There is no evidence than NAM + R increases NAD+ more than NAM alone.
That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking.
The study I quoted was for skin, so not that germane. Apologies.
This discussion notes at least transient heptotoxicity:
https://livertox.nlm....gov/Niacin.htm
My point is that nicotinamide is not completely benign and people should be somewhat careful with it. And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct.
1) "That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking." Ah, but that's not what you asked. You said that NAM + Ribose increasing NAD was just a hypothesis. It isn't. It definitely increases NAD, and arguably does so as well as NR.
Does that mean that the ribose increases NAD even more than NAM alone? Not necessarily. Is it bad to include it? Probably not. It's a relatively small dose of ribose.
Is it riskier than NR? Definitely not. NAM and ribose are supplements that have been used for decades.
NR supplementation is new. The number of reports from members of connective tissue problems with NR is a little concerning. The long-term issues are not well-understood. If NR were not a (rather uncommon) natural substance, it wouldn't be for sale; its long-term safety isn't demonstrated.
2) "This discussion notes at least transient heptotoxicity: https://livertox.nlm...ov/Niacin.htm" I'm afraid I can't find any reference to NAM in your link, just to Niacin, which is processed through a completely separate set of pathways.
All evidence of niacin toxicity is from sustained-release formulations. No one completely understands the story with niacin (no money in it), but it appears that the transient elevations in liver enzymes is a part of the beneficial effects on cholesterol levels and composition (ie LDL vs HDL). It appears the the elevations in liver enzymes is a part of the clearance process rather than 'damage.' It's a not a good idea to keep high levels of blood niacin round-the-clock.
It also may not be smart to keep high levels of NR in the body round the clock.
Very high levels of NAM--especially round the clock--might not be a good idea, either. (But your reference doesn't mention NAM. For someone who lectures everyone that two components aren't the same as a compound of the two components, that's odd.)
These are all very potent vitamins. Super-high levels of Vitamin D also aren't smart. Super-high levels of most things aren't smart.
I thought everybody knew this already. When the drug companies tested Niacin against Statins, they made sure to use sustained-release Niacin for just this reason--to increase liver enzymes.
3) "And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct."
Sometimes yes, sometimes no. Welcome to biochemistry.
There is some evidence that NR is a loosely associated compound that is split into NAM and Ribose during absorption. (And, like most loosely complexed compounds, likely actually exists in an equilibrium state.)This is a poorly understood area, as it is all new. There are also quite likely a number of conversion pathways that haven't been discovered (there's some evidence for this).
We don't know. But the evidence for NR being somehow unique and especially bio-friendly is quite weak.
4) NAM is the main 'salvage' pathway from NAD+. So taking in NR, or Niacin, or even NMN, will result in more NAM being produced.
So, if NAM is a problem, we're in trouble with NR, Niacin, and even Tryptophan.
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I'm not an N+R advocate, but I'm messing around with the protocol(s). So far, I've got more out of it that I did from NR. I'm not sure what that means.
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That said, the real thrust of this thread is Turnbuckle's idea that you can favor fission over fusion, and cycle between the two.
To me, whether this needs NAM + R, or only NAM, or even NR, is beside the point.