dlkmd
#122
I believe latest count is about 80. This is NOT placebo controlled trial. People with an ME/CFS diagnosis can have their doctors contact us if they want to consider enrollment.
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dlkmd
#123
Safety labs are done at baseline. Rapa is tapered up to 6mg/wk over 6 weeks and then next set of labs are done 4 weeks later. At each safety lab draw, additional study labs are drawn for a variety of proteomics, gene expression, etc
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dlkmd
#124
@Kerstin_Holz
“GF is GrapefruitJuice which enhances the bioavailable dose approximately 4-5fold.”
The problem here is what are the actual numbers, what dose is this equivalent to, what does this actual do to the peak and trough serum levels?
Does 4-5 fold equate to taking 24-30mg dose weekly? Very doubtful or the adverse effects would be significant.
GF may save money-can buy lower doses of rapa-but it is still a black box. Back in the dark days of HIV when the antiretroviral cocktails hit the streets, it was common to do this but it was the same black box. Then big pharma realized ritonavir could do this in a more measurable/controllable way (same in Paxlovid) and this was a game changer.
Personally, I feel safer knowing the exact dose I’m taking. I strongly suspect the GF trick works differently for everyone, ie we are each different and have our unique CYP450 enzyme systems.
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People are augmenting their rapamycin with GFJ for many reasons including availability and cost.
Some people are using GFJ to extend their limited supply, some are doing it for cost-saving reasons. I am from a generation that believed “waste not, want not.”
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GFJ has been shown in studies to multiply the dose of Rapamycin by 3X, not 4-5X.
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SNK
#127
Are you sure it is set 3X for everyone? I thought it differs from person to person a little and the mean/average could be 3X?
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Thanks for your reply re how often to do labs. I’m learning some basics here but so much is over my head, it’s as if ya’ll have a PhD in chemistry. I’d love to enroll in the study but am 70 - I’ve never understood age limits. Would the study be interested in hearing from those like me in an unofficial manner, not following their protocol but just to give some added side info?
You have to take genetic polymorphism into account: „ The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. “
I checked my Sirolimus blood levels and they were a little more than 4 fold higher the day after I have taken them with grapefruit juice than without.
There is a high interindividual variation.
I am hesitant with ritonavir as we had a black box warning here in Germany.
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SNK
#130
That was my exact point as our friend @DeStrider seemed to suggest that everyone MUST only get a 3X 
. If I remember correctly from these board a dude (forgot exactly who) a while back had claimed they got close to 7X. Clearly different people will get varied results, there simply can’t be any other way.
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Jjazz
#131
It is important to remember that we measure exposure in the blood, and see a 3x multiplier for grapefruit in that tissue only. But, there are some lines of evidence that suggest that enterocyte (intestinal cell) exposure is the key place where longevity impacts are manifested:
https://www.nature.com/articles/s43587-022-00278-w
Since grapefruit is inhibiting CYP3A4 directly in enterocytes, the exposure multiplier in these cells is likely far greater than 3x. Once the drug enters systemic circulation, liver enzymes will reduce the exposure level in the blood.
Other lines of evidence suggest that liver is the key organ for longevity benefits. Who knows which is right?
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I can only speak for myself, but I have been taking high-dose rapamycin with GFJ for over 2 1/2 years.
My liver and kidney tests are fine as are my lipids and glucose.
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sudiki
#133
what is your dosing time period. weekly, 10 days, 2 weeks etc?
Step 1
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wait an hour
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I did a blood test last monday and was pleased to get the results on Wednesday, tuesday would have been better.
I also did a blood test on Friday which is a really broad spectrum test. I have previously been taking 6mg with an accelerator and not noticed side effects (other than disrupted sleep). Hence I am now trying 16mg with an accelerator because I can cope with a week of disrupted sleep. The last time I took Rapamycin was 22nd June and I was prior to that on a three weekly cycle. I did not take it on the next cycle because I had a couple of gigs to play and did not want to have any issues with sleep. My next gig is early September.
I intend to get a blood test in each of the next two weeks. I am juggling up in my mind which labs to use.
I am not sure when I will next take Rapamycin (or how much to take). I have tried Pomelo, Grapefruit and Pomegranate as enhancers. I prefer the taste of Pomegranate, but have not noticed any difference.
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I have been dosing weekly.
sudiki
#136
are you still at 5mg +GFJ/weekly? I was taking 6mg/wk no GFJ, but decided to go to GFJ to extend my supply (and as a bonus, save a little money). I am at 4mg +GFJ now every other wk with no noticeable side effects (except a few neck pimple/boils but i have always had acne so not sure if it’s from dosing or just me being me). I have some labs being done next week so will see what blood sugar and lipds are. The plan is to go to 5mg next time I dose and that will be my max dose. I haven’t decided if i should dose weekly or biweekly as i read different info. on this and everyone seems to be a little different. I wanted to make sure that my body has time to “recover” before the next dose but again; I don’t know if I need to.
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This is where I take a different approach to people. I see Rapamycin as someting that is having a continual, but reducing effect on the body. It is not like some exercise that lasts an hour and then the body needs to recover. Instead it is an effect on the cells that starts a few hours after taking Rapamycin and reduces in its effect on an exponential basis (not necessarily exponentional, but we should assume this).
Hence on a simplistic basis you can consider that it has an effect for a number of days (above any one given threshold).
Rapamycin has positive effects (in encouraging autophagy), but also has negative effects (in reducing stem cell production.). Hence what we need to do is get the balance right between encouraging autophagy and stopping stem cell production. I have gone for a particularly high dose this time. I have not noticed any particularly different effects, but because I take citrate and also hectodose in melatonin I strengthen the immune response in a different way.
Once I have finished reviewing this cycle which will involve at least 2 weekly blood tests I will decide whether to stick with this higher dose with accelerator or go back to 6mg plus accelerator.
Whichever way I think Rapamycin will have material effects for about a week and possibly more, but I have no gigs to play and I think I will handle any sleep disruption without any broader impact.
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Yes, but I am thinking about doing it every other week.
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sudiki
#139
That’s what I’m planning to go to on my next dose; every other week @5mg+GFJ.
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Thank you for ending the guru debates. That isn’t really helpful.
Regarding lipids, I have been taking 8mg every other week, no GF, just the rapa. I have been on a statin before beginning rapa.
My lipids and HbA1C actually improved over 6 months on rapa. Now, I can tell you I did more HIIT exercise and reduced my bread and rice after using a CGM and discovering those spiked my glucose, so I attribute the improvement in glucose to exercise and diet, but still, quite positive that my markers improved while taking rapa.
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In recent Huberman podcast, peter attia mentioned that they had raised funds privstly to finish the projects
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