Depending on exactly when you are taking the grapefruit juice in relation to the rapamycin - your effective dose of rapamycin could be as much as 3.6 times higher than the dose you think you are taking - so that 20mg could be 72mg, which is extremely high. If you do this on an ongoing basis, you really risk immune system suppression - which could be very bad.
Just want to make sure you know what you are doing when you take the rapamycin and grapefruit juice.
grapefruit juice (GFJ) also can really cause problems with other medications too - so I hope you aren’t taking any other medications.
I take a lower dose weekly but definitely see this effect on ‘dosing day’ and a little into day 2. Can’t think what the mechanism would be but perhaps it is crossing the blood brain barrier?
Endogenous neuroprotection has been shown to be, in part, due to changes in mTOR signalling pathways and the instigation of productive autophagy. Inducing this effect pharmacologically could improve clinical outcomes. One such therapy already in use in transplant medicine is the mTOR inhibitor rapamycin. Recent evidence suggests that rapamycin is neuroprotective, not only via neuronal autophagy but also through its broader effects on other cells of the neurovascular unit.
According to my reading, Rapamycin is mainly an auto-immunosuppressant and an anti-inflammatory drug. The cases where Rapamycin has had an adverse effect, i.e. developing pneumonia, etc. were in patients whose health and immune systems were already severely compromised. Many studies include patients taking 4 - 5 mg daily for more than a year with few adverse effects. That is a higher total dose than I am taking through the “pulsing” protocol.
If you were to use Google Scholar as a search engine and Googled; “Rapamycin and autoimmune suppression” or Googled “Sirolimus and autoimmune suppression,” you will find the results are mostly positive.
Rapamycin is also an anti-inflammatory, which is mostly a good thing.
My main objective with higher dosages of Rapamycin is not to increase lifespan. I believe lower doses are sufficient to achieve that. But, because I am 81 yrs. and in good health, my main objective is to stop and/or reverse cognitive decline. I have not noticed much decline in long-term memory or the ability to solve crossword puzzles or sudoku puzzles, but I have noticed a decline in working memory i.e.: Where did I put that screwdriver, hammer, etc. This causes me to take more time in completing tasks because of time spent looking for things.
Effects of Rapamycin on Insulin Brain Endothelial Cell Binding and Blood-Brain Barrier Transport:
“Rapamycin is an exogenous compound that has been shown to improve cognition in Alzheimer’s disease mouse models and can regulate pathways downstream of the insulin receptor signaling pathway”
There are many other references supporting this to be obtained through the Google search engine.
Look into ketone esters.
This is an older video, published 8 year ago;
“Unconventional But Effective Therapy for Alzheimer’s Treatment: Dr. Mary T. Newport at TEDxUSF”
Also the paper{ “Rapamycin in ischemic stroke: Old drug, new tricks?” ] linked above, posted by member 'Guywholikessleep" mentions “lithium carbonate”.
“Rapamycin can reduce endothelial cell death and improve junctional marker expression following ischemia in vitro. mTOR-dependent (rapamycin) and mTOR-independent (lithium carbonate) autophagy inducers were used in brain microvascular endothelial cells (BMVECs) in an oxygen and glucose deprivation (OGD) model and also an MCAO model, demonstrating a beneficial effect on BBB integrity”
I would used/am considering using/adding lithium orotate.
The lithium oratate is a supplement and is absorbed better.
I am not taking high dose, Dr Thimineur is the one taking high doses. The following are quoted from his post in other forum:
"The biweekly dose is 30mg sirolimus without grapefruit juice. Every 6 week dosing of 90mg was 30mg sirolimus dosed with grapefruit juice. There are GI side effects dosing over 40-50mg at once so grapefruit juice is required to avoid these side effects when taking more than that amount. "
I have been using lithium orotate for several years now, since 2016.
“In modern medicine, lithium is used to encourage mood stability in bipolar disorder and is also being considered for the treatment of memory impairment.” Lithium study helps scientists unlock ageing puzzle - BBC News
In addition to possible mental and life extension benefits, I have found it to be a great mood stabilizer and helps with anger management, mood, etc.
It usually takes several weeks to feel any subjective effects.
This is absolutely one of my favorite supplements.
I started with 4 mg/3wk, quickly moved to 6mg/2wk, then thanks to Brandy111 I started using 4mg with GFJ. I did this for a couple months. When I learned about the life extension test I ordered 2. First test was used after 10 days because I wanted to make sure the level was low enough to switch to 10 day. Value was 1.3. I think this is low enough.
Then I tested in the morning 2 hours after taking 4+GFJ and it came up 37.6.
I am a long time user of Berberine, which interferes with cyp3a4 also.
FYI. As a physician I have negotiated pricing for sirolimus including lab draw free at LabCorp for $49.
I am hoping to monitor labs to start getting data on formulation effectiveness and dosing schedules.
Three points would give us the info we needed.
CMax. Ideally 2 to 3 hours post dose.
Mid Point: 96 hours post after CMax assessment
Trough: Approximate based on calculated half-life.
Have you guys checked your 3 or 12 hour sirolimus levels with and without grapefruit puree? This is info we all need to know. If interested, I have research pricing on sirolimus with LabCorp.
A simple method is just track a fixed power/heart rate curve. For example what is your HR at steady state 125w. Then reduce to 50W and see how long it takes for HR to reduce to 80%,
Just to confirm that is 37.6 ng/ml? Not PPM. Is so that is a very good level.
Did you take GFJ prior to or with the sirolimus?
What concentration? 1 or 2 mg.
What formulation did you use? Pfizer Rapamune or Generic. If so know the brand?
Dr. Reddys is triangular with number 53 or 54.
All these details make a difference.
I did drink GFJ, probably 24 oz. Otherwise I think I was fasting that day and it was first thing in the morning.
It was for sure Generic and almost certainly Biocon. Rapacon. Just a line across the top of the tablet. 1mg. I had some other generics at the time from Wal Mart, and it’s been awhile, but I’m pretty sure. I think I wrote about it on here and probably said.
I don’t think there is any difference in these tablets and I’ve used several kinds. They all give me clues that tell me I’m getting the real thing. I just tested because I like numbers.
Saliva won’t work for sirolimus. But I would be happy with an at-home microtube draw and stoked for bloodspot. These are doable but need more people checking levels so we can go to a lab and offer at least a few hundred or more samples a month to make it worth their while to update systems.
Yes both purity and efficacy need to be confirmed. I am working with a vetted supplier of nanoparticle sirolimus in Asia that has 3rd party testing and we will be sending the final ingredients to a lab in Israel to do pharmacokinetics. Price should be less than $2 mg. This would be available without an RX.
For labs or the meds? We want to run 4 more people comparing levels to generic and then send the samples to Israel for full analysis. It will be a few months. I’ll let people know.
Low doses of rapamycin in the range of 4-6 mg/week, or 1 mg every other day, can also induce an inflammatory syndrome. Unfortunately it did with me, starting with transient pruritis and joint pains, and ending with the exacerbation of an immune-related myocarditis condition that I was taking it to prevent.
I had new and more frequent heart pain - once after a weekly dose of 4 mg and once after a 6 mg dose. Then after switching to 1 mg every other day, I had new mild, but continual heart discomfort with new left shoulder pain on and off for 2.5 weeks. Toward the end of that episode, I ran some blood tests and found by CRP had shot up from 0.8 to 25.4. I also had low hemoglobin and hematocrit, and a high neutrophils/Lymphocytes ratio of 3.1. So that’s the end of that experiment, for now.
I am not ready to give up so will take a break for a couple of months and may try again, possibly with lower dosing and longer intervals, while monitoring my inflammatory markers more frequently.
