The old NR thread moderated by Bryan_S had a lot of discussion about sub-lingual NR a few years back.
I believe that even had some impact on HPN using a formula with no fillers so it would work better.
Since then, we've had a lot more research come out indicating a substantial % of NR is likely digested to NAM, or quickly converted to NAD+ in liver and very little is freely circulating as NR in blood.
To me, this more recent research does make NR IV and sub-lingual NR sound like promising options to get more NR to cells outside the liver. Although Bryan_s no longer recommends it
There is no definitive conclusion that most NR is converted to NAD+ in the liver and even less evidence that NR is decomposed to N+R. Let’s not continue the arguments here.
All we know now is when you take NR, your whole body benefits from liver to brain and to skin. It would be nice to know the mechanism of NR transfer inside the body, but it doesn’t affect us taking advantage of NR.
Here's a few quotes from the MOST RECENT review of NR, NMN, NAD+ metabolism:
"a substantial fraction of orally administered NR is likely converted into nicotinamide by first-pass metabolism in the liver or by hydrolysis in the blood circulation before its uptake into other tissues in vivo (Figure 2)"
"Furthermore, it has recently been reported that NR, but not NMN, is unstable and quickly degrades into nicotinamide in murine plasma or fetal-bovine-serum- containing culture medium "
They do believe SOME NR reaches other tissues intact:
"strongly supporting the conclusion that at least part of the compounds administered reaches the target tissues before being degraded to nicotinamide. "
So if they are correct, it is likely the additional benefits from NR (vs NAM) are mostly due to the % of NR that makes it through to cells outside the liver. And if we can increase that % it would be to our benefit.
Just because NR isn't 100% available to cells throughout the body doesn't mean it is the same as NAM.