Predicting rapamycin metabolism with genetic polymorphisms

I notice that some people here are trying to use blood tests to determine the rapamycin concentration to try to see if the dose they take is good or if they might need more or less than they are taking to reach the desired concentration. This is good, however I wonder if it is possible to predict to at least some degree whether a person will need a relatively high or low dose of rapamycin by examining polymorphisms in genes that metabolize rapamycin in the digestive tract and the liver and predict if the person is a fast or a slow metabolizer. This could be beneficial as an addition to blood tests and also for those that can’t take a rapamycin blood test.

It is now getting quite inexpensive to sequence your whole genome so knowing what polymorphisms you have is not so difficult. The difficult part is predicting the overall effect of several polymorphisms on the rapamycin metabolizing enzymes. If there is some one or two major polymorphisms in the cytochrome P450 genes that has an unusually large effect if a person has a certain genetic variation then that could be useful. However it’s also possible that the metabolism is determined by a complex combination of several polymorphisms none of which stands out as having large effects making it practically impossible at this time to predict the overall rapamycin metabolizing speed of the individual.

Here are two studies showing different metabolism of rapamycin depending on CYP3A5 and CYP3A4 polymorphisms.

Has anyone looked into the polymorphisms involved in rapamycin metabolism sufficiently to determine if they are of significance for practical use?


I am supposedly an ultrarapid metabolizer per Genomind. I started Rapamycin at 1 mg per week for two weeks and have worked up to 2 mg per week for two weeks (I started slow because I have neuroimmune disease - ME/CFS/Lyme/Fibro - as well as diagnoses of EDS and MCAS, neurological autoimmunity, et al.).

I seem to clear Rapamycin fairly quickly. I feel well for about 4 days at 2 mg per week (135 lb female, 5’9") and on day 5 notice that it rapidly wears off and I feel like crap for two days before my next dose.

I’m guessing, solely based on my own experience, that ultrarapid CYP450 metabolizers may need more frequent dosing or taking a higher weekly dose to avoid the sharp drop off in Rapamycin blood level and subsequent return of symptoms.

I’m moving up to 3 mg this week, and will keep increasing 1 mg per week until I hit 5 or 6 mg. I may adjust my dosing when I have more insight regarding my response to the drug. So far, neurological symptoms have improved, as has pain and crushing fatigue/weakness. I’ve been sick for 11 years now and have done dozens of hardcore treatments (IVIg, Rituxan, PICC antibiotics, many FMTs, exosomes, peptide injections, Ketamine, every psych and Parkinson’s drug available, etc., etc.). Although I’ve gone from bedridden to up and about, I’m still ill and feel like the ME dementia worsens every year.

So far, Rapamycin is the only thing that has seemed to have touched the neuroimmune “dementia” that started when I got sick at 44; it seems to be helping other symptoms as well.

Dosed at 3 mg today and feel well, better at the higher dose.


Keep going with it - hope you continue to improve and ultimately heal all your ills.

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Genomind. Interesting. Did they provide information on your genetic variants for CYP3A4 and CYP3A5 or just for CYP450 in general?

I’m glad to hear about your success with rapamycin and yes I agree that you may need more frequent dosing if you are indeed metabolizing it faster.

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Hello, Genomind reports on variants of 6 “key” CYP450 genes, have a look at the following link:

I definitely process alcohol and drugs faster/differently than other people… will have to figure out dosing frequency when I get to higher doses (to see if I still get the sharp taper I seem to be experiencing at lower doses of Rapamycin).


Thanks. That’s interesting.