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NAD: The Key to Aging Gracefully - Episode 304 · Gladden Longevity Podcast

• 0:00
  So NAD actually acts like a fuel to drive many of the repair processes in our cells.
• 0:06
  we've got an army of DNA repair enzymes and we've got an army of proteins called sirtuins that are monitoring cellular health and switching on things that are protective.
• 0:18
  all of these functions in our cell require NAD as a fuel to actually drive this repair.
• 0:24
  And this is a really fundamental point that is very misunderstood within the industry is that we cannot get NAD from our diet.
• 0:35
  Our cells actually have a pathway in it that makes and recycles all the NAD that we need.
• 0:41
  And this is called the salvage pathway.
• 0:43
  NAD is not naturally found at high levels in the blood.
• 0:46
  NAD needs to be inside of the cells because that is where all of the pathways that it interacts with are found.
• 0:54
  So yes, an NAD IV will get NAD into the body.
• 0:58
  but it's not putting it into the right place.
• 1:00
  It's putting it into the blood.
• 1:02
  And because NAD is a very large and charged molecule, it does not easily diffuse into our cells.
• 1:38
  Welcome everybody to the Gladden Longevity Podcast.
• 1:41
  I'm your host, Dr.
• 1:42
  Jeffrey Gladden.
• 1:43
  And today we are tackling the big questions in life.
• 1:48
  How good can we be?
• 1:49
  How do we make 100 a new 30?
• 1:51
  How do we live well beyond 120?
• 1:53
  How do we live young for a lifetime and how do we develop a 300 year old mind?
• 1:58
  And right at the center of those questions are the hallmarks of aging, which are basically biological processes that
• 2:06
  accelerate aging as they play with each other.
• 2:08
  And today I'm going to be talking with Dr.
• 2:12
  Nichola Conlon.
• 2:14
  We've spoken with her before on the podcast.
• 2:16
  She uh has a PhD in biochemistry and is the developer of a product called Nuchido Time.
• 2:25
  That's N-U-C-H-I-D-O, Nuchido Time.
• 2:29
  We'll talk a little bit about the origin of that name, but it's a
• 2:32
  a very comprehensive integrated product to boost NAD levels.
• 2:36
  And I think you're going to find this conversation really fascinating.
• 2:40
  We talk about NAD, its central role in the hallmarks of aging and anti-aging.
• 2:45
  We talk about why it declines, how it declines, how to actually build it.
• 2:49
  We talk about IV NAD, what that may be good for and what it's not particularly good for.
• 2:55
  ways that it might actually be harmful.
• 2:57
  We'll talk about other products, precursors, et cetera.
• 3:00
  It's a really good scientific comprehensive conversation around NAD and the ways to optimize it.
• 3:07
  think you're really going to enjoy this podcast.
• 3:10
  Welcome everybody to the Gladden on Jeopardy podcast.
• 3:12
  I'm your host, Dr.
• 3:13
  Jeffrey Gladden.
• 3:14
  And today I'm being joined by Dr.
• 3:16
  Nichola Conlon.
• 3:19
  it's two o'clock in the afternoon here in Dallas and it's 8 PM for her in London or someplace in England.
• 3:25
  I don't know where you are.
• 3:26
  Maybe you're, I don't know where you are in England, but you're someplace Newcastle Okay.
• 3:31
  the furthest north you can get basically in England so opposite end to London.
• 3:37
  Okay.
• 3:37
  Well, I remember back in, I don't know, medical school days, there was a Newcastle ale or something that we used to drink.
• 3:45
  I don't know if it ever came out of Newcastle, but uh maybe it did.
• 3:49
  don't know.
• 3:50
  So that's right.
• 3:54
  Yeah, that was it.
• 3:55
  That was another lifetime ago, but all good.
• 3:58
  So you're a Newcastle.
• 3:59
  So, know,
• 4:00
  It's really a timely topic, always, I think, in the longevity space to be talking about NAD.
• 4:06
  And, you know, as we sort of expand on the hallmarks of aging, we're now up to about 16 that we're looking at.
• 4:12
  It's always interesting to see how NAD is kind of at the either
• 4:18
  close to the center or at the center of optimizing so many of the hallmarks of aging these days, right?
• 4:25
  It seems like that keeps expanding.
• 4:26
  I don't know if that's your impression as well, but it's fun to see.
• 4:30
  You know, and a lot of people always ask me, they always say, why is it out of everything that you could have chose to develop or study or really put your effort and focus in a why
• 4:41
  did you choose NAD?
• 4:43
  And one of the main reasons was because throughout all of the time that I have been involved in this space, you know, really over well over a decade now, NAD has always kept
• 4:54
  coming back, as you mentioned, is kind of this molecule
• 4:57
  that seems to be at the center of a lot of, if not all of the hallmarks of aging.
• 5:04
  There's more and more evidence every day that seems to be appearing that is linking a depletion in NAD with driving the hallmarks of aging or when you actually replenish NAD
• 5:15
  with actually improving multiple hallmarks of aging.
• 5:19
  So I think even now,
• 5:22
  it's pretty safe to say that it is one of the only molecules that seems to have this really pleiotropic effect where it's actually impacting multiple different things in one
• 5:33
  go.
• 5:33
  And as we know, that's really important because all of the hallmarks of aging are not standalone processes.
• 5:41
  So, although as scientists, we like to kind of group them into these very neat boxes.
• 5:47
  m They're actually all linked and they're all influencing one another and you're never going to get a real impact if you only target one of them.
• 5:56
  So I think that's what's really interesting about NAD and certainly the research that continues to come out in this area.
• 6:04
  Yeah, I think that's right.
• 6:05
  think for the audience, way that I think it's easy to understand this is that these hallmarks of aging, which are essentially biological processes that sort of degrade with
• 6:15
  aging, but then also because of their degradation, accelerate the rate of aging, they actually play with each other.
• 6:23
  And so it's kind of like a tornado almost kind of spinning up, right?
• 6:27
  So when mitochondria don't work, then
• 6:30
  You don't have enough ATP, you can't repair your DNA.
• 6:32
  When DNA is not repaired, your telomeres get short, blah, blah, blah, blah, blah.
• 6:35
  And it keeps sort of playing off each other.
• 6:38
  it becomes a complex part of the complexity of reversing aging is actually how do you stop a tornado, right?
• 6:46
  When, when it's feeding off of itself and feeding off of all the other hallmarks.
• 6:50
  And so when you have a
• 6:52
  There are a few things that will come in there.
• 6:54
  NAD is one.
• 6:55
  A couple other things that come to mind.
• 6:57
  Spermidine actually has an impact around most of the hallmarks as well.
• 7:01
  So does fasting, like a five day fast, mimicking diet can have an impact on most of the hallmarks of aging.
• 7:07
  So it's interesting to look at that.
• 7:11
  And then also when you look at really very novel age reversal,
• 7:16
  strategies like epigenetic reprogramming, like the David Sinclair paper that was published in July of 23, were using a chemical cocktail.
• 7:24
  They were able to reprogram epigenetic age, of mimicking the Yamanaka factors, which is, you know, kind of a cellular reprogramming.
• 7:33
  You know, one of the things that happens in those more youthful cells is they're able to produce more NAD and recycle more NAD and use more NAD, right?
• 7:40
  So it's really, it's all linked together.
• 7:45
  So that being said, know, one of the things that impressed me about your product, Neuchito Time, was really how well thought it out it was.
• 7:54
  You know, how well thought out.
• 7:55
  It's not just, take some NMN or some nicotinamide riboside or even some niacin or something and just load that into your system.
• 8:03
  There's a much more sophisticated thought process there and maybe you can share that with the audience.
• 8:08
  Yeah, absolutely.
• 8:10
  And I think, you know, as you've just said, when we're looking at anything in biology, especially in aging, it's all very complex and there's never just one thing at play.
• 8:20
  And
• 8:21
  what was always interesting to me was how complex the NAD system is in our cells.
• 8:27
  You know, often people just think, oh, it's just this one molecule.
• 8:31
  It's important.
• 8:32
  It declines.
• 8:32
  Let's just top it up.
• 8:34
  And that's the end of it.
• 8:35
  But actually what we know is that there are multiple processes going on in our cells that are not only using NAD, some of them are recycling it, some of them are actually depleting
• 8:47
  it, some of them are making
• 8:49
  it, some of them are recycling.
• 8:51
  There's all sorts of things going on.
• 8:54
  And for a long time as scientists, we knew that NAD fundamentally declines as we get older.
• 9:01
  This is observed in...
• 9:02
  all studies that have been done, it's observed in all species that it's been studied in.
• 9:07
  So it seems to be a kind of universal decline that we do see with age.
• 9:12
  But what was never really understood was exactly why it is declining.
• 9:17
  And usually if something has declined in the body, there is a root cause to the problem.
• 9:22
  So for a long time, a lot of the focus was not on why it's declined and how we fix the root cause.
• 9:29
  but on the fact that let's just top NAD levels up in any way that we can, whether that's by using pure NAD in an IV or an injection, or using things like NAD precursors, which are
• 9:43
  probably the most famous way to boost NAD, things like NR, nicotinamide riboside, or NMN, which is nicotinamide mononucleotides.
• 9:52
  And what these molecules are, which have been used for many, many years now,
• 9:57
  or effectively precursors, so like the raw material that your body uses to make NAD.
• 10:02
  So the idea behind these products is that if NAD is declined in the body, let's just give the body more of the raw material and hope that it converts it into NAD.
• 10:13
  And which seems very simple, but actually when you start looking deeper at the science behind NAD and more importantly, the more recent research that is coming out, which now
• 10:24
  explains why NAD is declining, these products don't really make as much sense anymore.
• 10:30
  And to kind of go into that in a little bit more detail, what we, now really know is that there are two major root causes of the decline in NAD.
• 10:40
  The first one.
• 10:41
  is that as we get older, our cells have more damage and they have a higher demand for NAD.
• 10:49
  So NAD actually acts like a fuel to drive many of the repair processes in our cells.
• 10:56
  So, you know, we've got an army of DNA repair enzymes and we've got an army of proteins called sirtuins that are monitoring cellular health and switching on things that are
• 11:07
  protective.
• 11:09
  all of these functions in our cell require NAD as a fuel to actually drive this repair.
• 11:16
  So as we get older, our cells have been around longer, they've got more damage, they've got more inflammation, and ultimately they need more repair.
• 11:23
  So we start to see an increase in the demand for NAD as we get older.
• 11:28
  So that's one reason.
• 11:29
  And then right at the same time, what we see is that our capacity to actually make NAD also declines.
• 11:38
  And this is a really fundamental point that is very misunderstood within the industry is that we cannot get NAD from our diet.
• 11:49
  Our cells actually have a pathway in it that makes and recycles all the NAD that we need.
• 11:55
  And this is called the salvage pathway.
• 11:57
  And a key problem that we have when we get older is one of the main enzymes in this salvage pathway declines with
• 12:04
  age.
• 12:05
  So we end up in a situation where not only has that demand gone up, but also ourselves ability to make and recycle NAD has also gone down.
• 12:14
  So you end up with this perfect storm of right when demands increased, production has reduced and you get a massive depletion.
• 12:21
  And what we wanted to do is kind of go, okay, know, precursors can get you part of the way.
• 12:28
  You know, we do know that they do get converted into NAD and we do see a small NAD boost.
• 12:34
  but you need to actually fix the root cause of the problem if you want a more sustainable method to actually increase NAD levels.
• 12:41
  And that is exactly what we developed, a product that actually fixes these root causes of the problem.
• 12:47
  Yeah, and I think that's right.
• 12:50
  So it's really a wheel if you're trying to visualize this of NAD precursors becoming NAD being used up and then being recycled through this enzyme.
• 13:00
  And it's kind of like if your recycling mechanism goes down and your demand goes up, then you can see you're going to end up in a shortage.
• 13:09
  And there's another piece to this equation that I know New Cheeto Time addresses, which is CD38.
• 13:15
  portion of this.
• 13:23
  Yeah, absolutely.
• 13:24
  So what we know is that CD38 is a very important piece of the puzzle, as you mentioned.
• 13:32
  And what CD38 is, is it's a pro-inflammatory enzyme.
• 13:36
  So essentially when our inflammatory response is switched on, CD38 is part of the cascade that actually drives the inflammatory response.
• 13:46
  So every time we have an inflammatory reaction, CD38 gets turned up.
• 13:50
  Now what we know is that as we get older, sometimes that inflammatory response is not quite turned off.
• 13:59
  fully.
• 14:00
  So as we go throughout life, we kind of get small amounts of this inflammation that's still switched on that builds up in our body and it acts almost like small, like a
• 14:10
  smoldering fire.
• 14:11
  And we know it's incredibly damaging to ourselves.
• 14:14
  And part of this is actually linked to higher CD38 expression.
• 14:19
  So you will see in an older person that they will have more CD38.
• 14:24
  And the key link here with NAD is that
• 14:27
  NAD is actually one of the drivers of CD38.
• 14:30
  So when CD38 is switched on, it is using up a huge amount of our NAD supplies.
• 14:36
  So this is the link between the fact that high levels of chronic inflammation as we get older are actually further driving down our NAD supplies.
• 14:47
  And this is something that actually has a profound impact on our NAD levels.
• 14:53
  You know, some of the studies have shown that even by addressing this problem, you can increase NAD levels by 50 % just by addressing this wastage problem, shall we say.
• 15:05
  The other issue is that, and again, something that's not really spoke about much is when you are boosting NAD, what you need to make sure is that the NAD that you are creating is
• 15:17
  actually going towards beneficial processes.
• 15:20
  So you want the NAD to be going to DNA repair enzymes.
• 15:25
  You want it to go in to be activating the sirtuins.
• 15:28
  What you absolutely do not want happening is it to be activating CD38.
• 15:33
  And this is a real risk because actually CD38 has what is known as a high affinity for NAD.
• 15:41
  And essentially what that means is that if NAD is available in the cell,
• 15:46
  The CD38 enzyme will grab it and use it before the sirtuins can use it, before the DNA repair enzymes can use it.
• 15:53
  So you really do need to make sure that you inhibit CD38 as part of your NAD boosting strategy to make sure the NAD is going to beneficial processes.
• 16:05
  Sounds like the Russian economy, right?
• 16:09
  You've got corruption that's basically pulling off the NAD.
• 16:12
  Then you've got a mechanism for recycling that's declining, right?
• 16:17
  The manufacturing is declining.
• 16:18
  Then you've got an increasing need because of ongoing damage.
• 16:22
  So this is how you set up collapse, right?
• 16:25
  This would be how you would set up economic collapse.
• 16:27
  If you're thinking about it in economic terms for the cell.
• 16:31
  It's almost economic collapse for the cell if NAD is the currency here, right?
• 16:36
  it becomes a, it's a huge mess.
• 16:38
  And you know, one thing is then driving the other thing to become more worse.
• 16:42
  And you end up in this cycle, which is why it is so important to actually address these root causes rather than just trying to ignore all the problems and, know, chuck in some,
• 16:55
  guess, chuck in some new currency or chuck in some new raw material.
• 16:58
  Yeah.
• 16:59
  to print money to overcome the problem, right?
• 17:01
  So staying on the economic bandwagon here.
• 17:05
  You know, the interesting thing is if you're just throwing NR, NMN, or even NISIN into the mix alone, is now you're sort of stacking up bricks in front of a machine that's
• 17:17
  distracted and things are going haywire anyway, and they can't really make good use of it, right?
• 17:22
  So one of the things that you've done, I think,
• 17:25
  both wisely, interestingly, and expertly is to actually navigate all the elements of the system to where you're providing not only the precursors, but you're also accelerating the
• 17:37
  recycling at the same time you're blocking the CD38, right?
• 17:40
  So it becomes a more comprehensive approach.
• 17:43
  Do want to talk through a little bit about the studies that you've done that have shown the impact of the synergy and maybe compare that to people that are
• 17:53
  thinking about IV and AD versus kind of what you're doing.
• 17:56
  That might be interesting.
• 17:58
  Yeah.
• 17:58
  So, I mean, essentially what we're trying to do is make the cell act like it did when it was young and when NAD production was kind of in full swing, because we know in youthful,
• 18:10
  healthy cells, our body makes and recycles all the NAD it needs in this salvage pathway.
• 18:15
  Literally as NAD is used up, it gets broken down into a precursor called nicotinamide.
• 18:21
  Then this nicotinamide gets scooped straight back up.
• 18:25
  and recycled back into fresh NAD again.
• 18:28
  And really it's a very clever way of the cell not relying on a critical molecule from the outside, but it also means that as NAD demand goes up, because NAD is being used and
• 18:42
  broken down in the precursor, it also means there's more precursor available to then meet the demand in the cell.
• 18:48
  So it's a very clever system that is set up that does work really well.
• 18:52
  and when it's working efficiently.
• 18:54
  But the key problem here, especially in this pathway, is the rate limit and enzyme NAMPT.
• 19:01
  And basically, the less NAMPT you have, the less of this recycling process happens.
• 19:07
  And that is the key enzyme that we see actually decline with age.
• 19:12
  So I think what you see is if you don't address this problem and you ignore
• 19:19
  this pathway and you just take NMN or you just take NR, what happens is some of that will go into the system.
• 19:28
  It will get converted into NAD, but then it's used once and it's essentially broken down.
• 19:34
  And when it's broken down, it gets converted into one of its precursors, which is nicotinamide.
• 19:40
  But if this salvage pathway, this enzyme is not working to recycle this nicotinamide,
• 19:46
  what we see happen is it actually starts to build up in the cell and it gets to the point where the cells like, actually this is too much, we need to get rid of it.
• 19:55
  So instead of this precursor being recycled into fresh NAD, the cell actually methylates it and excretes it out of the cell.
• 20:04
  So again, what you start to see is you start to see an increase in another enzyme, which is called NNMT, which is a methylated enzyme.
• 20:13
  which becomes over expressed as the cell is struggling to actually get rid of this excess nicotinamide.
• 20:20
  And this is a problem because it can cause methyl donor depletion because your methyl groups should not be getting used for this process.
• 20:28
  They should be getting used for much more important things like DNA repair, et cetera, et cetera.
• 20:33
  But they start getting used for this process.
• 20:37
  And this becomes even more of a problem if you are taking huge amounts of precursors, because suddenly you're getting piles and piles of these precursors in the cell that the
• 20:49
  cell simply can't deal with.
• 20:51
  And we do see in some of the human clinical studies that have been done on things like NR and NMN that we see an increase.
• 21:00
  in methyl nicotinamide.
• 21:02
  So basically as they increase the dose of the precursor, it increases NAD to a certain point, but then it doesn't matter how much they increase the precursor, the level of NAD
• 21:13
  plateaus.
• 21:14
  And that is because the cell can't keep converting it into NAD.
• 21:19
  And then what you see is the levels of this methyl nicotinamide, this excretory product keeps going up and up and up and up.
• 21:26
  which again shows us in clear solid evidence, this is not a theory, this is in a human clinical trial, that the system is becoming overwhelmed and it's starting to have to
• 21:37
  change other elements of its physiology to deal with this problem to maintain homeostasis.
• 21:43
  So, you know, that is a key, a key part of why we wanted to design something different.
• 21:50
  You mentioned very briefly m NAD IVs and also probably NAD injections that have become very popular.
• 21:57
  mean, a lot of issues around not only the theory behind this, but now some of the clinical evidence coming out.
• 22:04
  Because a lot of people kind of think, well, you know, if NAD is declined, can we give the body pure NAD and will it just go into the cell and get to where it's needed?
• 22:14
  But what an NAD IV or an injection does is it actually puts NAD into our blood.
• 22:21
  And NAD is not naturally found at high levels in the blood.
• 22:25
  NAD needs to be inside of the cells because that is where all of the pathways that it interacts with are found.
• 22:32
  So what we see and what I've spoke about for a long time now is the fact that yes, an NAD IV will get NAD into the body.
• 22:41
  but it's not putting it into the right place.
• 22:43
  It's putting it into the blood.
• 22:45
  And because NAD is a very large and charged molecule, it does not easily diffuse into our
• 22:52
  cells.
• 22:52
  It struggles to cross the cell membrane and it certainly needs a very special transport, a protein or carrier to get it in.
• 23:00
  And the majority of our cells simply don't have this pathway to get it in.
• 23:04
  So what we see is that the NAD is going into a person's blood and it's effectively getting stuck there.
• 23:11
  Now there have been two clinical trials, which I always find astounding that there are still only two clinical trials looking at what happens to the NAD considering the amount
• 23:22
  of clinics that are actually doing NAD IVs.
• 23:24
  And one of the clinical studies showed that the NAD is rapidly degraded into precursors.
• 23:30
  And then some of these precursors are then taken up.
• 23:33
  in which case you've got exactly the same problem as just taking an oral precursor.
• 23:38
  The other paper, more alarmingly, actually showed that not only did IV NAD not increase intracellular NAD, but it triggered an inflammatory reaction.
• 23:51
  So they saw increased levels of IL in the leukins in the bodies.
• 23:56
  And again, this is worrying because obviously, like we...
• 24:00
  We don't want to take NAD to increase inflammation.
• 24:04
  But again, you know, looking at this from a purely physiological theoretical point, NAD is not found in huge levels in the blood.
• 24:13
  So if you're suddenly putting a huge dose of NAD into the blood, that's usually only found inside the cells, the body's thinking, my goodness, what's happened?
• 24:23
  Has there been a trauma?
• 24:25
  You know, has there been something that's caused the cells to release a lot of their contents?
• 24:30
  and it perceives it as a trauma or a threat.
• 24:33
  So it initiates an inflammatory reaction to deal with this perceived trauma.
• 24:38
  So again, I'm really happy to see these studies now coming out because it supports something that I've kind of been saying theoretically for a long time.
• 24:48
  Yeah, it's really interesting.
• 24:49
  We've never been huge fans of IV NAD.
• 24:52
  I know there are some particular indications where it seems to be useful, like an acute alcohol withdrawal or opioid withdrawal or situations like that.
• 25:01
  It can actually be have a very salutary effect.
• 25:04
  And yet I think for the kinds of reasons that people are running into a clinic to get an IV of NAD, I think it's actually counterproductive.
• 25:12
  um Even though it's well intended, it's counterproductive, right?
• 25:15
  That's why I think understanding the biochemistry the way that you do and basically architecting a system to elevate intracellular NAD levels, the way that you've architected
• 25:27
  it becomes really kind of the most intelligent approach.
• 25:33
  I will say that in our practice, one of the things that we have also found to be helpful is
• 25:40
  Um, using an ozone sauna to oxidize NADH back to NAD to change the NAD to NADH ratio in a favorable way.
• 25:52
  And what we've found is that when you, uh, take something like Neucheto time, um, and you, you load this into your system and then you jump in an ozone sauna.
• 26:04
  Oh my gosh.
• 26:05
  So like the next three or four days, you can feel like Superman or Wonder Woman, right?
• 26:10
  mean, it's just, you really get an amazing boost in NAD.
• 26:15
  You can feel the ATP that comes off the mitochondria from it.
• 26:18
  if you throw in some, either some D ribose along with some vitamin B2, some riboflavin, I mean, the next thing you know, it's like, my gosh, let's go climb Mount Everest.
• 26:29
  So it's been cool.
• 26:31
  what?
• 26:32
  never heard that combination before, so that's really interesting.
• 26:36
  But again, from a scientific standpoint, it makes total sense because we know that NAD is a redox molecule.
• 26:45
  And so therefore it naturally flips between two states.
• 26:49
  One of them, it's oxidized form, which you see written as NAD plus, and the other it's reduced form NADH.
• 26:55
  And what we know is that as you get older,
• 26:58
  the ratio starts to shift more towards NADH and that's not the direction you want it to be going in.
• 27:05
  You want to have a higher ratio of NAD+.
• 27:09
  So that's really interesting to use that in combination with the ozone therapy.
• 27:15
  Yeah, it seems to work really well.
• 27:17
  And we'll take some molecular hydrogen too, actually, just to help kind of mop up, if you will, some of the uh oxidative stress, the excess oxidative stress you might get from the
• 27:27
  ozone.
• 27:28
  So anyway, it's something we've kind of biohacked our way into just looking at, you know, what can we do to optimize this, since that's the question we're always asking.
• 27:37
  And that seems to be quite honestly, the hot ticket.
• 27:40
  In fact, I'm going to no, no pun intended.
• 27:43
  think I'm going to do that after this podcast, just cause I got in late last night from a flight that was delayed and I'm feeling like I could use a boost.
• 27:51
  So yeah.
• 27:53
  Yeah, that sounds like the perfect boost.
• 27:55
  And we know things like travel, any jet lag, anything like that is also something that depletes NAD, probably because what we haven't...
• 28:04
  discussed is, you know, not only does NAD naturally decline with age, but lifestyle is also a huge thing that impacts our NAD levels, meaning that in some people it will decline
• 28:16
  quicker than others.
• 28:17
  We know people that travel a lot, people that have circadian disruption, and we see depleted NAD levels in those people.
• 28:25
  So yeah, definitely jump in that, eh in that chamber later and yeah, get those levels back up.
• 28:32
  Yeah, very cool.
• 28:34
  So, you know, one of the exciting things that I recently discovered on a call that we had was the fact that you've been able to kind of refine your packaging, if you will.
• 28:46
  In other words, it used to be that the daily dose was about six capsules and now I think it's down to three.
• 28:51
  Do you want to talk about how you did that without compromising the delivery of the product?
• 28:58
  I think people would be interested.
• 28:59
  when we first developed the product, our aim was to get a product out to market that actually works and has good science behind it.
• 29:07
  my PhD back in the day was actually all surrounding bioavailability of active molecules, of drugs, of nutrients.
• 29:16
  So I was always very particular.
• 29:19
  and very picky about what formats of different ingredients that we used.
• 29:24
  So for example, we've spoken a lot about how we uh target CD38.
• 29:31
  Now, the way we target CD38 is through an active ingredient called Apigenin.
• 29:36
  We know that Apigenin is a very powerful inhibitor of CD38.
• 29:41
  And so we wanted to include this in our product to actually m inhibit it.
• 29:46
  And unfortunately, there's a lot of hype about using purified active molecules.
• 29:53
  So for example, a lot of the studies on apigenin have used pure apigenin.
• 29:58
  They've put it in cell culture.
• 30:00
  They've shown that it inhibits CD38, which is great.
• 30:03
  But the reality is that in nature, apigenin doesn't exist in a pure form, which means that you cannot just take pure apigenin orally, and it will not have the same effect because it
• 30:14
  can get damaged in the gut.
• 30:16
  So in order to get these active ingredients into the body in stabilized form, often what you have to do is use m plant extracts.
• 30:24
  So in our formulation, you'll see we use m parsley extract.
• 30:28
  And everyone's always like, why on earth?
• 30:30
  What is parsley doing in this product?
• 30:33
  But we know parsley is a very good source of natural epigenetin.
• 30:36
  But that means that you have to use quite a lot of the active ingredients to then actually be able to get the effect.
• 30:43
  So the result was that when we did our initial clinical trials, the formulation wasn't in capsules.
• 30:49
  It was something that you just have as a powder and drink it and it had its effect, but it tasted horrendous.
• 30:57
  So that was never going to be acceptable to consumers.
• 31:00
  So it had to be encapsulated.
• 31:02
  And when it was encapsulated, that's when we realized it's six capsules.
• 31:06
  So because we just wanted to get a product out there that worked,
• 31:11
  we were much more concerned about having the correct doses and having more capsules than trying to cut it and have less capsules and, you know, and get it out there.
• 31:21
  So that's why when we initially launched, it was six capsules.
• 31:24
  But since then, and because we actually launched back in 2019, believe it or not, ingredient science is really advanced.
• 31:33
  So some of the ingredients that we use have now become much more purified and extracted.
• 31:40
  meaning that we can now use lesser amounts of the raw materials to get the same amount of active.
• 31:46
  So a key difference, just again as an example of something we've changed, is the alpha lipoic acid.
• 31:53
  So alpha lipoic acid is a key part of the formulation.
• 31:57
  It's one of the ingredients that helps to switch on the NAMPT enzyme, this salvage pathway enzyme.
• 32:04
  Um, but a key problem that we always had was the bulk of this raw material that had to be used to actually get the desired efficacy, in the cells.
• 32:14
  And that's because alkaloid proic acid is an incredibly unstable molecule.
• 32:18
  So you need to use way over, and to ensure that by the time it's degraded in the body, got through the gut, that there's enough left to have its active, its active role.
• 32:27
  Now, when we launched, we used the best product or the best
• 32:31
  format that was available but since over the years there have actually become new versions available.
• 32:38
  So for example the ALA is now available as an ALA salt and this actually massively stabilizes the alpha lipoic acid meaning that you can use a huge amount less to actually
• 32:50
  get the same active benefit in the body.
• 32:53
  So through various tweaks like this, we've been able to actually get the formulation down into three capsules, which has been a big advantage em for consumers taking it.
• 33:06
  You can take all three capsules in one go with food.
• 33:10
  And again, because we are very scientifically credible and we want to back everything that we're doing, we actually went and did another full clinical trial to prove that it works
• 33:21
  just as well.
• 33:22
  as the six capsule.
• 33:23
  So we did a head-to-head clinical trial to actually show that it still has the same benefit as well.
• 33:29
  Because what we haven't mentioned is we have done a double-blind placebo controlled clinical study on the product, which certainly for supplements is pretty rare.
• 33:38
  And also in the NAD space is pretty rare because there's a lot of products out there that make a lot of claims, but don't actually have any research in humans to back it up.
• 33:47
  Yeah, no, it's really great.
• 33:51
  It's nice to see how you continue to kind of think through the product and find ways to optimize it, not only for efficacy, but also just the convenience of taking fewer
• 34:00
  capsules, right?
• 34:01
  I mean, there is such a thing as capsule fatigue of people who are taking a lot of different supplements.
• 34:06
  So that's super helpful.
• 34:08
  Yeah.
• 34:10
  goal with Nishido has always been how do we get this science out to people and make it as user friendly as possible, whether that's user friendly in terms of the education and
• 34:21
  people's understanding of it, or it's user friendly in terms of the price and cost and, you know, acceptability of people actually being able to take it.
• 34:29
  Because, you know, as well as I, that these things can actually have a real significant impact on people's life.
• 34:36
  and when they improve their cellular health on the inside, it really does have an impact.
• 34:42
  Tell me about the name Neuchito.
• 34:44
  Where did that come from?
• 34:45
  It sounds like it rhymes with Dorito, but it's...
• 34:49
  So, so, no, it's, it's, it's a made up word, but it does have some basis to it in the longevity field.
• 34:56
  because you, will have, you will know of the blue zones.
• 34:59
  So the places in the world where, you know, people seem to live to a great age and in relatively good health compared to a lot of countries in the world.
• 35:08
  And one of the famous blue zones is Okinawa in Japan.
• 35:11
  and they have a saying, which is Nishi Kusui, which is food.
• 35:16
  is path to long life.
• 35:17
  So we sort of stole the Nushi bit and put the dough on his way.
• 35:21
  So it loosely kind of has a meaning, but also it's very much made up because it's very hard to get a name that you can trademark.
• 35:28
  Right.
• 35:29
  That's true.
• 35:30
  That's true.
• 35:30
  It's hard to get a name you can trademark.
• 35:32
  Cool.
• 35:32
  All right.
• 35:33
  Well, that's good.
• 35:33
  I didn't realize it was connected to Okinawa.
• 35:36
  So good to know.
• 35:37
  All right.
• 35:38
  Cool.
• 35:38
  sense behind it a little bit anyway.
• 35:41
  So what's on the drawing board for you guys?
• 35:43
  Anything, any other things you've got up your sleeve there in terms that you're working on or perfecting this?
• 35:49
  I mean, in terms of this product, we are always trying to do further clinical research on it.
• 35:55
  And a lot of this is based on customer feedback.
• 35:58
  So more and more, we get all sorts of customer feedback and some things begin to trend where we're hearing it time and time again.
• 36:07
  And as a scientific company, we don't like to rely on anecdotal data or, know, customer reviews or quotes.
• 36:15
  We like to get some solid evidence behind it.
• 36:18
  So we continue to do smaller studies looking at some of this feedback that we're getting.
• 36:23
  So like a key one that we've done was a sleep study because we were getting so many customers saying that they were noticing an improvement to their sleep quality.
• 36:32
  A lot of our customers have the aura rings or the Woot bands.
• 36:35
  They were noticing improved deep sleep.
• 36:37
  They were noticing better HRV.
• 36:39
  So we wanted to do a study to actually measure this.
• 36:43
  So we did do a three-month sleep study.
• 36:45
  Now granted it was a questionnaire-based study, it was using something called the Pittsburgh Sleep Quality Analysis, but we did see in all of the 30 participants that 26 of
• 36:56
  them all saw a significant improvement in sleep quality and the four that didn't just saw nothing change.
• 37:03
  So that kind of confirms that something is going on here to improve sleep.
• 37:07
  Again, theoretically, it makes perfect sense.
• 37:10
  NAD is very important in regulating circadian rhythm.
• 37:14
  And so we know that it does have a role in sleep.
• 37:17
  And so from this, we then want to go on and do a further sleep study, which is then using tracking devices to actually really measure this.
• 37:26
  And the other thing we're really interested in is studies surrounding
• 37:29
  What happens if you improve cellular health on the inside?
• 37:32
  Does it have visible and noticeable changes to things like skin quality on the outside?
• 37:37
  And we've done some studies, again, looking at skin quality with m special skin analyzer cameras that take pictures of different layers of the skin.
• 37:46
  They take pictures of the pigmentation, rosacea, redness.
• 37:50
  And we've saw improvements to these parameters as well.
• 37:53
  And the other area that we're really interested in is menopause, because a huge number of the positive feedback from customers that we get is actually perimenopausal and menopausal
• 38:03
  women that say how much of a real difference it's made to their brain fog and also energy levels.
• 38:11
  So we're looking to actually set up a study with specifically with this category of people.
• 38:17
  and to get some data behind that.
• 38:19
  So that's kind of where we're focused on this product.
• 38:23
  But in the, you know, in the backend, again, we're actively researching company.
• 38:28
  I have PhD students that collaborate with universities.
• 38:31
  We do a lot of research and a big area of interest for us is senescence.
• 38:36
  And that's got some really exciting projects that's ongoing and that I can't say too much about now, but.
• 38:43
  It's kind of all taken away in the background.
• 38:45
  And as you know, Senescence and NAD also has a very powerful link between them.
• 38:52
  That's right.
• 38:53
  No, that's exciting.
• 38:54
  That's very cool.
• 38:54
  I had not heard about brain fog for perimenopausal women or postmenopausal.
• 39:00
  know, men go through andropause also.
• 39:02
  I wonder if it would be helpful to them as well.
• 39:04
  It might.
• 39:05
  we do have men, you know, that report, especially in that sort of period of life, a significant improvement, especially in things like brain fog, because men do get that as
• 39:15
  well.
• 39:15
  It's usually a bit more gradual onset as opposed to women that really notice it because it's usually quite drastic.
• 39:23
  And also, if you look at the hormones in women, things like estrogen are, when they drop, they're incredibly...
• 39:30
  pro-inflammatory because estrogen normally keeps inflammation at bay.
• 39:34
  So when estrogen suddenly plummets, you get an increase in inflammation and then you get it is right at the time when NAD is massively declining as well.
• 39:41
  So you almost get this perfect storm.
• 39:44
  So even if you're not addressing the hormones and you're only addressing NAD, you do see a significant improvement.
• 39:50
  Nice.
• 39:51
  Yeah, no, that's really cool.
• 39:52
  So with the sleep, are you finding that people are taking their Nuchido time at bedtime to get the best results with sleep or just when they take it?
• 40:01
  to take it in the morning or as close to the early in the day as you can take it with your first meal of the day.
• 40:07
  And that's just because, um, any of the actually naturally fluctuates throughout the day.
• 40:11
  It's not a constant.
• 40:12
  Um, and it's these fluctuating levels of NAD that actually helped to regulate switching this circadian cycle on and off.
• 40:19
  Um, and it's better to, it's kind it's not the time at which you take it.
• 40:24
  It's just the fact that your whole NAD cycle.
• 40:27
  m is functioning better.
• 40:29
  So it has that influence over the circadian rhythm as opposed to when the whole NAD cycle is all disrupted, it doesn't have that strong influence as it should to switching on and
• 40:39
  off those circadian transcription factors.
• 40:43
  Yeah, nice.
• 40:44
  Awesome.
• 40:45
  Well, lovely to catch up with you again.
• 40:48
  Really nice progress that you've made.
• 40:51
  And really congratulations on being able to condense the formulation to three capsules.
• 40:56
  We just got a hold of some of those in the office here, I don't know, a few weeks ago.
• 41:00
  And people are enjoying having to take fewer capsules.
• 41:02
  That's been great.
• 41:03
  So.
• 41:04
  no, I bet.
• 41:05
  No, thanks.
• 41:05
  been really nice to catch up as well.
• 41:07
  It's always good to have a really detailed science chat with someone I appreciate.