How To BOOST Energy, Reduce Inflammation, And Live Longer! | Dr. Andrew Salzman

NAD is a critical factor in our energy when the cell produces energy it's actually a complex mechanism it starts of course with the food we eat and ultimately that fuel that that food that we ingest is changed and modulated until ultimately provides molecules of energy that the cells can use throughout the body and NAD and the mitochondria are absolutely Central to that process when the sugar

or protein or whatever we eat enters the cell it enters into various Pathways and in these Pathways the food stuff which typically as an example might be glucose is then modified and cut and shaped and NAD plays a critical role in this process there are three separate sequential processes in the cell which produce the ATP and in each one of these NAD is generated to a

certain extent and without that NAD we ultimately cannot finish this sequence this cycle which leads to ATP so NAD is sort of the transfer agent that goes from the food to the final product which is ATP which we can use in the absence of NAD you can't make ATP so any potential part of life as we ate and as we have various processes that reduce NAD

we are putting the number of factors in this process for example we can't make ATP as well so when you're 20 years old and you're running down the field for the football you've got a lot of NAD and a lot of ATP when you're 60 years old you start to notice quite a difference of course yeah look at the muscle of a 60 year old or

of an 80 year old because when we're 80 we're still doing a lot of stuff today but what you're going to see is there are fewer mitochondria these powerhouses of energy they're fewer of them that's a problem but with each within each individual one they're not making enough NAD and of course they're not making enough ATP now if you're a couch potato you're sitting there and

you're watching the seven o'clock news you're probably not going to notice that but if you try to run up the stairs carrying some groceries or God forbid run down the football field the age of 70 or 80 you don't have the capacity to ramp up and generate the NAD and ATP that would be required to be competitive with a youngster so we start to feel it

as we get older now in the overall picture this NAD deficiency is much more than just energy although energy let's start with that discussion because that's the key point but there are other things that I will come to which show the broad effect of having lower nads It's Not Just Energy but focusing on energy we now know in humans that with time with age every year

it's a little less NAD available to us we know in animal models if we artificially suppress the amount of NAD those animals can't perform as well and we have even more data which show that if we supplement and restore and bring back the levels of NAD to where they were when we were younger we can do a lot more so NAD is a critical factor in

our energy now what's interesting recently is that this whole story of NAD has been tied into other mechanisms and other Pathways in the cell that we didn't realize for example we now know that and he is involved in inflammation it's involved in in pain and as we get older we're all feeling a little bit more painful and we're also having loads of inflammation we have more

inflammatory diseases so this deficit of NAD as we age is really causing a broad effect on our health yeah it's so important because you know I think as we're sort of unpacking the science of aging and Longevity which really has been neglected for way too long in medicine we're understanding that there are underlying Pathways that are in the body that are designed to repair regenerate renew

Pathways and and reverse that process so NAD seems to be really a key part of the story and uh one of the Hallmarks of Aging that I talked about in the book and it's really an important one I think probably the most important is that deregulated nutrient sensing in which there are four key Pathways that are sensing your nutrient environment mtor ampk sirtuins and Insulin signaling

Pathways and NAD works specifically on the sirtuins to to stimulates or twins when there's low energy states right so can you explain what um NAD does in the process of of helping us to regulate the sirtuins what the sirtuins do and why that's so important in longevity and aging because I think people need to understand the the science behind why everybody's talking about NAD and nmn

and NR and all these compounds that sort of have nice alphabet soup but what the hell do they do and how do they how do they work in the body on these ancient preserved Pathways that that can be activated to optimize our health well there are a number of different Pathways that are both immediate and intermediate and then long term and NAD seems to be playing

an important role in all three of them so in the most acute situation where you have an acute stress where you've lost um function or you've lost a blood flow like in a myocardial ischemia where you have a heart condition or or in a stroke where you've suddenly lost blood flow to your brains or instantaneous problems these are immediate problems and those settings NAD plays the

dominating role because it is regulating the ability of the cell to survive in an environment where oxygen has been suddenly removed so we can classify a whole bunch of conditions that are instantaneous that we have to deal with and that involves parp which we'll come back to later but there are Pathways that NAD is regulating or is a substrate for which we must have for an

acute problem so that those are the acute instant problems there are are inflammatory changes that are chronic or Subacute where NAD is actually regulating the amount of inflammation in the cell and that has a whole effect on the development of injury to our tissues cancer development a lot of a lack of healing so when we look at processes like diabetes metabolic disease liver disease and there

where there's colitis where there's chronic inflammation as we age that is also very important with NAD as we get into the longer term changes we're talking about genetic changes or regulation of genes and I think this is where you were coming at and then cartoons and parp are presently are known to regulate a lot of the different upregulated or down regulated expression of key genes so

in the case of sirtuins for example NAD is a necessary cofactor they don't function without the presence of NAD or they function a lot less they they modulate genetic transcription so they can upregulate and and depress various genetic changes which become important in aging and disease in the case of parp our own research showed and if you used to find what part is because I think

most people have never heard of that before yeah Park is a it's actually the most abundant protein in our nucleus but it is a protein that sits within the nucleus which is the center of the cell where all the genetic material is housed and there it is responsible for ensuring that the DNA is in good health so DNA is a very long long molecule and it

can be influenced or impacted by oxidants we're always exposed we're in an oxygen breathing environment and we have defenses against those oxidants but some of them slip through and when they do so they can go right into the nucleus of our cell and they can actually alter our DNA so our genes can actually be damaged after we're born by some kind of oxidant stress and they're

damaged in very different ways but one of the most important ways is called a Nick where the oxygen into the cell and it actually Cuts Like a scissors one two DNA strands we have two strands double helix but if you cut one of them it's called a single strand break and this is a very damaging effect on the cell if it accumulates can cause cancer so

we have all kinds of mechanisms in the cell to make sure that when we have damage to our genetic material it's rapidly repaired and part is the key enzyme that does that it's a key and that's mediated through NAD well when art recognizes when the enzyme is recognizing that there's a break it grabs onto that break and holds on for dear life and then it pulls

and pulls an NAD around it it makes a long chain of that NAD which helps do the repair so you which is a good thing so if because you want to keep your DNA repaired and if you have enough NAD you can affect the repair in your cells stay in good shape you're not allowing the DNA to be damaged so having any round chronically is very

good we know that animals that are deficient in park we can actually make animals now that don't have the enzyme these are genetic mites and they are much more prone to cancer so having a constant way to repair your DNA as you get older is absolutely essential and parp is the that that takes care of that so NAD is absolutely essential to having healthy part having

sirtuins operate at the right level and causing the upregulation and down regulation of various genes so that we stay balanced and as we lose NAD this balance falls apart and we start to see dysfunctional gene expression we start to see injury to various tissues which can kind of cascade as we age so NAD plays the critical role in maintaining that NAD level all the time becomes

more and more of a challenge as we get old because we're starting at a lower point yeah so NAD levels decline with age but what's really interesting about what we're saying is that is that the the body gets maybe a hundred thousand little Nicks to its DNA every day right by a Thousand Cuts but the body has its own built-in repair system like a repair truck

that goes out and this part is a key part of this repair system and the NAD is also involved in actually activating this for two ends which are part of this repair system is that fair to say I think most people don't recognize that to be in health it's not just a matter of the body doing a lot of good things to keep it so it's

the defense the body is on defense like a football team and in the case of Defending ourselves against oxidant stress and injury the body posted mechanisms and all of those are important it's like losing you know somebody in the front The Tackle or something in in a football team if you don't have a good defense you don't need a lot of offense to win to get

in trouble so the defense what are the defenses in the cell how does the cell protect itself all the time well first of all we have evolved mechanisms to take care of these oxidants directly we have antioxidant enzymes actually sitting throughout the cell around the nucleus and inside the nucleus and those are enzymes when they see an oxidant they come right in on it and they

remove it but in order for them to do that they have to have ammunition if you will to diffuse the oxidant and what is that ammunition it's a special molecule called glutathione to neutralize and take out this oxidant stress so glutathione it's the weapon they're using well where does glutathione come from it comes from a process in the cell which is completely dependent on NAD so

if you have NAD in the cell cannot produce glutathione and these enzymes they may be there but they can't work so NAD is applicable to protecting ourselves from the oxidants the very oxygens themselves okay so we have antioxidants that's the first line of defense it's immediate very fast very effective most of the time now so that's the fasting that NAD actually boosts the enzymes in the

cell that actually can make glutathione right every cell in the body has to make glutathione or it perishes and within the cell there is a special um donor electron donor called nadph which builds the glutathione and this molecule nadph is absolutely essential to us and it comes from NAD so without it being around we cannot defend ourselves from immediate threats in the oxidative sphere beyond that

if one of these oxidants slips through the line it's you know running towards the quarterback okay so the front line failed there has to be all right defense right something there to protect that quarterback uh and in that case uh the next line of defense would be this repair mechanism so the injuries happen the quarterback got hit but he has to get back up again fast

and keep working the cell has mechanisms built within it to repair the damage that's occurred and parp would be a classic example of that so NAD is at every stage it's the initial stage on the front line preventing the rusher coming in and then it's back farther if there's injury that's happened it's there to heal when NAD levels fall none of these things are there and

the whole cell starts to run into trouble and eventually if it spirals out of control and it cannot recover that's when the cell dies or perishes for example if you a classic example someone has a chest pain and they find out they're having a heart attack so they're not getting enough blood flow into their heart the muscle of the heart is suffering it's ischemic so that

is an immediate threat to the viability of the heart itself right there's all these oxidants flooding in right now so glutathione is right there NAD is doing everything it can to care but if the energy levels are not sufficient the glutathione levels fall and now the injury goes one step further right to the DNA you get the kicks then parp is activated NAD rushes in tries

to help there well all of these things are good and they can keep you from having a full-blown heart attack but if at any point the energy levels go too low that's it and at that point the ATP cannot be produced the glutathione is not made and you have cell death that is an infarction where the the tissue is actually dyed it's necrotic and it won't

recover and this is this is the most severe situation so so NAD is playing a role at every level trying to protect us from that chronic stress and then acute stress is like stroke and heart attack yeah I mean what you point out it's so important because so many of the disease of Aging like heart disease cancer diabetes dementia those are just way Downstream from all

these mechanisms that go wrong that we can influence and that's what scientists are talking about if we address the underlying root causes of Aging Hallmarks of Aging which NAD in part does a lot of we can actually do a huge job in preventing and even reversing some of these diseases and that's what's so exciting to me I think we like are reaching a turning point in

healthcare and Medicine where we're understanding the root causes what's really interesting I sort of want to unpack this a little bit because you you basically said that we need NAD which helps us create energy in the cell but also is involved in regulating antioxidant status it's involved in DNA repair and our epigenetic programming but it also has all these cross-purpose actions when you activate sirtuins which

NAD does it's the main one of the main actions of NAD is to activate the family of sirtuins these signaling proteins they they work on many of the other Pathways that relate to aging like for example mtor which is regulating your protein synthesis and inhibiting and regulating autophagy so it helps inhibiting mtor and help stimulate the self-cleaning and repair recycling called autophagy it reduces inflammation by

like inhibiting a big transcription factor that turns on all the cytokines in your cells called NF Kappa B it activates foxo which is another regulator of antioxidants in your cells it helps to reduce oxidative stress by the mechanisms you mentioned of increasing glutathione but it also activates another family of transcription factors called foxo which increases antioxidant enzymes that are built into our system it can help

reduce cancer by activating the tumor suppressor Gene called p53 it helps your mitochondria make pneumonochondria and improves the efficiency it helps improve insulin sensitivity and activates ampk it regulates our circadian rhythms and cogs so it's such a multifunctional substance you think you take a drug for one pathway I'm taking a cholesterol drug for lowering my cholesterol blood pressure drug prolong my blood pressure but the beauty

of these natural compounds that are that are our body's own medicines is that they work across the board on all these different Pathways and there are many redundancies in the system so that it's not the only thing that regulates these Pathways but that's why he makes NAB so powerful what's what are your thoughts on on how all these things connect and how NAD has multiple functions

I think 30 or 40 years ago when I was in medical school we went from class to class and we learned about different diseases yeah me too we had a rheumatoid class we had stroke class and we were told that there are these diseases that people just get right I mean suddenly a Parkinson's disease or suddenly you know suddenly of diabetes and so we would study

Jesus and this is sort of how the Specialties develop right but but I think it's come full circle because what we really understand is that it is there's really one fundamental disease which is called Aging and then these other medications which we see which we call diseases well I have Parkinson's disease but no you don't what you really have is the sequential accumulated process of Aging

that has dysfunction across multiple Pathways connect to each other and then we suddenly have what we oh you know we're 65 and now we we have diabetes where did that come from but it's not just like a hit or miss thing it is a sequential process and as you get older and as this aging process inevitably drives forward all of these mechanisms are at risk and

eventually one of them or more of them you know becomes a disease that we can categorize and call a disease but really uh it's a it's a generalized process and NAD is at the epicenter of all process so one different way to think about disease management uh I mean yes we need diabetologists we need all these good people who do all these good things but fundamentally

we need to slow and arrest or reverse this overriding inexorable aging process that is starting to degrade all of these different Pathways together and so the search is on now for more broad spectrum or more fundamental approaches than just disease specific ones and as NAD story what better candidate could there be than something that underlies energetics pain inflammation immune DNA repair tissue repair signaling and all

of the I mean this is a fundamental currency right prevention yeah insulin sensitivity all that right right I mean like we have currently like we carry a dollar bill in our pocket we can buy many many things but they all go back you better have that dollar bill so NAD is a fundamental driver of all of these processes and you just mentioned many mechanisms but there

are many others that we don't even know about yet I mean uh over in our research we're looking at new pain Pathways that are related to NAD we didn't even know about this until recently it was all story of pain related problems that have to do with NAD deficiency recently there's been a whole lot of research on prostaglandins and inflammation from NAD deficiency we didn't know

that so all these separate things that we talked about that we see in our patients they're starting to come together to a final comment or final initiating pathway and we better understand that pathway and and learn how to to manipulate it how to help it how to restore it and that's where my interest is in well I I tell you I barely able to sit in

my chair right now and not jump up and down and scream hello hooray hey finally somebody's getting it because I've been singing this dude for a long time and when you start to look at systems biology and network medicine what we call functional medicine it speaks exactly what you're talking about the diseases are just leaves on the trees we need to go to the roots and

the and the and the trunk of what's really going on with their biology and it has to do with exactly this thing that you're talking about which is this regulated function that accumulates over age that we can actually intervene with and create health and then all these diseases out there would prevent them or they go away or get reversed so that's that's what's so beautiful about

our kind of understanding of longevity science now it's sort of peeling back the layers and people are going wait a minute aging is a disease these are process we can treat there's a way to think about this differently the diseases aren't all these separate things they're all connected by these common roots and and it has to do with everything you're talking about and so when you

look at nav you know the mechanism of action it does so many different things from DNA repair to the activations or two ends to increasing energy production the cell to lengthening our telomeres which shorten to making new brain cells and making you bring connections reducing inflammation boosting uh mitochondrial function improving insulin existence and exercise performance it's really quite remarkable I remember David told me about like

a study where they had a mouse treadmill that only goes to like I don't know one or two kilometers and they never and they never saw anybody like Mouse go longer than that and then when they gave them nmn the thing just kind of broke the treadmill because it was like went three kilometers or something the secret now or the the trick now that once we've

recognized this is how do we get NAD levels back up how do we preserve them how do we preserve people who are reasonably healthy and give them Optimal Performance and how do we help people who have low NAD who are in trouble and get them back to a reasonable level so to do that requires like any medicine it means giving something to somebody that they're missing

so there's several ways that initially people started giving ad it made sense you have low NAD give the person any the problem with that is that NAD is is a chemical or a molecule that's made inside cells and it's so valuable and so important to the cell itself that they sell is very clever and it embeds within NAD it changes the molecule in such a way

that it can't leak out precious and so NAD has been designed to stay inside the cell and if you give a person NAD it it won't fall out of the cell once it's there but the big problem is it won't get into the cell so it is out of NAD that's great it's all floating around doing all this stuff but in order for it to work

it needs to be inside the cell now getting NAD into a cell is no mean feed because you've got a problem there it's it's it's it's designed not to cross cell membranes so what do you do so you see all these Health Products out there you know take NAD take this pill it's got a lot of NAD but the problem is yes you can get into

the body if you can't get it where it needs to go which is inside interesting but created the interest in other ways to boost NAD so what people did is they said well where does NAD come from naturally yeah how does the body make NAD well it turns out that there are two steps along the way first there's something called nmn and then there's something they

called NR and then there's something called NAD and so they thought well if we give the molecule before you get NAD that can cross the cell membrane more successfully it can cross the gut when you swallow it there all of these good things that could happen maybe if you took a precursor an earlier step so you'll see all these products now that have something called NR

right so nicotinine right now their studies and cell studies in human studies looking at NR and it seems to do good things first of all it gets in a little bit better than NAD but more importantly and significantly you can see the NAD levels go up in the cell when you take NR so that was a good thing and then people went out to the ultimate

step which was to give nmn and they asked is this a good way to deliver NAD will this will this do it first of all when you swallow a pill with nmn it crosses into the body a lot better than NAD and NRP and that's because the body has created a special shuttle in the cell that recognizes nmn when it's outside and provides a lovely tunnel

if you will for it to right through the membrane and end up on the inside of the cell so the body has neared away for nmn to get in there and of course once it's in the cell that's great because then it can be sliced up in form NAD and all is good and that's been shown so we now believe that the most efficient way to

deliver NAD is actually not NAD itself but it's in the form of nmn and that's why our Focus has been to use the nmn to make these necessary changes to boost NAD interesting now just to kind of loop back for a minute before we want to get into the delivery forums and what does and so forth is is do you know why NAD levels decrease as

we age is is this inevitable is there a way to prevent it can we naturally increase them is there any understanding about how that may work uh no there really isn't a lot understood on that okay good because I thought I missed it but I thought maybe you knew because you're the expert I'm like let's just go let's talk about where it's actually made the first

part is when you take sugar and again glucose is a good example and that is broken down by glycolysis and there you get that's spun out the next part is a cycle called the Krebs cycle and in that you take what comes out of glycolysis and you wizard around it with all these different enzymes and you make more NAD and then the last step is where

it enters the mitochondria which is the PowerHouse of the cell the ATP unit if you will of the cell mitochondria the NAD is grabbed a hold of and it is used to fuel the production of ATP which is the ultimate thing which comes out of the uh mitochondria so those are the three different things if I had to guesstimate where the deficit lies it's almost surely

in the last one so we don't think that as you age you lose glycolysis and you lose the Krebs cycle we think the mitochondria are really the point where with aging we start to see this degradation it's not just first of all it's in the number of mitochondria let's take a professional basketball player and they run up and down the court for 60 minutes they're not

even sweating okay how how on Earth would that be if you take the muscle out of Someone Like You know Michael Jordan you will be astonished what you see under microscope it's not normal at all the Wonder the number of mitochondria music can jump over the rim now to imagine the amount of mitochondria in that self so when he takes a quiet breath he's producing so

much more energy than I could ever even imagine that's why you can run up and down the court for 60 minutes because he's just loaded with these mitochondria bulging out everywhere in in the in the muscle cell then take the same guy and he's now 75 and he's still working out still doing his thing if you look at the number of mitochondria in his cell at

that age it's fewer now why is that well in the last five years we've learned a lot about what controls the number of mitochondria in your cell there's actually a pathway that tells us tells the body how to make or when to make or how many to make of these mitochondria so we now know that one of the stimuli for example is low oxygen tension so

if you were to exercise you're using up your oxygen very quickly and the muscle is in a state where it doesn't have enough it's hungry and that is as a powerful stimulus to make new mitochondria that's why a guy who's 75 who works out every day he will actually create new mitochondria whereas someone who's a couch potato he has no stimulus and so you won't see

those mitochondria being formed so the aging process diminishes our mitochondria and that's probably can't say for sure but this is probably the prime reason that NAD levels fall with agents yeah that makes sense yeah that's interesting you know you look at some therapies that are used for longevity for example uh they're like hypoxia therapies uh and and so when you look at millica bomba and Ecuador

they live a long time because they live at 17 000 feet maybe it's because of that or maybe you know when you use this technology called the cell gym which essentially takes you up to Mount Everest and then back down it makes you hypoxic it activates your mitochondrial production or when you use these hypoxium acid extra athletes do or when they go to the altitude to

go train for running a marathon they'll run it you know seven thousand feet where they're going to run in a thousand during the race because it actually helps them build more mitochondria so it's really all about little tricks and building muscle through strength training through the right amount of protein through actually using some of these compounds like nmn can actually help to maintain and actually activate

mitochondrial biogenesis making new ones and my energetics which is the efficiency through which we make energy in our cells right is that is that fair to say I think there's so many um serious athletes who who exercised an elevated altitude for that reason and it provides them well I mean you get the same thing I suppose if you're doing a lot of activity even at sea

level but being at an elevated altitude forces you into this domain where you're already stressing your your system with hypoxia and athletes who trained in elevated altitude and then come down are in far better shape right so they have a lot more uh loading of mitochondrial we call it mitochondrial biogenesis and that's just we now know how the hypoxia is actually influencing the creation of new

mitochondria we know the molecular pathway we know the molecules involved and those they haven't yet but those will become drug targets hypoxia factor and things like that hypothesis production factor hif is it responds to low oxygen environment but what would happen if you had a drug that could turn that on I wonder I wonder if that's how blood restriction uh Exercise Works is it's called Blood

Flow Restriction where you put let's say a blood pressure cuff equivalent on your arms or legs and then you weight train at much lower levels but you get far more exhaustion sooner and actually increases muscle synthesis better than regular strength training which is really interesting sure yeah it's the same mechanism and I think that we can do that through being active by exercising uh and ultimately

I think there will be nutrients that stimulate mitochondrial biogenesis there should be research going on both in the pharmaceutical space but also in the Natural Health Food space yeah for sure things that we can eat on our own or drugs that we can take perhaps but but we can change our lifestyle through the through what we eat if we can identify uh diets that potentiate hif

and other factors in the turn on mitochondria and I think that's a wonderful area of research yeah amazing so we're gonna we're gonna go into the forms of mitochondrial support with nmn and R NAD talk about the differences uh but before I do I want to talk about a few other topics related to NAB which has to do with um sleep it seems like this is

a benefit to sleep as well which I think I've never heard about and there's a new study that came out basically found that people who were part of this study and took anime and had better sleep duration better deep sleep better REM sleep um and and report a federal overall Improvement and Sleep Quality can you kind of comment on how that how that would work it's

just I don't understand the mechanism well I think there are two aspects there first of all there's the control of sleep we know that sleep deficiency leads to a loss of energetics loss of focus a loss of Peak Performance so some of that has to do of course with the brain in terms of it going through the processes that it needs to but also we know

that sleep is a systemic phenomenon and it allows muscles really all of our tissues to recover during the day so nmn and this is an early area of research but if nmn can potentiate better sleep that's going to translate in a better systemic response uh you're more rested and you had a better chance to recover so there's that effect at the central level with nmn on

the Sleep process and some of that may have to do with regulation of Sleep Centers we know for example that sleep is highly regulated by metabolites that have to do with energy the main Drive of sleep is adenosine and adenosine is accumulating during the day as we yeah and we're thinking and we're doing all of these things little by little we're breaking down ATP because the

brain uses ATP in a way that no other organ does the brain is consuming a vast quantity of ATP way out of proportion to everything including our muscles the brain is a an ATP consumer huge amount of I think that's 25 percent of the energy in your body is is in your brain so so that a prime area where you can't keep up and you can't

by the end of the day by nine o'clock or ten o'clock at night it is well documented that you have not been able to regenerate all of the ATP you've used there's always a continuous deficit from the moment you wake up you are not keeping up maybe 9 or 10 or 11 o'clock at night you have waste enough ATP that you cannot regenerate that the end

product that which is the um adenosine the final breakdown product has accumulated and adenosine is what causes drowsiness and ultimately sleep I mean ultimately so does NAB improve and adenosine production is that what you're saying so you you the NAD is responsible for taking the adenosine that's forming during the day and driving it back and and getting rid of it and keeping it Low by pushing

it back to ATP is used to make ATP so when you have ATP it breaks down to ADP and then to amp and then the amp broken down to adenosine oh we're gonna say oh gosh I just I can't believe I just got that identity monophosphate I didn't see triphosity yeah that's ATP amp okay adenosine right of course yeah I've never put that together if you

looked at the brain at six in the morning what is there it's ATP everything's fine you wake up you feel good you can conquer the world by four or five in the afternoon you've already got adenosine there some people even take naps as they get older but time it's 10 or 11 o'clock at night your your ATP levels are low and your identity levels are super

high and adenosine directly influences the it's a part of the brain and the midbrain uh which uh controls your arousal how awake you are and the adenosine directly causes you to feel sleepy when you're driving down the road in the morning and you can hardly keep awake your brain is flooded with adenosine very dangerous to drive and so what you need is to do one of

two things either get rid of the adenosine which is called sleep it's the best way to do that or you can take a drug which blocks the adenosine from binding to its receptor so even though you're swimming in the denosene you can block the adenosine from activating the denosene receptor and I would say that 99 of the American public does this every day because it's called

coffee coffee coffee so some people even have a problem in the morning and get going to work you know they get up and they drink two cups of coffee and it's really unnecessary frankly because you don't have much adenosine at six in the morning if you good night's sleep that is now if you haven't had a good night's sleep you haven't had time to remove all

the adenosine and you need your coffee at six in the morning to block it the better thing to do is to get some good sleep but if you want to stay awake and alert and bright-eyed and bushy-tailed people drink coffee it's a natural adenosine blocker so so that is the whole adenosine story now NAD is there in the brain to take adenosine one of the and

turn it back to ATP so if we had the fish and NAD around we would be able to go through the day with a whole lot more energy and a lack of sleep and then when we do sleep it improves the quality of our sleep yes because it's helping us to get rid of the adenosine sleep is a it's about many things fundamentally we've got to

get rid of the adenosine that accumulates during our day that's our job interesting all right so um okay next question has to do with a research paper that came out in mice that got a lot of play which basically got everybody in a kerfuffle which is that nmn NAD causes cancer can you speak to that study the challenges with it what's true because you you are

an expert in cancer a lot of your research has been on cancer you know this stuff inside out so can you unpack this for us and help us either understand why there's a problem or why there's not a problem well look it's one lab that's very focused on this is God bless them but they're doing the Lord's work looking at this but still it's one lab

and it hasn't it hasn't disseminated to other labs which have shown this oh okay let's take this guy and give him all the credit in the world that he's doing good job but so let's let's walk through those okay if you give nmn in cells that you you have the potential to actually stimulate uh tumorogenesis well what he later shows and and it wasn't discussed initially

but is that it's not the NAD levels that are are causing the it's not the element that's causing the cancer per se it's that he created artificially a very unusual metabolic scenario he dumped a bucket of enemy into the cells and there was uh so much anime that it overwhelmed the NAD so you had a ratio of Adam and very very high and NAD was normal

but the ratio was it was crazy crazily in favor of nmn and that can't happen and he later Studies have shown that if you have very low NAD and very high nmn yes that has the particular causing tumor agenesis but can that really happen no because if you ingest nmn it doesn't hang around and mind its own business it's converted to NAD that's what happens to

nmn it's not just uh you know saying hello I'm here it is rapidly transformed because it's a precursor into NAD so you don't get this one abnormal ratio of NM high nmn low NAD it's not going to happen in nature now maybe he speculated there could be people with a genetic defect where they can't convert nmn to NAD I don't know I mean in theory yes

you could have someone with this condition but I haven't seen it identified yet so under normal conditions where animals converted to NAD I don't think that scenario can ever play out it was an interesting lab trick if you will it's good to learn new things knowledge is power but yeah so what you're saying basically is he created conditions that would never happen in the living organism

in the test tube that actually could never be replicated it might potentially cause cancer so in a mouse so we kind of we're so far away from this being actually a viable scenario for humans that you don't think it's not right now now I think we should continue to all do research and that's a good thing I'm in favor of research I'll vote for that not

worrying right now about that no um now what was really also interesting on the positive side was it was a really interesting clinical trial on nmn it was in humans because we've done a lot of research in animals and David Sinclair and those guys Lenny guarante did a lot of work on sirtuins and Founders spiritual I could extend the life by a third of rodents by

taking this compound that stimulates your two ends was when NAD does but it uh but it turns out that uh humans are important to study too so I needed something not just yeast and mice and so forth and there was a clinical trial and a man that I thought was pretty impressive that I I thought would be talking about the safety the efficacy and what it

did in people who were middle aged was a double uh blind randomized multi-center placebo-controlled those dependent clinical trial which is the highest level of research you can do and and can you tell us about that study what it showed what take homes were and and I thought it was pretty impressive actually well what they're looking at there is basically the energy capacity of people and in

particular the ability to walk to go distances and they were able to show that there was a longer a capacity to to be functional so you were you had more energy and they looked at energy balance and they looked at insulin sensitivity and other things and all of these things seem to line up to tell a story that it was working so although it's a small

study I mean it's not a giant study and we know sure 80 people right that's right yeah it wasn't 80 or 800 people and it was a small number and therefore the differences that are identified you can question statistically about if they're there to really write home about but I think you know being in the right direction is positive there have been a number of small

studies like this and um there was the six minute walk tests has been looked at and and and people can walk further which is a holistic way of looking at the energy those are all positive but I would caution the audience that all of these studies are still somewhat small and I I don't think we're there yet where we can conclusively say that nmn is going

to be has been proven to engender um more energy in in animals yes it would appear in humans we also have evidence in uh cardiac function uh in humans that the cardiac function is better particularly in congestive heart failure so there have been some studies but as I say they're they're early and we shouldn't jump to conclusion that's being proven I think the pace of research

will definitely increase and the quality of research one of the problems with and NAD in terms of research is that it has not been yet driven into the classic pharmaceutical space and these are very expensive especially if they're and right now the motivation to carry out large randomized double-blinded placebo-controlled trial which can cost millions of dollars definitely and it hasn't been there yet because the pharmacy

the pharmaceutical companies don't own and I met so when you invest five ten fifty million dollars in a study you better believe or you must believe that you've got something that you own so that at the end of that your your evidence your data leads to financial outcome which means you can sell it exclusively that won't happen although there's one company in the US that's trying

exactly to do that to patent its exclusivity yeah I saw that so but this is the reason that NAD and NR and nmn have not enjoyed the large scale studies that you would need in order to exclusively um and it's a problem with all natural uh products if anyone it was a promising study because I thought that you know they reverse biological age they improved six

minute walking they helped improve we'll call sf-36 or to subjective quality of life and these were people who were taking a I didn't know they were taking a placebo or the compound so it was it was really well at the time but I think you're right it was a small study we need to know how to get more data spent a lot of time in my

life at the FDA you know we have all these fancy tests that people do and the audience may be that but at the end of the day and yeah it's fascinating you know the I was sitting there at the FDA and I was telling them all about these biochemical advantages of this and that and the guy looks at me and says I just have just a

simple question can Mrs Jones carry a bag of groceries up the stairs better or not that's it because if she can't all of this and the six minute walk is is a test where they they take a person and they're on a trend and they say walk and and walk as much as you can for for six minutes so we're gonna keep track of how far

you went so if you could walk 200 feet in six minutes you're hurting but if you can you know like a mile this means your your health is great right because everything is integrated your your cardiac function your respiratory function your metabolic status your NAD well that would be a that would be a run a six minute mile would be a run able to do that

when I was very young but but that's the point that six minute walk is really critical understanding the overall promise of a drug like NAD or nmn that can create and boost up the um the intracellular NAD levels and that's why in that study of all the things that I was impressed with more than the others was the fact that was the Walk You Can't Hide

You Can't fake it it's great well now let's talk about the practical application because you know there are people who recommend NR and there's companies that produce NR there's companies that are making nmn uh you can get nads of lingually like if your liposomal forms you can get subcutaneous NAD intravenous and maybe um and I'd like to sort of have you sort of take us through

you know what's the pros and cons of each because you know one of the things I want to bring up was was triggered by what you said earlier is that NAD given as a compound can't get in the cells very well uh and I had one experience with a patient I read this in other studies who had Parkinson's and we gave her ivnab and her Tremor

went away not permanently but uh for the short time she had more energy if she perked up was able to walk better I was like holy cow this is impressive but that would lead me to think that actually giving intravenous NAD can get it in the cell so can you talk about sort of these different forms and the pros and cons and whether I'm just making

this up about this woman or if there's actually something to that black and white I don't want to say that giving NAD cannot enter cells period that's that's not correct but it is impeded it's not efficiently taken up now having said that there are hundreds of different cell types and it might be that certain cells have such a quenching thirst for NAD that maybe they've evolved

shuttle mechanisms for NAD you're talking about Parkinson's disease and that's a disease which ultimately is regulated by a very tiny but very important tissue mitochondria and who knows maybe those cells in in the basal ganglia have a better ability to suck in NAD than other cells so I don't know that's never been studied but it is a mitochondrial disease Parkinson's is a mitochondrial disease that's that's

why I think it may be effective well Parkinson's it's a mitochondrial disease and it's also probably a disease in which the oxidant stress within certain select cells these basal ganglial cells it has has been um increased and why it's been increased you know as anybody's guess the most recent research Parkinson's that I've is really implicating Tangles and and and and um uh we call it precipitates

proteins from misfolding very analogous to alzheimer's which is some new work that's come out with Alpha synuclein and and it and it's thought that these aggregates might impact the amount or way that oxidants are developed in cells the whole cell starts to become a factory of oxidants and then injures itself there are also Parkinson's patients who have fundamental deficits in uh in in handling oxidants and

so to get NAD into the cells of a Parkinson's patient might be you know it might be a very interesting way to look at that we know that the model Parkinson's disease that are used today the most important one being the rotanone model which is from Emory Universe Georgia that is created by actually blocking the first uh protein the first enzyme in the mitochondria mitochondria in

the transport chain so definitely Parkinson's is somehow related as an example of of of NAD failure because the cells are not generating it's there's a deficit in the mitochondria and uh what your observation if it's correct suggests that maybe in that particular disease NAD might be good but the advantages of nmn are that there it is known at least in the intestine that there is a

specific huddle or the shuttle is a protein that's present in the membrane of the intestinal cells and it literally carries the molecule from the outside to the inside of the cell in a way that not happen so if it weren't for that the element could not the the NAD or any are element without that shuttle they can't yeah can't get in can't get it okay just

like a smooth pathway that that helps it across so that's a reason from an oral perspective to suggest that nmn might be good and those shuttles are present within the body as well it's not just on the intestine yeah but it's hard to get NAD because you have to take it intravenously or subcutaneously and the beautiful thing about nmn and R is that you can take

them as supplements so so what's energy NR and nmn and why should we be more focused on nmn which seems to be winning out the the horse race the shuttle is specific for nmn so even though NR is closer to NAD and it's easier to get into the cell it doesn't have the advantage of a built-in shuttle that God designed to move uh that uh material

from the outside to the inside nmn is first of all animal is a natural molecule by the way it's not just something we make nmn and so this shuttle is there for a reason it's to facilitate entry and we're just leveraging that when we give it therapeutically but that shuttle is is a fundamental issue it changes the whole question about how do you get the stuff

into the cells that heretofore will be just you know NAD just doesn't cut it now I do research with NAD and NR because there may be certain cells that function differently that we haven't examined so we should continue that and if you look at the literature there's far more studies of NAD than nmn by by many full so that was what began and um it made

sense they they knew NAD is important let's give it and see what happens but I think the the tide has changed and you'll see a lot more loading studies now where nmn loads the cell with NAD and that's that's going to be uh there'll be a bevy of studies like that clinical animal and even cellular you start to see a lot of them so you're saying

that the NR doesn't have the same shuttle to get the medicine or the supplement or the ingredient into the cell and a man which has a specifically designed to travel yes right yes okay well I want to talk about specifics and dosing and how we take it there's a product called uh Wonder feel younger nmn or younger nmn which includes not just gentlemen but a bunch

of other stuff so I'd love to talk about that product I know you're involved with the company I've been talking to them as well advising them tell me um you know why you think this is unique and different and what's important to know about it we begin with the premise that nmn is important nmn by itself is probably not the whole story because there are mechanisms

within the cell that are very active as you age that you have disease and these are going to interfere with the benefits of NAD talked about that already oxidant stress being the most important so when you add nmn to a cell and you get NAD in there it's good it's going to increase the glutathione levels it's going to mend all of the mechanisms the defense I

talked about but you have a lot of offense particularly as you get older a lot going on in this a lot of injury a lot of oxygen stress to ourselves well let's build a front line a defensive line that's more than just one guy let's build a whole defensive line and with with backups so that it's a team effort to suppress the damage of the Aging

cell so we were not castigating or denigrating enemn in any way it is the basis as I said it's the basis we're starting with but we have supplemented that now with additional team players Each of which has their unique role and together as a team in working in concert with each other we think we'll have a much more effective result so we chose supplements to fill

in the gaps if you will to make that front line that defensive line the first one was ergothionine again natural molecule as something that we ingest in our in in our foodstuffs and and that has very powerful and quite specialized uh antioxidant features that have effects on inflammation and on Cell Survival on Antioch and specifically and and so we we put it and it's very well

tolerated I mean another principle that in this concoction was Do no harm so we did not want create a model system where we had some good things in there but carrying some toxicity risk we wanted this to be very very safe based on natural products and that's something that could you know rear its ugly head with some toxicity we hadn't thought about Erica finding ergon findings

like an oyster mushrooms and black beans and liver and stuff right so it's found naturally in plants and animals we don't produce it you you don't make everything you you obtain that from your environment by eating various foodstuffs so that's a good thing almost like a longevity vitamin basically right yes and there are companies out there that are marketing uh not many but they're they're marketing

Ergo sign is a standalone and it makes sense that it would have benefit and that it could help with aging and help diminish a lot of the oxidant stress that you know we're we're prayed to then we added Resveratrol which is a polyphenol it's a simple molecule actually it's present in grapes present in red wine for example well known and it is also sold on the

market you'll see lots of instances where people are out there uh advocating the use of Resveratrol alone it's a weak relatively weak antioxidant it's not anywhere near as potent as the natural antioxidant mechanisms we have within the cell but it is adjunctive and is helpful not to stay I wouldn't recommend it much as a standalone because it's not that potent but in concert there's it has

specific types of antioxidant defense particularly in the cell membrane and lipids and various places in the cell and people who drink red wine a lot you have to drink a lot of the French for example are very enamored with red wine and in the fact that they're eating pastries and they have a lot of things that they shouldn't be eating so much if their cardiac consequences

are less than you would predict and one of the hypothesis that they're also drinking every meal with the big glasses plural maybe two but I wouldn't recommend drinking alcohol as a health the health strategy that's what the Frets are doing you know so they're they're drinking a lot of red wine so that's Resveratrol a very interesting molecule easy to purify and to add to the supplements

and moderately effective and then the last one I think is the most interesting one which is hydroxy tyrosol and this uh this came to me because you know I'm living in Israel right now and we're not too far from Greece and we have in climate here and uh everywhere in Israel and in Greece which is covered cupboard covered with uh with olive trees everywhere you look

that the Greek population that indulges in uh using uh special types of olive oil which I'll come back to has a lower incidence of a host of different diseases including Alzheimer's disease yeah and so there's quite a lot of research in Athens especially by some friends of mine they're uh some professors at the University of Athens and they've identified the elements within the olive that are

most effective in creating this antioxidant and anti-inflammatory effect and there are different molecules but most of these are polyphenols and the most important one is this um this olipurine and yeah polar opinion yeah and when you take people who are using a lot of olives in their diet uh they tend to have the benefits from that and what we now know uh we know a couple

things from this man's research there all olive trees are the same which I didn't know so every Orchard of Olives is actually quite difficult thousands no they're not the same studied and when you when you do analysis in the Olive from a cultivar to cultivar Orchard to Orchard there are vast differences second thing uh and so his research has identified uh orchards in Greece that are

incredibly uh High have incredibly high levels of these particular polyphenols second thing is that how you treat the olive has a dramatic effect on the survivability like an American Factory that's processing millions of Olives every day and all of that and olive oil you go to stop and shop and you buy olive oil unfortunately the processes used there to get there have decimated the very most

important molecules the these these uh polyphenols that it's oxidized them and they're not active so in order to receive this benefit you have to treat uh you have to use virgin olive oil and and from these special Orchards and on and on and off now most people can't find that olive oil in the store but we know that the hydroxy tyrosol is very special in uh

creating this effect so what we've done is take pure hydroxy tyrosol not olive oil but the part of the olive oil that we care about and that is what we've added together with the Resveratrol ergothionine and the nmn yeah actually I'm in Sardinia right now where I'm teaching a longevity Retreat and uh there's olive trees everywhere and uh it's interesting they have like uh Wild Olive

sometimes they actually hand pick them and they'll drop the ground they press them right away they make sure that the and I wouldn't it's all about tasting and you can hear it you can taste the different qualities of olive oil and when you you can actually taste that that kind of polyphenol content because it's a little bit of acidic and bitter in the back of your

tongue so you're uh you're absolutely right these are powerful molecules and olives and olive oil and I think that combination is great um so I think I think um any last thoughts so we're we're looking now uh in models where we explore these combinations to better tease out how the juxtaposition of these different players has an effect on these outcome endpoints and to try to understand

how they're interacting with each other and supporting each other but it's definitely a team effort approach that was the concept biologically to bring a team an offensive offensive line yeah or defensive lineman and then to put them together in the right fashion well it's like olive oil red wine and mushrooms and you can kind of add that within a man and you get you've got this

product it's a younger anime which I love um and what's interesting about this product also is the dose is high a lot of the doses of mm and are out there are low they're like 250 or if you take two it's 500 but actually clinically it seems like the dose needs to be much more like 900 or a thousand to get the most benefit right and

this is actually done at a lower cost I'm sort of surprised a lot of these products are really expensive but this is actually a reasonable cost for that higher dose well there are reasons for the dose selection the two reasons first let me Begin by saying always Do no harm right so that's the place you begin at where you do not want to use a dose

of a material that has the potential to harm but the safety profile has been so uh unremarkable with anime to date from people's experience and animals although there haven't been large formal toxicology studies but the data out there suggests that this is a well tolerated ingredient so therefore it makes sense to use more of it if there's why would there be a benefit because we know

that certain Pathways particularly on inflammation are very tightly related to the amount of NAD that will be there so a small amount of NAD doesn't cut it the the specific there's a very special pathway in the cell regulating inflammation this is a pathway it's a fancy name called NF Kappa B but it's basically a pathway in there which turns on all our inflammatory genes at once

like a symphony yeah that's what I was talking about the direct conductor lifting the Baton and the whole Orchestra plays it once and so that's NF capital B that's the that the Symphony conductor and when you turn that on you get what's known as a cytokine release and an extreme example you get cytokine storm and we now all know that word because of the last few

years with covid that's why covid patients die because this pathway is turned on incredibly all at once and you get this massive release of problem and a man suppresses and I'm sorry NAD suppresses that pathway specifically so but you have to give enough of it to get there so we specifically gave a high dose of nmn so we could suppress that pathway and so that we

could be sure that the mitochondria was enjoying a full benefit so there was a very careful decision about elevating the amount of nmn to do that if you love that last video You're Gonna Love the next one check it out here and based on these really robust data of tens of thousands of people 90 plus percent of Americans probably 99 Americans aren't efficient in something and

and and the major deficiency is about 90 percent are deficient or more in