NAD+: A Quantum Leap in Biohacking | 1122 | Dave Asprey

You're listening to the Human Upgrade with Dave Asprey. You're listening to the Human Upgrade with Dave Asprey. Today's episode is an Upgrade spotlight. These are episodes where I bring in a guest to explain how and why they built something that can benefit your life, something that's going to save you time, increase your energy, improve your performance, maybe extend your lifespan. And in this episode, we're going to talk about nad, which is what some people are calling the aging molecule. I'm not sure I'd go that far, but I have been a major proponent of NAD over the past 10 years. And before that, one of its precursors, called niacinamide is something that we've used for 30 years in the field of longevity. We just know a lot more about why it works. Dr. Greg Kelly joins the show from the Neurohacker Collective, where he's the senior director of product development. And I've worked with the Neurohacker Collective, also known as Qualia. You've probably heard them talks about both ways. I'm an advisor to the company and a shareholder, and I think they do fantastic work and very innovative work. He was last on the show for episode 1009, about a year ago in January of 2023, talking about senolytics and zombie cells and a new product category that Neurohacker pioneered. And this time, we're going to talk about a different approach to raising nad. By now, everyone and their mother in biohacking and longevity knows about NMN and nicotinamide riboside. But there's a little bit more to it than that. Dr. Kelly, or Greg, as I'm going to call you, welcome to the Human Upgrade.

Thanks for having me back on the show again.

Let's go into it. I said everyone and their mother has heard of NR and nmn. Maybe your mothers haven't. So walk me through. What is NAD from your perspective in the human body and why do we care?

Yeah. So I want to just start at a high level. The audience is going to be familiar with the term like genome, the collection of all our genes. That's the om, you know, the gut microbiome. The OME there is the collection of all of the gut microbiota and their genes. So what scientists sometimes talk about is the NAD plus metabolome. So NAD plus molecule, but all the other molecules that go into making it, things that are made from it. And the way I tend to think of it is think of these different molecules. We'll just use NAD plus as an Example, to start as big hubs in our cells and mitochondria. And a hub you may think of, like. Name the busiest airport you've been to in the last year, Dave.

Probably lax. Good guess. Although Dubai was pretty busy, too. Who knows?

Yeah, so we've got these major airports, big hubs, lax, Miami, Chicago, o', Hara, Dallas, that lots and lots of passengers flow through every day. And in ourselves, these hub molecules like nad, think of NAD as being akin to the airport, but many, many NAD molecules pass through it every day, so they're passengers. But NR and NMN would be like smaller airports that feed into that. So we want those planes to go from where they started and arrive at the NAD terminal. Right. We don't want those passengers stuck there. And then we want the passengers that are in the NAD plus airport to go on to their next destination, which may be nadh, which is critical to make ATP or nadp, and nadph, which is critical to make antioxidant defenses that help us, you know, detox and keep cells healthy. Or there's another airport that's called NAD consuming enzyme. So there's different enzymes in our body. One's called parps, that the parps are a family involved in DNA repair. We want NAD to be able to go in that direction. So fundamentally, when I think of nad, I'm thinking of the metabolome, like this collection of airports, and I want to make sure the passages flow, flow through to wherever they want to go and don't get stuck somewhere.

So I'm wondering, is, is like glyphosate or maybe a spike protein of some sort? Is that like the TSA that just gets in the way and doesn't do anything beneficial, or is that just me?

I would think absolutely. Like, metabolic stress of all sorts is the one thing that for sure dysregulates that whole transportation system. And we know that's a big metabolic stress.

And I'm actually teasing. I actually have friends in the tsa and it's a thankless job. So, yeah, there's always a few people who are cranky, and there's also a bun of people who are just there trying to get you through. So you guys have to let me tease you like I tease vegans, because they tease me back. What we're doing, though, is we're using NAD to power different pathways of longevity, on aging, on detox, on cell repair. And the reason that we're also excited about it in the field of longevity or just even in athletic performance, is more nad, more power More power, more whatever the body decides to allocate power to according to the way it allocates power. So if you were to come and do an upgrade labs and you have adequate nad, when you do the muscle building thing, you're going to put muscle on better than someone who can't make extra power. And if you're doing a longevity track at upgrade labs and you have adequate nad, then your longevity therapies work better. And one of the things that I used to do 10 years ago is I'd say, all right, everyone, let's line up for our NAD IVs. And I've done 20 NAD IVs. And it's quite expensive, and it's also very uncomfortable if you kind of feel like there's a weight on your chest and you're gonna barf. And I don't particularly enjoy it. And it seems like with what we understand with supplements now, you can get your levels of NAD inside the cells, get it up about what you could do with an iv, and it's a lot cheaper and a lot more comfortable. So I kind of feel like NAD IVs are kind of on the way down because you don't need to to get the results. What do you think about comparing the work you've done with multiple factors at the same time for the neurohacker NAD formula compared to IVs? I know you're biased, but you're also a scientist, so you're going to tell me the truth. If not, I'm going to tease you.

NAD is a big molecule. It's why if we take it orally, there's just enzymes that shred it before it gets absorbed in one piece. And it's a big molecule when we do it in an iv. So trying to get it intact into cells is challenging at best. There's some people that are convinced, based on actual science, that that NAD molecule has to be broken down into smaller things, like an NR as an example, to then get into cells. And it's probably limited how much of those enzymes are outside of cells to do that job to start with. So I think there's usefulness in NAD IVs. I also think it's not the most expedient or like you said, the most efficient way to boost intracellular amounts of nad, if that's our goal. And I think it's a legitimate goal to have as we get older, since it's well established that the amounts of passengers in that major airport are decreased progressively with each decade we get older.

Which is better NR or NMN or.

Niacinamide, you know, I think they're all slightly different. So one of the key things you see in cells and biology in general is redundancy. So when there's a really important molecule, which NAD is, there's often backup plans for making it. So if you think of nad, cells can make it from flushing niacin, nicotinic acid. So that's called the price handler pathway. It's its own unique way to get into it. I mean we could start even with tryptophan and we'd eventually turn that into something in that price handler pathway. But then there's another pathway that's usually called salvage pathway. In that pathway you've got niacinamide and NR that both feed, feed in to the NMN molecule in different ways. And then NMN again, it's just a big molecule. So the consensus is that NMN has to be broken down to NAM is usually how you abbreviate niacinamide before it can actually gain entrance. So I think all of these things increase NAD in the cells, but they do it in slightly different by coming from different airports.

Fundamentally it's kind of like which of the rivers that feed into the Mississippi is responsible for the Mississippi? Like well, maybe you should enhance all of them a little instead of just putting it all in one. And just in the realm of biohacking, when I started, before I knew the name for it, I'm like, I'm just gonna try one supplement and see what happens and then I'll stop it, then I'll try another one. And I just realized one day I'm probably not ever going to try all the supplements cuz I'll die before if just one month per supplement. There's too many supplements. And on top of that, what if two supplements amplified each other or just amplified different pathways of the same effect? And I literally said, you know what, I don't care if I take five things and only three of them got me the effect and the other two weren't harmful. I'm down because I want to feel the energy right now and feeling good and looking good and having energy, those are priceless. And I've spent a year. The first time I was recovering from severe adrenal fatigue and I took six weeks the next time because I used a biohacking approach, said maybe I should do more than once one thing. So I feel like our job is to break the big pharma viewpoint that there must be one thing that's a cause of it. That's a, a untested and false assumption. And what you're doing with the NAD plus formula that you have is you're feeding multiple pathways at the same time. Which is why I think it works as well to get levels up as you're going to see with a lot of people who do IVs.

Yep, I agree. I think that redundancy is super important.

Now, one thing we haven't talked about before we go into how you're doing this is sirtuins. You talked about parps before and what's a sirtuin? I read about these in my longevity book, and a lot of longevity listeners may have heard of these. But define sirtuins and talk about the latest research on what NAD does for sirtuins and longevity.

So sirtuins are basically their enzymes. So they're products of genesis proteins. And there's six sirtuins, so one through six. But that family of enzymes, I think just in the biggest sense is involved in cells responding to stress, mitochondria responding to stress. Depending on the family member, it may be more in the cell, another family member be more in the mitochondria. And so one of the things like. So I took biochemistry 30 years ago, and at that point NAD was prominent in biochemistry, but for its role in fundamentally two things, the creating ATP. So that's the NAD NADH redox pair and nadph, which is another redox pair, that's our detox antioxidant defenses. So what eventually became known more about 20 years ago is that there's this entire other use case for nad, independent of those things, where the NAD molecule basically gets eaten or consumed to drive these enzymes. And one family of those enzymes is the sirtuin family. And so you need NAD to basically activate that family. And then sirtuins, I think of where they really shine is allowing cells and mitochondria to respond to metabolic stress. Not so much in like, oh, like sirtuins are gonna make you live super long. But I think there's just so many things that cause metabolic stress. We want a fuel supply of NAD to be able to deal with it. And then the PARP family, that's a DNA repair family of enzymes, they also consume the NAD molecule. Right. So that third use case I just think of as the consumption use cases. We need a certain amount of NAD just to be consumed. And just to put it in perspective, like riboflavin also is something that is used in a redox pairing, an fad, fadh, and the daily value of riboflavin I don't know, like 1.2 milligrams. The daily value for like niacin niacinamide is more like 16. And the reason is because in the toggling between the redox pairs, eventually the molecules get used up and eliminated. But they're conserved somewhat. Right. They just go and flip them back and forth. But when NAD is consumed, you're using it up. So you just require a lot more of that CO factor because it's being consumed many, many times through a 24 hour day.

So you want to raise sirtuin levels for longevity cognitive performance. And to do that you have to raise NAD levels. And to raise NAD levels you do it via different pathways that all lead to more nad.

Yeah. And what's thought is that one of the reasons, and there's many one, the of that NAD tends to be lower as we get older is because some of the consumption pathways are basically eating most of it, leaving the other one starved.

That makes so much sense. And it's a relatively complex biochemistry. If you're listening to this and your eyes crossed, that's okay. What's going on here is we have a bunch of really smart longevity and supplement scientists getting together saying what are all the things we could do at the same time to raise nad to get all of these downstream longevity anti aging benefits. And if you look at what they first started NAD IVs for, it was actually for alcoholics because when they would do a bunch of NAD IVs it would fix their mitochondria and then they would stop craving alcohol in a surprising amount of the time. So I, I believe having enough energy in the body is an anti addiction strategy because even down at the cellular level, the cells, when they have enough energy, they feel safer and more able to handle the world around you, which means you're less likely to reach for a substance. And yes, there's trauma, yes, there's all sorts of other things. When you start at the very high levels and you work all the way down into the subcellular stuff, it always ultimately equals energetics. So I don't know if oral raising of NAD has that effect, But I know IVs do. And I believe oral is now reaching the same efficacy as IVs because you're doing multiple pathways and IVs are just straight NAD. And also cost effectiveness like orders of magnitude more affordable to do. The Neurohacker formula versus IVs. So what did you put in there? After all the research and all the different pathways, what is in the qualia.

NAD plus formula, niagen nicotinamide riboside, which is by far the most studied form of that nutrient for increasing NAD levels and doing other things. In humans, we also put a bit of the flushing niacin form, but below threshold. You should flush to support that way of making it and then some niacinamide. Right. So we wanted to cover those three different ways of making it. But then one of the things that I think is so underappreciated, right. I know when I was originally hearing about nad, the thing I constantly hear is like, oh, well, NAD is super important to make ATP, which is true, right? Like, that's one of its oldest known functions. That nad, nadh pairing, can't make ATP without it. From carbs, from fats, you name it, NAD is involved. But what I've never heard anyone talk about is how instrumental ATP is in making ATP. Right? And so just quickly like to make NAD from nicotinamide riboside, that's two steps, right? So you go and basically changing over planes somewhere. But the second one requires ATP to make it from niacinamide. The same. It's two steps, but the second one requires ATP to make it from the flushing niacin. It's three steps, but two of the three require ATP. And I know you know the name James Clement.

Oh, yeah. He's done the show a couple of times. Known for 25 years, the longevity guy. Right.

So he did a study, probably about 2018 or 19, it was published, called the NAD Metabolome is dysregulated in plasma with aging, something along those lines. And what I found super interesting about that human study is in nad, levels first were declined with age. So we expected that. But other airports in the metabolome, some of them had fewer passengers, some of them had more. So it seemed like in some instances, the molecules were stuck somewhere, not getting on to the next stop in the metabolome. And at the time, I pulled up a biochemistry drawing, and what popped out to me is that there was ATP in all these places, but anywhere, ATP was the front end of that. So the place in the metabolome before that is where people were stuck, or these molecules were stuck, and the other end of it was where they were lower. So the unifying thing that helped me make sense of what he saw in that study, with some molecules being normal levels, others being too high, others being depressed, was that anywhere ATP was needed, work wasn't getting done to move things along. And flux is what ultimately matters in cellular health. And so one of the things we did in this qualia nad product is we wanted to do things that supported ATP. And another thing I don't hear mentioned enough is that whenever you see ATP, think ATP magnesium complex, the two are always together in our cells and mitochondria. So without that magnesium complexed on to ATP, ATP wouldn't do any work. So because of that, we wanted to make sure there was magnesium in this product to help create the flow through this complicated network of molecules.

One of the things that I think every one of the listeners is doing is taking magnesium in one form or another right now, because I've been talking about it for so long.