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解說 NR vs NMN 之間的關係 - 川御

2023年3月5日 TYScience

許多人也會有興趣了解如何有效地提高體內的 NAD+ 水平,以及 NAD+ 前體 NR 和 NMN 之間的差異。在 Rhonda Patrick 博士和 David Sinclair 博士的採訪當中,可以得出數個要點:

根據最新的研究報告,需要口服高劑量的 NR(煙酰胺核苷)才能有效。 對於體重 180 磅的成年人,需要近 2000 毫克的 NR 才能產生效果。

NR 不會增加肌肉 NAD+ 水平,似乎也不能有效提高耐力。

NMN(Nicotinamide Mononucleotide)的口服檢測劑量相對較低,在200-400mg之間,有效提高體內NAD+水平,有助於治療線粒體疾病和提高耐力。

還提到我們不直接消耗NAD+,因為它是一個大分子,不能直接被細胞利用。 單獨攝入高劑量的煙酰胺實際上可能會抑制 Sirtuins 和 PARP,從而阻礙 DNA 修復功能。 NAD+補充需要其他物質。所以要補充NAD+ 就很難以食物及日常飲食獲得,也需要使用到川御 NMN補充劑。


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 showed 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., A.O. 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.

部份訪問談話內容節錄如下:

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 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...

<Sourse: https://www.foundmyfitness.com/episodes/nr-vs-nmn-dosing-effects-on-nad-levels>

 

如有興趣也可以了解一下川御NMN

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