Biohacking rapamycin's bioavailability

Back in January, my well meaning MD arranged for me to get sirolimus capsules from a compounding pharmacy.

This seemed great to me at 1/3 the price of an ordinary prescription in the US, until after a few months the benefits I had gained in the previous 6 months started reversing.

I then learned about the de minimis bioavailability of the medication in non-acid-resistant capsules from further reading on this site. The compounding pharmacy doesn’t have acid-resistant capsules.

I further learned more about the general low bioavailability of rapamycin taken orally even as acid-resistant tablets.

This has me thinking and wondering what we can do to increase the bioavailability.

Does stomach acid account for the low bioavailability?
If so, can we hack the problem?
Some thoughts follow.


While perhaps not specifically addressing the stomach acid question, this site has extensive discussions about using grapefruits or grapefruit juice. Its use tempts me, but without identifying a specific and standardized dose of grapefruit juice this seems an inexact method.

Acid-resistant capsules hack

My doctor pre-prescribed sirolimus 2 mg tablets for me and the pharmacy gave me the following:

Screenshot 2023-05-24 at 1.12.22 PM

I had ordered “acid-resistant” capsules, with the thought of putting an entire non-acid-resistant capsule into an acid-resistant one. I appreciate from the forum that these over the counter acid-resistant capsules don’t resist much acid.

Still, one can readily oder such capsules online in a size, into which one could slip several of these 2 mg tablets (whole).

Used like this would the capsule provide a bit of additional protection against stomach acid, delay the absorption of the rapamycin until it gets into the small intestine and thereby improve the bioavailability?

Resistant starch

I take resistant starch (Bob’s Red Mill Potato Starch), a prebiotic to support my intestinal microbiome. It doesn’t digest in the stomach making its way even into the large intestine.

I wondered if anyone has experience with taking rapmycin with resistant starch and whether it might serve as a carrier to get more of the drug past the stomach acid.

Thoughts and other suggestions appreciated.


I was surprised at how long an enteric-coated capsule remains in the stomach.
This article contains more information than you will ever want to know about drug absorption and passthrough in the stomach.

IMO: After reading (most of it) the best practice as suggested by RapAdmin who takes his rapamycin with a fatty meal (sardines if I remember correctly). is to take it with a fatty meal and enough liquid to reduce stomach acidity. I have used grapefruit juice in the past and it works as an excellent aid for the bioavailability of rapamycin. The problem is it is just too variable so you don’t know if you are getting the equivalent dose each time.

“After an overnight fast, three adults received together with 200 mL water at two different occasions on a crossover basis: (A) 5 spherical enteric coated tablets of barium sulfate and (B) 50 cylindrical granules of barium sulfate coated with ethylcellulose. No food was consumed until 4 h after dosing. The number of tablets and granules remaining in the stomach were determined by periodic roentgenography. Data after administration of the tablets in one of the adults indicated 80 % gastric retention at 2 h.”


Interesting. Thanks for posting the link.
It has me thinking more.
Wouldn’t taking baking soda with the rapamycin reduce stomach acid and improve bioavailability?

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My fasting and rapamycin protocol looks as follows:

I try to eat only some veggies the day before the Rapa dose. Like salad, home made Nattō or Tempeh. I avoid anymal products.

1h before the Rapamycin dose, I’ll have one Grapefruit. With the Rapamycin I’ll have 40g of chocolate 90% plus some Brazil nuts or macadamia. In addition I’ll take Ca-AKG, spermidine, quercetin, fisetin, resveratrol, astaxantin, vitamin D3 + k2 and Carnosine.

Afterwards I’ll fast for at least 24h. Lately I’ve completed 4 days but that’s rare.

I know that we don’t have any data on interactions between these supplements and rapamycin. It’s just my best guess that there could be a positive effect.


Reading the Zydus Sirolimus packaging it refers to “film coated”, but does not seem to say whether the film is at all acid resistant or whether it is functional or not.

Does anyone know which of the standard Rapamycin manufacturers provide enteric coatings?

When I first started taking rapamycin I bought both Zydus and Rapacan.
I ran a little test to see if one was superior to the other. I added hydrochloric acid to distilled water until I reached a ph of ~1.5. Then I heated the solution to appox. 98 degrees f.
I dropped a Zydus and a Rapacan into the solution at the same time and made a time-lapse video. There was no significant difference in the dissolve time. Below are 3 pics from the video. They both were completely dispersed in about 10 min.
Since the time in the stomach is up to 2 hrs + I don’t think it matters.
I am going to repeat the experiment using some enteric-coated capsules I bought, but I don’t think there is going to be a big enough difference to escape the stomach acid.
Rapcan is on the left, Zydus is on the right.



I think you can safetly assume that all the major generic companies have some sort of coating to allow a reasonable level of bioavailability, otherwise the drug would not work at all for its main application in organ transplant patients (and that news would spread quickly since the result would likely be fatal).

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This is an interesting idea, but I have not seen anyone experimenting or reporting on anything like it. If you want to find out, the best way would be to do blood sirolimus testing comparing with, and without…

See: How to get a Rapamycin (sirolimus) Blood Level Test

Thanks for the responses on bioavailibility. I am sort of assuming the generics tend to have similar bioavailiblity, but if there is any specific blood testing results that would be interesting.

After my issue with the compounding pharmacy (see 1st post on this thread), my MD wrote me a new script for a generic Sirolimus. I posted photo it above.

I’ve started at 14 mg once per week, 2 mg over what I took prior to the compounding pharmacy mess.

I should have everything on track, but the experience piqued my skepticism, so I had a test done.

See attached image.

Because of access to the blood draw and scheduling I had blood taken 48 hours after my weekly dosing (of 14 mg). Not looking for maximum or minimum levels. I just want to make certain I get reasonable levels.

Results → Sirolimus, Lc/ms/ms (mcg/L) = 4.6

Does this give me the blood levels I should expect taking US sourced generic Sirolimus 48 hours after dosing?

I’d appreciate some interpretation of the result.
Thanks in advance.