The Peter Attia Drive - Qualy #57 - A primer on NAD+/NADH, its effect on lifespan/healthspan, and a review of the supplements

Episode Date: November 12, 2019

Today's episode of The Qualys is from podcast #02 – Rhonda Patrick, Ph.D.: the performance and longevity paradox of IGF-1, ketogenic diets and genetics, the health benefits of sauna, NAD+, and more.   The Qualys is a subscriber-exclusive podcast, released Tuesday through Friday, and published exclusively on our private, subscriber-only podcast feed. Qualys is short-hand for “qualifying round,” which are typically the fastest laps driven in a race car—done before the race to determine starting position on the grid for race day. The Qualys are short (i.e., “fast”), typically less than ten minutes, and highlight the best questions, topics, and tactics discussed on The Drive. Occasionally, we will also release an episode on the main podcast feed for non-subscribers, which is what you are listening to now. Learn more: https://peterattiamd.com/podcast/qualys/   Subscribe to receive access to all episodes of The Qualys (and other exclusive subscriber-only content): https://peterattiamd.com/subscribe/  Connect with Peter on Facebook.com/PeterAttiaMD | Twitter.com/PeterAttiaMD | Instagram.com/PeterAttiaMD

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So without further delay, I hope you enjoy today's quality. So there's one more topic I just wanna get get to, we can spare a bit more time, which is, which is NAD. The precursor is the whole stick. You've spent a lot of time thinking about this. What is your current thinking on, does having more NAD to NADH matter? The thing about the NAD. I guess I should provide context for people.

Why am I asking this question? So there's lots of supplements out there now that are either giving NR or NAD. And the claim is that these things can enhance longevity. You could live longer and that also you live better. You have more energy, all of these other things. And so in the mitochondria, you have complex one, which converts NADH to NAD, and the idea is we do know that as you age, that ratio of NAD to NADH goes down. And so part of the thinking is, well, and this is outside of the CER2 and pathway, but

this is upstream of that. But if you give more of either the precursor or NAD, you're basically fixing something that is getting worse as you age. Yeah, so the question is, why does it go down? And I think there's multiple reasons for that, at least, that's been shown in literature. NAD is a very important co-factor for mitochondria. I mean, obviously, mitochondria are making NADH and that hydrogen, the proton is used and electrons are used to basically generate energy through the electron transport chain.

And it's also generating the mitochondrial membrane potential by kicking out the proton. So that's really important for mitochondrial function, respiratory function, energy production, which is like the key of everything, right? But in addition to that, you have, as you mentioned, Sir Tuenz, which are histone deacetylases, which have a whole host of functions that they're doing,

regulating tons and tons of different pathways. There also seemed to be very important for health span. And then in addition to that, there's host of functions that they're doing, regulating tons and tons of different pathways, they're also seem to be very important for health span. And then in addition to that, there's very important DNA repair enzyme part that literally syncs up NAD. I mean, it's like an NAD sync. I mean, it, you know, so, you know, we're constantly having damage. Where does it reside that enzyme? Where in the cell? Yeah. Is it nuclear? It must be, right? Yeah. And the reason I ask is, how do we know that these supplements that we take

orally are going to actually reach their bioavailability in the place we want them? Okay, but that said, we'll come back to that after. I think it's in the nucleus. I mean, it would make sense to be there, but yeah. Otherwise, it shuttles there, but I think it is. It's very important for repairing DNA damage. That's one of the major sinks and actually inflammation. All these things are upstream of part activation. The more that's happening, the more parts being activated, you have NAD going there. One argument just to make sure I understand what you're saying is, look, if you're getting older, you're going to have more DNA damage.

That's just stochastic. Yes. And if your little guy that repairs it requires NAD as fuel, that would explain one reason potentially why NAD would decline as we age. Yeah, and it's certainly a sink for it. Yeah. And the other, so the other thing is, well, if your immune systems constantly, you know, activated to more inflammation, you have all that energy is required. So NADs

being consumed more for that as well. So that's sort of another thing. Basically, NAD levels decline with age and it's probably because it's just getting used up more. Or the other, the alternative is, you know, is there something else going on in terms of like this whole salvage pathway? There's another pathway that you can do to regenerate NAD, and if that's kind of going wrong. And I think there's some increasing evidence for that as well. Would that make Metformin a bad idea from this standpoint? Because Metformin inhibits complex one. So Metformin lowers the ratio of NAD to NAD.

Does it? Has that been shown? So you're saying it should lower it? It should lower it. Now, of course, that's counterintuitive because we know it activates AMPK. So I probably have to sit down and think about this, but we do know Metformin inhibits complex one. And we know that complex one turns NADH to NAD, which makes me wonder, is it possible that Metformin would impair DNA repair through that mechanism by reducing substrate. I have no idea.

Well, I'm gonna write that down. That's something I'm gonna have to look into. Because I wasn't aware of the, and I didn't understand that link, but yeah. Yeah, I think that's a major one. I literally think that's a major sink for it. I think that the part is, I think it's just like going there. Yeah, so the animal evidence, you mentioned some of this

supplements, you know, precursors that can form an AD, I think that the animal evidence suggests that it can, at least in rodents, improve health span, particularly in models with like that are heavily dependent on mitochondria, like muscle, my opathy models or something like that, I think that was one. And also the brain. So I think those are the two organs I've seen like major positive effects with NAD supplementation.

And then there's some of course pilot clinical study that is showing that yes, you can take, for example, nicotinamide riboside and it does seem to increase NAD levels and plasma and a dose dependent manner. Now again, you raise the question. We have no idea if it's getting in the middle of it. Is it getting in the cell? Is it getting in the mic?

Now, we do know in animal manner, now again, you raise the question. We have no idea if it's getting in the middle of the room. Is it getting in the cell? Is it getting in the... Now, we do know in animal studies, I think that has been shown because it's affecting the mitochond... Like I said, there was animal models of myopathy and stuff and mitochondrial function was improved and all that stuff. So in animal out models, it obviously is affecting mitochondrial function,

so it must be getting to the right place. I don't know why I have found myself kind of skeptical of this. I think it's good to start with skepticism. I mean, I think that NAD levels are, you can increase them with fasting. So when you fast, you know, as you mentioned, you convert NAD into NADH in the presence of energy because that's basically when you have a substrate like glucose or fatty acid, that's when you produce NADH or FADH2.

So in the absence of those substrates, then you start to make your NAD starts to build up. So back to your metformin question, you said. I know who to ask. I definitely know. I'm gonna ask Nav Chendell. He will know the answer to this question. I thought a lot of his work when I was in grad,

him, Ralph D. Bardini's, I did it because I was doing a lot of cancer metabolism, mitochondrial function not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure.

I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure.

I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. I'm not sure. and I was leaving town the day they were coming in the town. So we hung out for three hours near the airport and I was just reminded of how much fun it is to talk about mitochondria. Yeah.

For sure. I hope you enjoyed today's quality. Now sit tight for that legal disclaimer. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional healthcare services, including the practice of medicine, nursing, or other professional health care services, including the giving of medical advice. And note, no doctor-patient relationship is formed.

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