Peter Attia· MD
What about NR nicotenomide ribocide? How is that treated by CD38? Uh it's not it's not metabolized by itself. NR eventually in the cell has to make it back to NMN which is one is is on the on the salvage pathway that we talked about. Uh so NR is you know is is is less bulky less big than NMN. So it is able to get into the cell but eventually it makes it into nicotine NMN and then goes back into the same pathway. So eventually they all come back to the same. So do you think that there's no difference between the same amount of NR and NN? No, there clearly are some differences um especially in all the really complex biochemistry that happens in terms of getting them into cells. You know there are the problem with NR and NMN is that you are if you think about what the approach is you're essentially you have a pool of NAD which is a sink think about a sink full of water and you keep you know it's leaking that's your CD38 that's that's the leak at the bottom of the sink and you keep pouring more NMN more NR inside of it you're just going to you're just going to accelerate you know the leak or you're going to make it you're not going to solve the problem basically maybe you'll reestablish the val the level at a normal semi-normal but the churning through is is problematic now why is the churning through problematic because some of the byproducts of CD38 for example are um u cyclic ADP ribos uh so there's two forms of ADP ribos not cyclized and cycized cyclized activates um calcium signaling and so there's a whole aspect of the biology of CD38 that's linked to calcium signaling. So I think I do worry about the supplementation with the NR and NMN. Um, I do worry about it. I'm not discounting them. I think clinical trials are ongoing. There's dozens of clinical trials. So we will soon identify something that in which it has a benefit. Again, if you think about the the metabolism of these metabolites, um, it's incredibly complicated. There are effects on the microbiome. There are effects on, you know, different absorption by different cells. Just literature, hundreds and hundreds of papers, I think way beyond what your audience probably wants to hear. But um uh and I would say, you know, at this point, most of what you can buy as supplement have doses that are so low. This is where there's an important discordance also when we do experiment. We've seen amazing things in in laboratory animals in terms of supplementing with an RNN. This is where the excitement comes from. But typically these animals are getting 10 times more than what you're buying as a supplement. And the reason is I think you know grass uh sort of status is given to these companies to give a small amount. Yeah. Grass meaning generally regarded as safe. FDA's criteria for giving something that is naturally occurring that doesn't requine went from 7 to 15 um I guess two questions would be has that been reported elsewhere is there do we is that a known phenomenon in the trials that are testing NMN are they measuring homoyine to see if that's I must have read it somewhere because I was I was you were looking for it I was looking for it And then the second question is how would you then tolerate 10 grams of NMN? I mean if one gram is doing that what I mean now you're you would deplete all one carbon. What does that does that mean you wouldn't even be able to alter your epiggenome in ways that might be favorable?