So many things to cover. Let's start with how NR elevates NAD in different tissues in mice. /1
Our approach uses quantitative targeted metabolomics. This means we measure concentrations of NAD+, NADP+, ADPR, NAAD, NMN, NAMN, NR, NAM, NA plus several methylated/oxidized forms of NAM & other compounds simultaneously. Ppl that use cycling assays cannot get quantitative data/2
Ppl that use metabolomic methods without internal standards do not get quantitative data. Ppl that don't know how to properly extract samples or that sacrifice animals at different times of day do not get valid data. /3
Our data showed that oral NR has a different time course than NAM or NA in elevating liver NAD metabolome & produces more NAD than the other B3s per equivalent dose. See this figure plus others in the same article nature.com/articles/ncomm… /4
NR clearly acts as NR in elevating liver NAD. In 15', if you have put NA, NAM or NR in a mouse's stomach, you see that form of B3 in the liver. In liver, NR and NAM behave differently. NR produces much more ADPR than NAM, suggesting that high dose NAM depresses SIRT activity. /5
In other tissues, there is a complication that you cannot see circulating NR in blood because of an extraction issue. However, you can see NR elevate cardiac NAD in failing mouse hearts that spike up expression of the NRK2 gene and depress NAMPT. NAM can't do that. /6
Other genetic & pharmacological experiments show that NR acts as NR in heart, skeletal muscle, nerve & brain. Both NAD & NMN work as NR in multiple target tissues. There is no credible evidence for transport of NAD or NMN into any cell no matter whether injected or taken orally/7
There are additional experiments that address bioavailability in mice, rats & humans that we are doing. It's irresponsible to make claims that have not been vetted by peer reviewers so we'll leave it there for now. /end
