#12

By the way - My belief is that Dr. Green does not have his patients do any rapamycin vacations to clear any inhibition of mTORC2 that may be happening.

I believe @AgingHippie is a patient of Dr. Green’s and perhaps he can either confirm or correct me on this issue.

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#13

Looking at the molecular structure, rapamycin is like a key inserted into a tiny keyhole between two large proteins FKBP12 and FRB. I wonder how rapamycin can dislodge/wash out from this tight combo once its bonded together. If you look at 2016 mouse trial report, its still effective six month after termination of dosing.

#14

Hi Pollux, welcome to the site.

I have not looked closely at the molecular structure - where did you see that described in detail (which paper was best for this?). Would this explain the long half-life of the drug also? Could you give me a link to the 2016 mouse paper you mentioned?

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#15

Hi Admin: an example of the image is here

1297×531 110 KB

the 2016 mouse trial report is here:

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#16

Oh yes - that mouse paper. I interviewed the lead author on that paper (Alessandro Bitto) last Monday. I’ll try to publish the transcript next week.

Yes - very interesting. 3 months of a very high dose of rapamycin (equivalent to 378ppm), gave almost the same lifespan increase as taking a lower dose (42ppm) from 20 months to end of life.’

The whole dosing schedule / level issue is so interesting and needs some really good studies to tease out the optimal approach… this is something that could be ongoing for the next decade I suspect.

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#17

I started as a patient of Dr Green Oct 14 & the plan was 6 mg / wk w/ no vacation.

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#18

Yes. To confirm. I am a patient of Dr. Green, for about 7 months. The regimen is 6 mg / wk without a cycling off…

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#19

I find this interesting because maybe around 80% of 6mg is cleared in a week. Doesn’t this suggest a huge buildup, say in a year of use?

#20

It doesn’t keep building up. I ran into this question a couple of years with some other prescription drugs. Assuming 80 % cleared in a week, right after second week dose you have 6mg plus 1.2 mg of the first week dose, or 7.2 mg in your system. However, in the coming week 80% of 7.2mg is cleared. If you do a spreadsheet you see that the level peaks at 7.5 mg right after your weekly dose and a minimum of about 1.5 mg in your system just before a new week’s 6 mg dose. The big unaswered question though is: Do we want this??? Would we be better off with a day or more of total clearance? Hopefully we will have answers in the not too distant future.

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#21

As a non-expert, my current bet is to extend the time period so as to provide a greater washout while also permitting a greater dose. That’s what most of the researchers seem to be doing – i.e. a 2 week schedule. I’ve decided to delay the next dose until the level falls below 0.25 or 0.5 ml, using reasonably conservative assumptions. I have no idea if that’s best but it seems to me to be safer than a weekly strategy, even if only at 6 mg. Using that metric, I plan to slowly increase my dose until side-effects or I reach what Dr Blagosklonny is doing.

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#22

Peter Attia is doing 6mg/week and is no longer cycling off of it, per his most recent podcast with Matt Kaeberlein. I’m not convinced washouts/cycling are necessary, given that they don’t do it in the animal studies and we’re basing the life extension benefits on those same studies. I am however going to carefully monitor my lipids, HbA1c and white blood cells.

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#23

Definitely a valid approach. I find it interesting that the 6/1 wk strategy is so different than the 12/2 wk one. And arguments on both sides. I didn’t think of this at the time I met Dr Green. He prescribes the 6/1 regimen but he himself changed to a 12/2 a while ago & is now doing a 20/2. As is Blagosklonny. I’m new to this & am not at all tied to a particular strategy.

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#24

Me either! I’ll definitely change it up in a heartbeat if new data comes out and/or my blood counts decrease, etc.

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#25

I have a question regarding dosing. Like many people, I use the Blagosklonny dictum of maximum dosage without side effects. However, I dont know how much of a side effect should be considered. I’ve seen side effects that are so subtle as to be unnoticed unless I am diligently looking for them. Like maybe is that a chancre sore? but if it was, its gone the next day, or like feeling great an hour after ingestion but discover I am unable to do my usual cardio, which otherwise wouldnt have been noticed. My guess is that others are like me and continue to escalate dosage provided the side effects are minimal. I wouldnt exceed what Dr Green and Blagosklonny practice, but I’m wondering how others apply the rule.

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#26

Yes - for me I am slowly increasing and keeping a diligent watch on blood testing results. As far as what are the side effects I’d be concerned about… I’m fine as long as they aren’t side effects that are negatively impacting my blood work in a significant way, or that impact my life in a significant way. The worse side effect I’ve gotten is a 1 square inch rash under my Fitbit. It happens consistently and would probably not happen at all if I didn’t wear my Fitbit (the rash moves to whichever wrist I’m wearing the Fitbit on) - under the wrist strap. But its not a big deal - so I am still slowly increasing my dosing. Right now I’m at 12mg per week - and may move over to 20mg to 24mg per two weeks as I’ve been at before xmas and my covid Booster shot.

In comparison Acarbose has caused major side effect of “gas/flatulence” that is really hard to tolerate if anyone else is in the house with you… The side effects of rapamycin have been minimal, and similarly with Empagliflozin now (10mg) - I’ve seen no noticeable side effects.

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#27

I find that with acarbose if the meal has a good mix of protein and or fat, then the side effects are not bad, but if I use it let me eat a full plate of cake it’s a different story…

I would compare it to eating a lot of fiber as part of a balanced meal, vs mainlining pure fiber.

Acarbose inhibits the enzyme that breaks down carbs into glucose. So it basically turns your carbs into insoluble fiber.

Does dr green tell people to take their rapa with a fat source? That does seem to increase absorption rates (though not like grapefruit juice)

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#28

FYI
Matt kaeberlin just posted this on Twitter

My take: Rapamycin is a specific, clean mTOR inhibitor. Metformin is a dirty drug that tweaks the mTOR network indirectly, but hard to predict effects on mTOR or relevance of those effects in vivo. Resveratrol even dirtier, not an effective mTOR inhibitor at any reasonable dose

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#29

I am surprised that Resveratrol is a dirty compound as I have been taking it in powder form combined with NMN after reading of its anti aging benefits ?

#30

How to decide on washout?

I took serolimus for a year - lost a lot of visceral fat, felt great and was able to add muscle with weight lifting. I added weight which appeared to be muscle due to dexa scan showing very low body fat.

Decided I should do a break - it has been 5 weeks - and now I have started to gain fat around my middle. No dexa to confirm this fat gain… Definitely have noticed a reduction in sexual appetite - anyone else?

58 yrs old, on bio-identicals and excercise everyday.

I understand Matt Kaberlein does a washout of 6 months?

I’m worried I am negating any gains I made with this washout.

Feed back or other perspectives?

Thanks!

#31

Hi, this is an ongoing topic of conversation with no good data to support one approach or another. You can see the longest thread on this topic here: Rapamycin Cycling (Time Off) - Who Is Right?

Also: Rapamycin breaks?

and Rapamycin breaks