More Rapamycin Might Not Be Better

More Rapamycin Might Not Be Better – I upped my Rapamycin Dosage to 38ng mL on average for the past 7-months

Looking back on my Rapamycin history. After dosing on 6mg Rapamycin/Sirolimus for one full year, I decided to do a biological test to see if I was getting any benefits internally. Based on reviews, TruMe seemed to be a good one for DNA Methylation through a spit test. My results not only impressed me, also but the CEO of the TruMe Company with a 12.4 year difference. Biological I was 51 years and chronological I was 63 years at the time. Explaining to the CEO I was taking Rapamycin and Metformin – she felt it was an accurate assessment of my biological age 51 years. Congratulations!

I stopped the Metformin due to off and on diarrhea spells and it making me gassy. I re-tested with TruMe 6-months later - partially to confirm that the test was accurate the first time. I was not too surprised to see I was now biological age of 52 years - chronolgical age was 64 years with a 12 year difference. I had lost almost a half year so a bit of acceleration, but felt pretty good.

It was during this time, based on Mikhail Blagosklonny’s comment to go as high as possible without side effects and other users looking at going for a higher dose, that I started using Rapamycin with Grapefruit Juice (GFJ) – I was hitting ranges of upper 30’s to 56 ng/mL and having 3-day bouts of diarrhea. I finally was able to get some consistency at 6mg Rapamycin and GFJ and hitting 36 ng/mL based on my LabCorp tests. This was my dose regiment (6mg and GFJ) from late July thru end of November.

My third and most recent TruMe test came back a week ago and had me 54.2 years biological age to my 64.8 chronological years.

I had lost some ground. My biological age increased almost 2.5 years in the 6 months. So it would appear that the higher rapamycin dosing has caused me to lose some of the anti-aging benefits I gained on a lower dose. To be 64 chronological years with a 54 biological age is not bad, a 10-years difference. But, it was better when I was doing a lower dose with an almost 13 year’s difference between the two.

Here are my TruMe reports in order from 1st 2nd and 3rd - current.

But read on – my accelerated aging on a higher dose of Rapamycin gets worse.

TruAge Test by TrueMe past 3-tests.pdf (123.5 KB)

Another biological aging test being used by the PEARL Rapamycin Human Clinical Trials is GlycanAge, so I decided to try it. This uses a blood sample - more thorough, more accurate and more expensive. I did my first test at age 64 years – I had been on rapamycin at 6mg-8mg only doses for 1 year 8 months. My report came back that I was 37-years biological age based on my glycans and lack of inflammation. A 27-year age difference from my chronological age. As I stated, feeling more Rapamycin might be better, after that test I significantly upped my Rapamycin dose to 38 ng/ml to 56 ng/mL and took on a very lean/shredded body look. Very little body fat anywhere. After 7-month of the higher Rapamycin dose I re-took the GlycanAge test. I was a bit surprised and disappointed to see I had lost 15-years biologically on the higher dosage since my first glycan test. My latest GlycanAge test has me at biologically 52 years and chronological age 64. A 12-year difference and nothing to complain about. But, it had been much better 27-year difference. I feel like I won the lottery and then pissed it away. Very frustrating. Here are my GlycanAge tests.

GlycanAge results November 2022.pdf (92.2 KB)

When I significantly upped my rapamycin, on both my TruMe and GlycanAge tests I had aged faster in the past 6 months. My routine is pretty consistent in food, supplements and exercise. In the past 7 months the only significant change to my diet/supplements and exercise routine has been the significant increased Rapamycin dose weekly. Perhaps I was taking my MTOR1 too low for too long and my MTOR2 has been affected. I don’t know. But, at least for me it appears more Rapamycin is not better. I want to try and regain back my better biological age numbers.

I am re-evaluating my higher dosage regiment and have decided to go back to the 6mg dose again with Acarbose - not Metformin – and no GFJ. I have never had a rapamycin break in the past 2.5 years of use. I have used Rapamycin every week non-stop. I am thinking of doing a reset. Going off rapamycin for one month and slowly reintroduce it 2mg first week; 4 mg second week and settle on 6mg at third week. Maybe take a month break from Rapamycin every 6-months is in order too. I will do this new protocol and retest with TruMe and GlycanAge in 7-months and see where I am. Hopefully, I am able reverse and also slow down the aging to my prior numbers.

I am definitely a rapamycin believer. My health issues resolved or improved with rapamycin include: eliminated choking issues (dysphagia); eliminated arthritis; decreased varicose veins; enlarged open veins; thickening of skin (crepe skin gone); significant improved memory; increased energy and euphoria; improved gums; increased muscle strength; reduced visceral and other fat from my body.

The best we can do is keep testing. Find a few baselines and test any changes we make. I was expecting to have at minimum stalled or slow my age progression with the higher Rapamycin dose.

Seeing an acceleration in aging on two very different tests has me concerned about taking higher doses of Rapamycin. In my case, it appears that more Rapamycin is not necessarily better. As Drs. Peter Attia & Matt Kaeberlein state, it is about the dose. Both are Rapamycin users - neither one doses higher than 8mg and take breaks. On this site - we guess, we try, we learn and we share with each other.


Very valuable post for me. I had thought the only downside to taking too large a dose of rapamycin was the negative side effects. Now I see that one must also consider the possible decreasing of potential positive effects on health and longevity when one takes too large a dose of rapamycin.


Very nice post. Thanks.

We know from the Mannick study that low weekly doses worked for an improved immune response. There’s no reason to think that low dose wouldn’t work on other organ systems as well.
I will also stick with low dosing that I’ve done for 5 years.


This apparent decrease in age reduction when using tests such as the Glycan and Levine age tests is puzzling. Perhaps we are still looking for the right markers.
I was very fit for my age when I started rapamycin. My Levine spreadsheet test gave me an epigenetic age of almost 18 yrs younger. After a few months of rapamycin, my epigenetic increased and indicated that I was only about 7 years younger than my biological age.

What I am wondering is: Has anyone on the forum who was very fit, to begin with, experienced an increased reduction on the Levine, Aging Ai, or any other age tests?
You seem to be the only one reporting, except for me, a very low epigenetic age on the Levine or other epigenetic tests and an increase in epigenetic age after starting rapamycin.

I don’t see (I may be wrong) any significant reporting of reductions of epigenetic age in humans after starting rapamycin by Dr. Blagosklonny or anyone else.

This seems like an unexpected result. You would think by this time there would be shouts all over the forum saying: “This is how much rapamycin reduced my epigenetic age”
Yes, I have seen a few positive comments regarding positive epigenetic age reduction, but most comments seem to be wondering about any positive effects as regarding epigenetic age reduction.

Yes, I have personally experienced many positive effects from rapamycin and plan to keep on taking it, but epigenetic age reduction is not one of them.


I’m still skeptical of the current commercial epigenetic (methylation) clocks. They often vary widely from day to day, even hour to hour. The GrimAge still seems to be the best… but it’s still not commercially available. I’ve heard Levine’s new upcoming epi clock might be far better at removing the noise. But for the time being… I just wouldn’t put too much stock in these.


True - not a lot of great biomarkers for age. But, these have shown some consistency within what they measure and that is what concerns me is both show an acceleration. I did expect something would happen with a significant higher dose - just not that! lol.

Just letting the commnity know - we all have to try and figure this puzzle out.

I definitely would like to take the GrimAge test and see what the Horvath test says.


For what it’s worth. I didn’t see any significant change in my Levin calculation going from 0 to 6mg (no GFJ). I just started 12mg (no GFJ) last month, and I will see how that changes things in a few months.


How many milligrams were you taking at a time (I assume with grapefruit juice)?

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Yep. Was doing three 2mg pills
… 6mg total… with GFJ… was hitting 38 ng/mL on Labcorp test.

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I am very leery of the epigenetic tests. As I have found out, when I use the Aging.Ai blood age test, I come in at 28 years old (19 years younger). Two years ago the results were 26 years old. So very consistent results.

When I did a blood analysis using the Levine calculator, I got 35.6 years (11 years younger).

I did an epigenetic spit test in January, and I came out as being 66 years old (19 years older). Then I did it with the same company again in September after Rapamycin and it came out to be 59 years old (12 years older). Now, did I really get 7 years younger in 8 months? And why is there such a discrepancy between the blood and spit tests? Right now, the tests are not very reliable IMHO if you want pinpoint accuracy.

Michael Lustgarten, a very health conscious individual who is an exemplar of health IMHO has the exact same problem. One test says he is 9 years younger at 40 and another says he is 7 years older at 56. It’s mind boggling. See video below.


That makes sense to me. I believe grapefruit juice has the effect of multiplying my dose by 6 for me.


I think functional tests are better than many of the aging clocks which can come out with materially different values from the same test subject.


As far as dosing, I will say this. I think lower doses don’t do much (1-3 mg).

You can start feeling the beneficial effects as the dosage increases, and I think you are making permanent changes to your physiology as you increase the dosage. So, going up to 20 mg on a bi-weekly schedule will probably have a significant impact if you do this for a few months/years. I think you should high dose for a few months and then back off to a maintenance dose after you have affected the change afforded by a high dosage.

My reason for thinking this is those old mice who receive treatment for a period of time and then stop end up having similar benefits to mice who maintain the same dosage to the end of their lives. I think that Rapamycin makes permanent physiological changes at different dosage levels and you want to hit those highs, make those permanent changes, and then back off so that your triglycerides and blood sugar levels don’t stay elevated for too long. These factors probably influence the age tests more than the changes that Rapamycin makes. That’s my thinking anyways.

As Dr. B constantly states, mice who received high doses of Rapamycin lived longest.

In middle-aged mice, just 3 months of high-dose rapamycin treatment was sufficient to increase life expectancy up to 60%

The dose used was 8 mg/kg/day through injection. If we literally translate to a normal human, that’d be like 700 mg daily!


Regarding Dr. Blagosklonny’s statements that higher doses equaling longer life extension, that is correct, but keep in mind:

  1. Research mice live in a pathogen-free environment, so any immune supression from very high doses of rapamycin will be less of an issue for them, than for humans that don’t live in a pathogen free environment.

  2. You can’t just do mg/kg extrapolation for mouse injections of rapamycin. I don’t have it in front of me, but I think you need to divide by 12 the mg/kg dosing to get roughly human equivalent dosing, and of course you have individual variations so we don’t know what the true blood/sirolimus levels would be in terms of equivalent dosing.

  3. The three-month dosing done by Matt Kaeberlein’s lab that gave 60% increase in lifespan was 60% increase on remaining lifespan (not the same as the ITP study lifespan increases which are calculated on increase from median or 90th percentile Max lifespan. The 60% increase in remaining lifespan is about the same as the results seen in the ITP studies but it is interesting because it suggests that 3 months (in mice, which may equate to 7 years in human terms) of extremely high dosing may be about the same in terms of efficacy as lifelong lower dose of rapamycin.


So why risk increased side effects when you can coast the low dose for the rest of your life?


Yes, no one should go out and take 700 mg of Rapamycin a day. Even if you divide it by 12…

However, if you compare the 1, 2, 3, 6, 8, 12, 20 mg weekly or bi-weekly, the first few doses seem miniscule while the latter seem almost on target. The crux of the matter is that we still don’t know.

As for pathogens, yes, we do have more pathogens, but we also have more treatments like isoconazole or antibiotics that mice don’t have.

I think that taking a 20 mg (no GFJ) bi-weekly dose for at least 3 months may give you some additional long term health benefits. That’s my goal (so about 6 mg + GFJ). Of course with a slow ramp up and I will back off if the side effects get worse. It’s my best guess, and I am pretty sure that no permanent damage will be done if I am wrong.

Rapamycin feels like it is an everything to gain and nothing to lose proposition. Although we may change our minds later on with new information. You have to take the plunge at some point…


How long you take Rapamycin before you notice that your health issue improved or resolved?


I don’t use epigenetic clocks but many of my blood (most concerningly A1C) and health markers moved in the wrong direction after a couple of months at 12mg/wk… I’m back at 5mg again now.

Atm it’s truly a leap of faith to be taking Rapamune because, other than body fat, there’s no objective evidence that it is benefitting me.


Have you done full blood tests and tried the Levine phenotypic calculations and aging.
Ai website?

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Well since all the key markers moved in the wrong direction (other than body weight) I think it’s safe to assume my biological age didn’t get younger…

Edit: looks like testosterone and CRP improved very slightly