When mice get NMN or NR through an IV, their bodies quickly break it down, send it to the gut, where gut bacteria turn part of it into another form that gets recycled back to the liver to make an important energy molecule—so the gut-liver loop is key, even with injections.

What we've found so far suggests that enterohepatic circulation may play a key role in NAD+ synthesis in the liver after IV administration of NMN or NR in mice. Our analysis of the available evidence shows that even when these compounds are delivered directly into the bloodstream, they are rapidly metabolized and transported to the gut. There, gut bacteria appear to modify part of the NMN or NR into a form that can be recycled back to the liver [1]. This recycled compound may then contribute to the production of NAD+, a molecule vital for cellular energy and function. The evidence we've reviewed leans toward the idea that this gut-liver loop is an important part of the process, even with intravenous delivery [1]. We only analyzed one assertion, and it supports this view—no studies we reviewed contradicted it. Still, the total number of studies behind this assertion is limited, and we cannot rule out that future research may change our understanding. Right now, we don’t have enough evidence to say how much of the NAD+ synthesis depends on this cycle or whether other pathways can compensate if it’s blocked. Our current analysis shows that the body may use a roundabout route—sending IV-administered NMN or NR to the gut first—before rebuilding it into NAD+ in the liver. This highlights the gut-liver connection as a potentially important player, even when bypassing oral intake. Practical takeaway: Even injections of NMN or NR might rely on gut involvement before helping liver cells make energy molecules—so gut health could matter more than we once thought, even for IV treatments.