Its actually rather funny… during the past 20 years of rapamycin / sirolimus use, the entire goal was the opposite (how to keep the blood/sirolimus levels above a certain level … I think above 5ng/mL (or in the range of 5 to 15 ng/mL), for transplant patients so that the donor organs don’t get rejected.
Now that we’re using it for longevity, our goal is the opposite (sort of), to make sure trough levels get down to some nominal value, to minimize side effects and mTORC2 inhibition. So - you are right - we don’t have any hard and fast rules for what that lower target is. We need to develop it. Dr. Green just gives a rough rule of thumb to help make it simple for people, which may be enough.
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The reason for using 5 half-lives is because after 5 half-lives the through level will have reached steady state levels. If the trough level after 5 half-lives is very low, you know the drug is not accumulating significantly with repeated doses. Taking a rapamycin trough level blood test to find how long you have to wait to get a very low concentration would also be useful, but rapamycin blood tests aren’t so accurate at very low concentrations. One lab I know of only gives a level of <1 if it’s low, which doesn’t tell you whether you have 0.5 or 0.7 or what.
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Genja
#104
But that begs the question: what is the level that qualifies as “very low”?
And since a typical Half-Life time for wrapamycin metabolism is just a bit under 3 days, only those taking it about once every 2 weeks will have five have lives to work with.
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The thing is, no one actually knows the half-life in any one individual.
"The half-life of rapamycin is about 3 days, or 58–63 hours. In a study of long-term, low-dose oral rapamycin, the mean half-life was 38.7 hours
Also it may not reduce in a manner similar to the decay of a radioactive particle in the sense that there is not just an exponential curve, but something more complex.
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That is kind of arbitrary, but considering that kidney transplant patients usually aim for levels of 5-10 ng/mL I would say at least ten times lower than that.
True, but the important point is that your through level will reach steady state after about 5 half-lives regardless of whether you take it every two weeks, or weekly or even daily. That’s why you have to measure after at least 5 half-lives, because only then will you know what your through level will really be when continuing to take rapamycin regularly.
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Vlasko
#108
Glutathione is another marker that could be tracked over time.
Marek Diagnostics offers glutathione testing through Labcorp for $59.
Glutathione levels may diminish with age:
“We found that the rate of intracellular glutathione synthesis and glutathione concentrations were markedly lower in the elderly than in the young humans. This glutathione deficiency was associated with increased oxidant stress, because plasma markers of oxidant damage were elevated in the elderly. Treating elderly subjects with brief oral supplementation with cysteine and glycine improved both the FSR and ASR of glutathione to levels observed in young humans. An important consequence of this increase in glutathione synthesis was a significant decline in both oxidative stress and plasma markers of oxidant damage in the elderly to levels similar to those in the young control subjects. These data indicate that a major contributor to glutathione deficiency and associated oxidative stress in aging humans is a diminished rate of glutathione synthesis, which in turn is due to low availability of its precursor amino acids.” Source study (1)
If tested before and after one begins supplementation with glycine and NAC/NACET, it might also give an indication of how well the supplementation works to boost levels.
Here are example glutathione results in someone who is 29 versus 57 years of age:
–
(1) Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation.
Rajagopal V Sekhar et al. Am J Clin Nutr. 2011 Sep.
PMID: 21795440
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Vangamo
#109
I just bought 300 tabs of 3mg Siroboon from Pramod-Affix Impex from Indiamart for 240 USD plus 30 USD shipping, 30 cents per mg. I took 6 mg 5 days ago and I haven’t felt any side effects. Does anybody know where I can get Rapamycin Cream?
See this link for buying rapamycin cream in the USA. I don’t know if any international sources… Where to buy Rapamycin Skin Cream
Or search on diy rapamycin cream on the site here to see how to make your own.
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does lifeextension use labcorp or quest?
[and what providers use quest?]
LabCorp - Yes, just checked on the place where I go.
They should tell you on the LifeEx website - because they have to send you to a location to get the testing done.
I looked at my blood tests that LifeEx sends to you afterwards, but nowhere does it say the name of the lab.
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doug-s
#113
hi all!
so, i got tested for rapamycin 24 hours after dosing 6mg. the results were <0.5ng/ml; the stated reference level is Reference Interval: 3.0-20.0, Unit: ng/mL. but the normal dose for regular patients that use rapamycin for non-aging, unlike those of us here is much higher, no? so, is my <0.5ng/ml result ok after 24 hrs? i weigh ~145lbs
thanks,
doug s.
That seems low. What type of rapamycin (brand) were you using?
The target level for transplant patients is a consistent 5 ng/ML, dosing daily, but that doesn’t mean much for longevity people.
Most people here don’t test 24 hours after dosing so I’m not sure what the “normal” level is at that period of time. A few people have reported it I think - but its not super easy to find these reports given the number of posts here in the forum. I’m going to test my levels next week at 3 hours, 24 hours, 48 hours, etc. to get my curve.
Related: Timing of sirolimus blood test to check effectiveness
I think @Agetron might have tested after 24 hours - and might be able to share his levels at that time. Anyone else?
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Ah - just was this from the AgelessRX pharmacist:
Get your blood level checked and you want to target a sirolimus level around 5ng/ml at 24 hours post ingestion. Max 10. Right now, this is my best guess. I should have more data to back this up in a few months
Source, this post: Lots of side effects, Opinions needed - #12 by szalzala
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cl-user
#116
24h is a good time for a test if you only take 1 data point. That said this is pretty low at 24h which means that either your absorption is poor or you are metabolizing very fast. Could also be the rapa itself depending where you get it from.
You can check the absorption by taking a blood test at 2~3 hours. This will give you the absorption peak Note that this absorption peak in itself is meaningless because it’s before the distribution phase to the organs but it’s useful to determine if you have an absorption issue.
Did you take it on an empty stomach?
You should take it with some fat like olive oil or a fatty meal to increase the absorption.
In addition, you can also increase the dose or use GFJ.
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doug-s
#117
hmmm… seems i’m off the mark quite a bit. but if i’m at or below 0.5ng/ml at 24 hours, i wonder how that translates to if i were tested at 1-2 hours? it seems i want to be at 5ng/ml at 24 hrs, not 0.5ng/ml.
i took it in powdered form from leapchem - a source i chose because it’s listed in the nih’s pharmaceutical supplier list, and it was cited as the supplier for a product in one of the nih’s research studies. i figured if it was ok for the nih, it should be legit. and it cost ~$260 for 1g shipped. it was only exposed to room-temp conditions for a few days, and it’s been at -5c since i received it.
regarding what was in my stomach, i took it at noon, after not eating since the night before. but when i took it, i prepared a smoothie - ~24oz; the contents of which were 1 tbsp baking soda, 1 tbsp moringa leaf powder, a half cup plain yogurt, a bit more ice cream, 2.5g borage/flax oil/fish oil pills,1 tbsp olive oil, 4 partially thawed frozen raw eggs, and ~12oz of water. i drank about half 10 minutes before taking the rapamycin, and the rest when swallowing the pill. i put the rapamycin in a #4 gelcap, and then put that inside a #1 acid resistant enteric capsules.
i’m wondering if my less expensive capsuline enteric caps didn’t hold up as well as they should, and whether it would be worth it to get the more expensive drcaps that are now mfr’d by lonza… or whether i should use two enteric caps, one inside the other, instead of the inside cap being a regular gelcap. or try a different “breakfast” to go with it? or up the dose, to, say, 10mg and see if it has any effect?
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This is one of the key issues with buying powders… nobody has done the extensive validation that the specific capsule options get the rapamycin into the small intestine where it will be picked up by the body.
It sounds like your protocol was generally ok (food/fish oil, etc.) but the big variable is the capsule, and to a lesser extent the powder raw materials.
If I were you I’d try different capsules. Or move over to the tried and true generic rapamycin providers, either in the US or the Indian Zydus siromus / Eris (Biocon) rapamcan which has been well tested in labs and via blood tests.
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doug-s
#119
well, the capsuline caps i ordered were tested following the usp protocol, but not w/real live humans. the drcaps were tested with real live humans. i just ordered 100 #4 drcaps and 100 #2 drcaps from https://purecapsules.co.uk hopefully, the #4 caps inserted into the #2 caps, inserted into the #1 caps from capsuline, will result in a better 24 hr test result. the cost of the 200 drcaps, plus shipping, was $73.47 usd.
doug-s
#120
well, i just got tested again, 24 hrs after ingesting 7mg, and the same results. but this time, the sirolimus was put inside one #4 drcaps, which was put inside one #2 drcaps, which was put inside one #1 cap from capsuline.
so now i’m thinking that the powder i got from leapchem is no good, even tho the company’s other products have been used by the nih, and it’s listed on the nih website as a legit supplier. it’s hard to imagine that sirolimus inside of two of the drcaps, which were tested in humans, and inside a third capsule that was tested according to usp protocol, would not protect the sirolimus on its journey to the small intestines. does anyone know of a supplier of powder that’s been verified, and is readily available, without having to jump through too many hoops?
thanks.
