I’ll add a PET scan is about $100-200 in India. @Joseph
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Ive been using 5mg of everolimus with 500g metformin once per week for 9 months
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Very interesting. Everolimus molecule size is about 5% bigger than Rapamycin. And there’s no difference in charge, so all other things being equal you’d expect rapamycin to cross the BBB marginally more easily
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Any side effects? Though that is still a pretty low dose, equivalent to about 3 mg sirolimus. Do you plan to go higher?
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desertshores, you may have shared this elsewhere, but can you share your aggressive rapamycin dose?
I started at 5mg/week with no amplifiers other than EVOO.
Then worked up to every 14 days at 20 mg. with ruby red grapefruit juice and EVOO. That proved to be too much as I got diarrhea every time at that dose. Since then after experimenting with doses that did no cause subjective side effects I settled on 5mg/ weekly with Bioperine, EVOO and RRGGJ. This I tolerate quite well and probably gives me an effective dose equivalent to 15 - 30 mg weekly.
The non subjective problem is my current ferritin levels are below normal. This may not be because of rapamycin, it may be because I am getting too old to give blood twice a year. Right now I am off rapamycin for awhile until I get my ferritin levels back into the normal rang.
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Thank you for the reply. This is very interesting. I was on 24 mg every other week and just switched to 12 mg every week to experiment and see how I feel. I’m 58 years old and thinking of adding GFJ to the regimen. Interestingly enough my ferritin has been below normal the past two labs. I don’t each much iron in my diet but in the past year it has been in the lower end of normal but still in the normal range until my two most recent labs.
I’m not too worried given I have been following Mangan’s advice and wanting a ferritin number towards the lower end and I also donate blood every three to four months.
Question for you. What is your GFJ protocol? How much GFJ and when in terms of before/during/after you take the rapamycin?
Thanks
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I drink 8-10 oz of Florida’s Natural Ruby Red grapefruit juice at about 90 minutes before I take my rapamycin. I also swallow my pills in about 2 tbs of EVOO.
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I’m planning on adding grapefruit juice to my regimen and seeing if any negative outcomes on labs on physical issues. Thanks for this info.
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Note, they talk a fair a bit about how rapamycin and everolimus penetrates the blood brain barrier in this vide:
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Besides molecular size, there are other ways to pass the BBB, notably active transport.
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Just noticed this is a paper I was reading, where they were dosing as high as 4mg/kg of rapamycin the mother mice (not the pups they were later testing)… they talk about dose-dependent permeability of the blood brain barrier to rapamycin…
References in the above:
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Zhang Y., Bokov A., Gelfond J., Soto V., Ikeno Y., Hubbard G., Diaz V., Sloane L., Maslin K., Treaster S… et al. (2014) Rapamycin extends life and health in C57BL/6 mice. J. Gerontol. A, 69, 119–130. [PMC free article][PubMed] [Google Scholar]
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Hadaczek P., Beyer J., Kells A., Narrow W., Bowers W., Federoff H.J., Forsayeth J., Bankiewicz K.S., Borlongan C.V. (2011) Evaluation of an AAV2-based rapamycin-regulated glial cell line-derived neurotrophic factor (GDNF) expression vector system. PLOS One, 6, e27728… [PMC free article] [PubMed] [Google Scholar]
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Banerjee S., Gianino S.M., Gao F., Christians U., Gutmann D.H. (2011) Interpreting mammalian target of rapamycin and cell growth inhibition in a genetically engineered mouse model of Nf1-deficient astrocytes. Mol. Cancer Ther., 10, 279–291. [PMC free article] [PubMed] [Google Scholar]
Source:
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I just want to add a subjective experience.
I’m 20, male.
Last time I dosed 1mg rapamycin (1st day of a 3 day fast) I got anxiety at night on the first day when driving my gf home. (Mild hallucinations in corner of eyes)
I did resistance exercise on day 1 and 2.
2nd and 3rd of the fast I was OK!
The reason I’m saying this is because it affected my behavior and I read in a paper that rapamycin treated mice had more anxious behavior compared to controls in a maze.
So did it cross the BBB for me, is it something else?
(I do not have an anxiety disorder.)
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Possible that even 1mg of rapamycin is to high at your age?
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Have you had anxiety and mild hallucinations in corner of eyes previously?
If you want to know whether it is causal, you can do a self-blinding experiment.
Meaning you put rapamycin tab with a filler like creatine in non-transparent 00 capsules, and then just creatine in another one. Put the placebos in one bottle, and the others in an exact copy of the bottle. Mark the bottom of the bottles to say which contain rapa. Mix the bottles and randomly take one capsule. Look at the bottom of the bottle next day (or a few days afterwards) where you have marked if it is placebo or not. Then you fill up the bottles again so they have the same amount of capsules, or remove one from the one bottle you didn’t take.
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Yes, with a bad weed trip. I had drunk a few beers and combined it with weed and then the hallucinations started in the corners of my eye. Lasted an hour.
(This was more than two years ago, stopped smoking and drinking)
Also with high dose fish oil (6g/d) gave me noticeable anxiety.
Good idea. I’ll look into making myself a test subject!
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I realize this is an old thread but it is of great interest to me. It would seem easy enough to measure rapa/sirolimus levels in CSF (spinal tap) to determine BBB penetration.
Lets just say that peak dose somehow results in more rapamycin crossing the BBB. Then it would seem using EVOO would be contraindicated if a high Cmax is your goal because EVOO smooths out the peak over a longer period resulting in a significantly lower Cmax and larger AUC.
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To come back to this. I didn’t do a blinded test on myself, but, I took a higher rapamycin dose (2mg) and it had no discernible effect on me, maybe an effect on my sleep.
I also did a 3-day fast a week prior to the 2mg rapamycin dosage and again, no hallucinations/anxiety.
My small theory on what contributed to the anxiety/hallucinations that time:
Most likely: 1. It was my first 3-day fast and my first time entering ketosis. I think my body just struggled a little and I became hypoglycemic.
May have played a role: 2. My electrolytes intake wasn’t on point. (Hand numbness when my arm was higher than my heart) in proceeding fasts I found out it was my potassium : sodium ratio, so I adjusted and that fixed it.
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