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

**Peter Attia, MD** (0:05)
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So there's one more topic I just want to get to, if we can spare a bit more time, which is NAD.
The precursor is the whole shtick. You've spent a lot of time thinking about this. What is your current thinking on, does having more NAD to NADH matter?

**Rhonda Patrick, Ph.D.** (1:20)
The thing about the NAD-

**Peter Attia, MD** (1:22)
I guess I should provide context for people. Why am I asking this question, right? 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 Sirtuin pathway, but this is upstream of that, but if you give more of either the precursor NAD, you're basically fixing something that is getting worse as you age.

**Rhonda Patrick, Ph.D.** (2:03)
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, serotuins, which are histone deacetylases, which have a whole 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 PARP that literally syncs up NAD. I mean, it's like an NAD sync.
I mean, so we're constantly having damage to our...

**Peter Attia, MD** (3:00)
Where does it reside, that enzyme?

**Rhonda Patrick, Ph.D.** (3:03)
Where, in the cell?

**Peter Attia, MD** (3:04)
Is it nuclear? It must be, right?

**Rhonda Patrick, Ph.D.** (3:06)
Yeah.

**Peter Attia, MD** (3:06)
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.

**Rhonda Patrick, Ph.D.** (3:19)
I think it's in the nucleus.

**Peter Attia, MD** (3:21)
It would make sense to be there, but yeah.

**Rhonda Patrick, Ph.D.** (3:22)
Otherwise, it shuttles there, but I think it is.
So, it's very important for repairing DNA damage. And so, that's one of the major sinks in actually inflammation. All these things are kind of upstream of PARP activation. So, the more that's happening, the more PARP's being activated. So, you kind of have NAD going there.

**Peter Attia, MD** (3:41)
So, one argument, just to make sure I understand what you're saying, is look, if you're getting older, you're gonna have more DNA damage. That's just stochastic.
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.

**Rhonda Patrick, Ph.D.** (3:57)
Yeah, and it's certainly a sink for it, yeah. And the other, so the other thing is, well, if your immune system's constantly activated too, with more inflammation you have, all that energy is required, so NAD is being consumed more for that as well. So, that's sort of another sink. Basically, NAD levels decline with age, and it's probably because it's just getting used up more.