NAD+ ⇒ NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR

[daviddean]

Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters for each. A comprehensive concept that connects NAD+ metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health.

Reference (Full text available)
https://www.ncbi.nlm.nih.gov/pubmed/29249689

[Drdavid]

It is an exciting time for NAD+ especially in the field of aging. I agree that NAD+ holds some of the factors that can slow the aging process. In fact in Alzheimer’s disease it has been shown through animal models that DNA damage can be repaired, improved cognition and motor function can be achieved through NAD+ intermediates.
Something so simple that can bring such profound results is incredible and it is amazing that this information is not be provided to the general public through national media sources.

[vandan]

It is an exciting time for NAD+ especially in the field of aging. I agree that NAD+ holds some of the factors that can slow the aging process. In fact in Alzheimer’s disease it has been shown through animal models that DNA damage can be repaired, improved cognition and motor function can be achieved through NAD+ intermediates.
Something so simple that can bring such profound results is incredible and it is amazing that this information is not be provided to the general public through national media sources.

Can you kindly point me in the direction of the different pathways of NAD+ v NMN. It seems I had mislead myself thinking NAD+ was simply a derivative/more refined molecule from the metabolism NMN...

[Fred]

It is an exciting time for NAD+ especially in the field of aging. I agree that NAD+ holds some of the factors that can slow the aging process. In fact in Alzheimer’s disease it has been shown through animal models that DNA damage can be repaired, improved cognition and motor function can be achieved through NAD+ intermediates.
Something so simple that can bring such profound results is incredible and it is amazing that this information is not be provided to the general public through national media sources.

Can you kindly point me in the direction of the different pathways of NAD+ v NMN. It seems I had mislead myself thinking NAD+ was simply a derivative/more refined molecule from the metabolism NMN...

Did you check out the article he posted? The link is there and it explains how NMN turns into NAD in the cell.

[vandan]

It is an exciting time for NAD+ especially in the field of aging. I agree that NAD+ holds some of the factors that can slow the aging process. In fact in Alzheimer’s disease it has been shown through animal models that DNA damage can be repaired, improved cognition and motor function can be achieved through NAD+ intermediates.
Something so simple that can bring such profound results is incredible and it is amazing that this information is not be provided to the general public through national media sources.

Can you kindly point me in the direction of the different pathways of NAD+ v NMN. It seems I had mislead myself thinking NAD+ was simply a derivative/more refined molecule from the metabolism NMN...

Did you check out the article he posted? The link is there and it explains how NMN turns into NAD in the cell.

Thanks Fred (sort of), my question is simply - what is the difference between taking NMN (and having it metabolised into NAD+) and taking it as NAD+, if any.

[Fred]

Did you check out the article he posted? The link is there and it explains how NMN turns into NAD in the cell.

Thanks Fred (sort of), my question is simply - what is the difference between taking NMN (and having it metabolised into NAD+) and taking it as NAD+, if any.

There are no human trials of oral NAD that I'm aware of. Only of NADH and Q10 in CFS. So it's hard to compare it to NMN. We need better pharmacokinetic data on both.

NAD is in the cells in food we eat. It gets broken down through digestion and rebuilt into NAD in our cells.

In rats oral NAD gets broken down to nicotinamide, NR and NMN in the gut and some of that NMN may be absorbed in the small intestine by a newly discovered transporter.

[vandan]

Did you check out the article he posted? The link is there and it explains how NMN turns into NAD in the cell.

Thanks Fred (sort of), my question is simply - what is the difference between taking NMN (and having it metabolised into NAD+) and taking it as NAD+, if any.

There are no human trials of oral NAD that I'm aware of. Only of NADH and Q10 in CFS. So it's hard to compare it to NMN. We need better pharmacokinetic data on both.

NAD is in the cells in food we eat. It gets broken down through digestion and rebuilt into NAD in our cells.

In rats oral NAD gets broken down to nicotinamide, NR and NMN in the gut and some of that NMN may be absorbed in the small intestine by a newly discovered transporter.

Now I'm completely confused. NAD converted into NMN? Doc, can you shed any light on this matter?

[Drdavid]

Fred is completely correct. Honestly, we really dont have a great deal of research on NAD in humans so it is rather murky. However, I can say that in the clinic we see a distinctive pattern with both NAD and NMN. NMN appears to have more strength and recovery associated with it and NAD seems to deliver focus and clarity. Please be aware that these are just a few of the differences that I have seen in patients. What is interesting is the fact that health benefits are delivered with both products. I think as the research becomes available we will see distinct differences between these two substances. In a chemical cascade minute differences can cause great changes in the end product. Below are two articles that I think will help clear this up or muddy the waters even more. By no means is anyone trying to be elusive in answering your question but it is still unclear as to how this particular intermediate actually works.

Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.
NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR.
Yoshino J1, Baur JA2, Imai SI3.

https://www.ncbi.nlm.nih.gov/pubmed/29249689

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
Christopher R. Martens,corresponding author1 Blair A. Denman,1 Melissa R. Mazzo,1 Michael L. Armstrong,2 Nichole Reisdorph,2 Matthew B. McQueen,1 Michel Chonchol,3 and Douglas R. Seals1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876407/