You know this is probably way too woo-woo for this forum, but I agree with you. Not only on the basis of the animal studies which you reference, but it seems like so many things in nature operate on a oscillatory or cyclical basis that I just have a strong feeling that brief but profound inhibition of mTOR is going to work better than a chronic mild suppression. I could end up being totally wrong once we finally understand the optimal dosing strategy, but for now I’m slowly working my way up to relatively high but infrequent (once a month for me as a young person) dose combined with fasting to hopefully eek out a bit more mTOR suppression without continuing to up the dose. I guess only time will tell.
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As prophet1 pointed out, the mice are not being dosed several times a year (or the mouse equivalent) with antibiotics: they’re kept in specific pathogen-free environments, eat autoclaved food, and aren’t subjected to the common injuries that can provide a vector for many bacteria.
Under controlled experimental conditions, rapamycin does improve survival against tested pathogens in mice — but in humans, lower numbers of neutrophils and increased risk of infections are listed as risks right on the label, and some rather nasty ones have been reported on this forum.
Despite some dramatic rodent evidence and some provocative anecdotes in humans, I do think our current understanding of the role of the microbiome in human health is still largely unclear and certainly not equivalent to the risk of not using them when infected. We don’t see women coming off of a round of antibiotics for a UTI or people put on them for surgical prophylaxis suddenly developing obesity, metabolic disease, mental health problems, or cancer, despite rodent studies suggesting that we might see all of those things, and the introduction of antibiotics was accompanied by a dramatic surge in human life expectancy. By far the larger risk with self-experimentation with rapamycin is clearly the risk of infection as such.
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Blagosklonny’s advice… hmmmm. I thought you might find my rapamycin dosage and its effects on my biological age over the past 2 years and 8 months of interest. I started rapamycin in August of 2020 at a weekly rapamycin dose of 6 mg.
After one year on the 6 mg weekly dose, I
decided to do my first biological aging test – TruMe Methylation test of my saliva. My chronological age was 63 years and I was pleased to see a biological age of 51 years. I retested with TruMe four months later in April 2021 and again was pleased to see my biological age holding at about 52 years. Nice!
I also took my first GlycanAge blood test around this time in May 2022 and had an astonishing reading of 37 years biological age.
Blagosklonny states,” In mice, the higher the dose, the longer lifespan. Therefore, in humans, the highest dose that does not yet cause unacceptable side effects (maximal tolerated dose) may be optimal for longevity. If (unacceptable) side effects develop, the dose should be decreased. In other words, anti-aging doses are maximal doses without side effects in a particular person. Then anti-aging doses are individual and side-effect-free by definition. Furthermore, if we do not know what exact doses are needed, there is no need to use doses that may cause potential side effects.
Thinking about Blagsklonny’s statement - a year ago in May 2022, I decided to drastically up my rapamycin dose 6x’s so I was now taking about 36 -38 ng/mL weekly based on my LabCorp tests. My rationale for upping my dose to this degree was from the comments above by Mikhail Blagosklonny.
I dosed at 36-38 ng/mL weekly for approximately 7 months – I did have edema/swelling of the ankles and some puffiness of my face when dosing (I did not consider these to be significant side effects).
Looking for improved biological age or at least no progress in aging I retested with TruMe and the GlycanAge tests in November of 2022. I was surprised and disappointed to see that my biological age did not improve but actually went up – meaning I lost anti-aging benefits. I went from a GlycanAge of 37 biological age to 52 years. My TruMe Methylation test showed I also lost the biological age of 2 years in 4 months. I was now 54 years Biological age according to TruMe. Not good.
After consulting with GlycanAge researcher, Dr. Alex Aleksander Vojta I went back to a lower rapamycin dose of 6 mg – 12 mg weekly and retested after 5 months. With GlycanAge I regained back 5 years now testing at age 47 biological years. And on TruMe, I also had a reduced biological age reading back to 52 years. Nice reversal. See attachments.
It is all about the dose. Too little medication and you might see no benefit. Too much, and negative effects such aging faster might appear, and at the right dose – it is the sweet spot. maximum benefit – less issues of side effects.
My takeaway is that despite Dr. Blagosklonny’s thoughts that more is better – it is not with me and two different biological tests (one blood - GlycanAge and one saliva-TruMe) measuring different areas showed a parallel and equal decline in aging benefit from too much rapamycin. I am sticking to a 6mg – 12mg rapamycin dose and will retest in 7-months.
I am hoping to see a continued slow, small incremental increase in my age. Here is to a healthy 100 years+
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Is this with an accelerator such as grapefruit juice or just 6mg as it comes.
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Hi John - My initial dose of 6 mg was using pure pills the first year and a half.
Doses for higher the ng/mL where all with grapefruit juice for 7 months.
Example I took three pills each one 2 mg rapamycin for a 6 mg total of medicine. Then, swallowed with grapefruit juice one red grapefruit for the multiplying effect of 6x’s the power. Labcorp test showed the amount in me.
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desert shores, you willing to share your iron related numbers in your recent labs including ferritin?
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What is your current dose and schedule? Weekly, how many mg, with or without grapefruit juice?
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Hi Matt,
For the past 5 months… and currently, I am taking one 2mg rapamune pill with the juice of one red grapefruit squeezed by hand… about 5 fresh fluid ounces… getting back a 3x’s increase or 6 ng/mL on LABCORP sirolimus test.
I might up my dose to two 2 mg Rapamune pills on next round… looking for no less than 6 mg or more than 12 mg in my blood.
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Thanks for sharing. My Ferritin went down to 20 three months ago. My diet does not include much iron food and I was donating blood every three months. So in past three months, did not donate blood and took 27 mg of chelated Iron twice a week. Labs last week had my ferritin at 30 and I am good with that. I’m also like you----I don’t have any negative symptoms for low iron.
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I believe as does my primary physician, that my iron stores were depleted from donating blood too often. It makes me wonder if the Red Cross ferritin test is accurate or if they have a lower standard. In any case, my doctor advised me because of my age, not to donate blood anymore.
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Desrtshores, I’m holding off blood donating for the rest of the year and going to see where my iron levels are. I’m good with a ferritin around 30 but don’t want it to get lower. I’m 58 years old so going to experiment with not donating and see what happens.
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Forgot to ask Desertshores: what ferritin level would you be comfortable obtaining?
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I would like to keep it within the “green” zone, so I would be happy in the 25 - 30 range.
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Juicy little tidbit I stumbled across today. If it’s been previously mentioned, sorry.
This may explain many forum members have had such diverse reactions to the same dose.
It shows the necessity of testing if we really want to have any I idea of the actual dose we are receiving and why it is nearly impossible at this stage to determine the ideal dose.
Has Matt Kaeberlein noticed this effect in his dogs and is he doing a blood test to determine the peak for the same dosage in different dogs?
“Despite utilizing these multi-component delivery systems Sirolimus is absorbed from the intestine variably, with some patients having up to eight times higher exposure than others for the same dose”
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Wow. That really does make it a crapshoot. However, I think that 8X factor includes the GFJ, EVOO and other modifiers as well as some people would have less of the CPY enzyme naturally. Also, it’s hard to go above 100% absorption.
… ummm Michael Kimberlain… Matt Kaeberlein… might want to add Fisetin to that stack of supplements.
Just messing with you, buddy. But, this is incredibly important to dosage.
And, I do regular rapamycin trough and C-max testing with Labcorp. The only way to really know what is happening in you.
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didn’t I read somewhere that mice have very high mTOR compared to humans?
where is the source of this suggestion regarding lifelong lower dose efficacy?
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Have you done new tests since this post that provided you with some objective evidence that you are benefiting from rapamycin?
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