#149

See this post for information on translating mouse dosing to human dosing:

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#150

Generally, I believe people only see mTORC2 inhibition if dosing daily for many weeks. I think that is the most common situation. But there may be outliers.

Not a bad idea to track neutrophils, etc. - but I seem to recall that you have a hard time getting blood tests, so not sure how you would do it.

Dudley Lamming mentioned to me that he thought we should be tracking TREGS (T-regulatory) cell test, but I have yet to find that for people to be able to get (in the USA) easily at reasonable cost… If anyone finds some good options, please post:

** TREGs (T-cell Regulatory Test)** (Test details ), Labcorp TREGs test

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#151

Thanks, I can’t get a Rapamycin blood level test performed here. (Albeit someone recently pointed out a lab abroad where I may be able to get my blood levels of Sirolimus tested). I am able to get my other blood work, such as lipid values, CBC, etc.

Either way, thank you very much for posting that study: very interesting for sure! The female rodents had similar serum levels of Sirolimus to the male rodents in this study when 8mg/kg/day of Rapa was administrated IP. (I thought to have read previously that the same dose of Sirolimus can result in higher serum levels of Sirolimus in female rodents. But this was not the case in this study). So the female rodents experienced a decreased lifespan at a dose of 8mg/kg while male rodents experienced a significant increase in lifespan. Remarkable, once again. Did Kaeberlein or Blagosklonny (or anyone) ever suggest what may be a possible explanation for such a gender difference?

#152

No - its unknown, and not seen in humans.

And yes - as you mentioned, The ITP studies of rapamycin (14ppm and 42ppm) done earlier did see the differential effect in male/female response with higher blood levels for the same dose in female mice.

The study mentioned above at 8mg/kg was injection, so different delivery method than the NIA ITP rapamycin studies which are all oral/feed based.

As a funny aside, I talked to Allesandro Bitto about this study and the reason they did IP injections of the rapamycin was because they didn’t have the budget in this study for the high doses of eRapa, so they went for the cheaper option of the injections (IP). Its easy to forget that everyone has budget limitations… and the studies get modified as quotes for supplies come in!

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#153

@RapAdmin. Thanks once again! Interesting, so based on these two studies it seems only oral Rapa administration may result in higher serum levels of Sirolimus in female rodents - and not IP administration. Do we have any other studies that support that notion? I should get my own serum levels tested either way; the more I read, the more I’m convinced of that.

Sorry for all the questions. I feel a bit stupid, but I still don’t understand how to translate those mouse doses to human doses based on the table you linked in your post. Do we have any ‘simple explanation’ anywhere for ignorant rodents :-)? And sorry, really last question: but do you happen to know what dose resulted in the highest increase in lifespan in female rodents in studies? Or should I not be so focused on this gender difference seen in rodent studies.

#154

Check the list of all the rapamycin mouse studies here: List of all the Mouse Studies Showing Rapamycin Lifespan Extension

Since we don’t see the same differential effect in humans of rapamycin in terms of female blood / sirolimus levels vs. male blood/sirolimus levels, I don’t think its something to put a lot of emphasis on.

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#155

One thing to keep in mind. Dr. Green prescribes more rapamycin I suspect than any other doctor. He is interested in longevity. And he recommends that his patients take 6 MG per week without grapefruit juice. Not 10, not 20, and not 30.

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#156

You are very right.
And M Kaeberlein and P. Attia are taking 8mg/kg once a week for 8 weeks and then a whashout. Guessing their weights just by observing them, they might weight 85 kg, then their dose is ~0.09mg/kg
Kaeberlein decided to give 0.15 mg/kg to dogs (all of them of large size) in the TRIAD clinical trial for dog life extension. According to the table that @RapAdmin shared above 0.15mg/kg is equivalent to ~0.083mg/kg for humans. So there you go, I will stick to the ~0.08mg/kg for my weekly dose for the time being.

Unfortunately, there is still the problem of translation of times from rats/dogs to humans (1 week in dogs/rats = How many weeks in humans?)
Anecdotically, RapAdmin told here that his toe nail fungus went away after ~1year on Rapamicyn. Kaeberlein said his shoulder pain went away in 8 weeks. Can anyone share what is the recommendation of Dr. Green about how many weeks does he keeps his patients on and how many weeks off? Or are they using Rapa in a continuous manner (no whashout)?

Cheers,

#157

There was one in vitro study that found rapamycin may start to become ototoxic at high levels.

“Our experiment demonstrates a dose dependent damage of the auditory HCs. Low-dose concentrations of rapamycin (10 μ M) had no toxic effect, while 50 μ M and 100 μ M rapamycin result in dose dependent HC loss.”

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#158

Dr. Green recommend 6 mg per week. He did not make any recommendations for cycling off absent some reason to do so such as a bacterial infection.

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#159

This is interesting, but it seems that this is a study being done on “5-day old rats” - so the effect you’re seeing is a developmental impact on very young mammals… and this is a well known problem; blocking mTOR during early development causes all kinds of problems; its extremely important in development to have activated mTOR.

Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro . Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells.

But this is not the same, nor is it relevant to, adult rats, or any other mammals.

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#160

Do we have an indication as to dosing levels and molar concentration?

#161

Hi Agetron, sorry for asking another wuestion. Was that 6mg with gfj?

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#162

Yes… approximately from April 2022 until end of November 2022… I was taking 6mg in pills and one fresh red grapefruit that I would hand squeeze and take with pills.

Side effects seemed to be elevated Blood Pressure went from lower 130’s to mid- 150’s. With pulse up to 100… normal pulse 72

Watched it this way for months… figured it was rapamycin. Since dropping my dose to 2mg with grapefruit juice… approximately 12 mg in my blood. B/P and pulse back in the normal range.

On dose day…and the next day can feel my heart racing… beating through out my body… in my arms and chest and head… and ringing in ears.

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#163

Take care buddy! Those don’t sound like good side effects! Ringing in the ears and higher BP may have cardiac effects.

I am taking 5 mg + GFJ, biweekly and I have noticed my wound healing has really slowed. I have a blister on my finger and it is taking a much longer time to heal than in the past.

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#164

Thanks Chris,
I do monitor pretty consistently - even do the Blood Pressure Check next to the Walmart Pharmacy - every time I am in the store.

All very stable - even when my B/P was higher - it didn’t seem to affect anything - workouts, no headaches… plenty of energy. But, yes - glad to be back in the 127-134 range systolic and 72 to 80 diastolic From charts I am in the.60 to 64 years minimal 121/83 normal 134/87 range.

The ear ringing or tinnitus goes away a day or two after my dose. Just very strong initially. As rapamycin is suppose to help hearing - I do not mind it. My hearing is excellent.

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#165

I have had a similar result. I use a weight belt at the gym and have shrunk out of my belt while getting stronger. I also dropped from size 36 jeans to 34. I think I last wore 34 when I was 16. I started taking Rapamycin around the same time as Ozempic (I’m an actual diabetic) and was not sure which drug to attribute the great result to.

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#166

Grapefruit juice, at least if taken only when taking rapa, and not dosed daily, primarily inhibits CYP3A4 in the entrocytes (i.e. the gut) and not in the liver. So, it primarily increases the amount of rapa that is absorbed from the gut, not the processing by the liver once it is absorbed (including not significantly affecting first-pass metabolism).

Therefore, it would be expected that taking Rapa with grapefruit is essentially the same as taking a higher dose of Rapa. I.e., say that grapefruit juice at the time of taking Rapa results in a 3x levels. So, whether you take 6mg Rapa, or 2mg and grapefruit juice, the result should be the same. The same amount would get into you, and then would be processed at the liver and excreted at that same rate.

I always assumed Dr. Green’s admonition was probably to prevent people who either didn’t know about the effect of grapefruit juice, or hadn’t put the required research and thought into it, from going “gonzo” with their Rapamycin dosage.

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#167

GPJ affects 3A4 both in gut and liver, but less so: Exposure‐Dependent Inhibition of Intestinal and Hepatic CYP3A4 In Vivo by Grapefruit Juice - Veronese - 2003 - The Journal of Clinical Pharmacology - Wiley Online Library

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#168

Folks, I’m planning to try 28 days of 2mg EVERY OTHER day. I’m inspired by the recent papers from Ai-ling Lin that involved daily doses of 1mg for 28 days. I’m doing 2mg every other day because. . . well, because I only have 2mg pills.

I’m in the same demographic targeted in those studies. I’m late 50s and am an APOE-4 carrier.

I typically dose Rapamycin at 6mg w/ GFJ every other week. If often take a month or so off at random intervals. I skipped the last dose and figure that I will do this 28 day dosing strategy and then lay off again. Somewhere around the end of week 2 I will get a Labcorp test to see what my blood levels of Rapamycin are. Maybe I will do that again at the end of the 4 weeks.

I’m open to any feedback from the community.

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