Rapamycin dosing schedules and bacterial infection induced cancer/mortality

While rapamycin can suppress the immune system (and especially make one susceptible to bacterial infections) while one is on it, it has also been shown to boost immunity after a wash out period.

This effect of rapamycin makes me a fan, because it suggests that even a short intervention duration can provide benefits even after the washout period!

HOWEVER, I have been wondering if the commonly used weekly or biweekly doses can have drawback when it comes to bacterial infections by making them persist as long as one is taking rapamycin (Many folks are always ON).

Currently this is considered to be okay because one the rare occasion of bacterial infections, one can always take anitbiotics.

My concern is when it comes to asymptomatic bacterial infections, or infections that we don’t yet know may be causing other conditions. I wondered about this again today after reading that prostrate cancers can be caused / exacerbated by certain bacterial infections.

See also,

https://journals.sagepub.com/doi/full/10.1177/1756283X12473674

So would you think a regular period OFF of rapamcyin which is more than a week or two long be useful? How long would the OFF and ON periods be then?

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As a healthy late 20s with regular exercises and good diet, and doesn’t have any chronic disease, I’ve had once a severe Staphylococcus infection on my nasal epidermis.

I’ve also once had a severe pain on right lower quadrant abdomen on the 5th day after taking rapamycin, it made me suspect it’s an Appendicitis, but luckly it wasn’t.
Hence the Appendicitis possibly induced by suppression of immune system by rapamycin is also a concern.

There was a case report of a renal transplant patient having appendicitis that were attributed to infection by Strongyloides, when she changed from tacrolimus to sirolimus in the 8th month after transplant.

Maybe a longer off period of rapamycin is a safer protocol I guess?
Also I want to know if there are efficient and reasonable ways to reactivate mtorc2, so that we can lower the risk of bacterial infection?

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Yeah, I’m leaning towards longer OFF periods as well, even though many are convinced enough to be always on. If not for a longer OFF, I might lean towards doses similar to those being taken by others but with a longer gap in between.

I’m not sure if one necessarily needs to be on rapa all the time. See this paper (study on mice) :

“These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome”

I’m curious about what specifically reactivate mtorc2 as well. Maybe particular amino acids activate mtorc2 more than mtorc1?

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If you talk to some researchers, (e.g. Matt K.) they are not convinced about the increased risk of bacterial infections from the typical anti-aging doses of rapamycin… its more about an expectation around this just because of the historic use of rapamycin in transplant patients…

As, I cover in the “Side effects” page:

Dr. Green stated in one of his newsletters to patients:

Five years and 760 patients have revealed that the single major risk of weekly Rapamycin is increased risk of bacterial infection." He suggests having antibiotics (like azithromycin) on hand.

But I note:

[Note: There is some very significant disagreement about Dr. Green’s above statement, by other medical professionals I’ve talked to with experience with rapamycin. Bacterial infections, and use of antibiotics to treat them, is extremely common in the USA. I found it very hard to get good numbers on the typical percent of a population in the US that get bacterial infections each year, but this document from PEW Trusts suggests that antibiotics in the US are prescribed at a rate of 838 for every 1,000 people (measured in 2015) - which suggests upwards of 84% of Americans (or at least their prescribing doctors) think they have a bacterial infection each year severe enough to require antibiotics. Dr. Green has suggested only 5% to 10% of his patients get bacterial infections in any year, which suggests a much lower than average rate of infection than normal for rapamycin users. Moreover, it is not something that the users of rapamycin that participate in forums suggest is a common issue. So, take this with a grain of salt until more data is provided by Dr. Green.]

Of course - in your specific cases it may be an issue. I know that @LeeJohn has been on some pretty high doses for a guy in the 20s age group, so that may be a risk for him.

I’m not familiar with any mTORC2 enhancers yet… if anyone finds data on this, please post.

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From what I’m able to gather from limited data, the bacterial infections are primarily skin based and in younger males. Maybe females but not as clear. That would suggest a specific type of organism in those with perhaps less mTOR activity.

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Dr. Green’s assessment about the major risk, and also personal experiences with staph infections (even though these are minor), made me wonder. Again, in my post, the infections I was worried about were the potentially asymptomatic type, or the ones that end up promoting cancer — so even if antibiotics are available, folks may not even think to take them.

Great to see different opinions from other researchers.

That’s interesting if rapamycin didn’t increase risk of bacterial infections, but there are more cases of skin infections in younger males.

Younger males are generally more prone to acne due to overactive sebaceous glands (I am also one of them)

Maybe there are other pathways inducing skin infection, such as the disturbance of skin microbiome, or disturbance of the production of sebaceous glands (hence more infection cases of younger male)…I don’t know, however thanks for information and I will still look for the related papers.

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