Although I am with you on this I think one issue is the impact on WBC (much that in theory a low WBC is a good thing - and I have that in spades). WBC has a delayed impact because of the average lifespan of White Blood Cells. Hence it is not just getting a reduction in Rapa that matters, but also the knock on effects.
Interesting that both Quercetin and curcumin share those functions. I did not know that. Thank you for sharing.
When I use them together they have a good effect on my wellbeing, in form of increased mood and a minor high. Qurcetin Phytosome from Thorn taken on empty stomach together with Green Tea Extract 725 mg. And after approx 1-2 hours I take 400 mg Curcumin BCM-95.
In theory, they can have a minor inhibitory effect on mTOR and also a weak activating effect on NRF2. But they are far from clean substances, and they have a host of other effects so it is hard to say what actually causes the effects I get from them. And also, they might act in synergy when it comes to absorption and to crossing the BBB? Which can explain why I don’t experience the same when I take them in other combinations.
Yes Curcumin + Quercetin is an exciting combination. (+ Green tea but extract not green tea)
This paper about "improving the oral bio availability of beneficial polyphenols through designed synergies” gave me some clues to the potential synergies between polyphenols…
Someone asked me why I sometimes go on a 20 mg bender, so I thought I’d explain my rationale here. Actually, the 20 mg is 6 mg + GFJ + EVOO which I calculated to be about a 20 mg equivalent. Then I would wait 2 weeks before taking my next dose. Why would I do this on occasion?
- According to Dr. B, high doses of Rapamycin are better. Mice receiving a high dose of Rapa lived the longest.
- High-dose Rapamycin permanently cleared up a patch of allergic skin on the back of my hand that a low dose of Rapamycin could not. Therefore, IMHO, a high dose has different effects than a low dose. These effects can be permanent like what happened to me.
- Risk of a bad side-effect is low even at high doses as many people have tried much higher doses with no bad side effects.
That’s my rationale for trying a higher dose. Honestly, I am experiencing many different physiological changes since starting Rapa, but it’s hard to figure out which supplement is causing them. It could all be Rapa or some interaction between Rapa and other supplements I am taking.
- Generally better mood. I find I am more alert, less angry, less anxious, more thankful, and generally happier. I know that Rapa gives me euphoric fatigue for a day or two after dosing, but not sure if it is causing the other effects. Could be the NAC and/or lithium.
- Better memory. I am pretty sure Rapa is involved here.
- This one is a bit odd. I ‘creak’ more. My knuckles crack frequently (did not before). When I turn my head sometimes my neck will creak (did not before). Sometimes when I climb stairs, my back will creak (did not before). It’s not painful, just a bit odd. It’s more of an internal instead of external noise. Does anyone know what this is?
- In my lower right hip area, on occasion I will get a pulsed vibration at a regular interval like a hiccup. My guess it is a minor muscle spasm like a hiccup. It’s not painful, just odd. Anyone have any idea what this is?
- My skin feels smoother and almost more like plastic. Collagen related?
Again, I do take quite a few supplements, so I don’t attribute all of the above solely to Rapa. Just some physiological changes I have noticed.
You take 6 mg of Rapamycin with EVOO and GFJ and count it as 20 mg.
Could you please remind the formula you have been using to calculate the dose as well as amount of EVOO and GFJ.
Under normal circumstances, only 10% of your Rapamycin makes it through your digestive tract. The other 90% is destroyed by enzymes. Grapefruit Juice (GFJ) disables this enzyme somewhat and increases the absorption to 30-35% according to research.
So, GFJ multiplies the effective Rapamycin dosage by 3-3.5X according to the literature. You must drink the GFJ 1-4 hours before taking Rapamycin to get the effect. I eat 1 whole grapefruit each time. I prefer pink. White is too nasty.
Taking Rapa with a fatty meal increases the absorption of Rapamycin by 30%. I drop my Rapa in two tablespoons of EVOO and drink it as a shot. Not sure what the mechanism is here, but again I am relying on scientific studies.
Taking Metformin 1-4 hours before taking Rapamycin will also enhance the absorption of Rapa, but I do not know by how much.
Taking turmeric/curcumin will REDUCE the absorption of Rapa, so I avoid taking it on days I am taking Rapa.
Some people (@Agetron) have tested their sirolimus blood levels and have found a 6-7X effect with GFJ. I am being conservative in my estimations, but theoretically, I may be getting double what I think I am, or far less. I can tell you that it is impossible to go over 9X though!
Unfortunately, I haven’t found a good Sirolimus blood test here in Hong Kong so I am really shooting blind on my N=1 experience and am relying on the research statistics.
Honestly, with the safety profile of Rapamycin, even if I am taking a 40 mg-eq every 2 weeks, I am not worried about any serious side effects. Although I may face Montezuma’s Revenge…
I would probably intersperse a large dose with 2-4 weeks of smaller doses. Variety is the spice of life…
In the short term dosing of rapamycin I think this safety profile is quite well documented, as covered in this paper that documented some people’s high dosings with no long term negative consqequences:
But please do keep in mind that the longer term use of high dose rapamycin / everolimus has been identyified as having some greater potential risk… below are some examples in a high dose (e.g. 10mg/day) everolimus study for cancer patients (admitedly a serious and complex situation already, but … there was a death due to e-coli sepsis).
Rapamycin is not a risk-free drug, especially as you increase doses above the regular 5 to 8mg dosing once per week level.
The most common Adverse Effects (AEs) of everolimus therapy were laboratory abnormalities (100% of patients) and infection complications (83 episodes in 15 patients). Infectious episodes of pharyngitis (67%), diarrhea (44%), stomatitis (39%), and bronchitis (39%) were the most common infections. They were mostly mild or moderate in severity (grade 1–2).
In two cases, life-threatening conditions related to mTOR inhibitor treatment were encountered. The first was classified as grade 4 pleuropneumonia and Streptococcus pneumoniae sepsis, whereas the second was classified as death related to AE (grade 5) Escherichia coli sepsis.
A 27-year-old woman with TSC was started on everolimus
treatment because of AML of the left kidney
(60 Å~ 48 Å~ 36mm in size). The other signs of TSC were
facial angiofibroma, hypomelanotic macules of the skin,
and shagreen patch. The diagnosis of TSC was made
12 years earlier when the patient underwent nephrectomy
because of a large tumor of the right kidney. The
patient received everolimus at a dose 10 mg/day and the
trough concentrations of the drug ranged from 4.08 to
5.08 ng/ml. After 3 months of everolimus therapy, a
reduction in AML was observed (40 Å~ 31 Å~ 20mm in
size). During treatment, hypercholesterolemia (309 mg/
dl) and transient leukopenia (3.2 Å~ 109/l) with neutropenia
(1.34 Å~ 109/l) was observed. She also reported
oligomenorrhea. After a gynecological consultation, a
functional ovarian cyst was identified and contraceptives
were prescribed. However, 2 weeks later, she was
admitted to the gynecological unit because of subabdominal
pain and an ovarian cyst (64 Å~ 53mm in seize)
on ultrasound examination. Torsion of the ovarian cyst
was suspected. On the day of admission, WBC was
9.2 Å~ 109/l, the absolute neutrophil count (ANC) was
6.6 Å~ 109/l, the hemoglobin level was 10.8 mg/dl, the
PLT count was − 275 Å~ 109/l, and the C-reactive protein
concentration was 8.0 mg/dl (normal < 5.0 mg/dl). The
patient was advised to continue intake of contraceptives
and everolimus. The next day, the general condition of
the patient aggravated. Her blood pressure was low (85-
/50mmHg). Her WBC and ANC decreased (WBC
−2.4 Å~ 109/l, ANC − 1.8 Å~ 109/l), whereas the hemoglobin
level (11.0 g/dl), the PLT count (185 Å~ 109/l), and coagulation
tests were normal. Computed tomography of the
abdomen and pelvis showed AML of the left kidney (size
as in the previous examination), an ovarian cyst measuring
65 Å~ 50 Å~ 40 mm, and fluid in the retroperitoneal
space with density of the blood. Further aggravation of
her general condition was observed. The patient was
transferred to the ICU and she died after 2 h with
symptoms of shock and multiorgan failure. Blood and
urine cultures collected when she was in the ICU were
positive for Escherichia coli.
Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening
would that translate to 10-16mg bi weekly? or 15-32mg every third week?
I am trying to find a reasoning for my schedule. Even after taking my first dose of 1mg I noticed some side effects that I am not sure I liked. Especialy some three days after I got some strange pimples popping around my face and one cyst starting to form in my eyebrow… luckily it subsided. I noticed that my tonsils are on the the border of an infection (I am really susceptible to strep throat… even sometimes get peritonsillar abscess)… I feel also cranker sore forming on the tip of my tongue since Tuesday. I never get those, so maybe it is rapamycin? But that all calmed down. Maybe side effects would be easier to tolerate down the road, maybe it is the part of what makes it effective. I remember going on a two week fast some 15 years ago just as an experiment and I ended up with two or three abscess which I explained at the time to myself as a way of immune system cleaning process.
Yes, I would agree to NOT take very large doses of Rapamycin daily or weekly. If you want to try a large dose (20 mg-eq or more), I would give it 2-3 weeks before your next dose to let it all clear out!
What dosage of Rapamycin do you take every 2.5 weeks?
4 mg (1mg/day for 4 days), repeat in 2 weeks after the last dose.
Thank you for the prompt response. Why 1 mg/day rather than 4 mg per week or 2 weeks?
My primary purpose is to keep transplanted kidney. Don’t want to shock it with a one time high dose. Such protocol works well for my situation. Dosing is very individual and you are supposed to find what works for you.
Understood. Makes sense!
Yours is exactly the protocol I am using except for the dose. I use 5mg rapa with GFJ and EVOO. I try to get the max dose without producing diarrhea. The 5mg regimen for me is just about the max I can tolerate. I may drop that down if my ferritin levels don’t improve.
First of all, I will like to thank the entire Rapa community in this website for all the great information. Without this group I wouldn’t be anywhere close from getting started.
Yesterday, I got 300 Tablets of SiroBoon 1 mg ( Sirolimus 1 mg ) from Kachhela
Today I took 1 mg tablet with GFJ and a tablespoon of EVOO. I fell normal all day, now a bit tired as I woke up early this morning looking forward for my first dose.
Every 7 days I plan to increase to +1 mg with the same protocol until I reach 5 mg.
I’m wondering if it’s safe to take 5 mg with GFJ and EVOO per week or if I should take the Sirolimus alone.
How low is your ferritin level? What was it before rapa? May be it is safer to take rapa without GFJ or EVOO to keep the steady level?
It all depends on your body size. Larger folks can safely take more than smaller ones, IMHO. I am twice the size of some of our smaller members, so it makes sense that they shouldn’t take the same dose as me. I have not encountered any serious side effects yet, and have gone up to 6 mg with GFJ and EVOO. But everyone is different. A few folks have experienced ankle swelling, and that’s when I would back my dosage down. Or in the case of any other serious side effect. I don’t count canker sores, rashes or diarrhea as serious, but that’s my own personal call.
The plan to take 5mg is what most people do. If you haven’t already, I definitely recommend you read these threads:
Ideally you should work with a doctor. They typically prescribe between 3mg to 6mg in a once per week dose. Going above that and risks start to increase. Regular blood testing is valuable (e.g. every few months or so) to help see what the impact on your body is.
Be sure to study this thread: Side Effects of Rapamycin (part 2)
and watch for side effects.
A high fat meal with rapamycin increases bioavailability by about 30%.
Grape Fruit Juice can increase by 350% to 600% or higher… so you are effectively getting the benefit of 3.5X to 6X or higher times the dose of rapamycin you are taking. The danger here is that for many medications (some statins, etc.) this can cause an overdose situation which can be very dangerous and cause serious damage to your liver. Really read up on this if you are considering this. Its not recommended by any doctors, because of this risk.
If you go higher in dosing above 6 to 10mg in a given week, because of the long half-life of rapamycin, you risk having a buildup of rapamycin in your blood and over time that can cause mTORC2 inhibition and immune system supression. This can make your body more susceptible to infections, and while most of these infections are treatable and mild or moderate in severity, you can read above of studies in hospital / cancer situations where people have gotten severe infections and at least one death has occured (see post above).
I don’t know what my ferritin levels were before I started rapamycin. My ferritin levels were being checked by the Red Cross before my blood donations and were in the normal range but they didn’t give me a number. Approximately 3 months after starting rapamycin my ferritin level was 39ng/mL then over the next 6 months I gave blood twice. When it was last measured on Feb. 23 of this year it had dropped to 6ng/mL.
That sounds like something to have checked by a doctor. It might or might not have a connection with the rapa. A quick google suggests it might be caused by lack of RBC (presumably not if they allowed you to give blood) or lack of iron. In either case, that’s a big drop.