Note on Niacinamide and PARP Inhibition

In reference to that posting about niacinamide, I was going to mention that I don't think niacinamide is at all effective as a PARP inhibitor in vivo. I discussed some of the issues surrounding that area of controversy in a past posting (http://hardcorephysiologyfun.blogspot.com/2008/12/nonoxidative-pentose-cycle-prpp-and.html). That's just my opinion, and those issues are resurfacing again in the context of the regulation of transcription by ADP-ribosylation. I've seen articles suggesting that niacinamide or some prodrug type of derivative of niacinamide could be used to regulate ADP-ribosylation, but the capacities of niacinamide to increase poly(ADP-ribose) levels (in that old posting, I cite some research showing that) and to induce feed-forward increases in PARP activity strongly offset, in my opinion, any PARP inhibition or beneficial transcriptional changes, such as by an enhancement in ADP-ribosylation of proteins, that niacinamide may produce in vivo. I know there's excitement about influencing some of these mechanisms, and I know that the issue of niacinamide as a PARP inhibitor looked interesting and promising in the past. But, as some of that research I linked to in the old posting shows, niacinamide tends, in my opinion, to have the opposite effect in vivo. It can increase PARP activity by providing more NAD+, and it can also increase the formation of nitric oxide and reactive oxygen species by enzymes that display NADPH oxidase activity (many enzymes), etc. I'm not going to get into a discussion of the problems I see with some of these popular areas of NAD+ related research.