Are there supplements that enhance Rapamycin?

What supplements do you take to enhance the effects of Rapamycin?

My layman’s understanding of how Rap works:
Rapamycin > mTOR inhibition > autophagy engagement > lysosome activity

It’s this lysosome activity that generates all the benefits at the cellular level. I found this interesting:

“During stress conditions, autophagy can lead to cell survival through lysosomes activity. Autophagy relies on lysosomes to degrade harmful, dysfunctional cell components and misfolded proteins. It then converts these parts to amino acids and sugar to reuse. TRPML1, the main calcium channel, is critical in regulating lysosomal function. Without this, cells become cluttered as we age. Rapamycin activates this channel, regardless of mTOR activity, and enhances autophagy dependent on TMRPL1. It may contribute notably to the anti-aging effect of rapamycin.”

For myself, I get a surge of sustained energy after the first 3 days when I take my weekly Rap, that gradually tapers off over the 7 days. I enjoy this so much that I take my Rap on Friday morning so I can have optimal energy to enjoy weekend activities Lol

So, are there any supplements that can be taken along with Rap to enhance autophagy and lysosome activity?


Hey Rufus - great name!

Not really a supplement like Acarbose which I highly recommend. Are you on TRT? Testosterone Replacement Therapy. If you are no longer looking at having kids - some say it can affect sperm.

Past 4 years have been on TRT cypionate 1ml which is 200 mg once a week injected in thigh. My testosterone is 1100 to 1500. Feel great, energy, libido… great muscle tone… fat reduction.

I take my TRT 4 days after rapamycin 2 mg with a cup of fresh grapefruit juice . So MTOR2 turned on when getting near my trough of rapamycin.

Keep turned off MTOR1 opposite of turned on MTOR2 so they aren’t simultaneous… or in conflict.


There seem to be a few supplements / compounds that help with autophagy (not sure if they are synergistic)… Trehalose and Spermidine come to mind. Also, Fasting is a good way to boost autophagy. But its still early days… we don’t have a way to measure autophagy in the clinic yet, so lots of guessing going on.

Here is some reading on the topic:

Here: How Rapamycin Extends Lifespan (mechanism and implications) Discussion

Here: Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

Here: Measuring Autophagy in Body and Brain, Comparing Autophagy Activators

Here: What’s autophagy? It’s the ultimate detox that doesn’t yet live up to the hype

Here: Spermidine delays aging in humans


A very interesting line:

“ rapamycin activates this channel, Regardless of mTOR activity .”


If you take grapefruit juice 1-4 hours before Rapamycin, you effectively triple the amount your body absorbs. But that’s similar to taking 3X as much Rapamycin. However it may do the same to other medications you are taking, so you really need to check first.

Taking Rapamycin with a fat source increases absorption by 30%.


Melatonin is thought to help with Autophagy

I think Menaquinone-7 (a type of vitamin K2) also helps, but don’t immediately have a link.


In digging around some it may be that “calcium channel agonists” may enhance the effectiveness of Rapamycin, Quercetin could potentially do this. I found this interesting:

“quercetin enhanced the L-type Ca2+ current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca2+]i”

If autophagy is using the calcium channel perhaps the Quercetin would be synergistic… it’s a supplement that has other benefits as well so I may give it a try.

Off topic but somewhat relateed, Rap’s use of the calcium channel may explain why some, like myself, experience elevated blood pressure.


No TRT but it’s something I have considered… there is a longevity theory that makes some sense to me, in that you can’t stimulate growth and longevity at the same time, one is at the sacrifice of the other… but perhaps the way you are approaching it might strike an effective balance.

How do you acquire your cypionate?

btw, Rufus Dawes is just my profile name LOL, he is a famous Civil War hero and have always thought it was a cool name

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Bad press for decades had me steer clear of Testosterone Replacement Therapy “TRT” as it is called by my physician and for insurance purposes which covers the cost.

No energy, weight issues… muscle decline - aging stuff. Went to my physician and was diagnosed as low “T” 350-400. I get mine by “T” physician prescription from the local pharmacy.

Current research is seeing likely TRT is needed as men age. Like women need estrogen.

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Vitamin k2 … There are a few studies showing autophagy of cancer cells Here’s a decent recent study:

" a half-life of about 10 min" I think the paper is wrong on this. Every other source I could find said the half-life is 20 to 50 minutes.

I had no idea melatonin had such a short half-life. Is this one of the reasons you take such high doses?

I am a big believer in the anti-aging effects of melatonin and I have been taking it in doses of 3 to 10 mg for decades.

Could you please expand your rationale for taking, what many would say are extremely high doses, of melatonin and the timing you use?

Melatonin: Expiration and How Long It Lasts in Your Body | Sleep Foundation.

My rationale for taking relatively large doses is a combination of no negative side effects and positive effects.

That is an entirely personal experience and does not have to be anyone else’s experience.

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To rephrase my question: Are there any studies showing the benefits of very high doses?
I now take 20 to 60 mg nightly and really don’t feel any subjective experience over 1 to 10mg nightly. Can I expect to see any changes in any of my blood markers from taking these higher doses?

AFAIK there are atudies on the anti cancer effects of high doses. My view is that there are no studies implyjng any harm although there is a study about small hamster testes. I have no tested the effects on fertility, but i have 5 children and am not concerned if in improving my health i have lower fertility.

It would be good to have more detailed study of dosing at my level. However, I am happy with my own outcomes. I do weekly bloodwork.

There are more than one areas where i think i am an outlier and i tend to try a lot.

I had not read the 10 mi half life. I would quite like to know the precise details of how melatonin is processed. I think the curve for high doses is different. I have searched this, but not found anything.

Yes - we have a whole thread on increasing the bioavailability of rapamycin, which I guess is somewhat equivalent to the main question @RufusDawes had regarding “enhancing rapamycin”

But - great caution should be exercised here due to potential for liver toxicity… read up and tread carefully: Improve Bioavailability of Rapamycin (2)


There seem to be quite a few studies on breast cancer reduction, especially at higher doses.

Something women should consider.

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Have used them for years. Great quality testosterone, no prescription needed.

The liver toxicity is not from the GFJ but from the ketacanazole, correct?

No - GFJ interactions with other medicines: The key issue is you have to be very careful if you take other medications in addition to grapefruit juice (or ketocanazole, etc.). Common medications like statins, blood pressure medications and others can have bad effects when taken with grapefruit juice - so talk with your doctor and do research before considering this.