I am puzzled by people intent on making sure that NR does not reach the gut. They use IVs, injections, sublingual, or liposomal delivery, purportedly to improve bioavailability. But the gut should actually be a primary target for NR users.
You can see in the diagram above how faulty tight junctions in the intestine might allow toxins to leak into the bloodstream.
A new study says that drinking alcohol causes gut barrier leakage, and NR restores the gut barrier. For anyone who drinks alcohol — which is maybe most people — this is a huge reason to deliver NR to your intestines via oral NR supplementation, and not try to bypass the GI tract.
“We found that ethanol increased intestinal permeability, increased the release of lipopolysaccharide (LPS) into the circulation and destroyed the intestinal epithelial barrier structure in mice. Nicotinamide Riboside (NR) supplementation attenuated intestinal barrier injury. Both in vivo and in vitro experiments showed that NR attenuated ethanol-induced decreased intestinal tight junction protein expressions and maintained NAD homeostasis. In addition, NR supplementation activated SirT1 activity and increased deacetylation of PGC-1α, and reversed ethanol-induced mitochondrial dysfunction and mitochondrial biogenesis. These effects were diminished with the knockdown of SirT1 in Caco-2 cells. Conclusion: Boosting NAD by NR alleviates ethanol-induced intestinal epithelial barrier damage via protecting mitochondrial function in a SirT1-dependent manner.
Intestinal permeability is not a good thing. It at least causes inflammation, and is also associated with celiac disease, inflammatory bowel disease (IBD), and metabolic liver disease -- although scientists are not yet certain whether intestinal permeability causes the disease or vice versa:
In the clinical conditions presented in the review, increased intestinal permeability has been demonstrated, but the central question of whether the barrier dysfunction is a primary event in the pathophysiology or a consequence of the disease is still not resolved in most diseases.
And yet here is another very recent study showing that a collection of nutrients including nicotinamide riboside can reverse gut barrier disruption.
...This specific combination of metabolic cofactors [including nicotinamide riboside] can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.
Conclusion
I have argued elsewhere that the alleged bioavailability problem for nicotinamide riboside is already solved by the doses involved, and indeed the partial degradation of NR in circulation or in the gut is not necessarily even a problem, since it is (1) not complete, and (2) provides additional distinct benefits, which as to the gut microbiome and to stem cells in the gut.
But even if in vivo degradation of NR were a problem, bypassing the gut does not appear to be a good solution, because the gut is one place where you would absolutely want to directly deliver NR, and there's an easy way to do it. So oral delivery of NR and partial metabolism in the gut may be a feature, not a bug.