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.
Would like to share some insight into the combination of NR and rapamycin. I'm 58 yrs old and have been taking rapamycin for 9 months cycling doses between .1mg/kg/week to .05mg/kg/wk and have appreciated multiple beneficial effects. Started taking NR after 6 months on rapamycin. Over the two months on NR (300-450mg/day) I noticed decreasing benefits that I had noted previously with rapamycin. Decided to stop the NR for a while and within several days the benefits of rapamycin returned.
The effects of rapamycin that I had noted were:
1. anxiolysis - felt much calmer and focussed
2. Stamina and energy improvements
3. Motivational improvement
4. Maintainence of ideal body weight without fasting
5. near resolution of eczema which had been quite severe requiring topical treatments daily (primarily hands, some lower extremities)
6. Near resolution of neuropathic pain of the left leg corresponding to an L4/5 left sided disc herniation with weakness, numbness and pain in the L4 distribution. Almost forgot that I had this problem.
All these benefits dwindled while on NR. Most interesting was the recurrence of eczema which again became quite a nuisance requiring resumption of topical treatments with progressive worsening. Somewhat later the neuropathic left leg pain began to return and became quite problematic again. I noticed I had gained several pounds of weight. I thought I was just developing tolerance to the rapamycin and resigned myself to that.
After stopping the NR supplemenation, there was almost immediate improvement in eczema with near resolution again after about 10 days. The leg pain improved after the 3rd day and was nearly gone again after about 2 weeks. The mood and motivational changes also kicked in again after several days off NR.
I'm going to try the NR again in several months to see if this cycle repeats. The most objective and clear change in all this was the eczema and the fact that the recurrence and subsequent disapearance of the skin condition corresponded to the worsening and subsequent improvements in the more subjective issues (mood/motivation and pain). This is quite interesting to me given the possible antagonism noted in the research you provided above.
Being cautious at first, I spent 4 months on 3mg per week. My weight is about 70kg. On this low dose I noted some increased clarity, less anxiety, more stamina and energy about 4 weeks in. This reached plateau in about 3 months. I then bumped to a cyclical dosing in which 2 weeks were 7mg followed by 6mg on the third week followed by 3 weeks in a row of 4mg. This cycle repeats every 6 weeks. Noticed a dose dependent improvement of all aspects at higher doses and a slight diminishment on the lower leg of the cycle
Approximately 5 months ago I started taking Niagen NR at 250mg daily in addition to my weekly intake of 3.75 mg of Rapamycin. I was aware of decreased motivation, and less stamina but did not attribute it to NR with Rapamycin. It appears that NR and Rapamycin may be antagonistic to each other. I am going to go off of NR for a few months and see if there is some difference.
Does anyone have any cycling suggestions or studies on NR and Rapamycin? I wonder if Doctor Green has run into this potential interaction between NR and Rapamycin.
So what’s the conclusion here? Has anybody tried taking rapamycin with nad+ precursor in intermittent fashion? That is taking nad+ precursor not together with rapamycin but rather waiting e.g. 5 days after taking rapamycin and then taking it for a couple of days and repeating the cycle with rapamycin. If so what were the results/observations?