Here are 2 articles about which citrus fruits inhibit CYP3A4 most (pommelo>grapefruit>sour orange) and which coumarins are responsible for it. Note that different citrus fruits have around 60 different furanocoumarins having different effects, but these block the CYP3A4 most: Epoxybergamottin was found to be the most potent inhibitor (IC50 = 1.5 μM), bergamottin and DHB had weaker inhibitory effects (IC50 = 10 μM; and both bergaptol and umbelliferone were found to be very weak inhibitors (IC50 > 125 μM.
There are nowdays new grapefruit cultivars made specifically to have low dose of the furanocoumarins to lower risk for CTP3A4 interactions in the general public - not something that people reading this specific thread want.
I have not found any good resource that can answere the question. How much Epoxybergamottin and bergamottin ther can be in bergamot extract, that some users of this site take. it looks that it depends on how the extract is made.
Are we using grafefruit in an attempt to save money on Rapamycin? If we had no spending limit would we just dose higher with Rapamycin? I did the GFJ for the longest time, but now I wonder.
Personally, I use grapefruit juice to extend my amount of rapamycin since I’m getting prescription, and I know it is top quality and can last a good 5-years, or more. Stocking up… I have a 3-year supply right now.
I just don’t trust Big Pharma. As popularity of rapamycin grows… so might restrictions… or availability. Currently, I get all my prescription medications Rapamycin, Finestride, Tadalafil, Minoxidil, Acarbose in 90 day increments… there are already supply chain issues… Walgreens pharmacy strikes, etc., who knows.
Not really paranoid… but, as I feel I am getting a biological benefit (approximately 15-years reversal), health span benefit… which can lead to a longevity benefit … not ready to have that pulled from me.
Plus, I can use extra pills for my hair tonic, toe tonic, adult kids and dogs .
LABCORP results show 1 pill of 2 mg rapamune with GFJ equals an 8.6 mg dose. Why use 4 pills, when one will do it.
Oh yes, that makes sense. Because GFJ, can affect the metabolism of many medications, and I take quite a few, I am thinking about restarting Rapamycin by itself.
Yes, I just started taking Ezetimibe, and I have to be careful with that one as it also is affected by grapefruit juice. I am assuming I will not take Ezetimibe within 5 hours of taking grapefruit juice (or just skip a day - probably safer).
Ezetimibe is wonderful though. I don’t feel tired after work anymore. Not sure why it gives me so much energy… It’s just supposed to lower my LDL cholesterol. But, I’ll take the energy boost!
@DeStrider my understanding is that GFJ and Ezetimibe alone are not contraindicated but most people on Ezetimibe also take a statin and some statins interact with GFJ. I think you are good if you are taking Ezetimibe alone or with one of the statins (like rosuvastatin) that are safe with GFJ
Ezetimibe and grapefruit juice are contraindicated and should not be taken together. A quick Google search will confirm this. As are some statins and grapefruit juice. I skip Ezetimibe on the days I take grapefruit juice.
“Ezetimibe therapy inhibited the absorption of omega-3 fatty acids. Patients receiving ezetimibe therapy may not receive the expected cardiovascular benefits from dietary supplementation with omega-3 fatty acids.“
@DeStrider i cannot find any information that says ezetimibe is affected by grapefruit. On the other hand I have found many grapefruit references to the combined Ezetimibe - statin medications.
The results of this in vitro assay indicate that ezetimibe is a measurable inhibitor of CYP3A4 (50% inhibitory concentration [[IC.sub.50]] = 7 [micro]mol/L) and CYP2C8 ([IC.sub.50] = 31 [micro]mol/L) activity in human liver microsomes.
in vivo, nor does it affect the pharmacokinetics of drugs known to be metabolised via CYP3A4
The drug also presents a complex impact on cytochrome P450 enzymes, as it is a metabolism-dependent inhibitor of CYP3A4. Ezetimibe does not demonstrate any clinically significant interactions with statins, fibrates, mipomersen sodium, levothyroxine or lopinavir.
Zetia isn’t known to interact with grapefruit or any other foods.
You were correct. The information I referenced was a combination of ezetimibe and Atorvastatin. It appears grapefruit juice is OK with only ezetimibe. Thanks for catching this!
On the other hand, I am now bummed that Ezetimibe cancels out the effects of my Omega 3 supplement.
So based on the research, I should probably stop taking Ezetimibe as the beneficial effects of lower LDL is cancelled out by the loss of benefits from Omega 3s. Well, that sucks. Thanks @Joseph_Lavelle for pointing this out. I guess I need to move on to bempedoic acid…
I am struggling with the Omega 3 vs. ezetimibe issue as well. Ezetemibe has a half-life of 22 hours, so alternating days won’t help much. For now I am stopping my eze for 3 days each week, and taking higher doses of Omega 3s on those non eze days. I will time the eze stoppage to not coincide with Rapa dosing which I take with a fatty meal. I’ll be very low fat/choles. on my non-eze days: no eggs, no oils, no animal meats.
I started taking rapamycin 10 weeks ago- 8mg Biocon Sirolimus every Friday with no negative side effects. I tested my rapamycin blood level two hours after taking on week 6 and week 8 (I buy the tests from Marek Health ($59)). My week six level was 17.1 and my week eight level was 10.6. I was a little disappointed with the 10.6- not sure why it decreased that day.
Last Friday morning (week 10) I took only 4mg, but with grapefruit juice (no other food/beverages consumed). I drank 3 ounces two hours before, three ounces 45 minutes before and another 4 ounces when I took the rapamycin. Two hours later, I once again went to Labcorp for the blood test. The results came the next day and showed a blood level of 31.9. Wow! I’ve had no negative side effects (now Sunday morning).
I have read (here on rapamycin.news) that the average GFJ multiplier is 3.5. Well, I got 8x.
The bad news is that there doesn’t seem to be any consensus about dosage. Is the 31.9 too high? Or is it best to get it as high as possible without getting bad side effects? Should I switch to every other week (14 days) and continue the 4mg with GFJ? What to do, what to do, what to do…
So far (after 10 weeks), the only thing I notice from my rapamycin intake is that a few of my grey hairs have turned black (I’ve been almost completely grey since age 30!). And, facial hair seems to be growing a little faster.
I’m going to do another rapamycin blood level test tomorrow morning (70 hours after my Friday dosage). And then again next Friday- looking for my trough. I’ll post those results, but not sure where (which topic) I should do it.
Details:
I am 68 y.o., 6’1" and 215 lbs.
I buy my rapamycin from Maulik at Vallabh Enterprise/Shreeji Impex @ 60 cents per mg.
I used Simply Grapefruit Juice (100% gf juice) that had been frozen for two months (4 oz in each of several ziplock bags). I had taken the gf juice in my second and third weeks (when I was titrating and only taking 2mg, but decided to stop the juice until I had blood tests after an 8mg dosage- I wanted to know my baseline.
@hitch I’m not sure how you are getting 8x? If you take rapa and get a blood level of say 10 and then you take the same dose several weeks later with GFJ and get a blood level of 30, that would be a 3x multiplier.
It’s possible I made up my own calculation based on dosage to rapa blood level? But, I did not take the same dose.
Most recent test with GFJ:
4 mg rapa with GFJ and my blood test level was 32 (31.9) - my calc says this is 8x (i.e. 32 / 4 = 8)
Previous test without GFJ:
8 mg rapa without GFJ and the sirolimus score was 10.6 – my calc would say that is about 1.3x
BTW- just want to point out again that Simply GFJ works great and it can be frozen (mine had been in the freezer for over two months). Much easier than using fresh grapefruit…
I use Simply too, agree it works great. I used 4+GFJ and got a level of 29, but like 1.5 hours later. It’s hard to catch a falling knife like that. I agree it’s probably not smart to check at the 2 hr. level because the value is changing so fast it’s not so useful.
You can’t do the calculation like you did there. I’ve said it before and it didn’t really soak in then either. You took a dose of Rapa. You checked the level in your blood as Rapa/unit volume. These are both numbers, but the units matter. If rapa is in mg, and the volume is in gallons, then the number would be different. They report it from the lab using standard units, but they’re meaningless for this purpose.
@hitch I was just trying to point out how the GFJ boost is calculated. For example 3.5 x means your blood value is 3.5 times the value without GFJ. So in order to calculate the boost you need to take the same dose twice, once without GFJ and measure the level 90 minutes later (Cmax). Then you let your blood levels from that dose dissipate to zero (usually about a week) and repeat the same dose under the same conditions but the only thing you change is GFJ 1-2 hours before taking the rapa. Again measure blood levels 90 minutes after taking rapa and divide that level by the blood level you got without GFJ to get the boost number. This is pretty reliably 3 to 4 x. You can’t predict or assume the “control” dose blood level, it needs to be part of your experiment because different people absorb and metabolize rapa differently. Some people take 4 mg and have a cmax of 4 ng/ml and some people take 4 mg and have a cmax of 10 ng/ml.
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