Impact and Optimise Your Longevity and Biological Age with NAD+

9:35AM Sep 6, 2022

Speakers:

Angela Foster

Intro

Dr Nichola Conlon

Keywords:

nad

people

cells

pathway

ageing

levels

activating

age

npk

angela

energy

enzyme

precursor

salvage

supplements

decline

cancer

body

older

repair

anything that you're doing, it's been to sort of create an energy stress in the body has been found to positively impact NAD levels. So that's everything from intermittent fasting and calorie restriction to exercise. So exercise is a well known way to actually boost NAD levels.

Welcome to the high performance health podcast with your host, Angela Foster, the show where we talk about everything you need to break through limits and achieve a high performance, mind, body and lifestyle.

Hi, friends, I don't know about you, but there's that distinct back to school feeling. It kind of never leaves you does it even though you've left school so many years ago. Now I have my kids going back to school, but the edges somehow changes and it just has that sort of beginnings of that autumnal feels quite nice kind of evenings are drawing in quite cosy. But yeah, so Mike is a bit off back to school. And what we've been doing actually last the last month in the female bio hacker collective was working all on a morning routines, and specifically how you can really supercharge your day with an effective morning routine and how you might change that for weekend vacations, but also school run days versus normal days. Because if you're anything like me, things are quite fluid, and they need to change. That was what we did last month in August. I'm so excited for this coming month's pump content, because we're going to be talking about how to optimise your nutrition for happy hormones. So I'm going to be sharing everything I know basically about how you can really navigate through those Peri menopausal years and make a smooth and easy transition, and what foods you should be including as part of your diet at different weeks of the month, and also what to do as you're hitting menopause and post menopause. So it's really exciting, wonderful, wonderful community of women over in the female bio hacker collective. If you haven't checked it out yet, then just head over to Angela foster.me. Forward slash bio hacker can find all the details there. We have a monthly challenge every single month, which is really practical. It allows you to put the things that you're learning into practice alongside the other members and also engage with them and get support from them. It's a really lovely community. And we also have a biohacking Book Club, which is super fun. And if you want to join in and read the book that's chosen, you can, if not, you get my cliff notes. And anyway, you also get access to special questions with guests on the podcast. So there's some members only content as well. So if you're interested in all of that, I'd love to see you in there, just head over to Angela foster.me, forward slash biohacker. Now, on today's episode, I have a treat for you. So I think one of the most confusing areas is what you should be doing to increase not just your lifespan, but also your healthspan none of us really want to get older and live kind of as many people do in reality. In the Western world, which is kind of the last 15 years with a poor quality of life, poor quality health and on a lot of medication. And things like hospital visits, I think what we really want is to be an optimal health for a very, very long time. And one of the things that super important if that's what you're focusing on is to really understand NAD it is the molecule of youth so to speak. In fact, without enough NAD you'd be dead in less than 60 seconds. So it's super important. The other crazy thing that I learned from Dr. Nicola Conlon my guest on today's episode, is that it has every 20 years, but not just from kind of your 30s, for example, but actually from birth. So from birth, this is having every 20 years. And it's confusing, isn't it? Because when you look at the science on it, what should you be taking? How can you upregulate that pathway, what works, what doesn't? You might be wondering, you've maybe done some research and looked at the salvage pathway and thinking what is that and how can I regulate it does fasting work? What should I take supplement wise? Well, we're going to be breaking all of that down. For you. It's such an eye opening interview and Dr. Nicola Conlon is a molecular biologist. He's super super knowledgeable in this area. She specialises in the study of cellular ageing, and after a career in drug development, she founded Nuchido laboratories to deliver disruptive innovation in the field of anti ageing, rejuvenation and healthspan. She has a real passion as you're here on this episode, for sharing the latest science with a skill for translating advanced science to help educate and support the wider population as she does break it down very simply. Her goal is really to help us age well and achieve our optimal life experience very similar to my own and along with leading scientists at Nuchido. Dr. Conlon has identified the right combination of targets to restore NAD plus production, bring it back to useful levels and lead it to in to the development of a breakthrough NAD booster called Nuchido. Time plus is something I've been taking for a number of months now. I've noticed what I've noticed most is really big improvements in my energy and my ability to kind of just to have that burst of energy in the morning I'm always quite energised, but maybe even more so now. And I also am sleeping better my sleep metrics look better too. So we're going to be diving into all that science now. So without further delay, let me introduce you to Dr. Nicola Conlon. So I'm really excited to have Dr. Nicola Conlon here today to talk all about NAD and optimising longevity. We haven't actually had anyone on the podcast yet talk about this necklace. So these will be a popular topic. So welcome to the show.

Thank you for having me, Angela. And I'm excited to be here to be able to talk all about it with you.

Yeah, I'm really excited to share all about it. Because I think, you know, many listeners actually listening to this will know and be familiar, but there'll be researching lots of different supplements and different mechanisms that they can use and things like fasting to activate those pathways. And then there'll be other people listening who probably haven't heard of NAD or what it is. So I think probably the best place to start. Is there. Can you kind of give a bit brief synopsis of what NAD is and why it's so important for the human body?

Yes, absolutely, I can give you a bit of an nad 101. To begin with. So NAD, I sometimes refer to it as probably the most important molecule that you've never heard of. And that's because if you didn't have any ID in your body, you'd literally be dead within 30 seconds, because it plays some really critical roles within ourselves. The first one is that it's incredibly important for energy production in our cells. And this is because NAD is part of the Krebs cycle, which is a cycle within our mitochondria, which are the energy powerhouses of ourselves, which actually make cellular energy. And without NAD ourselves literally couldn't do this, the pathway wouldn't actually work. So that's one really important role for NAD, which is energy production. The other side is the NAD actually act as a kind of signalling molecule in the cell, where it senses the levels of energy and our cell and then causes reactions which allow our cells to react appropriately to the levels of energy in the cells. So when we have high levels of NAD, it actually signals to the cells that cellular maintenance and repair needs to be switched on. So lots of pathways are activated that keep ourselves in good health. And when NAD levels are low, that means the cells kind of got a lot of energy, it doesn't really need to be as resourceful and energy. So your cellular maintenance and repair can kind of be turned down. So these fluctuate, fluctuate in levels of NAD in the cells kind of control cellular maintenance and repair being switched on and switched off. So they are they're sort of key things that NAD is really known for, and really important for.

And my understanding is and I think you share this research actually on your website is that it's sort of halves every 20 years. So and when is that from? So for example, my I've got teenage children, and the younger one, they presumably are there and ad pathways are working really super well. And the salvage profit which we can come on to in a moment, when does this process start to begin? Like when should people start to think about this?

From research that's been done, it seems like it declines from birth. So by the time you're age 20, you've kind of got half half the amount of NAD that you had when you were born, and in various different tissues. So that's quite significant to think that, you know, by the time which when it gets half, that's going to half again, that's going to half again. And what you see in tissues from humans and all sorts of mammals is that it does significantly decline. So it's like an exponential decline where you know, it's half and half and again, half and again. And this is a real problem, because this NAD decline that we actually suffer with age is actually being found to reduce first of all our energy levels because I mitochondria can't function as well, without NAD. And also, it means that these beneficial maintenance and repair pathways in the cell are also getting turned down. So if they're getting turned down, damage is accumulating within the cells. And this sort of manifests as the signs and symptoms that we associate with ageing. So it's thought that this decline in NAD with age does actually play a big role in our experience of ageing.

And when we look at people who are doing things like intermittent fasting, which can help to regulate that pathway, there's a sort of differences. So I think we have people listening that that do intermittent fasting, putting aside kind of the female menstrual cycle, and whether women should be fasting as long as we think more generally, is there an optimal period of fasting on a daily basis or an intermittent basis that we should be looking at to try and seek to up regulate that pathway?

I think what's known is that any level of fasting really is going to start to actually increase your NAD levels, and that's because basically NAD is acting as the link between some of the pathways that sense and energy stress, which at the end of the day is what you're trying to create with fasting. And then the downstream pathways that are activated. So when you fast, so you know, say you've gone for 1216 hours. Without food, what happens is something in your cells called a NPK, is activated. And that's like your cellular energy sensor. And that almost goes off like an alarm saying, Okay, there's no energy coming into the body, we're going to have to make sure the body's resourceful, and it's not wasteful. And it holds on to whatever energy and resources that it has. So a NPK actually, up regulates NAD levels. And then this rise in NAD is sensed by the cell, and that is what activates multiple downstream pathways. So anything that you're doing, it's been to sort of create an energy stress in the body has been found to positively impact NAD levels. So that's everything from intermittent fasting and calorie restriction to exercise. So exercise is a well known way to actually boost NAD levels. So in general, anything that's great in that stress, that little bit of stress that homeostasis in the body, actually beneficially impacts your NAD.

So if you're listening in to this episode, and you're thinking, I really want to try some Nichido, then you can get 10% off Nicola has been kind enough to share a special discount code with listeners of the show, all you need to do is head over to chido.com forward slash Angela, and enter Angela 10. At checkout, that's when you cheedo, which is a Nuchido.com/slash Angela and enter code, Angela 10 at checkout to get 10% off your order. And so by because I was reading some research as well, like with doing kind of high intensity interval training, for example, has been shown to regulate that pathway. And so I think for people listening, they we just came off actually in my membership, a metabolic flexibility month, and quite a few people there were tracking their flexibility with the lumen device, for example. And that device will actually sort of give you an indication if you've moved fully into fat burning mode, and you've depleted liver glycogen, then the recommendation that's made is if you're going to go and do a high intensity interval training session, you're probably going to have better output if you pre load with a little bit of carbohydrates to fuel that session. But when we're looking at this from activating those pathways, and amtk, it would seem that actually going and doing that exercise in a fasted state would be creating more positive stress in terms of hormetic stress on the body to regulate this further.

Yeah, absolutely. And personally, that's what I do. I do all my exercise in a fasted state in the morning. And you know, in that way, you're sort of prolonging and emphasising that NPK activation and a NPK that actually activates critical enzymes within the cell that actually produce an ad. So you're fundamentally altering the cell's ability to actually make more NAD and have it available to activate the beneficial downstream pathways.

And yeah, it's interesting, because that's what I do as well, I like to go and do it fostered for that reason. And I think the other thing I wanted to share, which I've heard you talk about before as well, and that you could go into for listeners is this is something that the body generally has what it needs, right, but it just it needs to activate that pathway itself. There is a little bit of interest. And we can talk about that in a moment in terms of bringing outside nutrients in but it has a mechanism for recycling. Could you just explain that before we go into things that are complementary to to help there? Yeah, absolutely.

So a lot of you know, NAD has been a popular thing within the scientific field for quite a while now. And but the science is really changing in terms of what we understand about NAD production, and also a decline in the body. And one of the major things that's changed is our understanding of First of all, how our body produces NAD, and why it's depleted. And it's been found that the major way that our body actually makes NAD is actually by recycling it. So it has a pathway called the salvage pathway in most cells, where when NAD is actually used by the body, so when it's used by enzymes and pathways, it actually gets broken down into some of its fundamental components which are called precursors. And the main precursor which NAD gets broken down into, is something called nicotinic. eyes. Now in young cells, they have this amazing capacity to be able to recycle that breakdown product that nicotinamide straight back into useful NAD again. And this is called the salvage pathway. And the majority of our NAD is actually made in this way when we're young. And if you think about it, it makes complete sense. Because NAD is so critical for the body. Why would the body want to rely on having to have some sort of external nutrients to make this NAD it needs to have almost a failsafe mechanism to be able to continually supply the cell with NAD no matter how much it's using. So when we're young, and it is used up, it's broken down into nicotine or made and the salvage pathway literally salvages it and recycles it straight back into fresh NAD that can be then used again for all the repair the maintenance, the mitochondrial function, and keeps getting recycled. Now the issue is, is that it's been found that our NAD levels mainly decline, because this becomes dysregulated with age. And the salvage pathway in older cells simply doesn't work as well. And the reason is, is because the main rate limiting rate limiting enzyme in this pathway, an enzyme called nampt, actually declines with age. So if you take a sample of someone cells who is older, you will find that they simply do not have as much of this nampt enzyme. So what that means is in older cells, where they are using the NAD and breaking it down in the waste products, nicotinamide, it's just not getting recycled. So cells are using it and using it. But it's not getting replenished like it should be. And that's a really important thing to bear in mind, when you're looking at, you know, restoring NAD levels or trying to impact NAD in any way. And just to emphasise how important that pathway is. Remember, we were just talking about how faston An exercise all increase the production of NAD while the way they do this is by directly increasing levels of this enzyme nampt. So all the beneficial effects of exercise fascin, etc, are happening, because they're increasing the ability of ourselves to use the salvage pathway.

Interesting. So I kind of and actually, it's interesting, isn't it, because if you look ancestrally, we would have actually had to be doing by necessity, a lot of these things right, and food wouldn't have always been super readily available, and definitely not the processed food that that we have an abundance of at the moment, we would have also had to work quite hard and exercise in a fasted state to get it. I always think like, even when you look at things like nature's sweeteners, right, we wouldn't have eaten tonnes and tonnes of honey, because it's actually really hard to get ahold of, and you're gonna get starting to get it and have to climb, sort of, it's quite interesting. And we would have been like cold swimming or bathing right in a in a lake or a river and having that cold exposure, we wouldn't have had central heating to keep us warm to presumably we actually would have been a lot better activating those pathways naturally than we are today when a lot of people are in a highly fed state most of the time.

Yeah, 100% agree. And something that I say all the time, is that if you want to make sense of ageing and ageing biology, just look at it through the perspective of evolution, everything in ageing starts to make sense, when you look at it, of why we've evolved to be the way we are, you know, all the pathways, all the things that go wrong with age. And it's all because we've evolved, you know, to live more like our ancestors. And then suddenly we've had these huge lifestyle changes and you know, the last 200 years, it's really, really short timeframe. And in terms of evolution, and how our bodies can evolve and change. Our bodies aren't designed to live the way we're living today. They're designed to go with long periods without food. They're designed to be you know, hunting down food and using a lot of energy and actually really go in a state of energy stress, where the cellular repair, you know, recycling autophagy DNA repair, things like that are activated to keep ourselves in good health. And unfortunately, you know, we just click a button on apps on our phones and order some food and don't have to move. And so ourselves aren't having the chance to go into this energy stress state, which is activating, you know, NAD production and activating all the beneficial downstream pathways.

Yeah, it's very interesting, isn't it? And also, we would had exposure to I guess to things, more things like wild plants that are growing, which again, have these hormetic compounds within them, right things like resveratrol, which I want to I want to come on to in a moment. I I think the other thing as well is when people are eating a highly processed diet, presumably they are then using more NAD and their pathways are not working as effectively. So they would they would be ageing at a much faster rate, right. As opposed to if you took two individuals, somebody who is highly sedentary at work, maybe travels by car to the office, gets food orders, Deliveroo eats most of the day up until they go to bed probably is quite stressed, doesn't sleep very well, versus somebody who is fasting, maybe going out for a morning walk moving around through the day eating an abundance of kind of plant based diet and things like that, they're gonna look quite different. internally.

Yeah, absolutely. The you know, you can almost bet they will have lower NAD levels. And that's for two reasons. Firstly, the things that they're doing in their lifestyle is ultimately going to cause more damage, more chronic inflammation, more oxidative stress, all of which are things that need repair. And that repair is driven ultimately a lot by NAD. So they're going to be having a higher demand for NAD in their body, which means it's going to get be getting used up. At the same time, they aren't putting that stress on their body, they aren't activating those pathways that are actually promoting its its salvage and recycling. So you've almost got the perfect storm where you've got this increased demand. And at the same time, you've got a decreased production and recycling. So ultimately, levels four, and you tend to see that not only in people with, you know, poor lifestyle choices, especially younger people or poor lifestyle choices, but naturally as we get older This is is generally what's happening. And you know, you could take a fit, healthy 60 year old, and they could have, you know, all right, NAD levels, they will have lower, but due to their lifestyle practices, they could have quite good NAD levels. And you could take a 30 year old who's you know, overweight has metabolic disease and prediabetes things from having a poor lifestyle, who's probably got just as low NAD as you would expect in a healthy, older person. So lifestyle massively impacts NAD levels, you know, metabolic syndrome, if you look at people's samples, who have some form of metabolic disease, whether that's diabetes, fatty liver, and they are characterised by low NAD levels, and also low nampt levels, that enzyme that that's critical for the salvage pathway. And there's a lot of evidence to show that some of these diseases can actually be really reversed, or made significantly better, by actually elevating NAD through some quite simple mechanisms.

And do you what about other things? I saw some research that NAD may show promise with things like treating cancer, do you think I mean, obviously, like cancer, that there is damage right to the DNA and to the cells themselves? Do you think that is it categorised that in people that have cancer? Do we see NAD levels that are lower in things like chronic fatigue, for example, which is really a mitochondrial disorder? And also I suppose another question, we were seeing such a rise in autoimmune disorders as well, is there any link between NAD and some of the autoimmune diseases we're seeing?

Yeah, and ad has been implicated in all of the things that you've just mentioned. And I guess it's no surprise because any of these in every cell in the body, a human, it's involved in so many different pathways, and I think in terms of NAD in cancer, so NAD is and in cancer incidence of cancer are inversely correlated. So what you see is as NAD levels decline, incidence of cancer goes up. And this is directly because NAD is so important for DNA repair. Some of the critical DNA repair enzymes are actually fueled by using NAD as a cofactor, which means that if they don't have any D, they simply can't work. And obviously a leading cause of cancer is is DNA damage and mutations that you know, then cause uncontrollable cell growth. So it's, you know, having high NAD levels is definitely something for cancer prevention, and to make sure that you've got adequate repair to ensure that cells don't become malignant. On the flip side, a lot of treatments and specific cancer treatments are looking at trying to inhibit NAD but only specifically in cancer cells. And that is because, you know, NAD so critical to any cell to be able to work and function. And that one of the ways of trying to get rid of cells you Do One is by cutting off the supply of something that's beneficial. So a lot of anti cancer drugs will try to cut off DNA repair enzymes or cut off supplies of oxygen or glucose or whatever it is that the cells are reliant on. And again, that's something that NAD has been researched for. And sometimes people wrongly interpret that as like, oh, well, NAD must cause cancer. But that's absolutely not the case. What all that evidence shows is that NAD is beneficial to a cancer cell, just as it is a normal cell. So you know, one of the ways to try and get rid of cancer cells is to restrict that useful thing, in the same way that they do with restricted DNA repair. But nobody would say that, Oh, well, we'll better not have any DNA repair in the body. Because what happens if it benefits a cancer cell? And so that's a bit of a common misunderstanding within within this field, especially by people who are just done to understand it. But you know, in a lot of diseases, NAD has been implicated neurodegeneration is another huge one, Alzheimer's, Parkinson's disease, you know, that, again, characterised by low levels of NAD. And actually, by restoring NAD levels, there's been trials that have demonstrated a significant benefit. So I think it's, it's, you know, it's a really, really exciting area to be involved in.

It's really exciting. I mean, so if somebody was, for example, that maybe that maybe they find that they are more like genetically predisposed to cancer for whatever reason, or there's a familial history of it, or, in fact, they have experienced cancer themselves, I'm going to come on to the kind of things that they can they can take in terms of supplements in a moment with you. But would there be a downside to those individuals or people that are receiving any kind of treatment? Because obviously, it's up regulating both sets of cells, right, the good ones and the bad ones? Are there any circumstances where people should be cautious about what they're taking?

I think if somebody knew they actively had cancer, then I think then personally, I would be cautious. But aside from that very specific circumstance, the benefit of having high NAD massively outweighs any potential risk. And you know, of any, any other reason why you shouldn't be taking it, at NAD, and cancer, like I say, are inversely correlated, you know, when we're young, we have super high levels of NAD that's very well known. And we also have the lowest risk of cancer. However, as that shift, changes, as we get older, there isn't, you know, it's not a coincidence that older people have who have lower levels of NAD have much higher incidence of cancer risk. And that's because the repairs not happening in the inflammations there, all of these things that create the right environment for cancer to grow. But NAD actually prevents all of those situations from happening in the first place. So you know, having high NAD is actually, you know, more looked at as it as a way to avoid getting into that situation in the first place, in the first

place. Interesting. And what about in terms of like increasing and optimising our own levels and those pathways? Let's say, somebody has, you know, maybe not been living the ideal lifestyle, the ideal diet for a few years. And now they're starting to think about this. Are we really just protecting downside here in terms of what we can do? Or can we actually lose things and begin to reverse our biological age?

Yeah, absolutely. So biological age. It's something I love talking about. Because unfortunately, most people have this mindset that our age is set. You know, we're getting older, it's inevitable, there's nothing we can do about it. But what biological age is shown, which is, you know, the age that you actually are within yourselves, as opposed to how many candles you have on the birthday cake. biological age is reversible. And there's a lot of studies now that have demonstrated that this is something that you can impact with some, you know, quite frankly, very simple lifestyle changes, and you're going to have a major impact. So So yeah, I think NAD again, is is linked to the health of your cells, which is ultimately linked to the biological age of your cells.

Perfect, was exciting, isn't is a really exciting area.

Yeah. And we've actually done a clinical study on our product, where we've measured biological age before and after. And so it'll be exciting to be able to talk about the results of that at some point in the future.

And you've is that a recent study, because there is also a study on your website, isn't there? Is that is that a more recent one that you've just done now?

That yeah, so we, we did an initial pilot study with a couple of people but we've done a bigger double blinded, placebo controlled crossover with 24 people now and those people all had the biological a Each tested before and after.

Interesting. And when you're measuring their biological age, what markers are you using? Because I know there's a range of different things that you can look at.

Yeah, well, there's a couple of different ways. I mean, what we used was something called a glycan edge, which is measuring the basically glycans, a little sugars, that are markers that are stuck on the surface of your immune cells. And basically, the patterns of these markers change quite predictably as you get older, so you can take someone sample and predict within a couple of years, how old they are by just simply looking at the pattern of these these glycan markers. So that was the way we did it for this study. But there are also other ways like looking at epigenetics. And so that's again, looking at patterns of markers, but this time patterns of markers that are stuck onto our DNA and our genes that affect gene expression. And you know, there's other things like telomeres, which are a little bit controversial, but you can use that to measure biological age. But I think ultimately, the best way is a combination of multiple. And you know, in the future when things become more established, but at the minute, we used glycan age, because that's one that we believe has some really robust science behind it.

And what kind of reversal were you seeing?

So it's a double blinded study, and it has the kind of blind have seen somebody get something happen. So hopefully, when it's unblinded talk about it, it's not the placebo.

Yeah. Okay, exciting. Can we talk as well, before we come come on to supplementation, which I do want to talk about to talk about sirtuins? And also, like, things like no man, for example, and what people should be thinking about here, because I think people get really confused and you can end up spending a lot of money and not actually getting what you need.

Yes. Okay. First question. sirtuins. So the sirtuins are, they always go hand in hand and are mentioned with NAD. And that's because the sirtuins are a group of longevity proteins, or enzymes that basically they sit like at the top of a cascade at that switches on a lot of downstream beneficial pathways. And that are involved in longevity. They're involved in repair. They're involved in basically you name it, if it's good for ageing and longevity, the sirtuins somehow are involved. The weight the reason that they are linked to NAD is that they are absolutely critically dependent on NAD function. So the searcher and isn't is essentially an enzyme, and it needs a fuel to power the enzyme and NAD is that fuel. So what you find is that when NAD levels decline, the reason that all that cellular maintenance and repair gets switched off is because there's not enough NAD to switch on the sirtuins, which are then coordinating this cascade of beneficial pathways. And conversely, when NAD levels are high, there's an abundance of NAD which means there's abundance of fuel for the sirtuins. They're getting activated, lots of the repair and pathways etc. And genes are all getting switched on. And you get these longevity and ageing benefits. So that's where sirtuins

turn on that transit the situation. So because we can, we can have searching and activating compounds in our diet, right. And a lot of people have heard about things like the cert cert diet, and things like resveratrol for Seaton and Mike matcher, and things like that, that they can start having. But if that NAD salvage pathway is not operating correctly, then you could be consuming lots of secure and enhancing compounds, but actually not making a difference. Presumably you've got to have both.

Absolutely. So you can take all of resveratrol in the world. But if you've got no NAD it's absolutely pointless. And

yeah, so you could be really overweight eating a highly processed, drink Matcha Green Tea all day long. Absolutely. No, you might get a benefit. Yeah. It's not gonna work on that pathway properly.

Absolutely not. So they act on a different site. They sort of work in a different way to benefit the search engines, but ultimately, sirtuins cannot perform their chemical reaction that they perform. Without NAD. It's absolutely critical.

Okay, interesting. So it really is a combination of nutrition, supplementation lifestyle that magic starts to happen. Before we come on then to the supplementary aspect. I know that circadian rhythm also plays a part here. Can you explain that?

Yeah. So NAD is an heavily involved in regulating your circadian rhythm. So actually, if you think your circadian rhythm regulates, you know, your sleep wake cycles, your hormones, your metabolism, everything and you know it peaks and troughs in this 24 hour cycle. If you measure NAD levels, NAD also goes up and down and peaks and troughs and the circadian way. But it's sort of slightly offset from your circadian rhythm. And that's because levels of NAD actually switch on and off some of the, basically the pathways that, for example, manufacture melatonin, and switch on some of the pathways that alter your hormones and your cortisol and other things that are involved in those rhythms throughout the day. So as you get older, if your NAD levels are declining, and you're not having that, you know that that pronounced fluctuation in NAD levels throughout the day, that then also goes on to impact circadian rhythms because it means that the NAD is not driving some of the pathways that switch on and off the melatonin production and everything else. So you can also see a suppression in the you know how pronounced those rhythms are as well. So what you find isn't that people who actually have youthful levels of NAD, their circadian rhythms stronger than in people who that have lower levels of NAD. That's when it starts to get toned down. And then people have sleep issues and other issues associated with that.

That's interesting, isn't it? Because a lot of people just accept that as a part of getting older, right? Just a standard part that you're going to be sleeping, shorter, less deep sleep, but actually by working on these pathways, you can improve that as well.

Yeah, absolutely. And I think a lot of people think, well, any of us just this constant thing. You know, it's a constant level, it's not it goes up and down throughout the day. It fluctuates. NAD by its you know, it's it's naturally made to sort of rise and fall, you know, it's the centre. So NAD is not like this linear thing in the Salar in the body.

Okay, interesting. And what about NAD levels? Is there any research showing how they might fluctuate around a woman's menstrual cycle? For example?

No, not that I've come across. But we you know, it's a super interesting area, you know, looking at how hormones and things like that are influencing NAD levels. And I'd be very surprised if something didn't come out soon, with some research on this.

Yeah, it would be really interesting, because when you think how that kind of affects sleep, and the vagus nerve and things like that, as well, so interesting. Okay, so then looking at supplementation, because I think this is where people get confused. And, you know, on the one hand, you've got a range of different supplements that seem to be, you know, made up of different compositions which want to go into yours that you've formulated and tested. But also, then people like, for example, Dr. Mercola, has come out and said, You don't need to be spending a tonne of money on this, actually, you can just take high doses of niacin. But my understanding is that if you're not optimising that pathway, you can take loads of loads of ice, and it's not going to make a huge difference. But you're the expert here. So if you could explain that, that would be really helpful, because I think people will wonder, you know, is this gonna work for

me? Absolutely. And I appreciate that. It's, it is a difficult area to get your head around. And there is a lot of conflicting advice, even, you know, throughout the scientific community, and there's a lot of argument over what's best. So you know, what I base our research on is what what the latest science actually is and what it shows of why NAD is declining and what the root causes are. And so in terms of boosting NAD levels, there are a few ways that people are probably heard of. And one way, which I definitely don't recommend is taking pure NAD in capsules. And that is because NAD is a very unstable molecule. So if it's just a pure, you know, NAD plus or NADH or whatever, in a capsule, there is no way that it will go through your gut and survive and get anywhere in the form that it's needed. So that's a definite no, no. And the way that people have tried to get around this is by supplementing with what we call precursors. So these are the building blocks that that the cell uses to make NAD. The common ones that people will know are the B vitamins like niacin, niacin, amide, actinomyces, and then you've got nr, which is nicotinamide ribose eyes and then you've got n n, which is nicotinamide mononucleotide. And the majority of people seem you know have heard of these types of ways to boost NAD. Now the way they work is they are just building blocks that the cell basically uses to make NAD and the issue with this taken these is And whilst they do boost NAD by around 40 to 60%, that's in the published clinical studies, that absolutely ignoring the reasons why NAD is declining. So I always get people to think of this as a bit of a factory scenario. So if you think of yourselves as a factory that's producing NAD, because that's essentially him what they are, and production goes down in that factory. And how would you try to boost production? Again, would you just say, oh, production has gone down. So we'll just order more raw material and hope that it gets converted into gets made into an ad? When actually, if you took a closer look, what you realised is that the reason production is down is because the machines are broken, because there's no staff because the pipes are leaking? Would you still think that it's a good idea just to order more or more raw material and hope for the best? No, probably not, you'd probably say, Well, we could do a lot better job if we, you know, employed more staff if we fix the machines, and we're plugged the leaking pipes. And so this is where we say the best way to actually boost NAD levels is to have a whole system approach and really look at the root causes of NAD. And what's going wrong. And the main root causes of NAD is because the salvage pathway isn't working as well. So what can you do to actually boost your salvage pathway to increase the levels of that nampt enzyme so that when there are precursors, and in the cell, when there is an ad in the cell, it can actually keep getting used and recycled, rather than just, you know, taking in more precursor, and it's not actually getting converted to NAD in the first place. The other thing is, you know, look at the processes that are wasting NAD because the other reason that NAD declines is because when we get older, you get a huge change in the cells and the way that they use an NAD one of the key ones, there's chronic low level inflammation. And that is something that we know people suffer with. As they get older, they're having this low level low grade inflammation. And that's known to cause the overexpression of something called CD 38 in our cells, and basically CD 38 is an enzyme that just drains NAD. It just sucks it out of the cells unnecessarily. And so just by inhibiting CD 38, just a little bit, you can actually boost NAD levels. So again, this is like looking at what the root causes are in the cell that are causing this decline, and then actually fix them.

And then how would you improve it CD 30 A,

you can use a projection. So this is a compound, it's commonly found in parsley. And you can use epogen in and there's studies to show in cells in vitro, that if you inhibit CD 38, even just a very small amount with apigenin, you can actually boost NAD levels by 50%, just by getting rid of the waste. So this is just as good as using a precursor. So can you imagine what happens if you take a whole system approach and you actually, you know, you have a precursor. So you've got some of that raw material available. And you inhibit these wasteful processes. And you activate nampt, you're basically fixing all the issues, and you're restoring the cell's ability to be able to make and use and recycle its own NAD again, like it did when it was younger. And I guess that's exactly the approach we've taken. And when we we've took this approach with our product, we find that it boosts NAD a lot better than just using a precursor. So and in terms of numbers in our pilot study, it boosted NAD by 242%, over 16 days, which is a lot better than 40 to 60%. And over

16 days, which is really interesting. And we're looking at because this is the other thing that I think people can get confused over is when Dr. David Sinclair talks, you know, he's got like a bucket of LML in his basement, he's taking very high quantities, a lot of samples, you look at supplements that you buy the tiny amounts of this when you formulated Nichido. How have you optimised the levels there? Because I know like I've been taking it. And I've definitely seen, what I've noticed is improvements in energy. How How, how was that formulated to do that? If you see what I mean, in terms of the levels, how do people know that they're getting enough of what they need, because of the research you've done? Presumably?

Yeah. So when basically it's all it's all to do with my background. So before I found Nichido I actually worked in drug development and my before that My PhD was actually in the bioavailability and pharmacokinetics of drugs and nutrients. So that's something I'm incredibly passionate about is actually understanding, you know, how much of something has to go into an oral formulation to be able to go through the guts in the liver, etc, and actually end up in the cells at a concentration that will actually have some efficacy within the cells. So when formulating our product, that was a huge amount of work to get the right levels of the ingredients, and also the right combination of the ingredients. Because within our product, unlike an MN or nr, it's not just one ingredient, it's not just a simple precursor, it's, it's got a precursor in that we use, we actually use nicotine amide, which is one of the B vitamins. And the reason we use that is because nicotine amide, freely diffuses through cell membranes, it doesn't rely on a transporter to get it through unlike an RNN, which can't actually access all cells in the body, and the other ingredients in that they've all been selected based on the most bioavailable forms. So we met we mentioned apigenin, earlier apigenin, if you took that in its pure, you know, chemically synthesised form, shall we say, the bioavailability is actually very poor. However, if you take it in a format, that's a bit more natural, such as parsley powder, and which is what we actually include in our products. And it's readily absorbed by the body, and then the apigenin is actually released, once it's been absorbed, and then it's actually in a more useful form in the body. So that's why we see that it does indeed get into the cells intact in the way that we need it to do that.

Interesting, interesting. I was just looking at the ingredients that are in it, and then you've got, you've got Alpha Lipoic Acid, as well, in there, which I can see helps to activate a NPK. But that also is like an antioxidant in itself, right? And also helps regulate blood sugar from it if I'm remembering correctly.

Yeah, I mean, ala does a multitude of different things. The reason it's in our product is it's an activator V NPK, which, as we've discussed earlier, is incredibly important for activating the salvage pathway. And the other thing that alpha lipoic acid does is it activates another enzyme called MQL. One. And basically what this does, is it it flips an ad between its two states. So NAD can either exist as NAD plus, which is the oxidised form or NADH, which is the reduced form. And what we find is that if you activate and q1 it pushes the ratio of NAD plus to NADH towards NAD plus, which is the more favourable direction and whereas as you get older, it tends to drift towards NADH, which is not a favourable ratio. So ala also works within within this capacity as well to improve NAD levels.

Oh, interesting. And what about you were talking about the circadian aspect in terms of the way NAD this pathway works in the body? Is there an optimal time of day to take this supplement? Because when, when I've been taking it says to take three capsules twice a day. And I think when we chatted at the Health optimization Summit, you were saying just be cautious around taking it towards bedtime. But I was just curious, like if you can take it near to bedtime, is there any evidence that it would be better like when the body's doing its repair work, for example.

I think what we suggest doing is taking three capsules in the morning. And the reason for this is generally in the morning, people are in a fasted state. And as we know that the formulation has NPK activators in this is another way of almost prolonging that fasted state for a bit longer even though you know you're going to be eaten with your breakfast or your first meal of the day. It's a way of keeping that stress that signal to boost NAD levels kept on a little bit longer, even though you've almost stopped the fast. And so we would recommend starting it in the morning. And then again, we recommend taking it with the second meal of the day. Again, it's just you know, if you're eating that's naturally going to decline your NAD levels. And what we'll want to do is keep them high. So you know when nutrients comes in the body that's telling the body well there's no energy stress anymore, turn down a NPK you know, turn down NAD production. And what we're trying to do is keep the levels high. So we recommend just taking with food, you know, with your first meal of the day, and again, you know, four to six hours later.

Would there be any downside to then taking it again in the evening and taking Nine capsules,

we don't recommend going up to nine capsules, just because all the safety testing that we've done is on the six capsules. And also the levels of the ingredients that are within our product are actually pretty high. And some of them are, you know, at the max that you'd want to be taken. And again, some people say, Oh, my goodness, like, it's six capsules. And it's like, yeah, because that's what works. And you know, a lot of people don't realise that the levels of, you know, nutrients and vitamins and things that you actually need to be taken are way more than what are often on, you know, prescribed on the tub of a lot of the things that you see in the pharmacy, and which simply don't work because there's not enough of the good stuff in there to actually get through the gutter and through the liver and then to where it needs to do its, you know, do the magic,

but they do need to be taken with food is that for digestive reasons, or

we recommend it with food. The reason being is that some people don't tolerate taking, you know, multiple different tablets, on an empty stomach, we appreciate that a lot of people that are taking our product, perhaps practice fasting, and therefore we just say just take it with your food, and therefore, you'll just avoid ever feeling nauseous or anything like that. And when we've looked at whether it's should be taken with or without foods, it didn't matter. So just to avoid, you know, any risk of didn't choose to like that. Just take this boot.

Okay. Okay. So I think we have a discount code that you're going to share for listeners. I think it's my name isn't it is Angela tember we'll put it in the show notes in case those of you listening, I'm really enjoying. And actually, I'm going to be testing my biological age soon. So it'd be fun. And I've definitely seen what I would say is an uptick in energy. I guess one question I have for people that are going to going to take this, if they're taking any kind of B complex, should they then stop taking that, while taking this supplement?

Yeah, I always recommend is, if you take in any sort of form of vitamin d3, that you just you don't need to take it because you're going to be getting it entirely out of our product, you know, just have a look through the ingredients list, especially for people that take huge amounts of different supplements, check that there is no overlap with any of the ingredients. But, you know, a lot of our customers are people that were previously taken nr or that were previously taken and mn. And, you know, they've swapped to us in our product, because they understand the value it has in actually fixing the root causes of the NAD decline. And as you said, You've you know, you've experienced it and uplift in energy. And a lot of people do do report that. And you know, which verse isn't surprising, because, you know, it's actually fixing these energy problems in the cells and fixing the repair and things, things like that, you know, all our clinical data shows that, you know, we've got studies to show it is actually doing what we say it is, is doing in the cells we can see. And we've done western blot analysis, which shows it does upregulate nampt, which again, and are an event and the B vitamins don't do alone. And you know, so there is an added benefit of of going the extra mile and using an approach that is fixing the root causes of NAD decline. But the other types of benefits that people feel aren't just physical energy, but actually mental energy and brain fog, especially in in women who are going through perimenopause, menopause. That's a huge area of feedback we get from our customers saying how it's it's massively helped with the mental clarity and sharpness that they'd unfortunately, where I felt like they just didn't have it. And so I think that's another area for people to look out for. And also sort of mentioned sleep. Um, a lot of our customers report much better sleep and sleep quality. And if they've got a ring or a whoop strap or anything like that, that a lot of them often track it and again, report improvements in the quality.

Amazing, amazing. And do you recommend just taking this on an ongoing basis? Just every every month? Or is it something that you would cycle on an awful?

Yeah, we recommend, you know, it's something that you can take on an ongoing basis. You know, NAD can be viewed as an investment in your cellular health. Again, it's like one of those things that you can proactively do to actually keep yourself in good health rather than having to try and fix things later on. You know, so it's something you can take on an ongoing basis. I think we do have some cause demand that say, and you know, they're doing everything else for the health, you know, they're doing the exercises doing the fast. And so maybe they'll just take it when they feel like they need that extra support. And for one reason or another, but in general, the majority of our customers are on an ongoing subscription to Yeah, because they feel the benefits. And when when they stop, they've noticed,

amazing, but there's no so there's no like, there's no advantage to say write saying, I'm going to take it for 10 months of the year, and then cycle off for two and come back again and take it just to give your body for example, any kind of break where it's having to do this on its own without a bunch of precursors. What you're saying is actually no, you can just take it on a continual basis.

Yeah, not that we're aware of, from all the results and studies that we've done, you know, taking it on an ongoing basis to ensure that, for example, CD 38 is continually being inhibited. And so that it's not wasting NAD and to ensure that you've got, you know, increased activation of a NPK and the nampt enzyme, it's all something that just keeps going down with age, therefore, you've got to proactively keep trying to keep it up with age, and it's not a temporary thing

is only suitable for 18 Plus, is that is it for adults.

Yeah, because that's, you know, that's all we've we've tested it on in our clinical studies and our safety studies.

Interesting. Thank you so much. I know other people listening is gonna be really, really excited by this and want to go and find out more so we will link to your website, the chido.com. But where can people come and find you, Nicola. And I'm pretty active on social media and just connect with you.

Yeah, the best place to find me is on Instagram. And it's just at Dr. Nicola online, which you can you can add in the notes. But you know, although I spoke about NAD a day, my background is in ageing, well in general and cellular ageing, so attended to speak about a lot of other areas and aspects of ageing, if anyone's interested.

Yeah, you do you do share some exciting posts. I think I've seen you having you having what was it? Yesterday, I saw you having an infusion of of sorts was

I yeah, yes. ozone therapy, ozone therapy.

That was it. Yeah. So if you want to find out more about longevity, definitely go and head over and check out Nicola, Dr. Nicola Conlon, and Instagram, as Stefan account over there. And thank you so much for coming on the show today and sharing all your expertise. It's just been amazing to kind of just download all that knowledge on longevity for me, thank you so much.

No problem. Thank you so much for inviting me, Angela. I really enjoyed it.

Me too. Thank you. So if you're enjoying the show, then please make sure you like and subscribe to the podcast so you never miss an episode. And if you're enjoying it, please do leave us a positive review on iTunes or Spotify or whatever platform you're listening on, because it really helps to get the message out to a wider audience. And maybe you've got a question for me that you'd like me to ask a guest on one of my solo SOS bite size bio hacks, head over to my website, Angela Foster performance.com. And you can actually click on there to voice note your question for me for me to share on the show and the answer to it. Thanks again for listening, and I'll see you next week for another episode.

Thanks for listening. Remember to review and subscribe, you can grab the show notes, the resources and highlights of everything Angela mentioned over at Angela Foster performance.com You can also snatch up plenty of other goodies, including the highly helpful Angela recommends page which is a list of everything she personally recommend to optimise your mind, body and lifestyle.