Tried something different today for my weekly rap… normally I drink a 16 ounce glass of grapefruit juice an hour before, just regular GFJ bought at the store (not fresh squeezed or anything like that)… I take 4 grams weekly of Biocon brand, and normally I can feel it but it is not overwhelming or anything like that or give me symptoms… Today I soaked the pills in a tbsp of EVOO (extra virgin olive oil) for about 10 minutes before swallowing, took it with the olive oil right down the hatch. It seemed to really enhance the effect as it gave me a headache, and that is my number one symptom that I have taken too much of a dosage (I don’t get kanker sores)… so I may have to back off if I continue this approach. Does anyone else do this (GFJ + EVOO)?
I’ve seen many comments by people who take rapamycin with GFJ and a higher fat meal or EVOO shot, but I’ve never seen anyone soaking the pills in EVOO prior to taking them. Thats an interesting idea.
I suspect the variation you’ve experienced may just be the variation that is in the GFJ in terms of its furanocoumarins / CYP3a4 enzyme inhibition. It seems like depending on the grapefruits chosen, the type of grapefruit/age/processing approach, etc. you can get a wide variation in the effects. We’ve seen people report here anywhere from 2X to 6X increase in blood sirolimus levels with grapefruit juice, while I think a higher fat meal / EVOO is more consistent in its 30% increase in bioavailability (but to be honest, I have not read much research in this, its just that the "high fat meal/30% increase is mentioned in the package insert for rapamune).
I have heard that bottled GFJ doesn’t have the same effect as fresh squeezed, perhaps he should try with fresh squeezed?
Also the op stated “I take 4 grams”. I think he should clarify that he meant 4 milligrams. We have new people joining this forum each week and we don’t want anyone getting confused about the dosage.
I take 10 pills weekly (soon maybe bi-weekly) with GFJ + EVOO but i don’t know what it does, i just like the feeling. Only people that have done lab test without and with GFJ+EVOO can say for sure. Anyone else venturing a guess is simply blowing up smoke, and so are you with your supposed headache. I only added GFJ+EVOO when I read on these posts but couldn’t feel any discernable difference, never did lab tests.
You’re taking 10 pills of what?
10 pills of RAPA 1mg with GFJ and EVOO.
Wow, that could be a large dose.
That might be, but I like the way I feel (first 3-4 days after dose) better than with any other dose. Tried 1,2,3,5, and 6 with GFJ and EVOO, but 10 seems best for me, and to my surprise i never get the mouth sores or any other side effects from 10. always had them with 1-6 a bit weird but just stated what i experience. Though I’m contemplating going every two week since it is such a big dose (especially with GFJ+EVOO). Might try it that way.
That’s a really high dose… we’ve seen people here (from blood work) get anywhere from 3 to 6 or 7X increase in bioavailability with GFJ and EVOO, so you could be taking equivalent to 30mg to 70mg or rapamycin… which is far, far higher than is typically used except in some cancer clinical trials.
If not spaced apart by many weeks of time, you’ll likely get mCTORC2 inhibition and increased risk of blood glucose and lipid disregulation and immune system suppression. I’d be measuring my blood / sirolimus levels at trough levels prior to dosing following times…How to get a Rapamycin (sirolimus) Blood Level Test
I struggle to find a good way to determine the desired dose of Rapa. Do side effects necessarily come from mtorc2 block or just mtorc1 block? Are side effects good or bad?
Certainly, “feeling good” is not a good way to determine the answer.
Whenever I see people taking extremely high doses like this, I feel the need to remind everyone of the risks when you go to high dose rapamycin… people do get seriously ill and die (its rare, but it happens). See below.
Generally, rapamycin by itself is very non-toxic to healthy adult humans. There are no known overdoses on rapamycin, and people have tried (as much as 104 mg in a single dose I believe).
The big risk with higher dose rapamycin is due to the immune suppression issue, seen mostly in cancer studies where they are doing very high dosing of rapamycin or a rapalog (upwards of 10mg/day or as high as 45mg/day to 90mg/day…
Here is one such study, which Dudley Lamming pointed me towards. A young woman age 27 died in a clinical trail with 10mg/day of everolimus when she was infected with sepsis:
In a high dose (e.g. 10mg/day) everolimus study for cancer patients (admittedly 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.
Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening
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.
Full Paper here:
@RapAdmin Don’t scare me man, because I’ve become a raging bull at that dose 
Honestly, I plan on keep doing it at 10 plus GFJ +EVOO but I’ll do it every 2 weeks as opposed to weekly. The main reason being ZERO side effects and with all other doses I was getting mild diarrhea (didn’t bother me much nevertheless, and mouth sores very bothering). So, my plan is to keep the 10 pill dose but go on bi-weekly for next 3-5 doses and watch it carefully., I’ll report in here if anything bad happens.
As a side note, I had couple small infections that were persisting for like 4-6 weeks (on my forearm) from my earlier doses of RAPA (5pills +EVOO and GFJ) and within 3 days of starting the 10 pills with EVOO and GFJ they just cleared up. So yes, for now for me it is 10 pills of Biocon, with GFJ and EVOO once every 2 weeks!
But, for any reason I don’t show up on these board for like 6 weeks or so, just make a post saying something to the effect of: Let us all remember our dear friend @kansel for he killed himself with high doses of RAPA, may he rest in peace
If I have any signs of infection or sores, or rash, etc. - I typically would skip that week’s rapamycin dose and wait until everything had cleared up and was back to normal.
Dr. B says to gradually increase weekly doses until you get a reaction of some type (mouth sores, headache, etc.) then back off from there. There is a thread right now on a recent rap video, here is what one of the doctors says regarding the benefits:
“The exact mechanism by which Rapa extends lifespan is not known. Primarily because of mTORC1 inhibition but mTORC2 could be involved and process very complex. Dr K not convinced that all benefits are due to mTORC1, and that all side effects are due to mTORC2 inhibition.”
My understanding is that the benefit is maximized up the point where mTOR2 is inhibited, and that can be evidenced by the reaction… thus why Dr B says keep upping the weekly dosage until reactions are present.
btw, second week in a row with GFJ + rap pills soaked in a tbsp on EVOO 15’ before taking… similar strong reaction, stronger than with just GFJ alone, not as bad a headache this week but just a slight one
and yes I am taking 4mg per week