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Wow! Thatās a huge difference. Can you share how close to exactly 2 hours you were on all 4 tests? Also, aside from the one time with gfj were these all totally empty stomach first thing in the morning or was there food or evoo involved?
I have always taken my rapa at 9:00 a.m. for an 11:00 a.m. Labcorp appointment. The appointments have never been late- all of the tests were within a minute or two of two hours.
All of the doses were taken on an empty stomach- although I swallowed 1+oz EVOO with the 8mg dose that registered 12.9 (EVOO slows absorption? I read that someplace on this site)
I guess Iām hoping this is just an anomaly- I have 100 of the 2mg Siroboon pills and Iām pretty sure I canāt return them to IndiaMart!!! Iām thinking I might need GFJ to get them up to the desired range.
Sounds like youāve tested very close to 2hrs with all of your labs. I donāt see how a level of 3.1 can be possible other than the siroboon being much weaker than the rapacon. I wonder has anyone else on this forum taking siroboon has tested a peak?
We were just discussing why people shouldnāt be having their blood drawn two hours post dosing in another thread.
Also, the study mentioned in post 2 of this thread used Sirolimus liquid solution rather than enteric coated pills.
Pfizer has stated it takes an average of three hours to reach Tmax after healthy persons take the tablet on an empty stomach. āFollowing administration of the sirolimus tablet, sirolimus tmax was approximately 3 hours after single doses in healthy volunteers.ā
But this is for Pfizerās tablets. Thereās no guarantee that tablets from other manufacturers dissolve and get absorbed at the same rate.
My suggestion is that people wait five hours before having their blood drawn. Or longer.
I am personally on board with the idea that trying to directly target t-max is just too difficult. Itās better to have the sirolimus level drawn at 48 hours and then extrapolate the t-max from the data we have available to us (as described in the link above). And, it would be great if hitch would do that. But, just based on the info he provided there are very few possibilities. It could have been a lab error (unlikely). Or, it could mean the siroboon didnāt peak yet (seems strange it the level didnāt get a little higher than it did after 2hrs). Or, itās weak.
Well, as I just noted, Pfizer said the Tmax for their tablets on an empty stomach averages three hours. Plus, Pfizer uses nanocrystal technology, and part of the advertised benefit is āquicker onset of action.ā Thatās why I suggested waiting a minimum of five hours for other brands. Or even the following day for comparison purposes.
In case you didnāt see this postā¦ after going on 36ng/mL for 7 monthsā¦ based on Mikhail Blagosklonny recommendation to go high as possible with no side effects. You can have silent pathology. My biological markers aged decadesā¦ not good!
From Matt Kaeberlein who is the best: āI absolutely think itās possible that 36mg could be net detrimental to health while 6-8 mg could be beneficial. I am certain the optimal dose will be different for different people.ā
I am fairly typical and those high doses were not good for me N=1. I reduced back to 6-8 mg and my biological markers went back to a younger ageā¦ took 8 months to get there again.
You are getting high doses in your blood based on you measurementā¦ but does that equate to positive health benefits??
The argument of high doses to cross the blood brain barrierā¦ Matt Kaeberlein shoots down too. Saying peripherally the reduction of brain inflammation may be enough.
āI am fairly typical and those high doses were not good for me N=1. I reduced back to 6-8 mg and my biological markers went back to a younger ageā¦ took 8 months to get there again.ā
Which biological markers? Was Glycanage one of them?
Holy shit, Iāve also been using high rapamycin doses [thereās some evidence theyāve done more harm than good - my 2020 blood tests, before I used larger-than-small doses, were near-ideal on all dimensions], and will dial back (though I also have semaglutide now, which is probably better for me than rapamycin)
Is TruMe just the 1st-generation epigenetic aging clocks (Horvath/Hannum)?
As with all epigenetic tests, TruAge measures the amount of methylation of your DNA at certain regions that have shown a link to ageing. Their lab uses the bisulfite conversion techniquw; one of the three common methods along with differential enzymatic cleavage of DNA and affinity capture.
TruAge analyses the DNA methylation (DNAm) profiles of 9 small regions (loci) of DNA. For comparison, the original Horvath clock uses 353 CpG sites and his latest GrimAge clock uses 1,030.
So maybe 9 sites seems a bit low, however, even GrimAge only uses a fraction of the
28 million CpG sites in the human genome. There will always be a statistical error, and TruMe labs claim that their studies show an error margin of 4.6 years.
NOTE: the TruAge Explorer saliva test shouldnāt be confused with the more expensive ($399) TruAge blood test from TruDiagnostic which uses 900,000 methylation loci to determine your biological age.
I asked Matt Kaeberlein about increased biological aging correlation.
Matt said this: : Rapamycin dose - I honestly donāt know. I understand Mishaās (Blagosklonny) rationale for pushing it as high as possible until you get to side effects. My concern there is that you might be getting to side effects and not know it right away or at all (silent pathology) until itās too late to reverse the damage. I have no evidence for that, but itās a concern I have.
I absolutely think itās possible that 36mg could be net detrimental to health while 6-8 mg could be beneficial. I am certain the optimal dose will be different for different people.
I find it a little hard to reconcile the data we have from animal testing, with the issue of potentially negative impacts at higher dosing of rapamycin. Iām not saying it may not be true, I just donāt understand how it would be happening, and at what seem to be comparatively low doses ā¦ e.g. 36mg/in one weekly dose. It needs to be explored/researched more, that is for sure.
It seems that the mouse studies would suggest that we have a lot of headroom to explore in terms of higher dosing regimens (aside from the immune suppression issue). Per the data below:
