Rapamycin and cancer. What I’ve learned

Since the revelation of MB and his cancer, I’ve looked at this topic more thoroughly, especially human studies.

The first question is whether rapamycin Causes cancer?

There are studies , such as the Taiwan study, that indicate an increased incidence of cancer in rapamycin users. It’s important to remember that these are entirely in transplant patients on high dose therapy and in a generally sicker population. The meta analysis suggests an overall decrease in cancer, even in transplant populations, but primarily of skin cancer. Again, we have no human information on low dose intermittent usage and cancer prevention. No information.

Does rapamycin promote cancer spread/ metastasis?

I see no indication of this. I asked Alan Green this specific question regarding his own patient population and he responded with two words. “ No. Opposite.”. Surveys of people on low dose are also not revealing aggressive cancer activities.

Does rapamycin Cure cancer?
In some limited cases, but in general disappointing, and needs to be combined with other agents. A close inspection of figure 3 in this article in the excellent molecular journal explains this:

You’ll see in figure 3 that low dose rapamycin does have an effect, but also , to get cancer killing, you need to inhibit both mTOR 1 and 2 completely, as well as the three downstream targets of S6 K, 4 E- BP1, and the feedback loop of AKT. Virtually impossible on less than toxic doses. Needs to be used in combination with other agents. Not a good cure for cancer in humans.

Does rapamycin Prevent cancer in humans?

It’s already been mentioned that it may prevent the benign basal cell skin cancer, but again at transplant doses. But let’s remember that the Best defense, by far, is immuno surveillance . We must try to prevent immunosenescence of our B and T cells, stabilize and protect their DNA, and maintain their ability to kill pathogens and cancer cells.

Here’s an excellent review:

https://www.immunology.org/public-information/bitesized-immunology/cells/cells-t-cd8

Mannick has shown, in humans, that low dose, weekly everolimus, does in fact increase the levels of protective T cells as well as decreasing the nasty programmed death cells. The equivalent rapamycin dose would be quite low.

Here’s an excellent review of the importance of DNA damage as it relates to immunosenescence.

It specifies essentially 3 substances which have been shown to have value. Rapamycin in low dose, metformin, and spermidine. Spermidine May also protect against histone modifications.

It also points out that rapamycin has a long memory, in that patients were protected against viral respiratory infections for a year after stopping the drug.

We must also keep in mind that different individuals, and even tissue types ,will respond differently.

So I think it’s possible that low dose weekly rapamycin may protect our immune systems, which is very important in cancer prevention. There’s no direct evidence of course,and we may never have direct evidence.

Given rapamycin’s long memory, it’s tempting to use it for a period of time, say a month, and then use spermidine and metformin/ berberine on other months. I’m also somewhat concerned about immune over stimulation, so month breaks altogether could be considered.

I continue to believe that low dosage is important as well as an intermittent schedule. It’s still all lacking in much human data and clearly presents a certain degree of risk.

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Thank you for summarizing your research. Your findings, which are more in depth than mine, agree with what I have found as well.

As for Rapamycin, Metformin and Spermidine, I believe it is best to take all three simultaneously as I believe they are synergistic. I take Spermidine on the day of dosing Rapamycin and the day after to enhance Rapamycin’s autophagic benefits

Overall excellent summary. Thank you for your due diligence and investigation!

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You’re a smart guy DeStrider and your feedback is always appreciated.

What doses are you taking and what brand of spermidine?

Any exercise effects from metformin?

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I went through a DoNotAge phase so I am still using theirs.

I bought the 366 capsules a long time ago when Spermidine was a hot topic, and I use 4 capsules a week (2 each time). I mix it into my daily EVOO shot for better absorption. So I have about a 2-year supply.

As for the exercise effects of Metformin, I haven’t noticed any and neither has my father. But, I have not been tracking my exercise at all, so I doubt I would be able to “feel” any exercise effects from metformin. I do believe for the common man, the effects would be negligible unless you are a performance athlete. My father, who takes much more metformin than I do, has noticed great improvements from his exercise from Taurine. So I would assume that the benefits of Taurine trump the negatives of Metformin.

I do believe that the trio of amino acids - Taurine, Glycine, and Cysteine (NAC) are synergistic (and almost as important) with Rapamycin, Metformin, and Acarbose. I believe these are the 6 foundational supplements of longevity.

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I think you can throw away the spermidine supplements, I have double wood that is more potent than DoNotAge, but the more I read about this supplement the more critical I become. I do not think there is any uptake at all in your body by supplementing it. Most positive papers coming out on this compound is based on dietary spermidine. We all know that ITP failed miserably on supplementing mice with this.
If you use collagen/Psyllium/Fiber shakes daily, you can add 6 table spoons of wheat germ into that. Then you get 10mg of dietary spermidine that your body takes up and knows what to do with. Mixing collagen with fiber makes the bioavailability of collagen to be better also.
The best of all is that Wheat germ is very delicious ! use it in salads/yogurt’s also.

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Yes - I’m in this camp also regarding spermidine as a supplement. I used up what I had been using the past two years and have not re-ordered. The evidence seems pretty weak right now… I’m pausing unless some better data comes out.

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From what I’m seeing you’d need substantial amounts to have a clinical effect. More than supplements, and maybe more than foods for many people. Six tbls of wheat germ is a fair amount.

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I completely agree with all of you. I am using up the Spermidine I have and will probably not order any more until better data comes out. I just bought too much originally. I figured the best way to use it was when blood Rapamycin is high because it’s supposed to augment autophagy. So that’s why it’s taking me so long to use it up.

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While I agree with what you say, I think you may have missed out a third option - that rapamycin may also be cytostatic - and hold cancer in ‘stasis’.

There’s a very interesting story about Suren Sehgal (discoverer of rapamycin) who unfortunately died from cancer.

With all credit to @Krister_Kauppi for his work in uncovering this story. Shown below is a link to his excellent post/s.

https://www.rapamycin.news/t/suren-sehgals-self-treatment-rapamycin-dose-regime-for-colon-cancer/

Here is a quote from Ajai (sehgal’s son) in an article

But in 2003, after five years, Sehgal, age 70, decided to stop taking the drug. Otherwise, he told his wife, he’d never know whether it was really holding back his cancer. The tumors came back quickly, and he died within months, says Ajai. “On his deathbed, he said to me, ‘The stupidest thing I’ve ever done is stop taking the drug.’

Source: The discoverer of Rapamycin treated himself with Rapamycin to delay his own death from cancer | NextBigFuture.com

I think it’s one of the most touching stories that I’d read in quite a while :sob: …if only he had kept on taking the rapamycin.

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This reminds me of two things.

  1. Mikhail Blagosklonny talked about how Rapamycin blocks damaged cells to become senescent cells in this clip.
  1. David Sabatini talked in this podcast that in chemotherapy rapamycin blocks hair loss but when rapamycin is stopped then the hair loss occur.

This may go quite well with what Sureen Seghal experienced in his N=1 experiment. Can it be that Rapamycin blocked his cancer from growing and when he stopped taking Rapamycin then the cancer got an opportunity to grow? Do someone know if there exist any support that Rapamycin on those levels Sureen took can stop cancer from spreading?

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I think that at this point it’s just anecdotal evidence. When I was prescribed Rapamycin after kidney transplant almost 14 years ago, my nephrologist told me that in addition to protecting my kidney Rapamycin will prevent any cancer from developing/spreading. Did he base that on research or just was guessing? I don’t know and I didn’t ask at that time.

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The mice in the ITP trials were not immortal either.

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The mice in the ITP trials lived longer but they still died of cancer. This is because mice die of cancer mostly (90%). Rapamycin may delay onset of cancer though.

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This is what we all hope for!

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