and that we just don't know enough....I guess 10 hours is just a really rough approximation,..and doesn't really address levels or other locations...
It is important to point out that, although whole-cell NAD+, nicotinamide, and nicotinic acid measurements can monitor NAD+ metabolism at a gross level, knowledge of the metabolite concentrations in subcellular compartments, such as the nucleus, cytoplasm, and mitochondria, is crucial to gauge how NAD+ metabolism affects sirtuin and PARP functions at different cellular loci. Technical and experimental progress in this area is needed before it will be possible to describe just how NAD+ metabolism is coupled to NAD+-dependent signaling processes.
and this:
NAD+-consuming reactions are tightly regulated in mammalian cells, and NAD+ depletion can occur rapidly in cells exposed to genotoxic stress. Genotoxins damage DNA and cause DNA strand breaks. These DNA breaks are sensed by a DNA repair system, which includes PARPs and a sirtuin, SIRT6. The activation of PARP, in particular, causes a rapid synthesis of poly(ADP-ribose) at the site of the strand break, and when this system is overactivated, it can significantly deplete cellular NAD+. On the other hand, NAD+-forming reactions are apparently subject to regulation as well. Cellular NAD+ concentrations are linked to organism nutritional status and physiologic state (Guarente, 2006). For example, NAD+concentrations in liver increase 30% with fasting (Guarente, 2006). Thus, NAD+ metabolism is dynamically regulated by organism nutrient intake and genotoxic stress.
I guess the bottom line is what levels are optimal and how to sustain it...which will likely vary in different regions...given depletion variabilities, even with a possible 10 hour half live (in the liver....what about other body zones) I guess I'm feeling multiple dosings through the day seem wiser... or not? I guess we're still here:
In general, the mechanisms that alter human NAD+ metabolism probably include multiple processes, but the understandings of these mechanisms are currently very unclear and a considerable effort in this area is required before we know how NAD+ metabolism is controlled, how changes in NAD+ metabolism influence physiology, and how NAD+ metabolism might be manipulated for therapeutic benefit.
Is measuring NAD+ levels in various zones at varying dose regimines super expensive? Seems the most critical issue to us big sacks of water...in my humble, technically challenged opinion...
The most frustrating aspect of this is lef says 100mg... others 250.... crude mouse extrapolations say 10xs or more than this, and we are dosing all over the map with some financially comfortable folk doing 6 g/day! Oy!
I love insights... and we could use a few in this regard...
Edited by Vastmandana, 20 November 2014 - 04:31 AM.