In mice, a specific biological pathway called Preiss-Handler is the main way the liver makes an important molecule called NAD+ after giving NMN or NR, because when scientists turned off a key part of that pathway, NAD+ didn’t go up anymore.

What we've found so far does not support the idea that the Preiss-Handler pathway is the main way mice produce liver NAD+ after taking NMN or NR. In fact, the evidence we've reviewed leans against it. Our analysis of the available research shows that nine studies contradict the claim that the Preiss-Handler pathway is primarily responsible for liver NAD+ production following NMN or NR supplementation in mice [1]. Only one assertion supports this idea, based on experiments where a key part of the Preiss-Handler pathway was blocked, and NAD+ levels did not rise [1]. However, the weight of the evidence we’ve reviewed does not align with this conclusion. We don’t yet know all the details of how NMN or NR are processed in the mouse liver, but what we’ve seen so far suggests other pathways likely play a more central role than Preiss-Handler. The repeated findings across multiple studies pointing in the opposite direction mean our current analysis cannot support this pathway as the main route [1]. We also recognize that biological systems can be complex and context-dependent. Just because the evidence leans one way now doesn’t mean the picture is complete. As we continue to analyze new data, our understanding may shift. Practical takeaway: Based on what we’ve reviewed so far, it’s unlikely that the Preiss-Handler pathway is the main way mouse livers make NAD+ from NMN or NR. For now, other pathways appear more important, but we’re keeping an eye on future research to see if that changes.