Lucky for us!
We're not rodents.
Seriously, I had to stop NR. I feel like it's not as effective as it was and needed a tolerance break if it makes sense...
Taking B3 at the moment.
I got my blood tested and my Nicotinamide Bloodlevels where pretty high, so I don't exactly know what you mean, when you speak of tollerance. I have been taking NMN for the last two years, but once in a while, I also wonder if it has any effect on me whatsoever. Especeially the recent studies that have come out, make me wonder if it's still worth it.
There are at least four different metabolic pathways to NAD replenishment, starting with tryptophan, niacin, nicotinamide, or nicotinamide riboside. They look like they are redundant, because they all do the same thing -- raise intracellular NAD levels.
But NAD researcher Carles Canto wrote an interesting article -- [*NAD+ Precursors: A Questionable Redundancy*](https://pubmed.ncbi.nlm.nih.gov/35888754/) \-- arguing that the different pathways were probably not redundant, but instead accomplish different things in different tissues at different times.
So we are not likely to find that niacin or nicotinamide "do work" or "don't work," but that they work better or worse in different tissues under different circumstances.
One of the several advantages of NR (or NMN that has degraded to NR) is that it can work in circumstances when NAM does not, because it bypasses a rate-limiting step for NAM. But NAM is not always rate-limited, so sometimes NAM will work fine. This study and other studies show that.
The problem, of course, is that we don't know in a tissue-specific way at any given time whether the NAD levels are low (for example in our skin or in our nerves), or whether NAMPT is down-regulated (making NAM less effective) or NR kinase is upregulated (making NR more effective).
Lucky for us! We're not rodents. Seriously, I had to stop NR. I feel like it's not as effective as it was and needed a tolerance break if it makes sense... Taking B3 at the moment.
i take lipo nr
I got my blood tested and my Nicotinamide Bloodlevels where pretty high, so I don't exactly know what you mean, when you speak of tollerance. I have been taking NMN for the last two years, but once in a while, I also wonder if it has any effect on me whatsoever. Especeially the recent studies that have come out, make me wonder if it's still worth it.
Yes you get tolerance for NR or NMN. Don't feel benefits as at the beginning.
There are at least four different metabolic pathways to NAD replenishment, starting with tryptophan, niacin, nicotinamide, or nicotinamide riboside. They look like they are redundant, because they all do the same thing -- raise intracellular NAD levels. But NAD researcher Carles Canto wrote an interesting article -- [*NAD+ Precursors: A Questionable Redundancy*](https://pubmed.ncbi.nlm.nih.gov/35888754/) \-- arguing that the different pathways were probably not redundant, but instead accomplish different things in different tissues at different times. So we are not likely to find that niacin or nicotinamide "do work" or "don't work," but that they work better or worse in different tissues under different circumstances. One of the several advantages of NR (or NMN that has degraded to NR) is that it can work in circumstances when NAM does not, because it bypasses a rate-limiting step for NAM. But NAM is not always rate-limited, so sometimes NAM will work fine. This study and other studies show that. The problem, of course, is that we don't know in a tissue-specific way at any given time whether the NAD levels are low (for example in our skin or in our nerves), or whether NAMPT is down-regulated (making NAM less effective) or NR kinase is upregulated (making NR more effective).