Cycling Rapamycin with NAD+ Precursors
I have been taking the NAD+ precursor NMN (250mg daily, sublingually) for the past several months and have recently added Rapamycin (5mg weekly).
I was wondering whether it would be a good idea to not take the NAD+ precursor during the peak part of the Rapamycin dose (approx 60hr half-life). I was thinking of three days no NAD precursor following Rapa and then four days taking the precursor (maybe at a higher dose, say 375mg daily). My rational is as follows:
1. Rapa & the NAD precursors seem to work in different directions. Rapa is not about cell growth, but repair eg autophagy. The NAD precursors and especially NMN seem to be more about extra energy and growth - I'm thinking in particular of the mouse studies showing capillary growth in muscles and all of the anecdotal evidence of people increasing muscle mass etc (often from this site).
2. The study I have posted below seems to show an antagonism between Rapa and in this case NR, when it comes to stem cells in the gut (see bolded text). This is the only instance that I have found in a search of Pubmed, but since not much research has gone into looking at both of these pathways, I wonder if it is the tip of the iceberg.
3. From various sources it appears that homeostasis kicks in with NAD precursors after a certain while (though levels do not return completely back to where they had been). By skipping them for three days a week, could this perhaps be prevented?
4. Also save a bit of money on the NMN! (even if I increase the dose by 125mg on the on days it is still only 12 pills instead of 14 weekly)
I realise that although they both raise NAD+, NMN & NR are not the same, but until the science is fully elucidated, I am here assuming them to be.
I am very curious as to your thoughts on this, especially if you are also combining them.
NAD+ supplementation rejuvenates aged gut adult stem cells
The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. The treatment with the NAD(+) precursor nicotinamide riboside (NR) rejuvenates ISCs from aged mice and reverses an impaired ability to repair gut damage. The effect of NR is blocked by the mTORC1 inhibitor rapamycin or the SIRT1 inhibitor EX527. These findings demonstrate that small molecules affecting the NAD/SIRT1/mTORC1 axis may guide a translational path for maintenance of the intestine during aging.