No: the best-understood mechanism for negative feedback is from NAD+ itself, which works by inhibiting NAMPT activity; the route by which NAD+ is produced is irrelevant. Additionally, many of the other postulated feedback mechanisms are downstream of NAD+, involving the futile use or metabolism of NAD (by CD38, PARP1, nicotinamide N-Mmthyltransferase, etc).
This is an interesting discussion. It's been on my mind, and this piece out of ABN's "NAD+ boosting" discussion caught my eye. It seems to offer a solution. From what they describe, most NR is converted to NAM, before NAMPT converts it to NMN and then finally NAD+. Therefore, the negative feedback lowers NAD+ production. But NMN is after the NAMPT bottleneck, so there is no way lower NAMPT can lower NMN's ability to become NAD+. This means it can be successful used long term with continued NAD+ elevation - no feedback. Their graphic:
You'd think then that NMN was the total answer, sort of, but they continue....
However we believe including all four of these NAD+ precursors (NMN, NAM, NA, Tryptophan) makes this far more effective at boosting NAD+ throughout the body as they:
- utilize different pathways
- are metabolized at different rates
- vary in the organs they are effective at raising NAD+
According to Dr. Charles Brenner:
“Not every cell is capable of converting each NAD+ precursor to NAD+ at all times…the precursors are differentially utilized in the gut, brain, blood, and organs” (R).
Which makes sense for total body needs anyway, as they are different compounds, having different pathways and effects, and they do other things beside raise NAD+. Even so, they are saying NMN bypasses the NAMPT bottleneck, yet they still want to use other precursors!? Confusing. Strangely, even though they describe a product containing all this, I can't find that they actually sell it, as the product link goes to NMN PURE.
Thoughts?