Many people will also be interested in learning how to effectively increase NAD+ levels in the body, and the differences between the NAD+ precursors NR and NMN. Several key points can be drawn from the interviews with Dr. Rhonda Patrick and Dr. David Sinclair:
According to the latest research reports, high oral doses of NR (nicotinamide riboside) are required to be effective. For an adult weighing 180 pounds, nearly 2,000 mg of NR is required to produce an effect.
NR does not increase muscle NAD+ levels and does not appear to be effective in improving endurance.
The oral test dose of NMN (Nicotinamide Mononucleotide) is relatively low, between 200-400mg, which can effectively increase NAD+ levels in the body and help treat mitochondrial diseases and improve endurance.
It was also mentioned that we do not consume NAD+ directly because it is a large molecule and cannot be used directly by cells. High doses of nicotinamide alone may actually inhibit Sirtuins and PARP, thereby impeding DNA repair function. NAD+ supplementation requires other substances. Therefore, if you want to supplement NAD+, it is difficult to obtain it from food and daily diet. You also need to use Sichuan NMN supplement.
Quoted "So NAD, the reason it's called nicotinamide adenine dinucleotide is that it's got these three main components, and the dinucleotide is related to DNA. But that's beside the point. It's a big molecule (NAD+ itself) so that if you give a big molecule to cells, it doesn't get taken up. So we don't feed animals NAD. And we don't just feed them nicotinamide, which is the little end part of NAD because it's too small in that you need these other parts .";
"Nicotinamide, which is something you don't want to take high doses of because we've shown in my lab many years ago that nicotinamide will inhibit the sirtuins, and PARP as well, and interfere with DNA repair." David Sinclair.
Dr. Rhonda Patrick is a Ph.D in biomedical science and expert on nutritional health. Her podcasts and other videos can be found at http://FoundMyFitness.com
Dr. David A. Sinclair, Ph. D., AO is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. His new book <Lifespan: why we age and why we don't have to> hit #1 best seller on Amazon in Genetic Disorders & Diseases.
Excerpts from part of the interview are as follows:
Rhonda: So with the clinical studies, you know, I've seen a couple with nicotinamide riboside, but I guess the, you know, the question is with the nicotinamide riboside, there's been a little confusion about like, you know, whether or not nicotinamide riboside's even really getting converted into NAD inside cells and different organs other than the liver. This was this NAD flux paper that was done by Rabinowitz?
David: Rabinowitz?
Rhonda: Rabinowitz. Thank you. 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. So...
David: Yeah, we use double that dose for a while.
Rhonda: Yeah, so maybe, you know, this NAD flux study that showed nicotinamide riboside given orally didn't form NAD in the muscle, but it did in the liver could have been a dose-dependent thing?
David: It would make sense because we've done a lot of this in mice and now in humans, and that there's a threshold that you need to cross, you need to take a certain amount to get over probably the body's clearance mechanisms and then you get up to a level that plateaus after about nine days. And they may have just been under that threshold, so the body was just clearing it out. But you have to seemingly overwhelm that clear-out system, so that's why we do at at least 400 mgs per kilogram in mice.
Rhonda: And that's with nicotinamide riboside. The question is, I mean, that's like if you talk about a human equivalent dose for like a 180-pound man, that's like over two grams a day. And it kind of leads me to my next question, which was the most recent clinical study with nicotinamide riboside where they actually used a much higher dose than the original study that was done with Basis, the Elysium that had pterostilbene in it. This dose was like 1,000 milligrams a day and they looked at a variety of endpoints in addition to...I mean, they looked at endurance, looked at...
David: Right. It was Doug Seals' study.
Rhonda: Yes. And there was no statistical significance in anything. It raised NAD levels, but there was no statistical significance. There was trending improvement in the vascular system, but there was no effect on endurance. And I'm wondering again, well , if we go back to the human equivalent dose, what was given to the animals, that was still less than half. I mean, so the question becomes, is it not even making NAD in the muscle tissue at that dose or, you know , so...which brings me to the nicotinamide mononucleotide. You know, like now those studies have been done in animals at a much lower dose than 400 milligrams.
David: They have. Yeah. So we, in my lab, and at the company, Metro Biotech, we've been using a whole variety of different molecules and different... We're doing what's called pharmacokinetics. So there's a lot of literature that I could talk for another hour on. One of the big questions people ask me is, "Have you ever put NR and NMN head to head in a study?" And we need to do a lot more of those, typically they 're not done. And I'm unaware of it being done in humans at this point. But in mice, what we see... And for all the NR folks out there, please don't be angry, this is just data . I don't run the experiments, I just deliver the message. That at the same dose, NMN will increase endurance. And I forget what that dose was. It might've been 200, 250.
Rhonda: Yeah, 200.
David: NMN didn't increase... Sorry, NR did not increase endurance, but NMN did. We do find that for some parameters, and Matt Kaeberlein, who I mentioned earlier who, he works on dog aging now after doing the SIR2 extension lifespan. So Matt also has published that, comparing NR and NMN, only NMN worked in his disease model, which was a mitochondrial disease where those animals really need a boost of NAD. So one of the issues could be that NMN is a better molecule in that regard. It could be that maybe the mice just worked better than humans and we need a bigger dose. But what I'm working on, which is not talked about a lot because it's in the commercial realm, is there's been a team of seven chemists working on much better molecules than any of these two that I'm talking about, super NAD boosters...
<Source: https://www.foundmyfitness.com/episodes/nr-vs-nmn-dosing-effects-on-nad-levels >
If you are interested, you can also learn about Sichuan Yu NMN
