that it's whole body. So we're talking about it when Peter says transgenic Mouse he's talking about a mouse that has this trans Gene that causes it to express more sirtuin 6 than it ordinarily would and let's just assume although we don't know this for sure that the other genes in this mouse are functioning as they would normally
right.
So again just to summarize that that's 2012. We have this one transgenic Mouse you put cert six you overexpress cert six and all of a sudden the males were living 10 percent longer again to be clear. The females didn't experience a difference and that's not uncommon or unheard of in longevity research. They're generally our sex specific differences and you always have to read the fine print the first thing I always look at in a study when I see a difference in Sexes or frankly.
Any difference in longevity, but it's always great when they parse them out by sex is is how long did the controls live but I went back and actually looked at the kaplan-meier curves on that exact study. And yes indeed. I think that's a real effect. So let's take stock of now two pieces of information that I think we could say as probably true. It is probably true that in a handful of strains of yeast. If you overexpress cert you are going to live longer that tends to
Completely independent of caloric restriction. That's the single thing I can say with the greatest confidence and there is at least one transgenic strain of mice that if you get it to overexpress a different cert six, but again there these are homologs throughout the species. So we don't think it I don't think we need to get wrapped up insert two verses cert 6 you will at least make the male mice live longer but not the
females what sorts of things are Downstream of sirtuins and that question translated to normal English is
What is changing as a consequence of increasing the sirtuin could it be for instance? Well unlikely based on what we already know about caloric restriction in the fact that they are independent parallel Pathways, but is it something related to glucose metabolism? Is it something related to clearance of senescent cells? I'm just drawing out possibilities
here. You've hit two of the big three right off the top right? So we believe that when sirtuins are activated they're improving mitochondrial biogenesis.
They are increasing DNA repair. So that's probably the biggest one. And by the way, that's sort of what brings us to the the nid story and also reducing sass, right? So the soluble products of senescent cells. So Taps of in other words. Those are all three good things, right? So you Tamp down on senescent cells you increase mitochondrial biogenesis and you increase DNA repair. Those would be all great.
Things to do and we think that sirtuins are probably doing all of
them.
This business of DNA repair and reducing, you know, fragmentation or mutations to DNA that are naturally occurring has been a hot idea in the field of Aging for a long time. Is that because when x-rays became popular or post nuclear fallout that people showed accelerated signs of aging I mean, how did we get from DNA mutation to
Celebrated aging like
well, I mean, I think we know that as we age it's just a stochastic process right like given the ubiquity of DNA replication and the Fidelity of the system which is high very high but not perfect. There's going to be mistakes. Actually. This is an interesting question. So in 2016, I went to Easter Island with David sabatini and nav cendol and Tim Ferriss. So the four of us just took a trip to Easter Island to see the birthplace of rapamycin.
So it's kind of like a vacation
/ science Journey. That's a nerdy make it
was awesome. And you know, so just picture hiking around this incredible Island just talking about science all day. But this was an interesting question that I posed to nav and to David which was why do we see such a clear and present association with cancer as we age and why is it so nonlinear? So it's not just that cancer goes up with age it goes.
Like that, and I said, I'll offer two hypotheses, which is more compelling. Is it simply that as we're aging DNA replication again taking a step back for the listener cancer is a genetic disease meaning by definition. It is sort of the canonical problem with cancer is a genetic mutation that leads to two properties of a cell the inability of the cell to rep to
troll replication. So it interrupts cell signaling so cells replicate but then don't know when to stop and then the introduction of the capacity to spread this property called metastasis. Those are the two Hallmarks of cancer. So we know that that only happens in the context of genetic mutations, but why does this happen later in life and not at the beginning of Life with very few exceptions? And and so the question is is it because over time mutations compound is it because there are more mutations as we age or is there a third?
Issue, which is all of those things are happening normally and they're no more abundant when you're 80, then when you're 20, but your immune system can't detect them as well. And the truth of it is we didn't come up with an answer but it's probably all of the above. So it's probably that as we were aging we are undergoing more DNA damage and or at a minimum the DNA damage were undergoing is less amenable to repair and that's part of the thesis here part of the thesis. Here is as
Our aging we are less and less able to repair DNA and one of the arguments that put forth. Although we have we're not quite ready for this part of the story yet, but I'll just say it now and we'll come back to it is we don't have enough of this substrate that the sirtuin needs to repair DNA and that substrate is NAD. So again, remember the outside I said, look, there's two big categories to think about NAD. Most of what NAD is doing is operating as a cofactor for electron shuttling. That's the NAD and
Bah, electron transport electron acceptor Baba. Okay not consuming NAD just using it to pass electrons back and forth. But then over here we have this other category where we use NAD as a substrate it gets broken down and that's what the sirtuins are doing to repair DNA. Okay. So if that's true and if NAD levels are declining with age, it's a logical conclusion that should we give more NAD, right if you're running out of substrate to repair DNA.
And DNA repair is an important way to thwart aging it all makes sense. So we'll keep that over there. But before we do, I want to come back to one other story, which is the story of Sir to and activators. So what's the most famous sirtuin activator of all time? What is the heavyweight champion of sirtuin activators that has taken up 99% of the bandwidth in this space? It's a lovely little chemical called Resveratrol. Okay, so Resveratrol, which gained
A lot of Fame and notoriety because it happens to be found in Trace elements in the skin of grapes and therefore shows up in wine gained a lot of notoriety about 20 years ago. When one lab doing one experiment somehow was able to convince some people including a very large Pharma company that Resveratrol increased lifespan.
So the thesis was Resveratrol activates sirtuins sirtuin activation is important because of all the things we just said, right it improves mitochondrial biogenesis. It's suppresses senescent cells and it is enhances DNA repair. So if you have something that is such a potent activator of sirtuins and you give it to a mouse that Mouse should live longer now lots of experiments were done, but couldn't find that but one
Aunt was done, but it was a an interesting experiment. I've discussed this at least on to podcasts including one with Rich Miller who runs the ITP the interventions testing program, which later tested Resveratrol and found that it did categorically nothing in this one experiment that worked the investigators took a bizarre Mouse model where they force-fed it an enormously high fat diet and in doing so they created such an abundance of fatty liver.
That the livers of these mice encroach to the chest the thoracic cavity of the my so the mouse died prematurely because they couldn't breathe and in that particular Mouse model risk Vera trawl rescued the mice. So again, let's just assume that all of that is correct and it's possible that there were even errors there. But let's just assume that's correct. Let's assume so this is Resveratrol delivered orally. Yes in the food.
Yes, very high doses mega-doses the equivalent of barrels of great exactly like doses so high you could there really, you know, if you recall were both of an age that's old enough to remember this there was this period of time when people thought this was the explanation to the French paradox, right why on average the French live longer when they consume so much wine and the answer was it's got to be the Rivera trial turns out that's not true at all because yeah, you would need to be drinking your body weight and wine a day to get the doses of Resveratrol that were needed.
To produce this effect, but for whatever reason there was an effect which is if the thing that was going to kill you was your liver being so full of fat that it shot up into your chest so you couldn't breathe which I've never seen a human no matter how bad their fatty liver has been where that's been the case. But if that's if that's the problem you're going to face. It's possible at least based on this one Mouse experiment that you are going to live longer. But again, it turned out that there was no
no other replication of this in Mouse models that matter and that always comes back to the ITP the interventions testing program, which is the most robust tool. We have scientifically to measure these exogenously molecules. So the ITP is an ni a funded program that runs out of three independent labs and by independent, I mean, they're each doing the experiments independently, but they're they're in sync with doing the experiment but they're doing it in triplicate. So you have three labs.
Great Labs doing the experiments in triplicate and when they did the Resveratrol experiment and they did it in combination with the people who found the result of that study. So they consulted these people and said what dose should we give and they said do this do this do this and they did it and nothing there was no effective risk ferret raw land that result has been consistent across the board. So that's also a very important part of the story which was if Resveratrol.
Sister to an activator and I don't know if it really is it clearly has no effect on lifespan with the one little asterisks that says unless your body weight is 50% fatty liver, then maybe it
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So, let's see. Let's just take stock of where we are in the story. We got the whole yeast sirtuin situation, which is at least in some yeast sirtuin overexpression lives longer. No evidence that that works through caloric restriction truly. No evidence that's been known for 20 years. Now that paper was published in 2004 and that was a follow-up to papers that have been published in 2002 to 1999 Etc you later on you'd have the 2012.
Mouse study
So now the question is okay. How do you activate sirtuin? How do you recreational? Well, yeah Soso or more to the point. Why don't we just give people NAD? Okay. So the egg and the NAD story is NAD levels are declining with age in most tissues. It appears most prevalent in the skin of all places and I think we should come back to this because there's one interesting finding associated with augmented.
Venting NAD levels in the skin and my thought is I wonder if it has to do with the fact that skin experiences the greatest Decline and NAD.
It's also interesting because creating a sites and skin turn over every 28 days or so so you could imagine because it's a novel population of cells that they would have steady expression of sirtuins and NAD, then they simply die for whatever reason or that it starts off very high on day one of
And then tapers off quickly, but that's not the case. It sounds like yeah, you know on
average skin over the course of your lifetime will see about a 60% reduction in NAD whereas other tissues and this is now based on you know, animal studies the brain might see a reduction by 15 to 20 percent and the same would be found even in humans looking at the blood. So if you just sample, you know whole blood in people at the age of 20 30, 40 50 60 70 80, you're going to see about a 20%
Reduction in
NAD what about neurons? I mean, you've got the same set of central nervous system neurons your entire life. And of course some peripheral neurons as well, but there's some regeneration the periphery so we need to Scott. Let's just talk about brain. So unless you're talking about the olfactory bulb where you have constant turnover throughout the lifespan. You have the same hippocampal neurons, except a small population same hippocampal neurons cortical neurons retinal neurons that you were born with. Are we observing NAD levels tapering off as we
animals? Yes, obviously in humans were not doing that experiment.
But yeah now here's an interesting point in 2015 a study was published in pnas that looked at NAD levels in whole blood over time and it found indeed NAD levels were going down about 10 to 20 percent over four decades or so, but that same study said nadh levels were going up by the same
amount explain the role of nadh for people. Nadh is
the electron acceptor.
So when you when you the so let's maybe take a step back and like what? How do we why are you and I sitting here talking and not dead like as we have enough NAD, right, right what's going on? Right? So right you and I ate something at some point in the foreseeable past that contained chemical energy. So we ate something that was organic. So it had so primarily fats and carbohydrates contain carbon carbon bonds and carbon hydrogen bonds and those
Bonds contain a ton of energy. But how do we Liberate the energy? So we break it all down into these constitutive molecules namely glucose on the carbohydrate front and free fatty acids on the fat front and then our bodies break those things down further into smaller molecules that get shuttled into the mitochondria where the Lion's Share of our energy Liberation comes from and what we do is we take that chemical energy that is stored in a carbon to carbon.
A bond or a carbon to hydrogen bond and we turn it into electrical energy and people have heard this term. It's called the electron transport chain. So there were these four complexes in the mitochondria and there's an inner membrane and an outer membrane across which these mitochondrial these large mitochondrial complexes reside and what they're doing is they're building up a huge electron gradient by by breaking them apart and taking the electrons and transferring them between NAD and nadh so that at the end
They can do another trick which is transfer those electrons to a MP ADP and ultimately make ATP the finished product is water and carbon dioxide. So we eat and we take that chemical energy and food. We utilize oxygen in the mitochondria to make ATP carbon dioxide which we breathe out and water which we breathe and pee out. So what NAD and nadh are doing is playing.
An absolutely essential to life role in facilitating the transfer of chemical energy to electrical energy back to chemical energy ATP is just taking it from one chemical form in food to the electrical form is the intermediary in the mitochondria back to an electrical form of ATP. So you and I are walking around flush with ATP, which as we sit here right now, we're constantly firing off phosphates again now turning the chemical energy back into
Energy in a way we go. So yeah, this this whole NAD nadh thing is like, you know, it's a central to our existence as any form of respiration. So my point let's go back to the story. The story was NAD levels are going down as we age but nadh levels are going up suggesting that the total amount of NAD and nadh is the same and what's declining as we age should less be thought of as a reduction in NAD and should more be thought of as a reduction in what's called redox potential.
All the ability to do what I just said. So when people say NAD levels decline with aging the answer is yeah, but what's really declining as we age and this kind of comes back to what you said at the very outset like what's happening at the cellular level. I think what's happening is our mitochondria are not as good as we age and we have less redox potential
and I would say a fair number of so-called anti-aging approaches are targeting the so-called reactive oxygen species.
Our OSS which impede mitochondrial function essentially. This is an opportunity for me to call out the work that I think is at least intriguing which is the work of a colleague by the name of Glenn Jeffrey at the University College London. He's been in the field of visual Neuroscience for a very long time and a few years back. He started doing some experiments on animals and now also two studies published on humans showing that exposing the Aged ISO 40 and older to red light and
and near-infrared light for a couple minutes a few times a week can spare certain processes involved in Vision photoreceptors. How does this work? Well the idea this isn't proven yet. The idea is that it's reducing reactive oxygen species and thereby improving mitochondrial function in what is perhaps the most metabolically active cell type in the entire body. Not just the eye which are the photoreceptors so it's an
Getting set of studies again. We don't have all the mechanisms worked out but it brings us around again to this idea that mitochondria are vitally important for the functioning of cells things that impede the function of mitochondria can either reduce the output of and or kill cells and so anything that can improve Redux can potentially keep a cell around longer functioning better. So when I hear about the role of NAD in this pathway, I think like most people I think
Okay. Well, then I should just take more in ad and maybe I will age more slowly where I will replace some NAD that's missing is I aged in whatever cell type turns out that might not be so straightforward. Right? I mean, I don't want to jump to supplementation just yet, you know, but if we are to back up from NAD a little bit and look at the pathway leading to NAD, it's NR + MN and NAD will spell these out in a moment and this sort of competition that's
out there in the market is around either infusing or in some cases ingesting NAD directly.
Taking n MN which is the precursor to NAD orally haven't heard of anybody infusing it or taking oral form and are which is the precursor to nmn. My understanding is that NM n is simply an arm - a phosphate
group. Yeah, and and I'll take a step back from this before first to say the following again let because this topic is so confusing. I think it's just worth reminding everybody of what we now everything we've said and where it brings us, right?
So I'm not going to repeat the holster to and thing let's just leave that alone because everything we're on right now is Upstream of sirtuins. Yeah, it's basically like once you establish that we think sirtuins matter, even though they don't work through caloric restriction. And that's about the single most obvious thing. I can say they might still matter even though we don't have things that we figured out can activate sirtuins like Resveratrol. We don't seem to have things that we can give you that activates her to ins were now on to the next part of the story, which is okay, sir to
Matter, they don't seem to matter. We think sirtuins matter because of the few of these overexpression experiments and we're making a big
leap that
because they mattered in yeast they are going to matter in us that's a huge leap for which there's zero evidence.
Right? And I'm only leaping further to this discussion about how to increase NAD because I know that's in the back of people's minds. We're not we're not going to double click here just yet. I just want to frame that up because ultimately ultimately that's where we are headed in terms of
oh making decisions as to whether or not they should take n r or taken a menu and there were excused NAD or none of the
above. And the reason I'm being such a hard-ass about this Andrew is I spend so much time Fielding questions on this that I realize we just have to talk about this in xcore. She it just in the most detailed fashion possible so that people understand why right because it is just too easy, right? There's this great quote by JFK that I'm going to paraphrase that is basically people
You know, enjoy the comfort of opinion without the discomfort of thought right? So we need to sort of Lissa's this a podcast to get people to think and understand the entire history of this field so that they can actually make an informed decision about a supplement that I'm going to argue has very little scientific basis for its justification.
I would say scientific justification for longevity. I'll go on record now saying that I take NM
Men, and in some cases I will take n r and N MN and I observe this is just an of one self observational data. I observe a very clear positive effect, but I don't think it has anything to do with extending lifespan
and we should talk about both Health span and lifespan benefits when we get to that part, but we're supposed to bring us up to where we are. Now where you are with should people be supplementing NAD
We're basically at the point where we're taking a lot of leaps of faith and saying because NAD levels are going down and redox potential is going down. We believe supplementing NAD in one form or another makes sense. But before we do that, we should acknowledge something. Yes and a D levels are going down, but we have no reason to believe that raising NAD levels will correct the problem in other words if the body operates between
In this level and this level of NAD and if you go below this level you die and you go above this level you die and levels as you age go like this. Do we believe that raising into this does anything we have there's no evidence that says it does. So that's a leap of faith. It's okay to take leaps of Faith. You have to know you're taking a leap of faith. Okay. So leap of faith number one is the sirtuin thing leap of faith. Number two is the caloric restriction thing leap of faith number three is this matters in
Our species the species of Interest leap of faith for is you know the whole sir to an activator thing and now this leap of faith is if we just increase NAD levels in us, it will produce a positive benefit. Okay. So now how do we how do we do that? Now you get into the tactic? Okay. There are three ways to do it is you said one is you can intravenously take NAD, by the way, you could probably also orally take NAD. It would just break down in the gut into its constituent of products.
And then probably reform but for the purpose of how people actually do this, they intravenously get NAD because it's not orally bioavailable or as you said, they orally take to precursors and are and nmn my personal view on this is there's not really much of a difference in what you do. In other words at the end of the day all of these things are generally going to increase NAD levels in the blood.
So a couple of
practical notes I've taken and are in capsule form. I've taken nmn typically in powdered form where put it sublingually under the tongue. My understanding is you
done intravenous
NAD I sure have and
what you experience or niacin flush. No. I
took NAD in a as an infusion of probably done it five or six times and
For the first ten minutes of the infusion you feel like somebody stepping on your chest with a boot your legs cramp up you feel nauseous. I did not take the anti-nausea meds that was offered. I don't like taking things if I can avoid. I just figured I'll just experienced this. It was very uncomfortable to the point where you couldn't read a paper or a book you just you just want to be left alone. You actually get a little bit irritable you like. This is awful, you know, every noise in the room is a bit too loud during that.
First 10 minutes and then by
the way, do you know how many people have said to me that because of that experience? They know it must be doing something good when goodness to which I'm like, why don't you spread your legs? Let me kick you right in the nuts that's going to feel even worse. Is that doing something good like the fact that something feels so awful shouldn't be used as an explanation for why it's doing good
physiologically, right? I don't know what it was doing physiologically except making me feel miserable during the infusion there ways to adjust this even without the anti-nausea meds for
Instance you can slow the infusion. That's the typical way. People will put it in over the course of several hours anywhere from three hours to as brief as 30 minutes is kind of the record that I've heard about 4 500 mg of NAD, if you put 1,000 milligrams in there, obviously, it's more painful and you have to anyway, there are a bunch of practical considerations you feel now. Maybe it's Placebo, but one feels quite good.
And afterward so as soon as the drip is done you feel better than you did prior to the trip.
How do you feel if you just receive an IV infusion of the same
volume? I've done that because I've received saline drips. You also feel pretty good. Yeah, it's hard to disentangle these things and typically they'll put other things in the bag glutathione some vitamin C, you know, they tend to sell these as kits I decided to try it it it seemed fine. I did it when traveling.
I don't know. Maybe I'm due for another one soon. But for me the more typical way to try and increase NAD or whatever because I don't know what it's doing exactly but I like the effects of taking sublingual nmn the single most let's say Salient to me anecdotal data on taking sublingual nmn is that it makes my hair grow really fast. It makes my nails grow really fast and I do feel an increase in energy and I take it first thing in the morning
and what dose one and a half
G 1500 mg. So by the way, if you translate, you know the doses that they give mice in the studies where they're testing the efficacy are typically on the order of 500 to 1,000 milligrams per
kilogram.
Oh, yeah, I'm 100 kilograms.
Yep.
Well, okay.
So picture that the next time you're giving yourself some NAD or NR.
I'm not even approaching that. Yeah at all. Well, it's clear to me based on my read of the data that NR can cross the cell membrane directly
directly very easily. There's no obstacle to n are getting into cells
and nmn cannot because of the extra phosphate group.
So that if you take it sublingually or you ingest it orally it goes into the gut the phosphate group is cleaved and because of that the argument is that if one were to compare the benefits of taking N R vs N MN there more data to support and our as a precursor to NAD a more effective precursor to NAD than orally ingested nmn, but some people will say well I'll just take more nmn than I would NR and then this gets into the realm of costs. It affected interests it is
Stars to commercial starts becoming a battle between commercial sources and Van and I don't dispute that. NR makes more sense as a precursor, especially at dosages of you know, 300 to 600 mg versus 1500 mg. But I've opted to take sublingual nmn mostly based on cost and are at the dosages people recommend is quite expensive imagine. You have to take it at the mouse doses, right? You'd be spending about 300 bucks a day, right?
It's just it's not feasible. It's just not feasible. So, you know, I don't have a deep desire for my hair to grow faster or my nails to grow faster. It's more the increase in energy effect. Now, I will say that sublingual nmn is also a bit of a laxative. So they're all these and I say that, you know somewhat chuckling but you know, some people say makes them feel better. Well is that because you're you know, evacuating your bowels of few minutes or hours later and then you feel less bloated and you have more energy
It's very unclear. I think what has not been done. As far as I know is to compare orally ingested and are that's a 600 mg relatively high dose versus a gram of sublingual nmn and then actually measure blood levels of NAD if that experiment has been done and I'm not aware of it. I'm not aware of it then forgive me, maybe some will put in the show no captions, but I guess this gets down to the question of how many people are taking oral and our or n and Men.
Or are taking NAD infusions which by the way are quite expensive anywhere from three hundred dollars to a thousand dollars a drip. That's pretty expensive.
Think about what benefits are there yet? Like what are they getting out of this? Like, what are
they getting? Is it an acute increase in NAD that that what that causes them to live what a week longer. I mean we have no idea. So let's let's try to use data to answer the question. Right? So this is exactly the thing that the ITP the interventions testing.
Graham was designed to test and again, I would I would if people are interested in this they should go back and listen to my two discussions with Rich Miller where we go through gory detail of every molecule that has gone through the ITP. The ITP is hands down the most rigorous tool we have for testing molecules in anything other than the species of interest because we can't do these experiments in human. We cannot test lifespan interventions in humans for the obvious reasons. So what is the next best?
Thing. Well, it turns out it's doing it in a non inbred Mouse in triplicate in three institutions. Like you can't get more rigorous than this. The ITP has tested probably north of 50 molecules meaning it has done the same experiment 450 different molecules and very few have extended lifespan and a notable failure is NR NR was tested and I believe it was tested at a very robust.
Estos either 500 or 1000 milligrams per kilogram and there was no extension of Life. There was no improvement in health span. There was no change Mega dose and are Placebo same result conversely. Let's consider some of the successes of the ITP rapamycin. When you give rapamycin the first time they did it because they had a hard time formulating the rapamycin they weren't able to
I didn't tell the mice were like 21 months old, which is very old for Mouse. That's like a 60 year old mouse and at that point they almost aborted the experiment because they were like, well, what's the point nothing is going to work when you start this late including caloric restriction, by the way, although it has worked in one experiment but nevertheless it worked and when you gave rapid that late in life, it's still worked then they redid the experiment and they gave it earlier. It worked. Can I go flows in as I mentioned which is an sglt2 Inhibitors. It worked acarbose a drug.
That inhibits glucose absorption worked and interestingly didn't require weight loss. So the thesis behind giving acarbose to the mice was it's a caloric restriction mimetic a CR mimetic and it worked but then the but the but the treatment mice weren't any lighter than the non-treatment mice which actually goes back to something you said at the very outset which suggested that tight glycemic control independent of weight is a longevity benefit the same was true with the sglt2.
To inhibitor can a gaffe lozen sglt2 Inhibitors? Cause you to pee out more glucose acarbose prevents you from absorbing in your gut. So two different ways to regulate glucose. Neither of those experiments resulted in a lower body weight for the mice and yet they both lived longer again. There's something very important about regulating blood glucose. The other thing that worked is 17 beta assignments area 17 Alpha estradiol and it only worked in male mice. So again suggesting that
Well, we can come back to that. It's more than we want to get into at the moment. But Point here is there are very few molecules that have withstood the scrutiny of the ITP. It is it's a high bar metformin failed by the way for and the ITP is specifically for offsetting aging so it is lifespan, but it also looks at some measures of Health band, but it's primarily it is the gold standard for lifespan. Yep, because my understanding is that there are some studies that have explored the role of supplemented.
And our maybe Anna men as well, but certainly supplemented and are for sake of lowering inflammation to offset some of the negative effects of time zone shift alcohol have a few others listed here over nutrition.
Yes, so let's talk about that. So in 20, I don't remember what year was it somewhat recent study was published looking at NR with something called Terra stilbene.
So pterostilbene is believed to be a sirtuin activator like Rivera trawl. So commercially available product called basis and it was tested. There was a three arm study in humans roughly 30 people per arm so decent size study, right? There's a big study. So you take a hundred people more or less with fatty liver disease. Now, this was documented with an MRI of the liver. So they're looking at hepatic fat.
In the liver by Mr. And using this type of MRI, if your hepatic fat index is over 5% that's a high enough degree of what's called steatosis that you have fatty liver disease. Now, of course, this is not this is not a digital thing. It's analog right? There's a there's a spectrum to this. So, you know you start with just fat accumulating in the liver, but as more and more fat accumulates you start to get inflammation that results in
in scarring and fibrosis and ultimately you would get to cirrhosis. So just keep in back your mind the Threshold at which we would say, you're you're in the air you're get you're in the danger zone is once you hit five percent. So this study randomized people to either a placebo or a regular dose of this product or a double dose of the product and I can't remember exactly how much is in the product. I think it's either 250 or 500. So then that would be what the regular group got of NR and then the other group was getting to X that so
Either 250 and 500 or 500 and 1000. I don't recall. They also looked at something called the they looked at many things right? So they looked at all sorts of biomarkers and the primary outcome for this study was did you see a reduction of this hepatic fat via the MRI? So what happened so they did this study and lo and behold there was no difference. There was no difference in anything. Okay, so so
high dose at low dose there was no difference in how much hepatic fat you had at the end of the study. There was no difference in body weight. There was no difference in inflammatory markers. There was no difference in glycemic markers glucose levels liver function test any of those things. So in that sense, it was a null study, but they did one sub analysis which again you have to be very careful of because a sub analysis is not a primary outcome, but it's kind of
A way to go and parse the data and they did find one statistically one statistically significant finding which was if you limited the analysis to people who had a hepatic fat score below 27 percent. Remember I said, once you're above 5% you're sort of you have fatty liver disease. Well, they had people anywhere from you know, 10% to 40% But if they looked at people who were below 27 percent in
the low dose group there was a statistically significant reduction in liver fat if it sounds like I'm mashing ating I am let me say it again if you limited the analysis to people who had below 27 percent on this hepatic fat index the people who got the full dose had no difference. They averaged 20 percent at the beginning of the trial and nineteen percent at the end. No statistically significant difference the placebo group averaged 20 points.
Scented the beginning 20% at the end, but the single dose of the drug went from 20 percent to 15 percent which was statistically significant. It's not clear that that's clinically significant, which is a pretty consistent theme in this type of research never confuse statistical significance with clinical significance if I gave you if your blood pressure is 160 over 100 and I give you a drug that lowers it to 150.
T7 over 97 that could be statistically significant if the variance is small enough between people in the study. It has no clinical significance. I haven't changed the course of your life. So again that to me is one of the one of the two big findings that people point to to say, aha, there was some benefit in fatty liver disease with this. But again when you read the fine print which I just vomited out to you, I don't think anybody is
Get that going. Oh, we we just found the solution to Nathalie. The second study that people point to a lot was 20 21 or 20 22. This came out of a group at Wash U, I believe and they looked at nmn and they looked at glucose disposal. So in this study, they asked the question we're going to take two groups of people. You're going to get a placebo for a period of time or you're going to get nmn for a period of time and
we're going to then do what's called a type of glucose challenge where we look at how well you dispose of glucose with and without insulin infusion and in the placebo group, you would look at pre and post glucose. Oh pre and post Placebo treatment. Was there a difference in glucose disposal with no insulin know what about with insulin where you would expect to see much more glucose disposal no difference, but when you did that with the
Men group there was a statistically significant increase in glucose disposal with insulin infusion, but it was quite small. In other words. It was clinically very insignificant and just to make just a sort of figure out how insignificant it was. I went back and actually looked at some of the red light data because there's an interesting study that shines red light on a person's back and then does an oral glucose tolerance test. Yeah, and you can actually reduce like postprandial glucose by
8% It's got meaningful.
Well, not really. I mean not in this not in this patient population because these people were all pre-diabetic and they had very high glucose. So it was against another example of something that was statistically significant but not clinically significant and the same thing was true in this study. Right? But again people would would probably point to these stew two studies because they're in humans and you had this one if you squint and look really hard and take a Sub Sub sub set of the analysis on this one measurement. We saw, you know a result a responsive have had
That going from 20 to 15 percent which is still 3 X above the threshold to have fatty liver disease and in this other study you had this, you know, very very modest reduction heard me increase in glucose disposal. But I mean like we're you know, there's a saying in my in my sort of Mind Andre which is like if you have to resort to really interesting statistic imaginations to see something there probably isn't something very interesting there. Right? Right. I totally agree and I think you know
at this point I'm questioning whether or not I'm wasting my money taking Anna Manuel working on positive reason I take n r is really for these anti-inflammation reported purported effects. I just want to pay a little bit of attention to the whole commercial battle around this because I think it's relevant. I mean, I think right now as far as I know the FDA has essentially said that nmn should not be sold as a supplement but it is still being sold.
As a supplement, so there's a little bit of a ignoring of the end of the fda's request and are as far as I know is authorized for sale as a supplement.
Yeah, so it's generally regarded as safe. It has an FDA designation of grass, which means it is not
regulated generally recognized as safe.
Right? And so that means anybody can sell it the FDA will have no oversight. They're not telling you whether they're not going to
To put a stamp on it that says what they're selling is what it is and there you can't make a claim about it that isn't validated by some sort of study. So honestly and I think the whole nmn and our debate is irrelevant. I think it's just a commercial debate. I think it's literally just posturing about how can I carve out a different Market? I don't think there's a scientific reason to favor one over the other.
Well, you just answered the question. I was going to ask but I suppose the question therefore becomes is there any benefit to taking either of them or say but life span and there's one benefit I could find there's one benefit. I could find that I think is genuine. There are a few other really insignificant ones that fall into the category of goofy studies that cherry-pick by data mining. Okay. So there's studies that like gave people nmn and looked at a shotgun approach of many different things. Like did it change LDL cholesterol?
Chocolate drizzle triglycerides and the answer is oh, look, there's a small decrease but it was totally insignificant clinically, even if statistically significant and so it increased your, you know, six minute walking test or whatever and it's like a six-minute walk test or whatever in people who were in their 20s is irrelevant. It had no change in VO2 max. It had no change in any meaningful metric of performance one test one study. I could find that actually had what looked like a signal to me and it
it was a study that looked at skin cancer rates with and I can't remember if it was NR or nmn, but honestly, I don't think it matters because I think they're basically equivalent once just got a phosphate group on there. You might need to take a little bit more of the nmn versus n r or maybe a lot more who knows in order to get the same increase in NAD is my understanding. So this one study found somewhere between a 60 and 80 percent reduction in basal cell and
Miss cell carcinomas found no difference in melanomas. So again, you know this because you just did a podcast on this. Melanoma is the skin cancer that kills you but that's not to say that, you know squamous cell and basal cell carcinomas aren't problematic. They can be varied, you know deforming they can require pretty aggressive surgeries to address them. And so if indeed there is something that can reduce the risk of basal and squamous cell carcinomas that may be a rationale for taking it
and I should say that basal and squamous.
The cell carcinomas are very very
common. They are very common and they are very clearly associated with sun exposure in a way that even melanoma is more complicated and has a genetic component in there other things going on, but squamous and basal cell carcinoma are very clearly related to sun exposure. As you said, they're quite common and so, you know personally that's an experiment. I would like to see repeated because if indeed and our and or nmn reduce the risk that's significantly
Squamous cell and basal cell carcinomas. I think you could make a case that if you're an individual who's at risk for those things clearly. I'm not right. Like I've never had a sunburn in my life. I mean, I don't work outside. So it's like it wouldn't matter to me but there are a lot of people for whom either their skin color makes them more susceptible or their their, you know, their pastimes or frankly their their line of work makes them more susceptible, you know, maybe there is a case to be made for it there. If you could if you could literally take 60 to 80% of your risk away.
On squamous or basal cell carcinoma that could matter and by the way, I don't know if this is true, but you may recall at the out said the outset I said that when you look at all the tissues in the body where we see a reduction in NAD, do you remember what had the biggest reduction with skin? So there's a part of me that wonders like is the reason that the only place we see a really good signal potentially for NR + NM n supplementation is is in a skin cancer. Although it's not melanoma, which is the one we really want to see I mean if
This reduced the risk of melanoma. I would take it right because even though I'm dark skinned, I'm still susceptible to melanoma. So I just wonder that could be true in unrelated. But that's that's the first thought that crossed my mind when I came across that literature was hmm. I wonder if the enormous reduction in tissue NAD in this particular tissue explains. Why maybe there is a benefit to it. Assuming somebody is averse to feeling like they have an elephant stepping on their chest.
And they're going to pay $750 for it AKA and NAD infusion once a week and looked people may opt to do that people with the disposable income could do that drip it in slow or not feel nauseous increase NAD with the hope. Hope hope that maybe it's going to extend your life. Most people considering supplementation to augment the NAD pathway or going to default to either taking in our we're taking n
MN by the way, just going back to the group that have decided that
A thousand dollars for an NAD of infusion and dripping it in over two hours is a good use of their time. What do you think would be the Improvement in their lifespan? If they spent that two hours exercising
significantly greater interesting. All right snow
and and less expensive. But yeah,
you could also weight train for the first hour and then enjoy some food afterwards like Norton taught me that there are data showing that exercise in particular.
A resistance training improves the rewarding properties of food makes food taste better. We've all kind of intuitively experienced. So spend the first hour working out second our eating if you have an
extra two hours a week to choose between paying 1,000 bucks or 700 bucks for an idea infusion or you know, lift weights for an hour go for a half an hour walk and listen to your favorite podcast like the huberman lab and then eat a meal for having her like I can just think of so many better.
Ways to spend time and money. But anyway, let's let's not digress. Okay. Well, I'm going to pull a little bit from marketing text here, but I trust these showing really yeah. Yeah, I do because they have citations to support them and we can include the citations at these are not like I say, these are these are not linchpin Arguments for doing one thing or the other but we already established that NR
And nmn are quite similar except for the presence of a phosphate group on an are they gets cleaved
off. So again, you might have a slight dose issue. But at the end of the day, you're giving an R & R is freely taken up into cells. It turns into NAD. So this is all a big sort of shell game of how do you get an add up? And again, I think we've established and we can we can agree that that there is an increase in NAD at least in the blood and probably in the liver when you take
take exoticness NAD or a precursor. Let's learn our that's
yeah. Okay, right so great. Well, then you took the words right out of the data. I was going to refer to its right because I asked a few folks that helped develop some of the NR supplements like what are the data? Yep that support the use of NR for increasing an idea and they say an arc across the cell membrane directly and women cannot okay, but
you can just clean the phosphate group
exactly and are they claim? I'm not this is not my claim, but they claim the NR is
Quote unquote 25% more effective than nmn in raising whole blood NAD levels, but I'm guessing that that's probably mg 4 mg. Right? Okay. So then you just adjust the milligram dosage a little bit and so on what's entirely unclear is what raising blood NAD translates to in terms of getting more NAD into cells. I don't know
that specifically cells like skeletal muscles, right? I think based on Josh Rabinowitz his work. I also had Josh Rabinowitz on the podcast to talk about
this and I trust Josh on this much more than I would trust any marketing material because he doesn't have a dog in this fight, right. He just you know, he just does the work and what Josh is research sewed, which is basically NAD flux research has demonstrated that look the liver is probably the place of greatest uptake in addition to blood and that's about all we know like it's not clear how much of this is getting into other cells.
So, I mean that's the rest of it is just you know, I think rearranging deck chairs on the Titanic as far as like, how much does it really matter? And again, I don't even think it's worth arguing about whether NM n or n r is more bioavailable because to your point you can sort of adjust the dose and I trust that whatever you're taking and our nmn you are getting some NR into the cells and that's being converted to NAD, but we still keep coming back to the jugular question. Does that matter does increasing interest?
The cellular NAD matter when the system is so tightly regulated. So I think what you see is a lot of marketing material that tries to make the case that you can do it great. I'll grant you that you can do it. Does it matter does it matter in life span? The answer appears to be unambiguously know at this point. Does it matter in healthspan? I think that's what we're discussing.
There's something so sticky about the longevity field just so sticky about this idea that one could take something and extend.
Span and people don't want to be in the control group. So they're willing to invest significant amounts of money to do
it. Well, I mean, I think the bigger issue is like you can't do the longevity experiment in humans, and I'm sure that these companies that sell this and I honestly I don't follow this space. I don't know how many these companies there are out there. I can name two because the, you know five years ago, which was the last time I really dug into this. I knew who the two dominant players were for all I know they could be twenty companies today. They're
INR and nmn,
I don't know probably about 30 to 50 prior to this FDA ruling. Okay, which is kind of an interesting situation in its own, right? Yeah, you know what happened? There was the supplement and a men suddenly the FDA decided that it should not be sold over the counter anymore because there was a clinical trial initiated on nmn which
Usually makes an MN a drug for clinical testing and thereby can't be classified as a supplement any longer. That was the rationale As I understood it. But as with things like an acetylcysteine
that was more of a lobbying effort though. Right? Right. I don't think actually that was a scientific decision. I think that was more of a lobbying decision from a from a market protections from an IP protection
standpoint. And this had happened prior for n-acetylcysteine Knack, which some people take it Sam.
Mucolytic actually a great decongestant. Yep, if you're congested and it increases glutathione, that's my understanding and I believe somebody check me on this
decrease or increase glutathione
increases your outer thigh on as my understanding if I have that wrong someone will tell me quickly in the comments. My understanding is that in Europe neck might even be available by prescription in the u.s. You can still buy it over the counter but a few years back the FDA said, nope can't sell knock any longer and there was a push back.
Lobby to keep it on the market and you can still buy it on Amazon the same thing has more or less happened with Ana men and certainly within our although NR was never in question in terms of whether or not it should be sold as a supplement or not because as far as I know there's no clinical trial on an are at least not currently so there's a clinical trial on nmn which classifies it as an experimental drug. And therefore the FDA said, nope. You can't sell it as a supplement a few companies major companies.
He's pulled nmn from the market in the u.s. Many smaller companies just kind of watched and waited and continue to sell it and I checked prior to the beginning of this episode and you can still buy it online. But of course a lot of what we're saying today is kind of a why would you we're not really coming up with strong Arguments for taking Anna men at least not in today's discussion. Yeah. I mean again, I think the strongest argument I could make based on the data would be pretentiously on the on the on the base.
It'll cell and squamous cell carcinoma risk reduction if indeed those results are reproducible that again that's that would be justification again for the right individual wouldn't be a justification for me might be a justification for somebody but really the rest of it is.
Why why do you need to do experiments on this if you're selling a supplement when you don't need to make claims to sell a supplement? Like if it's a drug, you have to have an indication can't sell a drug without rigorous trials that demonstrate both safety and efficacy. I do think it's pretty safe to say that I do think nrnr probably safe. There has been some voice around the idea that NR could increase the risk of cancer,
right and the experts in this area.
Like Charles Brenner have pushed back hard on that arguing that the studies were not done. Well, is that I
recall I think that's probably fair. I don't think there's been a well done study in this entire field is part of the problem, right? So and that's probably too harsh a statement. But I this is not a field that's like, you know.
That's necessarily lending itself to the rigor that you would in pharmacotherapy. And I think there are probably you know, you mentioned Charles Brenner like I think Charles does good work, right and he works on many things not just this. Yeah, and and and by the way, I don't I don't think I don't hear Charles out there saying that n r increases
lifespan No, in fact, I don't want to quote him at all. But I think he would argue that sirtuins and our and a men should not logically or practically be linked to
Efforts to extend lifespan but that there are some interesting positive effects of augmenting and are as a means to increase NAD for sake of anti-inflammation and some of these other effects that we've been discussing.
Yeah, that's my understanding of his position as well is that I think he firmly agrees with what I laid down at the outset of this which is there's no meaningful logical connection between the relationship of sir.
Two ins caloric restriction and N are that's that's just a that's a shell game. That is empty. And and you're right. I mean, I think part of the reason why I think there's much better research going on with rapamycin is that there's really no commercial interest in rapamycin like nobody's going to make money selling rapamycin because it's so cheap. Well, yeah, it's actually not cheap, but it's a drug that is off patent rights. It is a drug that was approved by the FDA 25 years ago
so generic
Forms are inexpensive enough that no leave it or
not. They're not this is the irony of it is is generic. So rap immune is the brand drug that was initially approved in 1999. And today if you go and buy rapamycin you're going to not buy rap immune you're going to probably buy generic sirolimus or rapamycin and yet it's surprisingly quite expensive now. It's not enormously expensive as you're not taking much of it, but it's about
five bucks a milligram
That's pretty expensive. So you take an 8 mg a week. That's 40 bucks a week is probably what I spend on rapamycin that ain't cheap no relative to you know, and it's cheaper than some things I take but it's not cheap, but the point is like nobody has a commercial interest in rapamycin, right? It's sort of in a relevant drug. It's but the interest is scientific, right and and and the commercial interest is in what we call Rapid logs which are analogs of rapamycin that are being investigated by a number of companies.
To look at new indications, for example immunity immune function, right? So rapamycin historically is thought of as an immune suppressant because that's the context in which it was approved for patients undergoing organ transplantation. But you know, I think Joan Manic and Lloyd clicks teen when they published that paper in 2014 using ever roll Amis where they took a group of 65 year olds and randomize them to either a placebo
Bow or different Doses and dosing schedules of everolimus found an enhanced immunity in response to an influenza vaccine. Which again was for me. That was the turning point, right? That's when rapamycin went from something that was interesting based on the first ITP in 2009 to maybe we should be taking this in 2014. So between 2009 and 2014. I was kind of looking at the Curiosity of rapamycin and saying well cool that
It worked in mice. I don't think humans should ever consider this to that study, which was like wait a minute something's different. If you take rapamycin as a human at least every day, it seems to suppress your immune system. But if you just pulse it once a week as they did in that study, it seems to improve immune function which again means it's an immune modulator. It can go up or down in the immune system. That was really the the hypothesis that emerged from that experiment. And so now the question is could you design
drugs that are more specific to a more complex one, which rapamycin is not but you can get around that by dosing it intermittently. And then of course, you know, is it a drug that has efficacy in terms of other other things that can be tested in humans that are not longevity because you can't test lifespan in humans
obviously, right? You're 50, right? 50 years old 51 you seem to be vigorous you take great care of yourself.
How much do you think taking rapamycin for how many years have you been taking
it six
has contributed to your current state or
Vigor zero idea.
This is my opportunity to ask about your belief or lack of belief in biological aging tests because if somebody is going to experiment with any or all of these things, they may want to evaluate whether or not their biological age is changing and there are
A number of these tests available and people love this stuff. Love them. They love them. I mean who wouldn't want to see that? They are 51 years old, but their biological age is 37.
I just did a movement test the other day. So it's a it's a very fancy camera system where you got a million cameras on you and you go through this whole exercise. How high can you jump how far can you throw like, it was
awesome and then it gives you a movement age Andrew. I was 22, I believe it. I mean
I'm going to I should be I should feel amazing. Do you actually think I move like a 22 year old I mean are you freaking kidding me and you if I went and did that again tomorrow? I'd come back at 31 or something. There is so much nonsense in this type of testing. It is just you know, look, there's probably something to be said if I do that and I come out at 22 as I did versus 92 sure I would come I would grant you that if you took a
150 year olds and you put them through a movement test the ones that really really are struggling will come out older and the ones that really really are doing great are going to come out younger. So great. I guess it's not I guess I move reasonably well for a 51 year old but it's simply impossible to believe that I can do today. What I could do when I was 22 with respect to movement and strength and power which is what that was assessing your doing a lot of jumping single leg jump here do all this kind of stuff balance testing all sorts of things and and I guess I would
Say the gold standard for any of these biological aging tests has to be the following.
What is a better predictor of remaining years of life chronological age or biological age? That's to me the most important standard. So how old are you chronologically? I
turned 49 in six weeks.
Okay, so I'm sure your listeners will not like to hear this because they would probably hope and believe that you are Immortal, but some might want to hear that. I'm going to be taken out soon.
Okay, but let's let's just grant your mortality as a given based just on your chronological age an actuary would come up with a pretty decent prediction of how long you're going to live. Now. I would argue that that's a crude assumption because it doesn't take into account the fact that you're metabolically healthy that you do all of the things that you do, but just based on the fact that you are a man who is 49 years old and who doesn't smoke.
Those three things would give me if I were an actuary a very good prediction of your life expectancy. And because I'm not an actuary. I don't know the exact number but my guess is it would be predicted at this point at another 37 years. Okay. Well, I bought that chart my life and weeks. Yes. In fact, I bought two of them for reasons that are uninteresting but
I've watched that chart Phil not quite what you predicted but I put my estimated life span to be 95, right? That's fine. And then I have little lines on the side. Hmm of how much Vigor I felt from and just overall Wellness completely subjective of zero and being like completely cratered near death to 10 like is
best I've ever felt but you do that you make that note every how off
okay. So what I did is
You know from 10 to 15, I felt you know blank and then in my 20s, I actually didn't feel so great because I was I was working 80-hour weeks commonly. You can ask my former lab technicians. I was just talking to fucking win recently. And I mean I used to work to collapse not healthy 80 hour week, maybe 100 hours occasionally, maybe 70 maybe back to 40 but just too much work not enough sleep nutrition. Not great. Not just not doing the right things, but just gave gave my 20s to being in.
Lab, basically and a lot of my 30s as well. So I would say from 40 to 45. My Vigor was higher than in my 30s. And then now I track I would say about every two months. I'll start filling in that line and it's adjusted for by stressors and adjusted for by positive things in life. And the goal for me is to figure out what are the behavioral tools and other things I can do or take
that are going to keep the Vigor as high as possible Vigor well-being internal. Peace Etc. All of that combined kind of what I'm calling Wellness in this very subjective measure as high as possible as I transition to my 50s 60s 70s and 80s and I'm guessing that I'm going to have to do many more things in my 80s and 90s in order to maintain a similar hopefully level of vigor and well-being than I do now and the question is will I be able
Will too. Yeah, maybe maybe I might take a slightly different different different angle on that. But let me go back and make one point and then we'll come back to this point, which is actually really interested. Yeah,
because I think the chart is great. I think the chart more than any supplement for longevity gives you a more gives one a visual perspective of where they sit in this long Arc, and I don't think the brain is very good at anchoring us to the notion that
That we are mortal because if we think about that for you in a few moments too long makes us anxious and I think we are very good at avoiding that reality.
Yeah. Well it's as you said it's very difficult to contemplate finitude. So I actually want to talk about that because I think it's so interesting but I just want to make this point about the Actuarial point, right? So let's just say actuarially, your expectation is 40 years more at this point because you're 49.
Fine, you're a male and you don't smoke. So we believe you have somewhere between 35 and 40 more years of life predicted on the basis of your biological age. That's it. That's all I got going to live to whatever 88 to 91 or something. I'm making that up and that's like okay, I better get cracking on so stuff. So now let's pretend you went and did a biologic age test. Okay. So let's say you did that and let's say it came back and said you're 25.
So if I had a 25 year old male nonsmoker in front of me, what's his life expectancy?
Well, it's about 60 to 65 years.
Does that mean that you and rou
have 60 to 65 more years of life based on a fact that your biologic clock says you're 25. Do you believe
that no way? No, of course not
now this would be an easy thing to test not in humans, but you could do it in mice right interesting that to my knowledge that experiment hasn't been done. So
right out of the gate
when I look at people
Talking about their biological age, you know. Well, I'm actually 60 years old, you know chronologically, but my biological age is 35. My response is who cares truthfully like is that a good thing? Yes, probably but does it is it is it is it tangibly measurably meaningful like to have a biological age of 35 versus 40 verses 30 if you're 60,
I don't think I think we're
applying a very
False level of precision to something that might only need to be directionally true. Secondly. We don't really yet understand the biologic noise in that measurement. Right? So there are lots of things that we measure that are really noisy. So if I measured your I don't know let's think of something that's very biologically noisy your triglyceride level like your triglycerides are pretty noisy.
Unless I do something very important, which is standardized it by how long it's been since your last meal. Like if you ask me right now what might rigs are I have no earthly idea because you know, I probably ate three hours ago like and I don't remember what I ate. How much fat was in it how much carbohydrate reason I have no idea. So the only way you could really get a triglyceride measurement and put any weight to it is if you've been fasting for 8 to 12 hours, then we can at least say hey a triglyceride.
Level of 50 milligrams per deciliter is excellent. Whereas a triglyceride level of 120 milligrams per deciliter is lousy, but if you measured my Trig's today and they were meeting at this moment and they were 150 that could be totally reasonable even though at fasting levels. I'm at 50 so we know that because we know exactly what goes into the triglyceride measurement, but when you look at a biologic clock that takes into account your glucose level your vitamin D level your Epi genetic marker here or there. Those are
E noisy things so, how do I know when I measure it in you now versus when I measure it in you a year from now I captured you in the exact same space. I mean, I don't so it's for that reason that I just have a very hard time putting any stock in this now does that mean that in the future? We won't find some benefit in this I think we probably will I do think of all the things that go into it probably the epigenetic part of it would be the most interesting but
N what most people don't understand is sort of a dirty little secret is how difficult it is to measure the and to sequence the epigenome, right? So to my knowledge, none of the companies that are doing this. I may be incorrect on this by the way, but the last time I looked which was about a year ago, not a single company was correctly sequencing the epigenome on these things. So they were not able to accurately say what they were giving you an average representation of your methylation, but they weren't going base.
Pair by base pair and actually sequencing this the way we would sequence a genome. So again, it just is so much noise in this system and I just think it creates a little bit of a distraction for people truthfully.
Do you avoid going through the non? Let's just say the non traditional scanner at the airport. The one that might use higher levels of radiation. No, do you think about how many flights you take as a source of radiation? No, let's just
keep this all in context. So
The NRC recommends that a human being or at least an American should expose themselves to less than 50 millisieverts of radiation a year. Okay. So what that number doesn't mean anything to somebody so let me give people a sense of what that means. So how many millisieverts of radiation do you and I receive because we both live at sea level. So just ambient radiation living at sea level is one millisieverts a year.
Okay, so we just chewed up two percent of our annual allocation. What if you moved to Colorado now, you're a mile up that increases you from 12 to millisieverts a year. Okay. What if you had a CT scan of your chest CT angiogram while depends on where you got it done if you got it done at a really good place with a fast scanner and great software. Probably three millisieverts a year if you got it done at a place that's sort of average.
Might be 10 to 15 millisieverts. Pardon me per scan. Now, here's what's really interesting. By the way. I'm totally fascinated by this question, which is how much radiation is too much a dexa scan. By the way. You can't even measure how many millisieverts you're getting. So a dexa scan is like less radiation than a cross-country flight. So it's super super super low less than an x-ray or anything like that.
People who work in nuclear plants I'm told I haven't looked at the primary data on this but I've talked to people who incessantly do this. So it's possible. I'm a little bit off on this but I'm told that these people are at ten times that level of radiation exposure and sometimes higher so now they're not getting 50. They might be getting like 500 millisieverts a year and yet interestingly. They're not an increased risk for cancer. I'm not sure what to make of that.
But it suggests to me that we probably don't need to worry about things like airport scanners and flights. In fact, even if you look at pilots who do constant flights across the poles because you're going to get the most radiation going over the pole to my knowledge. There's no convincing data that suggests those people are at an increased risk of cancer either and they're you know, they're obviously at the upper end of what and a civilian would experience in terms of radiation. So I just
not convinced that that's like that's something we should be stressed about.
I think you just relieved a lot of people some unnecessary
concern. I want to go back to what you were saying earlier about what you need to do in your 90s versus what you're doing now. So you said you think that in the end you're 80's and 90's are going to have to work harder to preserve the Vitality that you have
now. Yeah, grip strength jumping cognitive function. I mean, I've got very good genes in terms of longevity on one side of my family pretty good on the other although not as robust.
I mean if I just look adoringly yeah, who knows right? I mean, but my sense is that I'll live to be 95 if you know barring, you know, bullet Buster
cancer. So I would say that yes, you're going to have to work hard in that last decade of life to preserve those things. But I think it's the work we do now that sets the stage for that. It's the foundational work that we do in this period of Our Lives, you know, you and I are only a couple of years apart, but I think
This is the critical decade. It's in your 50s your 60s and in your 60s and your 70s that I think is is the deciding time 50s to 70s to 60s 50s to 70s. So what is it about this this window that you and I are just entering now and why is it so important? I think it's important because we're we're getting to that point where aging does start to show up. Like I think if you and I are being brutally honest like we're kind of
The men we used to be and and and and again that just means like look like a night of poor sleep shows up more right when you were working in the lab as hard as you were describing it. You could probably walk through walls when you were
exhausted. Yeah short nap would reset me near completely. Yeah. I've got more colds and flus in that time because I wasn't taking such good care, but then again I was indoors more so it's an imperfect experiment but you're right. I think that as I've approached 59
I need to do more
give me to do more self care needs to be more mindful of what you're eating how you're sleeping how you're recovering from those workouts because we still do hard workouts. But recovery plays a greater role in other words. We're just not quite as resilient as we used to be. You know, I was telling somebody the other day. They asked me about my residency. I don't think I'm being hyperbolic when I say this I couldn't do one month of what I did for five years. I really couldn't do it. I don't think I don't think there's any there's no way I could go back to that level of sleep deprivation.
For a month let alone five years. So, you know, that's just a fact of Aging I think so, but what we have to do during this period of time is build up as much physiologic Reserve as possible. And so the important thing is we, you know, we have to stay in the game because compounding makes such a difference, right? So, you know, we're still young enough that we can actually put on muscle mass now, that's not always going to
Be the case. It's going to be very difficult to add muscle mass when you're in your mid to late 70s, it's doable but it's very very difficult. So instead we want to be putting on as much muscle mass as we can and increasing or at least maintaining strength as much as we can again, probably increasing it is unlikely clearly. We're not increasing power as we age right Andy Galpin has talked a lot about this the atrophy of the type 2 muscle fibers the to a muscle fibers.
Start to atrophy in your 20s and 30s. So I know I don't have a fraction of the power that I used to have and I know that because my vertical jump is literally half what it was when I was a
teenager and I was never mine was never very good. So it
doesn't matter how good it was. My point is like if you know what your vertical jump was at 18 19 20, and then you do it today. I mean, it's literally 50% and that's one of the purest tests of power. So Powers going down strength is going down but not as much muscle mass is actually not because remember that
It's the order in which you lose things right? You're going to lose power strength and size of muscle but again sighs still matters. It's still a glucose ink all these other things but we don't want to do is you know be out of the game. Right? What we don't want to do is injure ourselves and get a setback that becomes very difficult to recover from because you know, when you're our age if you're inactive for months at a time, it's it's going to be two to one.
Three to one ratio of in activity to activity to get it back.
What about energy sorry to interrupt but since we've been talking about molecules and energetic Pathways, what about energy just that get up and go let's just say after a decent night's sleep seven and a half hours waking up same time more or less 6:37 a.m. Probably for you or me. And why is it that as we get older we have less energy are
Mutual good friend the late been beerus used to ask about this used to say he called me and he was like Andy, why do I have so much less energy? Like I don't know how it was great question now, unfortunately, he died of pancreatic cancer. So there may have been other things going on, but that was prior to the cancer at least as far as I know. It's a very interesting question. Why do we have less energy and I don't think anyone's ever been able to answer that question.
No, and when you have kids you're going to be even more starkly.
Did with that because I think it's one of the things I am most Amazed by when I look at my kids, especially the youngest ones the boys who were 7 and 10 is what I just described as spontaneous outbursts of energy like their inability to sit still their kinetic desire to just like they will like if we're I remember once we were going to walk in through a mall and we're walking through the mall. They are sprinting ahead.
Head of us sprinting back sprinting ahead of us sprinting back. Like imagine if you and I were walking through the mall and I just started running ahead and running
back you be so sore the next day but it's like it just wouldn't occur to me to ever run unless being
chased right? Like it's just I mean like
like we now live a
life like I think our ancestors did which was you know, if we're not deliberately in the business of moving for a reason like you're exercising you're going for a walk for the
Take of going for a walk like you just wouldn't it wouldn't occur to you go and expend energy for no reason and yet kids do this. It's amazing and look it's going to go down by the time you were a teenager like just going from being, you know, sort of 10 to 18. There's probably a significant reduction in spontaneous outbursts of energy let alone where we are now, and it's a great question who maybe it's NAD
I don't know
maybe although up until now we've been talking about all these ways to try and increase NAD in the bloodstream and hopefully in cells and I don't know I take my enemy and my NR and I feel a little bit of a boost in energy, but I can't say that. It's so significant that I feel like I can Sprint back and forth Just spontaneously
these again, it's just so hard for me to imagine that any supplement or any drug including rapamycin which I think is the most
Most promising Jarreau protective drug, we have I just can't imagine that those things even compared to what good sleep good exercise and good nutrition do for your energy levels and vitality. And the reality of it is all three of those things are hard to do, you know?
Yeah, they specially if you're an adult like especially if you have a
real life, you know, you got kids you got a job, which is presumably many.
Listening to us right now. Like there's very few people listening to us right. Now whose only purpose in life is to take care of their health. Everybody's got something else they have to do which means you have competing interests for how do you take care of yourself? So to sleep is not easy, right? Like we all are busy as hell. We don't want to have to stop what we're doing to undergo a nighttime routine to put ourselves in the right head space to be able to sleep do all the things necessary give ourselves that eight hours in bed to hopefully get
In seven and a half hours of sleep even people like me who like exercise. I know you like exercise. It still is a sacrifice in terms of time. And and for many people it certainly for me food is the hardest of these. All right, if left to my own devices, I need for control loops all day. Like I love Fruit
Loops, right interesting by way of contrast. The food part is easy for me. I like healthy food. And do I like healthy new die just like all food. Okay, I like. Yeah. I don't like unhealthy food. I've wean myself off. I never really
I liked it that much. I mean I like a great-tasting slice of pizza or ice cream everyone smile, but I much prefer meat fish chicken eggs fruits vegetables rice OB, I just like that stung more weirdo. That way I suppose but on the topic of exercise as it relates to Vigor and Longevity, I'm intrigued by how some forms of exercise give us more energy.
Especially the same day and how some forms of exercise or even timing of exercise tends to deplete us because I think one of your major sort of calls to the public has been to move more for sake of their health span and life span, but because of the time investment that it takes to work out in a gym or to go for a run or a rock, I think some people think well that's a lot of time but if it gives you more energy and more Focus to do other things well, then it's great. So it's
Not just about living longer. It's about me being able to do more and I've noticed I don't have any science to back this up. But I'd love someone to run a test on this that if I complete my work out before 9 a.m. Even if I have to start it while I'm a little bit fatigued. I have more energy all day long, but that if I initiate that workouts a mid to late morning, I'm pretty tired in the afternoon. It's like I give everything I have to that work out and so it becomes a little bit defeating since I'm not a professional athlete or even a
Amateur athlete I'm working out for health spend lifespan, but I want to do exercise that gives me more life during my waking hours. I think somebody should study this and I'm convinced that it has something to do with the change in body temperature that occurs across the day and the additional change in body temperature that occurs as a consequence of exercise. That's my
hypothesis. Do you notice a seasonal change in that? Do you experience it more or less in one season or the other and
then thought about it that much but not so much not so much and I
I wonder whether folks like our friend Jocko willing or able to do so much. Yes so much Vigor that guy in part because he basically exercises at the just after the lowest temperature phase of the Circadian rhythm and uses exercise and presumably to drive himself out of that and get that, you know temperature increase that's the consequence of waking but in his case he's waking up so early for 30 is when he starts those workouts. So it's something for people to play with it's something that I don't think it's
Discussed enough which is yes, you should exercise do resistance training do cardiovascular training but play with the timing of those and see how at a given intensity. It impacts your energy levels for the remainder of the day. I think that's it. I think it's an important metric that again. I just don't see a lot of attention to because I think if people could experience the increase in energy that is the consequence of working out at the right intensity in the right way at the right times for them. They'd be
much more apt to do it. It wouldn't feel like this like spending money on something that sure will make you live longer but then you're depleted and you can't do cognitive work. There's something pretty impressive about the fact that as far as I know the last three let's just call them. I don't want to call anyone else specifically major pillars of the high-level administration at Stanford school of medicine to my knowledge were all five am Runners. There's something about early morning exercise and my good friend Eddie Chang is the chair of neurosurgery at UCSF. He's been on this podcast.
Known him since we were seven years old. He's an early morning exercise her and then he's got tons of energy all
day. What about the reverse causality there? Just think it's possible that there they have a whole they have a system of high energy that makes Jocko who he is or makes you know these people who they are and as a result of that they were able to work out five clock in the
morning. Yeah. I don't doubt it. I just have noticed that in the few times in my life where I've kicked my own but to get out and start working out.
Really early. I have more energy all day long. Sometimes I still require a brief nap, but it's a pretty striking effect as compared to you know, the 10 a.m. Workout effect. Yeah. So I've started setting a standard of trying to get my workout done before 9 a.m. So anyway something for people to play with because the more energy to live in your waking hours, perhaps not longer, but certainly have more energy in terms of output I think is a significant and undervalued parameter.
Let's quickly return to supplements. We think are converging on an answer about an r and a men and NAD, which is you don't take them. Correct. I take an r and N MN with not a lot of religious adherence. I should say if I ran out. I might not buy it for a while and the only observed effect for me is this accelerated hair growth which is a pain in the but frankly because it just means I have to get my hair cut more.
Often I'm not trying to grow my hair faster. But okay, what are some other supplements if any that you take that are peripheral to this pathway or separate from this pathway rapamycin as a prescription drug only, right? So are there any over-the-counter things that you take that you would Place into the lifespan category? Maybe they touch into Health span as well. I'm happy to list off what I do. But what are your let's just say top five at
least. Well, I don't
I don't take that many. So it top five would be a pretty exhaustive list. I think the other supplements that I take I do take EPA and DHA
in the form of liquid or capsule fish
oil capsules not because I have a an affection for capsule over liquid. It's just going to increase my compliance if I take I've done both and I noticed when I was taking liquid because you're storing it in the fridge. It's just it's just one more step removed and I was just less likely to remember to take it twice a day.
I take
Thera cumin and there's some reasonable evidence in MCI patients that their Acumen improves cognitive function. So I think there's a relatively low down side to the hypothesis that tharok human May preserve cognitive function again, I do I wouldn't put that in the category of like beat the table for it, right? I think it's just, you know reasonable evidence.
I take I do take vitamin D because interestingly despite the fact that I'm outside everyday without supplemental vitamin D. My levels are surprisingly low. How much do you take I take 5000 IU and that takes me from kind of a level of 30-ish to a level of 50-ish and there's you know, there's a lot of debate about how high vitamin D levels should be. That's a whole separate podcast.
As we could, you know waste time on that and 10 years. Yeah my appetite to talk about that one. Let me think. What else do I take as I sure do. I do take methylfolate and methyl B12. And again the the the rationale there is I do think there's some evidence that elevated levels of homocysteine are bad in and of themselves. So there's no denying the fact that
Levels of homocysteine are associated with bad things. That's unambiguously clear. Meaning there's an association between Badness and homocysteine. What's not clear? Is it causal now? There's definitely one mechanism. You can point to although again mechanisms are what they are. We just spent how many hours talking about mechanisms that theoretically make sense that never pan out but mechanistically homocysteine will inhibit the clearance of something called.
Metric an asymmetric. Dimethyl Arginine. Have you heard of these things SDM a and a dma so a dma and SDM a regulate nitric oxide synthase and homocysteine impairs their clearance and therefore when you have high levels of homocysteine, it pair it results ultimately an impaired nitric oxide synthase and therefore loik nowhere nitric oxide. So this has been proposed as at least one mechanism by which homocysteine might
Negatively impact vascular disease so and we also know by the way that a dma and fdma are cleared by the kidneys and therefore this might this is also proposed is one of the mechanisms by which impaired kidney function is impacts vascular health because that's a known right if your kidneys don't work. Well your risk of heart disease goes way up. So this is now proposed as a link between what we observe with homocysteine and impaired renal function. So,
We know that if you take methylfolate and methyl B12, you're going to lower home assisting that's abundantly clear. So the thinking is that that might actually lower a dmas dma and raise nitric oxide synthase again, relatively low-cost low-risk, you know thing to take at modest doses. I also there's probably some evidence that over supplementing vitamin B is problematic especially be 6, so I do because I'm pretty
for all nerve damage exactly. Yeah, so I don't supplement B6. I'm just taking a bit of folate and and methyl B12. Let me think what else do I take because I do take a couple other things.
Oh, I take magnesium L3 and 8 and ashwagandha for sleep.
I take slow mag, which is just a magnesium chloride slow releasing version of magnesium and I take methyl. Pardon me. I take magnesium oxide. So I take magnesium in three form. So I'm I'm long magnesium your carpet bombing the yeah, I'm big on magnesium right great for bowel function great for I mean, I don't know the last time I had a cramp in my life, you know, it's been years since I've had a cramp despite exercising in a really hot place like Austin Texas where I'm sweating like theirs.
No tomorrow whether you call it a supplement or not. I take I take like electrolytes. I take element which I should disclose. I'm an investor in that company. So I drink an element today. I take creatine monohydrate 5 grams a day. I take AG most mornings. Oh and I take pendulum the probiotic got it. Yep. As far as I know. There's no other probiotic that has any meaningful effect on the body outside of pendulum, right pendulums.
Because if you buy the argument that a probiotic for your gut needs to have anaerobic bacteria and at there's no value and giving you a robic bacteria, so you have to have something anaerobic. So Akram and Sia, which works through the glp-1 butyrate pathway is anaerobic and pendulums. The only company that can make it. I have no affiliation with this company. I think you should have the CEO calling cutcliffe on your show. She's an actual scientist and she's fantastic and
it's a really interesting story how they kind of developed this and how difficult it is to actually make an anaerobic bacteria. And so this is kind of an odd company because it's a supplement company, but they have to basically adhere to Pharma GMP conditions to make it because of the anaerobic Vats that you have to use infused with nitrogen to be able to make an anaerobic bacteria. So anyway, so I take three of their products I take something called glucose control I take polyphenol and I take Ackerman Sia, okay.
I think that's the
list. Okay. Yeah, I'll try and move through my list pretty quickly. I may miss one or two things and I don't know maybe we'll put the list some place online and fill in any gaps.
I definitely take ag ag one, you know live by typical a Drita been doing it since 2012. That's true take one or two servings a day three if I'm traveling and I'll generally do that first thing in the morning or in the evening for me. It's really about capping off the vitamin minerals that I might be lacking in my diet and also the whole adaptogen
- I think and polyphenols and I'm a very interested in pendulum because part of the reason I take a G1 is for the got Health aspect. I think just bowel movements are more where I'd want them. I mean it sounds kind of weird to talk about but you just feel better when your gut motility is right. I feel like it adjusts my gut motility. So it's neither too fast nor too slow.
So that's first and foremost.
I take a quality fish oil either the one that Agee makes or Carlson's in liquid form that has that lemon flavoring and I make sure I get above 1 gram per day of EPA. So that's usually a tablespoon sometimes two tablespoons.
I make sure that I get enough D3 typically from The Dropper 5000 IU per day approximately sometimes 3000 sometimes 7000. I kind of play around that and I test my blood levels. I also take methyl B12.
And I also take Tonga Ali. So I take one capsule of that in the early part of the day that has lowered my sex hormone-binding globulin freeing up a bit more testosterone. That's why I like it and I take a couple of green tea capsules in the morning. I drink yerba mate, that's more of a stimulatory effect. And I take the nmn in powder form sometimes NR as well. And again if I run out of that I tend to go long periods of time without I use element as an electrolyte so,
So people are probably noticing. This is all pretty basic. I take my case 10 grams of creatine monohydrate per day. Sometimes forget to take it. That's why I take 10 grams. I'll sometimes miss a day and I certainly feel the effects of that in the gym because of the greater water volume in the muscles, but there are a lot of data on creatine monohydrate for sake of either maintaining or offsetting some of the cognitive dysfunction associated with sleep deprivation, maybe aging altitude and some other things as well.
And then for a few months, I was playing around with let's say nicotine gums. I stopped doing that. First of all, I was dipping it and I ended up Lifting for an entire episode of the lecture even and podcast and I only realized later so I stopped taking it also because it gave me a kind of a tickin cough when I wasn't chewing it and then I felt like I needed to chew it and it's a little too stimulatory for me before.
If I take magnesium three and eight really bullish on magnesium as well apigenin 50 milligrams, which is essentially chamomile extract and thinning and occasionally. I'll take 900 mg inositol also or instead kind of mix those up and around and then I use a quality whey protein as a protein replacement that kind of thing and I've played around with various things like Sheila G and you know, sometimes get the sense that it's having an effect, but then I'll stop taking it.
For long periods of time, you know, there are very few things that I've stayed with for long periods of time and I basically just described what those are, you know, if ever someone were to design a supplement that would provide more energy all day long. That wasn't caffeine. I'd probably look to that but I ingest caffeine in the form of yerba mate and coffee. I've played around with caffeine tablets, you know, taking, you know, 50 milligrams of caffeine in tablet form. I mentioned that only because
Is it has a distinctly different feel than ingesting caffeine through liquid form? It feels stronger. And I don't know why that is. In fact, I there's a very well-known podcaster who drinks peppermint tea and takes caffeine tablets as a way to I don't know drink peppermint tea which sounds very nice and mellow but also get the stimulant effect. So anyway, that's pretty much it and then I do a lot of things as I know you do mainly based on suggestions you've made about getting so into cardio rocking weight vest walks and hikes.
Three times a week resistance training three times a week cardiovascular training one long one medium one short and I try and hit the sauna and the cold once a week. And yeah, that's pretty much it. I think they're a bunch of other supplements that are really interesting and kind of fun to play with if one wants to like 600 milligrams of alpha GPC or 900 milligrams of alpha GPC in a Double Espresso prior to a workout you feel different. It's a stimulant, but I don't like to do that, too.
Too often because of the increase in tmao that occurs and then you have to take 600 milligrams of garlic to offset that increase and
you start getting if we believe tmao
matters, right if you believe tmao matters and oh, okay, great even better. I'll maybe skip the garlic so things like that. I prefer to just eat garlic anyway, so there's a bunch of things like that that are kind of fun to play with as pre workouts. But yeah, that's the core supplement regimen and it's the one I've stuck with for gosh.
At least 10 years or in the case of a g you're more than you know more than that. So I should say because any discussion around supplements. I think it's going to you know have people picking up their ears to okay. This is like a sales pitch or something. I absolutely want to go on record. The thing is you choose to do and not do are going to have much greater effect on your health span and life span. That is the behavioral things in particular sleep exercise and nutrition sunlight etcetera.
Then anyone supplement that you're going to take so I do view supplements. I think through the appropriate lens, which is that they are indeed a supplement. They are not necessary many of them are simply sufficient to serve as an insurance policy or to augment mental and physical health, maybe longevity in ways that make it worthwhile given my disposable income that I want to devote to supplements, but I don't think you need them.
Yeah, I'll go even more extreme on that statement everything we have talked about on this podcast today whether it be NR NAD + MN Thera cumin magnesium this supplement that supplement all of that stuff while potentially mattering I would put in the category of was the Titanic serving Lobster or steak.
Look, I like steak more than Lobster. That's a relative discussion exercise sleep nutrition emotional health is the question of what was the heading of the Titanic? Okay. So I just want people to understand the magnitude of what we're talking about how you eat how you sleep how you train and how you take care of your mental health is the equivalent of what direction was the Titanic going with
Respect to the iceberg all this supplement bullshit that we just talked about is equivalent to where they serving Lobster or were they serving steak and was the band playing this song or that song? I'm not saying those things don't matter but just put them in the context of the direction. The Titanic is
going. Okay, so I completely agree with you exercise sleep nutrition and emotional health not listed in any particular order Peter and I both completely agree. Those are the critical for before we close.
Nrmn and AD.
And NAD in particular, how do we view this? Is it a pathway that we should be focusing on in terms of supplementation or infusions for sake of extending our life. My answer on that is no.
Yeah, I would say the same, you know, I don't remember who said this but someone maybe it was Nassim taleb said don't tell me what you think show me what's in your portfolio like meeting people who pontificate about this stock versus that stock. He's kind of like assuming it was him that said this he's like, okay, I don't care what you're telling me tell.
What you own that's going to show me your conviction so through that lens. Look, I'll show you my conviction on exercise. I'll show you what I do. I'll show you my conviction on sleep. This is what I do. I'll show you my conviction on all these other things. I mean, I don't take these supplements. I don't take them because I can't afford it's not that I can't afford them. It's not that there are any inconvenience to me to take them. I passionately do not believe they do anything for me. And why would I waste time money anything?
On something that I really don't believe makes a difference now again, I am always happy to be proven wrong and I am very happy to say that two years from now five years from now we could be doing this exercise again and in the presence of new information, maybe I'm not taking rapamycin and maybe I am fist fulling, you know, NR + NM n possible. I will I will reserve the right to change my mind for the rest of my life in the presence of new data, but as it stands today, I do not take these supplements.
And I have no foreseeable plan to do so until information
changes great. Thank you for that clear stance and the willingness to change it in light of new data Peter. So good to sit down with you again and talk science talk health, and in this case talk about the supplements that we're not going to take in addition to the ones that we do take we will do this again sometime very soon. Hopefully in Austin would love that. Thanks Peter. Thanks man. Thank you for joining me today for my discussion with dr. Peter a TIA.
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Thank you. Once again for joining me for today's discussion all about NAD and Longevity with dr. Peter a TIA and last but certainly not least. Thank you for your interest in
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