Rapamycin and Grapefruit Juice

#81

MAC asked - “Have you shared a CBC, curious about these markers, a typical negative side effect? Would be very interested.”

Now 2-years on Rapamycin. Higher dosage since April 2022 I have been on 6-8 mg rapamycin plus GFJ. No side effects except at 8mg rapamycin with GFJ had a few days of diarrhea. Since 6mg and GFJ - no diarrhea. My only side effect ever… never had healing, immune or mouth sores once. Here is my CBC last month after being on higher dose of rapamycin past 3 months - as you will see pretty normal. LDL-C is higher but no atherosclerosis. My Coronary Calcium Scan is zero. Testosterone might seem high but I had just had my 1ml 200mg injection 2 days before. LabCorp sirolimus test showed 56.9 ng / mL ( had a few days of diarrhea). This CBC is typical of all of them - every 3 to 4 months past 2-years. Normal.

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#82

MAC is this similar to yours?
At 64 1/2 years I think it looks solid.
Your thoughts?

You wrote: “You are taking a relatively high dose (with GFJ) although a trough level of 2.2 isn’t that high. This is an excellent data point to build from.”

TBH - I can live with this trough level 2.2 if it were much higher - then I might be concerned about MTOR2 inhibition and I need all my muscle growth and strength! LOL

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#83

It is easy to take a higher dose. Take more rapamycin. The reason people that are knowledgeable in the field don’t recommend combining grapefruit juice with rapamycin is because then you lose all control. Rapamycin affects everyone differently. When you start combining grapefruit juice with its uncertain multiplying effects, then all bets are off.

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#84

i use my BOA online wire transfer, $45 charge

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#85

In your view, not in others people’s view.

#86

Certainly not everyone’s. But in the June recent discussion between Dr. Green, Matt Kaeberlein and Dr. Blagosklonny, that was certainly the consensus view of all three.

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#87

I am waiting for my results from a recent panel. I don’t see that you’ve gone offside in your CBC, especially anemia and WBC, Neutrophils, etc. Your fasting glucose looks fine, I don’t see hbA1c. People in clinical trials taking daily rapamycin doses (far higher than yours, trough levels 5ng/L+) will certainly indicate anemic and low WBC markers, but you’re not even close yet. Even your TG of 175, this is typically far higher. And apparently you feel fine, no real side effects, still exercising. And we have good evidence some of these perturbations will revert lower over time. You are in an incredibly envious position of zero CAC (this could be genetic, a freebie) and excellent health (this is all YOU, kudos!)

But will you live LONGER at this level?

Pushing mTOR2 a bit off it’s setpoint is arguably part of the lifespan extension of rapamycin (but it comes with side effects), this is well theorized in the literature, and definitely a central cancer mitigation axis. Glucose dysregulation is part of the mTOR2 signalling axis, your fasting glucose seems normal.

I’ve been exercising my normal daily routine throughout my current dosing protocol, no impact. I don’t have all my Sirolimus results back (waiting for trough), but my Cmax exploration numbers were VERY high with definite lipid/glucose/anemic dysregulation. No significant side effects, but need a longer duration to fully flush out.

Muscle protein synthesis has mTOR and rapamycin mTOR INDEPENDENT pathways…just keep doing your strength training, and use it as just another biomarker. It’s far too complex to think simply that rapamycin = growth arrest = muscle growth blunting. Per MB, “rapamycin potentiates strength training”! They never gave mice barbells and a resistance training routine. Don’t worry, you can always reduce rapamycin dose, and everything will revert back, this is well established after 20+ yrs of rapamycin studies.

You will have to make your own decision about increasing dose…do you subscribe to MB’s mantra of taking dose as high as you can tolerate? And do you want to explore translating the mice studies showing higher dose = higher lifespan extension? We are all here because of the mice, so are we going all-in with the literature, or holding back? The mice only died of cancer, so do we tinker with mTOR1 AND mTOR2, or just pop a few mg/week and live in wishful bliss? Is hormesis part of the lifespan effects of rapamycin? If you’re not dysregulated in some of the key indicative markers, you’re not moving the needle.

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#88

I agree, the results are NOT reproducible, even within n=1. This is my ONLY qualm with GFJ, not because it dosen’t very effectively boost AUC at a lower dose. It’s not part of my protocol. It’s just introducing another variable, and being consistent with your AUC/trough I think is important when using biomarkers tracking as your guide.

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#89

To have a higher trough level without having to consume a larger dose, maybe take once every 6 days instead of once every 7 days?

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#90

That is actually a briliant solution without taking more medication. Higher trough and keep same routine 6 mg rapa and glass of fresh GFJ. Thanks!

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#91

zazim wrote - I would worry very much about someone who is new to rapamycin that comes to this forum for advice and reads this thread or the one on daily dosing and takes instruction from either or both.

Seriously appreciate your concern - but I also keep in mind that in the decades of rapa’s use I have not heard of a lethal overdose case [LD/50]. Or any severe side effects. Safer than aspirin according to MK.

From an earlier post: Rapamycin been used at extremely high dose (single dose) by a few people written about in case studies (see below) where the person tried to commit suicide by overdose using 103mg of rapamycin / sirolimus. The effects were minimal and not long lasting. So - the risk in the short term dosing seems to be extremely low.

There is no known LD/50 for rapamycin / sirolimus in humans (though some research suggests that consumption of over 800g/kg in rats may be an LD50, over 2500mg/kg in mice. So its a very non-toxic drug. Its also good to know that some people have pushed the limits (in a single dose) and that they’ve been ok. Here are the documented situations people have taken very high dosages of rapamycin / sirolimus.

Five cases of acute sirolimus overdose were reported – three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range.

Again, the Black Box reputation rapamycin was given decades ago is unfounded according to MK, MB, PA and Dr. Green.

I really believe we are safe - we might get no benefit, a small benefit or a big benefit - based on dose.

Having LabCorp tested the rapamycin in my blood a few times - I am confident of my GFJ multiplication which is closer to 5 x - not 3.5 that is touted. MAC reminds us we are all different and the benefits and results on one person is not universal. If you want to know what is happening - you have to take the available tests. Those tests give me peace of mind and a better feeling of control.

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#92

I’m with you on the grapefruit juice routine. Since I am very late to the game I must follow Dr. B’s advice on pulse dosing and dose as high as possible before experiencing unwanted side effects.
I used the same brand of ruby red grapefruit juice every time, 12 oz the night before and 12 oz an hour before taking rapamycin.
At 20mg with GFJ, a dose considered high by many, I experience mild diarrhea for a few days afterward. The dose I took was bi-weekly and I repeated it 3 times just to make sure it wasn’t just a one-time thing. I reduced the dosage and titrated it back up to 15 mg/w GFJ and found that this dose did not have any side effects except to raise my lipid levels. Only the triglycerides were outside of the “normal” range.
Right now I am still on a hiatus from rapamycin and plan to start again in a few weeks. That is why I am extremely interested in the dosage discussion.

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#93

Yes, I agree with most of what you say. Rapamycin is a much safer drug than its reputation. But I still tread cautiously. I can take Metformin like a champion, food, no food. No effects. I’ve never had to stop taking any supplement because of side effects. But the first day I took rapamycin it felt like something was biting my left arm. I took my shirt off to make sure. The next day I noticed 10 to 12 blood spots under my skin. The second week 2 on my other arm. It could be completely unrelated but perhaps not. It’s definitely not a toxic drug. You can’t overdose on it. But the side effects, short and long-term, are still unknown. But I believe the risk/reward ratio is decidedly in rapamycin’s favor. But I do notice that many people whose entire career is based in the longevity field do not take rapamycin.

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#94

Wow… definitely would be concerned about any skin eruptions or changes - big signal from the body. Some people, like me, respond very positively within about 3-months. Others after a year – Meh! Nada!

Coming into the start of my 3rd year I am more stabilized - all the areas that were showing decline have repaired and many issues gone for now. Actually getting pretty use to the current me and not remembering me of 2-years ago when I first started on a strong hunch from my research. I feel that at least 15 years has been given back to me. Let’s see what 70 looks like in 6 years.

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#95

Based on my experience in the last 7 months I am inclined to agree with this. It might actually have some applications for weight category sports because it seems to facilitate increases in strength without weight gain.

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#96

Yes, could be the new doping scandal. I’ve talked to many researchers over the years who have confirmed that there are mTOR independent and rapamycin independent pathways to muscle building. And my own n=1 over the past month on HIGH dose rapamycin…ZERO impact on my daily aerobic/resistance exercise routine, both during and recovery (and I’m full on clinically anemic)!! Of course, I have no way of measuring mTOR inhibition. Is this the theory at play or my n=1 physiological health reserve or both?

MB talks about rapamycin and muscle and sarcopenia some here.

In a private communication, he confirmed to me that he strongly believed rapamycin potentiates strength.

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#97

As I have found in my 2 years. More shredded - toned with strength increases.

I have more of a runner or swimmer physique now. But same strength or a bit more as when I had a muscle physique.

Seems odd to be 15 pounds lighter and stronger.

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#98

Apologies if you’ve mentioned it elsewhere but what’s your current protocol @MAC?

My n=1 data suggests a facilitation of strength with a slight decrease in absolute endurance. Decreases in body weight may mask the latter in a weight bearing sport like running.

#99

I will compile a summary and post shortly.

I can believe the slight endurance diminishment from an RBC/oxygenation shift dynamic. 99.9% of people might never notice; only high performance athletes with active monitoring metrics. Actually, I just did a V02max test, waiting for full report, but peak was 45 ml/kg/min, which is just entering into elite for my age group (the lab reference data)., although this is certainly much lower than true high performance elite (60+ ml/kg/min). And I don’t really train for performance, just general high CRF, and have been on high dose rapamycin for a month, AND definitely clinically anemic. I don’t have a previous V02max baseline to reference against anything. I see that I can jack my V02 max by just loosing a few kgs since the unit is normalized by weight.

I will be doing another down the road when fully into a regular rapamycin protocol.

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Beat that Agetron!

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#100

That’s good data. Will be interesting to track changes going forwards. Do you have much body fat left to lose?!

I’m very interested to hear your protocol as your arguments for higher doses have been slowly winning me over the last few weeks…

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