⚠️ New Product Alert ⚠️ Nicotinamide Mononucleotide Enteric Coated Tablets | 125mg

Hmmm, what's the reasoning behind that? The nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme doesn't use a methyl group. ATP is the key compound that helps NMNAT work. This is why I take NMN with CoQSol-CF. You could also add in Na-R-ALA/OptimALA, creatine, and ALCAR. It looks like some people are using the fact that nicotinamide riboside (NR) increases niacinamide (NAM) levels, which then puts a strain on the methyl-donor system as evidence that it should be done with all NAD+ precursors. However, I am not convinced of that. I could maybe see that with NR, as that can increase the levels of NAM a lot, which would use methyl donors. However, NMN is a direct precursor to NAD+. NR is not.

Take a look at the pathways.

It looks like the major proponents of this theory are trying to steer people away from both NR and NMN, and say that you should just take niacinamide and some methyl donors, but that's silly. There is research out there showing NR and NMN lead to much higher increases in NAD+ than NAM supplementation. They even link it on their article discussing the whole thing.

https://www.nature.com/articles/ncomms12948

These data establish that oral NR has clearly different hepatic pharmacokinetics than oral Nam. More NAD+ and NADP+ were produced from NR than from Nam. In addition, there was three times as much accumulation of ADPR, indicating that NR drives greater NAD+-consuming activities in liver than mole equivalent doses of Nam and NA. Though it has been speculated that NR would be a more potent NAD+ and sirtuin-boosting vitamin than conventional niacins45, these are the first in vivo data in support of this hypothesis.

Also, the idea that taking NAM instead of NMN has been tested. NMN stays in the body significantly longer than NAM, and has much less urinary excretion. So NMN can work to increase NAD+ levels for longer than NAM. The only reason to promote NAM over NMN is because it is cheaper. NAM is like insanely cheaper to make than NMN. So putting NAM, methyl donors, and ATP supporting supplements into a product makes is MUCH easier to have higher margins. However, the science does not support it.

https://sci-hub.tw/10.3177/jnsv.62.272

the urinary excretion of the SUM was lower in the b-NMN group than in the Nam group at 3–6 h after the administration. Moreover, the percentage on the urinary SUM was much lower in the b-NMN group than in the Nam group at 3–6 h. This result suggests that b-NMN is retained in the body for longer than Nam is. In addition, this result means that b-NMN has a higher turnover of salvage biosynthesis of NAD1 than Nam does. The resulting phenomenon accelerates the turnover of salvage biosynthesis of NAD1, which activates the SIRT1 reaction, because SIRT1 (histone deacetylase) needs NAD1. Deacetylated histone molecules induce DNA silencing, contributing to anti-aging and longevity.

Also, the people selling NR have been putting out BS articles on NMN for a while to try and sway people, saying that NMN itself can't enter cells, and that it has to convert to NR before it can. However, that was recently disproven, too.

Slc12a8 is a nicotinamide mononucleotide transporter

SLC12A8, or solute carrier family 12 member 8, is a protein encoded in both mice and humans. It is an NMN-specific transporter.

We have previously shown that NMN is absorbed from the gut into blood circulation within 2–3 min and transported into tissues within 10–30 min (refs 5,15). NMN is then immediately utilized for NAD+ biosynthesis, significantly increasing NAD+ content in tissues over 60 min. This fast pharmacokinetics has recently been confirmed by using doubly labelled isotopic NMN (C13-D-NMN), showing its rapid absorption and conversion to NAD+ in peripheral tissues15. It has also been proposed that NMN is converted extracellularly to NR, which is transported into cells and reconverted to NMN21. Recent studies, however, have shown that the analyses of in vivo kinetics of these NAD+ intermediates are affected by differences in sample collection and extraction methodologies22,23 (also see Methods). Therefore, it is critical to understand the mechanism by which NMN or NR is transported into cells or tissues. The fast pharmacokinetics of NMN led us to the hypothesis that there is an effective transporter that facilitates the direct uptake of NMN into the gut and other organs. Thus, we set out to identify this presumed NMN transporter in mammals.

NMN is rapidly absorbed in the GI tract, and can be immediately utilized for NAD+ biosynthesis.

How NMN is transported into cells has long been a matter of debate in the field of NAD+ biology. It has been believed that NMN needs to be converted first to NR by CD73 outside of cells, after which NR is transported into cells, likely through the nucleoside transporter, and reconverted to NMN by NRK1/2 (refs 21,30). Although this process can occur over the course of 24 h (ref. 21), such hourly kinetics cannot explain the minute-order uptake of NMN into the cell. Additionally, how to analyse the in vivo kinetics of NMN is also critical, and the results could be significantly affected by differences in sample collection and extraction methodologies22,23. For example, plasma samples need to be processed immediately after collection, as we did in this study, because freezing blood or plasma samples causes inaccurate measures of NMN levels. The results presented in this study strongly indicate that Slc12a8 is specific to NMN, not to NR, and its Km is consistent with a measured range of NMN concentrations20,25,26. Even NaMN, structurally very close to NMN, cannot be transported by Slc12a8. Furthermore, its dependency on sodium ion, but not chloride or potassium ions, and its insensitivity to WNK463 distinguish Slc12a8 from other known cation–chloride co-transporters. Nonetheless, because a very high, supra-physiological concentration of NR can compete against NMN, NR might be able to interact with Slc12a8 weakly. To elucidate the precise details of the structure–function relationship between Slc12a8 and NMN, it will be of great importance to determine the crystal structure of the Slc12a8 NMN transporter.

Look at that! The NMN-specific transporter is located in the small intestine of mammals, which is why we enteric coated our tablets. This allows them to deliver intact NMN right to where the transporters are. Then NMN immediately is absorbed into the body. NMN can then go multiple ways. It can bioconvert to NR, which then is uptaked into cells, converted back into NMN, then converted to NAD+, or it can proceed directly to increasing NAD+. If you look at the study saying that NMN requires conversion to NR outside of the cells to work, you can see the author owns stock in Chromadex, the people behind nicotinamide riboside...

https://pubmed.ncbi.nlm.nih.gov/27725675/?dopt=Abstract

J.R., M.J., M.B., S.S.K. and C.C. are employees of the Nestlé Institute of Health Sciences S.A. C.B. owns stock in ChromaDex and has received a research grant and serves on the scientific advisory board of ChromaDex. C.B. is co-founder and Chief Scientific Adviser of ProHealthspan, which distributes an NR supplement. M.E.M. has received research grants and serves as a consultant for ChromaDex.

LOL! Suuuuuure we can believe your study. Now a couple years later we have proof that NMN has its own transporter. Some researchers were arguing that NMN could be uptaked by certain cells directly in 2016, too.

https://sci-hub.tw/10.1111/acel.12461

So the data is pretty clear to me. A stabilized NMN in an enteric coated tablet is ideal for oral dosing, as you are delivering it directly to its exclusive transporters in the small intestine. Nicotinamide riboside cannot use this transporter, nor can other similar compounds. It's an NMN-specific transporter in mammalian small intestine cells. NMN can then go on to increase NAD+ directly, or by conversion to NR and back to NMN inside of cells. I don't see any reason this would put a strain on the methyl donor system, or require supplementation alongside something like TMG. I can look into the methyl donor side more, but the people promoting this idea are also promoting the idea that niacinamide supplementation with methyl donors and ATP supplements are a better strategy for increasing NAD+, even though there is clear evidence that NAM is nowhere near as efficient at increase NAD+ as either NR or NMN. That company also happens to sell a product with NAM and other ATP supplements. So fitting the evidence to show what they want has a financial incentive. There is also a lot of BS out there from the people selling NR trying to discredit NMN. However, the deeper I look, the more clear it becomes for me. Everyone here can come to their own conclusions, but look at the evidence. There's a lot of money in trying to make people buy NR over NMN. Don't fall for the rhetoric. Look at the science.