This new research examines what happens to NR, NMN and other metabolites of NAD+ in the bloodstream and how they effect intracellular NAD+ levels in peripheral tissues.
When added to the serum outside of cells, all NAD+ metabolites were effective at restoring the NAD+ levels and metabolic activity INSIDE the cells. NMN was the most effective.
NMN is not impeded at crossing the cell membrane, and is more effective at restoring intracellular NAD+ levels
Proponents of NR often point to studies that show NMN and NAD+ must be partially degraded to NR to cross the membrane of some cells, and claim this makes NR a better choice for supplementation.
The faster speed and effectiveness of NMN supplements has always made this position suspect. This research shows crossing the cellular membrane is not an impediment.
This research looked at kidney cells where NMN and NAD+ must be degraded to NR before crossing the cellular membrane.
Interestingly, the conversion does not seem to impact the ability to enter the cells.
They found that enzymes on the outside of the cells themselves (ecto-enzymes) perform this conversion and are ubiquitous.
For example, the ecto-enzyme CD73 can cleave NAD+ to NMN and AMP, and also dephosphorylate the NMN to NR and adenosine.
Researchers introduced various NAD+ metabolites to the serum outside of cells.
As shown in the chart above, adding NAD+ or it’s metabolites to the serum OUTSIDE the cells were all effective at restoring the NAD+ levels and metabolic activity INSIDE the cells.
In fact, NMN was slightly more effective at restoring metabolic activity INSIDE the cells.
This was in cells that NMN was supposedly disadvantaged by needing conversion to NR before crossing the cell membrane.