#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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#169

That’s a valid protocol. However, we really have no idea at this point which dosing strategy is optimal other than ‘It feels right to me’. I believe that by mixing up the different dosing strategies, we will simultaneously hit on the optimal and the suboptimal.

Of course gut-wrenching pain, diarrhea, or an outbreak of itchy hives may help inform us that we have not chosen an optimal dosing regimen. :wink:

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#170

I am in the faction who believes that mTOR should not always be inhibited. Hence I go for probably the least frequent dosing, but also possibly the highest peak.

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#171

Hi, I have been reading this post because I have been on 14 mg/week to improve ME/CFS symptoms Rapamycin for Chronic Diseases (ME/CFS,IBM,Fybromalgia,Others) - #25 by Maxi
but I got no benefit. One of our colleague felt better at 36 mg (although his dosing has been a matter of controversy because of formulation) Rapamycin for Chronic Diseases (ME/CFS,IBM,Fybromalgia,Others) - #18 by hamtaro
so I started to increase and I am at 25 mg. During the time at 14 mg I measured pik values twice:
Pik 3 Curves 14 mg Feb March 2025.pdf (90.1 KB)
This was with standard Rapamune Solution 1mg/ml as available from Pfizer in Switzerland. I took it without food nor GF or any other booster. Your comment above implies that 68 ng/ml is very high ? Maybe the solution is very bioavailable ? I have not yet measured pik at 25 mg. Any info on pik values and bioavailability of solution/pills or other advice would be welcome. Tnx.
P.S. I also determined my kinetic, Half Time ca. 45 hrs
Exponential_Decay_Report_Compact.pdf (128.7 KB)

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Rapamycin Update in 2025
#172

I take a higher dose than you, but much less frequently. I would worry about mTOR being always inhibited.

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#173

Tnx, I do worry, but life with ME/CFS is pretty bad and makes you take risks…I console myself with the thought that I am below 4 ng/l after 3 days, and this is the therapeutic lower level for transplants. Also I do blood panels with my immunologist every two weeks for safety, the only negative is a decrease of hemoglobin. The only other thing I had is a mouth ulcer in february when I started, none since. I am moving to 14 days as I plan to go to 30 mg. Fingers crossed.

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#174

He looks bad for 9%.

#175

What does this mean and what evidence is there for this comment?

#176

The OP.
Charles Nelson, 52

At 9%, he should look much better. He looks soft and flabby with barely a vein in sight. Kinda like a 14-year-old couch potato.

#177

Late to the game but those pills have no enteric coating (not sure if anyone has mentioned this yet) so while the GFJ amplifies, the lack of coating does the opposite. It might be a wash. Also, his body fat % comes from an impedance scale which is known to understate fat %. He’s got quite a bit more than 9% body fat.

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#178

Enteric coating has no effect, the issue with bioavailability has to do with solubility which requires nanocrystals etc.

#179

I don’t know about that. That rapacan he’s showing there is about the same as siroboon. He might need all the GFJ he can squeeze out of that big ripe one to get all those pills to show any significant amount of sirolimus in the blood.

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#180

That could be riskier than just using a proper brand: Grapefruit associated with increase in all-cause mortality

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#181

Completely agree about ME/CFS. It absolutely destroys your life.

I was unable to get a prescription for higher than 15mg compounded, so out of desperation, I have gone the GFJ route. So if we assume 15mg compounded = 5mg bioavail formulation, and then use GFJ (ruby red) theoretically it will get me back up to 15mg bioavail equiv, maybe higher. This is super speculative, and I will certainly start tracking my blood levels going forward, I think next month.

I will say I feel great at this dose. Everything feels back to normal.

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#182

Do you feel great at 15 mg compounded and GFJ ? Why do you use compounded Rapa ? I use Rapamune solution from Pfizer which is pure Rapa (1mg/ml) and get peak values of > 60 ng/l with 14 mg without GF, but no relief from ME/CFS. Following your 45/35 mg indication I have now gone to 25 mg, but not yet measured pik values. I am curious to see you peak values at a dosing which makes you feel well. Blood pik value is best measured at 2.5 hrs after intake. Let me know and good luck.

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#183

Why nobody uses the standard Rapamune solution from Pfizer (1ng/ml) ? Isnt it available in US ?
It s pure Rapa and excellent bioavailability. At 14 mg dosing I got >60 ng/l pik, see my above post.

#184

Yes, I feel great at 15mg compounded and GFJ. The reason I got compounded is they (agelessRx) told me the 15mg compounded was equivalent to 12mg regular prescription, (and yet it was the price of a 5mg regular prescription.) Also, I used some of it for toothpaste, etc. Anyway, if its actually equivalent to 5mg, the cost argument no longer applies.

How severe is your CFS/ME?
is it post-infection? is it slow onset or fast? Do you also have an autoimmune disease? Have you ever been on a large dose of a corticosteroid while you’ve had CFS/ME?

#185

It’s more expensive than Indian generics.

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