Interesting observations. So thinking about a 1000 mg/day dose. Given we want max amt directly to the tissues/blood over as long a time as possible, and likewise delay/minimize liver filtering and removal.
Sublingually, if you use larger doses (say 2 x 500mg), most of it does not get absorbed and you swallow it, similarly to taking a pill really. As a result most of what you thought you took sublingually gets directly removed in the liver. If you instead take smaller sublingual doses (say 10 x 100mgs), more is absorbed sublingually and gets directly into the blood and tissues, and less gets swallowed and so immediately removed by the liver.
On the other hand, the only hope for getting an oral dose to the blood/tissues is to overwhelm the liver and get some spillover in the blood. Of course, even that gets removed shortly by the liver filtering. So oral dosing makes no sense (and takes larger doses) unless you primarily only want to get to the liver.
For things you want to get into the blood/tissues, sublingual (and/or bucal) is the only logical, and efficient choice. As a bonus, the residual swallowed dose is used by the liver, but as it's supplied gradually over time in smaller amts, homeostasis response is limited. Am I missing anything?
Yes, that is what I was thinking.
Liu says that at 50 mg/kg, NONE of the NR/NMN escapes the liver. CD38 metabolizes to NAM, and is excreted from liver to bloodstream where other tissues must use their salvage pathway for NAD+.
Yet clearly they have different effect than oral NAM. Some must escape the Liver. Studies that show effectiveness often use 300-400 Mg/kg a day. Does higher dosages result in more making it outside the liver?
Trammel/Brenner show a 270% increase in liver NAD from a single dose of 1000 mg. That drops to 90% after 1 month, and 55% at 2 months (Elysium study).
That is the homeostasis I am talking about - liver centric. Liu says that is the source for most NAD+ in the body. ( I don't recall - what happens to NAD+ levels in other tissues over months of supplementation? )
Is that due to more CD38 being utilized to keep NAD+ levels in liver lower, and is that bad or good or neutral?
Perhaps that limits the amount of NAD+ that escapes the liver, and can be avoided or minimized by not relying entirely on the liver NAD+ levels to supply NAD+ elsewhere.
That is why I think the frequent smaller dosages may work better.
Edited by able, 24 August 2018 - 07:43 AM.