Peter Attia· MD
what they also showed was that you do increase nad in the muscle a lot when you supplement with the nicotinamide right aside but it all comes from nicotinamide that the liver had made and circulated them
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what they also showed was that you do increase nad in the muscle a lot when you supplement with the nicotinamide right aside but it all comes from nicotinamide that the liver had made and circulated them
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so that would suggest to me that if you're taking oral nad a pardon me oral and R or n MN you're pretty much just giving it to your liver which is not exactly the place you want it to be
the paper that will have come out by the time this podcast becomes available suggested that in our did not extend life span in our mice there are all the usual caveats maybe it would have if we'd given it at a higher dose or at a lower dose in addition we tried a little bit to detect it in various tissues there's a collaborator who looked at the brains and the muscles and the hearts and we were not able to demonstrate a consistent major change in nad levels in these tissues
Yes, that study he recently published just a few months ago looking at nicotinamide riboside and how orally, at a dose half of what typically is used in all the other nicotinamide riboside animal studies. So typically, they do 400 milligrams per kilogram body weight per day. I don't remember how long, the duration they were doing it. But in the NAD flux study, he did 200 milligrams per kilogram body weight, which is significantly less than what all of these other studies like the one you mentioned with Alzheimer's disease and other studies that have shown improvements in mitochondrial function in mitochondrial mutator mice, and also muscular dystrophy, and all that.
A higher oral dose was also done but only for nicotine my dry beside a dose of 200 milligrams per kilogram body weight of nicotinamide rai beside showed no difference compared to a low dose in terms of making nad direct from nicotinamide right aside in any other tissues other than the liver however more of the nad derived from the salvage pathway was found in the kidney muscle and the brain then at the lower dose
even at very high oral doses neither nicotinamide rai beside or nicotinamide mononucleotide appeared to directly be transported to other tissues other than the liver at least again at those doses that were measured however nicotinamide rai beside and nicotinamide mononucleotide were converted into nicotinamide which then transported to other tissues and some of that nicotine mine was then converted into nad
however the only nad detected in the brain was that which was salvaged from nicotinamide suggesting that neither nicotinamide right beside nor nicotinamide mine a nucleotide across the blood-brain barrier
the important point to address is whether nicotinamide right beside or nicotinamide mononucleotide can reach other tissues intact and directly form nad without going through that nad recycling pathway that I mentioned earlier called the salvage pathway the salvage pathway would mean that nicotinamide Rui beside or nicotinamide mononucleotide were first metabolized into just nicotinamide before forming nad instead of directly forming nad this is an important point because nad produced from the salvage pathway is subject to feedback inhibition and therefore cannot raise nad levels in tissues above a certain level
had to head comparison of identical doses of injected nicotinamide rai beside and nicotinamide mononucleotide produced more nad made directly from nicotinamide right aside in the liver kidney and particularly in the muscle tissue compared to nicotinamide mononucleotide
when nicotinamide rai beside or nicotinamide mononucleotide were given intravenously at varying doses so fifty milligrams per kilogram body weight or 500 milligrams per kilogram body weight directly produced nad was found in the liver kidney and muscle in a dose-dependent manner
it's possible that nicotinamide rai beside and nicotinamide mononucleotide can be transported to other tissues other than the liver at very very high oral doses but that's yet to be shown
what the study found was that at a low oral dose of around 50 milligrams per kilogram body weight of either nicotinamide ride beside or nicotinamide mononucleotide they produced very low levels of nad made directly from those precursors but only in the liver not in other tissues low levels of nicotinamide drive nad on the other hand were found in the kidneys and very low levels of nicotinamide drive nad were found in the muscles and also in the brain
the reason nicotinamide rai beside and nicotinamide mononucleotide are popular is because they can be transported into multiple tissue types including the liver kidney muscle and heart the brain is the exception neither nicotinamide right beside nor nicotinamide mononucleotide seem to be able to directly cross the blood-brain barrier
But there was a study, I think it was the Rabinowitz Lab published that this was in animals, you know, that even really, really high doses of both of these precursors, NAD precursors...both NR and NMN were unable to raise NAD levels in other tissues outside of the liver. So, muscle brain, for example, there was no change.