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Seemingly, Sinclair didn't want his work to show which precursor was superior in producing the result he was studying or he would have compared the two precursors. Which begs the question, "Was he simply looking for results to justify MNM?" Only Sinclair knows that answer, but certainly there is work that supports the premise that MNM is not superior to NR in producing NAD+. As to whether it would have produced superior results in this particular study, sadly, that is an open question, as NR and MNM are not the same molecule.
http://alivebynature...st-nad-booster/ CONCLUSION
This longterm NMN study indicates the importance of NAD+ decrease as a common trigger of age-associated physiological decline, and the possibility that supplementation to increase NAD+ can ameliorate some of this decline. Some questions remain about the NAD+ boosting effect of NMN. Even with continuous supplementation it does not appear to significantly raise blood plasma circulation NAD+ levels.
This quote below from the Trammel PHD work on NR and NAD+ proposes that NR is more effective than NMN at boosting NAD+
These points seem to indicate that NR is the most attractive NAD+ booster at present. However, NR and NMK are two distinct NAD+ precursors and additional research may find that effective interventions for age-associated physiological decline include some combination of NMN and NR.
NR contributed to the intracellular NAD metabolome more rapidly than NMN and increased NAD+ by more than 2 fold after 24 hours, indicating NR is kinetically superior to NMN.
Expanding on that last quote is chapter 4 in this study by Trammell that deals directly with contrasting MNM and NR
Novel NAD+ metabolomic technologies and their applications to Nicotinamide Riboside interventions
4.6 Discussion
NR (32, 37, 50, 52, 54-56) and NMN (34, 123-125) both counter metabolic and age related disorders. NR and NMN are studied as separate pharmacological entities, both augmenting NAD+ through separate pathways but converging due to the action of NAD+ in sirtuin activities. NR is either phosphorylated to NMN through the NRK pathway (7) or phosphorylized to Nam (126). However, NR increases five-fold after NMN injection (34) and other studies indicate NMN depends upon CD38, CD73, and NRK (35, 121, 127) for its utilization and suggest that NMN is metabolized to Nam and NR extracellularly. These studies did not eliminate the possibility that extracellular dephosphorylation is non-rate limiting and that NMN, though biochemically acting as NR, behaves identically as NR. We used LC-MS/MS and stable isotope labeled NR and NMN to measure their kinetic effect on the NAD metabolome. NR contributed to the intracellular NAD metabolome more rapidly than NMN and increased NAD+ by more than 2 fold after 24 hours, indicating NR is kinetically superior to NMN. In line with the 62 intracellular findings, extracellular NMN rapidly and dramatically decreased over 24 hours as extracellular NR rose. No labeled Nam was detected, suggesting hydrolysis, presumably as catalyzed by CD38, was not the primary route of extracellular NMN metabolism in these cells. The relationship of the two labeled compounds was seemingly linear and agreed with genetic evidence that NMN is dephosphorylated before it is salvaged. NR and NMN are not identical, interchangeable entities. The implication of these data to a biological setting remain to be shown in vivo. The possibility remains that NMN is an endogenous circulating NAD+ precursor as has been suggested (17). An extracellular Nampt (eNampt) is enzymatically active and could produce a constant amount of NMN from Nam. In the same report, NMN was reported to circulate at as high as 80 µM, leading some to suggest that NMN is a type of NR carrier that is dephosphorylated to supply NR around the body (2). However, the ability of eNampt to produce NMN appears unlikely given undetectable levels of its co-substrate 5-phosphribosyl-1- pyrrophosphate (18). Further, our group and others have failed to detect NMN in plasma (Chapter 5)(18). These discordant results may be due to the employment of HPLC versus LCMS. HPLC is technically more quantitative as the detector is not at the mercy of gas phase reactions such as mass spectrometers are, but HPLC UV-vis methods are incapable of providing selectivity for the metabolite of interest (Chapter 1.1-1.2). This is a very prescient example of the need for improved and accepted analytical procedures for the study of the NAD metabolome.
