Reversing Aging: The Power of NAD+, with Dr. Nichola Conlon

If we've got this really important molecule and it declines with age and it's causing all these problems that are driving the hallmarks of aging, then why don't we keep them high as we get older? And basically, if you can keep NAD levels high as you get older, you can actually impact the hallmarks of aging, slow them down, and actually reverse biological age.

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Hello, and welcome back to the Feel Freaking amazing podcast. I'm Dr. Wendy Trubo. Ed can't be here today, and he's going to miss out because we have Dr. Nicola Conlan. She is a molecular biologist who specializes in the study of cellular aging and the science of aging. Well, she helps people reverse their biological age and improve their health span. Her work has led to the development of a dietary supplement clinically proven to reverse biological age. Welcome, Nicola. It's great to have you here.

Hi, Wendy. Thank you so much for inviting me. It's a pleasure.

My pleasure. So you've referred to NAD offline. Can you talk about nad?

Yeah. So NAD is a really exciting space that I've. I've researched for a long time now, and NAD is being found one of these molecules that actually impacts many of the underlying cellular root causes of aging. So when we look at the aging process as scientists, what we see is that there are 12 key things that seem to go wrong in our cells that sort of drive the entire aging process. And these are famously referred to hallmarks of aging. And these cover things like DNA damage, senescent cells, inflammation, all sorts of things like that, which we don't have time to go into all of them. But essentially what we do need to understand is that everything to do with aging is driven by these hallmarks. And if these hallmarks get worse, aging speeds up. And if they get better, then aging seems to slow down. And NAD is something that has been demonstrated to impact all of these hallmarks of aging. So it's something that's naturally found in all of the cells in our body. It stands for nicotinamide adenine dinucleotide, and it's involved in hundreds of different cellular reactions. But I guess the two things that it's most famous for Are for energy production in our mitochondria and for repair in our cells. NAD seems to act as a fuel to drive repair processes. Now the reason it's linked with aging is because NAD is found to decline quite exponentially as we get older, as many things do. And as NAD goes down, it actually impacts the hallmarks of aging because our cells don't have enough energy to function correctly anymore. Repair starts to get turned down, we start to get damage in the cells, and this drives the hallmarks of aging. So a lot of scientists said, well, if we've got this really important molecule and it declines with age and it's causing all these problems that are driving the hallmarks of age, and then why don't we top our NAD levels up or why don't we keep them high as we get older? And basically there's been so many studies now in not only cells, animals, but even humans now that has demonstrated that if you can keep NAD levels high as you get older, you can actually impact the hallmarks of age and slow them down and actually reverse biological age.

Okay, so is it linear? Meaning I'm assuming you start out higher when you're younger and then it goes down as you age, Is that assumption correct?

To a certain extent. So whenever I do a talk about nad, I actually don't show, although it's an exponential decline. So you would expect like this linear graph. I actually show a bit of a strange graph for a scientist and it looks like a mountain range where it's going down, but it's peaks and troughs. And the reason for this is because yes, age makes NAD decline, but also lifestyle does massively impacts your NAD levels. So yes, it will generally decline as you get older. But if you have a very bad lifestyle, in particular drinking, excessive alcohol, sunburn, smoking, inflammatory diet, those things will mean your NAD will be depleted quicker. So it is lifestyle dependent as well.

What about stress? Like what about non exercise related, just lifestyle, psychological stress? What role does that have on depletion of nad?

So I don't actually think there's been any official studies that have looked at psychological stress and NAD levels. But from a theoretical perspective, you know it will drive down nad, because we know that stress induces cortisol, which is pro inflammatory and we know there's a direct link between the level of inflammation that you have in the body and your NAD levels, because a few of the processes that are involved in inflammation actually use NAD as a fuel. And actually NAD in terms of it's, it's like it's Like a. How would you put it? It's like a. A vicious cycle in terms of the damage. Because inflammation goes up, NAD goes down. That means there's even less NAD to repair the damage that inflammation is doing, which means more inflammation, which means NAD is going down even further. So we know that there is a link there.

Okay. So it makes sense to think that stress would deplete NAD because of the pathway you're talking about with cortisol. And then are people who. It's kind of like, is it a chicken or egg? So people who have an autoimmune disease, did the NAD deplete and then they weren't able to repair? Or did the autoimmune disease development lead to depletion of nad? And am I just making all that up anyway?

No, I think in specific conditions, you know, autoimmune, metabolic conditions, we know actually the metabolic condition or the autoimmune is contributing to the low NAD for whatever reason, and then the low NAD is then making the condition worse. So I think when it comes to conditions, there's ever. There's not usually a single cause. There are some conditions where we know NAD is one of the root causes. There are some genetic accelerated aging diseases where we know depletion of NAD is a direct cause of the disease because it's a genetic defect. And when there is not enough nad, there is no NAD to drive DNA repair, which causes DNA damage, which drives the aging process. Some diseases, it's the NAD first. Other diseases, it's the condition caused by other factors that then depletes the nad, and then that makes the whole situation worse. That is especially common in more of the metabolic conditions. So things like fatty liver disease, obesity, which develop mostly from lifestyle issues, but then cause massive problems with NAD depletion, which then have a major impact on a lot of other issues in the body as well as.

Okay, so now what can people do about it? Because it sounds like if lifestyle can deplete it, then lifestyle could potentially raise it. Is that an accurate thought?

It absolutely is. And we know that two really good ways of boosting NAD are inducing that energy stress through things like fasting and exercise. Both of those things have been proven in human clinical studies to actually elevate NAD levels. Because when that little alarm bell, that energy sensor goes off in cell, one of the things that it actually triggers is a pathway in our cells that produces nad, and this is called the NAD salvage pathway. And it effectively upregulates this pathway and tells the cell, okay, we have no energy coming in so we need more NAD to drive the mitochondria, and also we need more repair. So we need more NAD to drive these repair processes. So NAD production naturally goes up.

So there's a pathway to bring it up, and there's clearly things that bring it down. Why does it naturally decline? Do you have a sense of what goes on for the body? That it starts to just naturally go down over time?

Yeah. So we now, for a long time, it wasn't really understood why NAD declined, but now we really do understand it and there's two main reasons. So first of all, older cells just generally use more nad. So they've been around for longer, They've got more DNA damage, they've got more inflammation. All of these processes are using NAD as a fuel and they are literally draining NAD supplies. So it's a, you know, there's, there's basically more demand there. The second known reason is because our ability to actually make and recycle NAD as we get older in our cells also declines with age. So that pathway I just mentioned, the salvage pathway, it has a key enzyme in that pathway which has a very long name. So we have an acronym for it, which is na npt. But essentially this, this enzyme is the rate limit and step in this NAD production pathway, and that declines with age. So basically you have this situation where as you get older, not only is demand for NAD going up, but actually your ability to produce it and recycle it is actually going down. So when you put the two things together, you get a deficit. And this is why we see this exponential decline. We get older.

So can you take the enzyme?

You can't take the enzyme, but you can boost the enzyme. So exercise and fasting, they both increase levels of this specific enzyme. That is naturally what they switch on to elevate NAD levels. And then there are various other ingredients and supplements now designed to actually do this, to actually switch back on that enzyme.

I'll just talk about the supplements in a minute, but I think something you just mentioned a few minutes ago is really, really important for our listeners because our listeners are really into toxins and longevity. And toxins are a huge source of oxidative stress because the liver has to deal with it. And phase one, it takes it from the toxin to something more toxic, and then phase two binds it and gets it out. So if you get stuck in the middle, in the oxidative stress phase, you now, I would imagine, are depleting NAD because you have a state of DNA damage from the oxidative stress. Right. So so toxins are nasty food sensitivities, lifestyle choices like smoking, alcohol, sugar, sort of like the three devils in our lives. And then, so it sounds like not only. And because we're exposed to toxins everywhere, we're getting this constantly. And then we have psychological stress and then we have sedentary lifestyles, and then we eat what, you know, America's exported our food to the world to the standard American diet. So it seems like we're just compounding this whole issue over and over. Like it's just, it's not going anywhere, right?

Yeah, exactly. And I think it, you know, lifestyle can't be underestimated when it comes to NAD depletion. Anything that is damaging from for our bodies is depleting our NAD and using up those NAD stores. And at the same time, our modern lifestyles are turning down the processes that would naturally deal with this, that would naturally switch on the repair processes and, you know, switch on the pathways for detoxification and switch on any production. Because we're living these lives that our bodies aren't designed for. Everything in our cells, evolution is designed for basically getting us to the point of reproduction in one piece and finding some food, reproducing. That's it. We weren't designed to be living these lives that we now. So when you look at a lot of biology and a lot of the pathways, they only actually make sense when you view it through the eyes of evolution of what our bodies were designed for in the first place. And that is certainly not the modern lifestyle that we are leading. And I think a lot of people are unaware of, of, you know, actually why does it decline? Like, what is causing it? And you know, if something declines in the body, there's usually a reason for it, and it's usually better to fix the reason than just ignore it and just try and fil our bodies with, with, with more of the substance. Anybody who has followed the NAD space for any amount of time will have heard of molecules like NMN or nr, which are, you know, the preferred ways to boost nad. But, you know, they absolutely do not address the root cause of NAD decline. I always say, you know, if you had, if you had an NAD producing factory, imagine that was our cells and you went into the factory and you were like, right, let's look at why NAD production's gone down. And you saw it was because the machines were broken, the pipes were leaking. There is no way you would just go, okay, let's just ignore that and just, let's order more, more raw material and Hope more NAD comes out the end. You would say, okay, there's a serious issue in here. We need to fix the machines, we need to stop the pipes leaking, and that is how production is going to go up. We don't actually need more raw material. And that's just exactly the. In the NAD space, a lot of people are taking nmn, they're taking nr, and actually it's not what is the problem. We don't have a limitation. There is no evidence to show that. The reason our NAD goes down is because we don't have enough raw material. If you've got a decent enough diet, you will be getting enough of those raw materials. The issue is actually converting them. And there's now a lot of papers coming out showing that, you know, excessively taking things like NMN can actually be negative. It can actually drive inflammation. Because if you are putting NMN into a cell that's chronically inflamed, infl. The inflammatory processes have what we know, what we call is a higher affinity for NAD than some of the repair processes. So if NAD becomes available in an inflamed cell, the inflammatory pathways will grab it and use it before the repair pathways even get a look at. And so again, it's really important to, to look at these underlying issues before you just start tipping whatever back into the cells and hoping it's, it's going to fix the problem.

Okay, I know you've done a lot of work on this. Like, this is your life's work and, and you've also developed a supplement. Can you talk about it and talk about how it works and what is it?

Yeah, yeah, absolutely. So I, I left drug development in 2017 to found this company. And everyone thought I was pretty crazy when I said I was leaving my very credible job in drug development to be start a supplement company. Because, you know, supplements are snake oil and they don't work. But, you know, I'd seen how powerful some of these molecules were that were not drugs. And I wanted to give them the research and, you know, development that they deserved and the test and they deserved. So I'd learned about NAD and how important it was in the body and the fact that it could have such an impact on biological age and such an impact on cellular health. But right at this time, there was a lot of buzz about how do we boost nad? You know, NAD is this good thing, so let's just get it back in the body any way we can. And there were lots of different methods popping up of how people were boosting nad. Everything from trying to put pure NAD in a capsule and swallow it, which does not work by the way, through to do an IV drips and all sorts of things. And when I looked at everything, I was like, none of these things make scientific sense. We know now that the reasons why NAD declines is because of chronic inflammation in the body and the fact that this key recycling pathway that has the enzyme in it declines with age. And none of these products or any of these supplements or ways of boosting NAD are actually acknowledging that and trying to do anything about it. So what we wanted to do was basically develop a supplement that fixed the root causes of NAD decline. So it actually switched back on the body's natural NAD production pathway. It helped to reduce the inflammation that's driving the NAD decline and also helped to get around another issue that we haven't spoke about yet, but this methylation problem that comes up a lot when, when people talk about nad. And so, so that is what we set out to develop. And we ended up at this, this product, Nucido Time. Plus we did a full human double blind, placebo controlled crossover study that's now being published in a really good journal, a Nature Aging journal, and proved that not only did it boost nad, but it also actually switches on that key enzyme that declines with age, that NAMPT enzyme, and also reduces many biomarkers of aging. We saw that it reduced inflammation, it reduced glycation. It also was shown to reduce biological age. So we actually measured biological age in all of the participants as well.

Were your participants allowed to have chronic illnesses like diabetes or pre diabetes or hypertension? Like were they, were they allowed in if they had that?

So we, we generally were like the thing, the thing about our study that is different. So a lot, if you look at a lot of studies to do with aging or NAD specifically, they will use 55 to 65 year old men, usually with, with obesity or some sort of a metabolic dysfunction? Because that is the group that is most likely to show a result for us. I was very passionate about doing something a bit different because that's definitely not representative of the average population who could benefit from such a thing. So we actually use male and female in our study and we used huge wide range of ages, everyone from age 20 right the way through to age 80. And we were like, you cannot be taken various drugs, various supplements, have various diseases. So generally healthy people that we really wanted to eliminate the disease factor and just look purely at their NAD levels and is this boosting their NAD levels and what impact is this having on cellular health for somebody who is generally health, because ideally we want to be preventative and proactive rather than try to deal with conditions that have already developed. So that was kind of the thinking behind the design of our study rather than the classic, you know, pick your group that's most likely to respond type of trial.

Do you have another study going on with people who are sick to look at the impact of, you know, because the challenge is humans often respond to crisis, they don't respond to prevention, even though that's the ideal. You get humans in order and they're like, you know, I literally remember someone my kid went to school with. They had this failure to thrive and terrible GI issues and was always bloated and constipation. And the mother was like, I'm not doing anything and I'm not going to change his diet unless he has a diagnosis of celiac. And I was like, I really wouldn't wish a diagnosis of celiac on anybody because it's an autoimmune disease. But I was like, I kind of wish you have some reason to change your ways. And he ended up being diagnosed with celiac, so it was kind of good for him. But I just, I'm curious about whether you're going to do that with sick people, because most people wait for a problem to respond to. You know, maybe 5 to 10% of people want to be healthy for the sake of being healthy. And the rest of us, we respond to a crisis. So, like, what happens? What happens in that situation?

So, and it's a really tricky one for us because as a supplement company, we cannot talk about disease. So that is one key, key difference. You know, we can do all the testing, we can prove everything. But the difference between a supplement and a drug is that a drug is designed to treat a disease. A supplement is not. And we're not allowed to talk about disease. So we, you know, if we start to do trials and say, ah, supplement is going to cure whatever, then that's when it becomes a drug. And it very much depends which country you're talking in, actually. So the uk, very different to the US us You know, you can say a lot more as long as you've got the research to back it up. So, yes, you could say based on, you know, we measure glycation, we know glycation is a leading cause of arterial stiffness. We're not claiming arteries going to help with cardiovascular disease, but it's kind of like, you know, join the dots, because we've got the data to show that in the uk, very different story. Absolutely. Can't mention anything, you know, to do with glycation, because that is a registered claim for a supplement. So it's. It's tricky and it's very frustrating. And I always say that this is the big reason why the supplement industry is set up to fail, because no companies are going to. Are going to fund research to look at, you know, conditions when they can never actually talk about it, which is sad. But what we've done is we proved that our supplement boosts NAD in the human population. And what everyone else can see from a lot of other studies that are not our studies is how beneficial NAD is to so many different diseases.

What's in the supplement?

So in the supplement is a range of different ingredients. So it's not nad. That's what a lot of people say. They say, oh, why has it not got NAD in it? NAD itself is very unstable, so you cannot just put pure NAD powder in a capsule. It doesn't work like that. So what we have in is, first of all nicotinamide, which is a vitamin B3 derivative. It's one of the building blocks that your cell uses, this pathway that makes NAD in your cell to create nad. So it's like the raw material. Now, most of the supplements just stop there and just say, well, let's give the body more raw material and hopefully it will turn it into nad. But as we mentioned, that pathway that actually turns it into NAD doesn't function as well as we get older. So then we have a lot of other ingredients in there that are actually designed to switch that back on. So that key enzyme in the pathway, nampt, we have two ingredients in there that do that. One of them is called alpha lipoic acid. And the way that works is it activates that energy sensor in the cell that kickstarts NAMPT production. The other ingredient we have in there is something called Sephora japonica, and that is a flower extract and it contains high amounts of ingredient called quercetin. Now, this is something that, again, is hugely popular within the longevity space for multiple different reasons. And a lot of people say, well, why don't you use pure quercetin? Why do you use this flower extract? And the reason is because of bioavailability. So a lot of studies have been done in cells that put the pure molecule onto the cell, but actually when you're taking it orally, it doesn't work like that because these molecules never exist in their isolated form in nature. We also have parsley powder in there for the Exact same reason that it's got an active ingredient called apigenin in there. Again, don't want to take apigenin in its pure form because it's not absorbed. But when you take it as the more natural extract, it is absorbed and actually can get into the cells where it's required. So I'm, my PhD was actually in bioavailability. So I'm very particular about molecules because so many people just say, oh, this study was done in cells, let's just purify it and put it in a capsule. And then it never works because it's never actually found like that in nature. Yeah, so that's, that's some of the ingredients we include in there. Another one is green tea extract. The reason we use that is for an ingredient in there called egcg, which is a powerful active that actually what it does is every time NAD is used up in the cell, it's actually broken back down into its precursors, it's raw materials. And in young cells, our recycling pathway picks this back up and recycles it straight back into nad. But in older cells, that recycling pathway is not working properly. So what happens is the raw materials start to build up and then our bodies start to over express another methylating enzyme, which basically sticks a methyl group on the raw material and tells it to get out of the cell. And what the EGCG does is it prevents this from happening, so it gets rid of this methylation issue in the cell.

I mean, it's funny because some of the things you're talking about are pretty commonly used in the world of functional medicine. You know, alpha lipoic acid is everywhere, we're using it all the time. But then the, some of the egcg, like those are, are really commonly used. But then the extract from parsley, you said, right?

Yeah. Apigenin. Yep.

Yeah. So those are. I'm not using that as frequently, so it's just very interesting. So how do people feel when they're taking it?

So the sort of top reported benefits from, from the supplement are first of all, physical energy increase. And secondly, very close second is cognitive function, a reduction in brain fog. And these two things are not surprising because we know mitochondrial dysfunct function contributes to a reduction in energy, tiredness, fatigue, brain fog. And we know that NAD is integral to mitochondrial function, so boosting your NAD will improve that. The third most reported thing is actually improvement to sleep. And one thing I haven't spoke about is the link between NAD levels and sleep. NAD is very important for regulating Your circadian rhythm, which is your 24 hour, not just sleep, wake cycle, but cycle across the entire body, regulating all sorts of different functions. And as you get older and your NAD levels go down, the fluctuation in NAD levels throughout the day actually influences your circadian rhythm. So as NAD goes down, circadian rhythm isn't as strong and we get disrupted sleep a lot more as we get older. And actually boosting NAD can actually help to regulate that. And we've done another study, which was a sleep study, and it's not been published yet, but we saw out of 30 people, 27 people had an improvement to sleep, a significant improvement to sleep. Three had no change. Nobody got worse.

Okay, and do you have to take this forever or is this an episodic? You know, you take it for three months, then you stop for nine. What has, what's the way you take it?

So we recommend that people take it for at least three months to begin with. Obviously, we would recommend people take it continuously as an investment in cellular health. It's better to keep your energy levels high rather than let them drop off, damage, accumulate, and have to fix the issue. We do. Obviously, some people don't want to take supplements continuously for whatever reason. We know from our clinical study that after six weeks everything returns to baseline. So we would say if you are going to stop, you wouldn't want to be stopping as long as six weeks. And because the levels of the enzyme will go back down to wherever you started at and will go back down as well. But we, you know, the majority of our customers will do take it continuously because they, they actually feel a benefit. And I think that's interesting because a lot of people that take supplements often report like, I don't really know if it's doing anything, I don't feel anything. So the fact that so many people feel a benefit, I guess, isn't that surprising because we know NAD is so important for many functions and can, you know, can cause chaos in the body when it goes low.

This is fascinating, Nicola. Like, I mean, I, I've spoken on NAD and telomere health and mitochondrial health, but just looking at it from this different sort of aspect is fascinating. So thank you. Okay, so I feel like we've touched the surface and I'm assuming that people are going to want to follow you, find out more about you. Where, where can people get in touch, find out more about you and follow you?

Yeah, so I, I do a lot on Instagram, mostly. So not just about nad, but about all aspects of aging and cellular aging. And my Instagram handle is just my name@rnicolaconlan. And if anyone wants to know a bit more about our dietary supplement, my company is called Nuchido. N U C H I D O and again, you can find us@nichido.com or on Instagram. And you know, a major passion for both me and the company is not just products, but it's education and really helping people to understand some of the science behind all of these longevity things and, you know, how we can implement it into our life. So we do a lot of education and blog posts and you know, just if anyone wants to learn, definitely head to one of our pages.

I think this is great. Okay, listeners, you got it from the source. Dr. Nicola Conlin. She is the founder of Nucido and also a molecular biologist and we just talked about nad. So follow her, like her, do all of that. And then, Nicola, thank you for being here. This is really cool. And now I'm starting to think about, like, okay, I don't do this, I don't do that. I don't drink, I don't smoke. But I have stress. I'm like, okay, I think I need to move more and stress less. So thank you for this because it's always good as a reminder, right? Like, how do we healthfully age and improve our health span? So thank you. Thank you for being here.

You're welcome. Thank you for having me.

My pleasure. And thanks to listeners for joining us for another episode of the Feel Freaking Amazing podcast. Have a great day. Inspire and empower someone else by leaving a five star review so they can transform their lives too.