Let us recall again everything we have studied so far in this thread. Sure niacine and niacinamide are absorbed through similar pathways, but since any enzyme that uses NAD for any non redox process cleaves it into niacinamide, the end ratios will always be the same. Unless I see evidence pointing otherwise, everything I've read states and clearly shows in humans and mammals that niacinamide is
the major stable form in the serum no matter the source used to supply the vitamin. Again, this makes sense as all NAD non redox processing chemistry results in niacinamide as the byproduct, including the activity of Sirt1. That is, higher Sirt1 activity will produce more niacinamide, and is self limiting.
Tau pathology is quite complex. Why does it occur only very late in life, after reproductive age has come and gone, as a consequence of neurodegeneration? CR has been shown to
activate Sirt1, though you are right that this
activity can be modulated differently in different tissue types, but the fact is, activation of Sirt1 is a neuroprotectant that fights Alzheimer's as shown in other studies, including
this one. So I'm skeptical of that study, Michael, especially since Sirt1 was not knocked out, and since numerous other studies have shown directly the opposite. In fact,
here's a study, Michael, that shows that Sirt1 is greatly reduced in Alzheimer's patience, but not normal disease free humans of the same age group, and that Sirt1 loss correlates strongly to tau pathology and death, not the other way around. An even stronger counter to that triple transgenic study in mice which was using human proteins in the mouse brain - and which challenges that system as being an accurate model for Alzheimer's studies.
Also, we know, since normal in vivo concentrations of niacinamide are always high enough to mostly inhibit Sirt1,
that Sirt1 is turned on by naicinamide processing into NAD by Nampt. So even additions of lots of niacinamide wouldn't inhibit Sirt1 anymore than it always is, but if Nampt is activated, would actually serve to turn on Sirt1 instead. As stated by 100YearsAgo, this is an upstream event that relieves inhibition of Sirt1 by processing niacinamide. This is due to activation of Nampt switching the cellular energy state to an increased ratio of NAD/NADH, and NAD/niacinamide. Here's a nice
overview connecting all these ideas. Obviously, activating Nampt would be expected to be highly beneficial, and apparently AMPK is one such activator. Anything that activates AMPK would be expected to turn on Nampt, and in turn activate Sirt1 - and Sirt1 will respond in a tissue specific manner, which is why it's activity is not globally the same (which is a good thing).
On a final note, it's also important to remember there are more sirtuins than Sirt1 in mammals and humans, all the way through Sirt4 at least, and all have similar functions. Though Sirt1 is the one primarily looked at, these others are surely playing rolls that might confound the results from CR and other experiments. For instance,
here's a paper showing Nampt activity upregulating Sir(t)2 in mice fibroblasts.
To answer FunkOdyssey and rwac: nicotinamide riboside, or nicotinic acid riboside will be rapidly converted to niacinamide/niacine in the gut prior to uptake, and in fact, this conversion is the rate limiting step in niacinamide/niacine absorption. So, taking the riboside form would be only different from taking straight niacinamide in that it'll be absorbed slower, as niacinamide, into your blood stream.
Edit: Oh, and Michael, that second paper you quoted does show resveratrol significantly increasing the life span of every other day feeding mice, which is a curious result, and it did increase standard feeding mouse life span though just beneith the threshold of significance. At any rate, it proves the issue is more complex than any single molecule alone can address, as is expected, and resveratrol is just one tool in the tool shed.
Edited by geddarkstorm, 19 January 2009 - 07:38 PM.
