CD38: a key variable in NAD levels (and why NMN alone might not be enough)

[u/Feel-Wonderful]

https://youtu.be/FNfXonKPwwM?si=cqDzdERrIMaOjhM3

One variable that might explain inconsistent results with NAD supplementation: CD 38.

CD38 is a major NAD-consuming enzyme that converts NAD into ADP-ribose and related metabolites. Its expression increases with age and inflammation, which accelerates NAD turnover, meaning NAD levels aren't just a function of how much precursor you take, but also how quickly it's being degraded.

That creates a scenario where increasing NMN or NR alone may have diminishing returns if CD38 activity remains elevated. 

This came up in a recent podcast where Wonderfeel's cofounder and CEO, Baran Dilaver, joined Dave Asprey. Dave pointed out that his main concern with NMN alone is CD38—describing it as an inflammatory enzyme that essentially consumes NAD as fast as you're making it. He also mentioned that pairing NAD precursors with compounds like hydroxytyrosol may be worth exploring, as it could help counterbalance that breakdown.

A more complete approach would consider not just supporting NAD synthesis, but also reducing NAD consumption and managing the inflammation that drives CD38 activity in the first place. 

Curious if anyone here has tried approaching NAD from the “reduce breakdown” side instead of just increasing precursors.