All:
I find this very surprising:
Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00257
A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+
Ross Grant, Jade Berg, Richard Mestayer, Nady Braidy, James Bennett, Susan Broom and James Watson
... no data are currently available on the fate of directly infused NAD+ in a human cohort. This study therefore documented changes in plasma and urine levels of NAD+ and its metabolites during and after a 6 hour 3 μmol/min NAD+ intravenous infusion.
Surprisingly, no change in plasma NAD+ or metabolites (nicotinamide, methylnicotinamide, ADP ribose and nicotinamide mononucleotide) were observed until after 2 hours. Increased urinary excretion of methylnicotinamide and NAD+ were detected at 6 hours, however no significant rise in urinary nicotinamide was observed.
This study revealed for the first time that i) at an infusion rate of 3 μmol/min NAD+ is rapidly and completely removed from the plasma for at least the first 2 hours, ii) the profile of metabolites is consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity and iii) urinary excretion products arising from an NAD+ infusion include NAD+ itself and meNAM but not NAM.
The full text is not available, and their phrasing is a bit odd: "no change in plasma NAD+ or metabolites ... observed until after 2 hours" implies that such elevations were seen from that point onward, but if so, why not put that (with the numbers) in the abstract?
They looked at plasma NAD+ (etc), not eg. whole blood or RBC, so one might speculate that it's rapidly absorbed into RBC — but there's no evidence that this happens AFAIK, and if that happened, you'd expect to see it rise in plasma first and slowly be taken up. OTOH, they saw "increased urinary excretion of ... NAD+ ... at 6 hours," so it doesn't seem to have just been broken down (especially since there was (initially?) no rise in plasma NAM or NMN, and no increase in urinary NAM either. There was a rise in urinary MeNAM, consistent with conversion to NAM and then methylation to detoxify it, but how did it get there? Again, what happened in the "missing" 4 hours in plasma?
"the profile of metabolites is consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity" might answer some of this, but it's not clear how: NAD glycohydrolase catalyzes hydrolysis of NAD+ to ADP-ribose, and NAD+ pyrophosphatase hydrloyzes NAD+ to ADP and NMN, but they saw "no change in plasma ... ADP ribose and nicotinamide mononucleotide ... until after 2 hours." It would, however, at least partially explain there was no NAM anywhere to be seen, with perhaps some NAM being produced and converted to MeNAM.
Certainly, it doesn't seem that IV NAD+ is used much, since its use by SIRTs or PARPs leads directly to NAM production. Amounts matter, however: if there was a ton of MeNAM and little ADPR or NMN at any time point, that might imply significant consumption of NAD+ by these enzymes (and/or CD38 and/or CD73). But, again, silence, and no numbers.
Very odd. And these investigators are NAD+ enthusiasts (albeit not necesarily intravenous NAD+ enthusiasts).
By the way, NPR recently did an exposé on IV NAD+ addiction scammers clinics.