FWIW, I do TRF, so I only eat within a 4-6 hour window. I take my once a week 6mg dose of rapa on an empty stomach about an hour after waking up, so an 18-20 hour overnight fast. However, it’s preceded by my taking my daily empagliflozin dose, which I take within 5 minutes of waking up - get up, wash hands, do a fingertip glucose monitor test, take empagliflozin with water. Wait one hour. Take rapamycin. Wait 90 minutes. Drink one cup of fresh matcha tea. Wait an hour. Breakfast prep 30 minutes. Eat breakfast. So no food or caloric drink (sip of water with empagliflozin) 18-20 hours before taking rapa, then nothing for 90 minutes, drink matcha tea, and then breakfast 3 hours after the rapa dose. Very few supplements on the day of rapa, and day after - only vitamin D3, vit. K complex (K1, K2 mk-7, K2 mk-4), boron, magnesium, one 500mg EPA (day after). No taurine or any other supplements. Medication as usual - empagliflozin, pitavastatin, soon: bempedoic acid, ezetimibe, perhaps one day: telmisartan, pioglitazone. No exercise the day of, and day after, just walking. Approx. 50 hours after my dose of rapamycin, the level in my blood was 5.6 ng/mL - after 11 weeks of 6mg rapa a week.
I did a very simple ramp up to 6mg: week 1 - 3mg, week 2 - 4mg, week 3 - 5mg, week 4 - 6mg.
Currently on break fom rapa (due to recovery from dental surgery). I will resume with 6mg immediately.
The main reason your blood rapamycin levels differ so much is because you’re measuring it far too soon after dosing. At 2 hours post ingestion you’re going to be close to the sharp peak level and because the peak is so sharp, a small increase or decrease in the speed of absorption can make a huge difference in the level you get from the blood test. If you really want to test what effect it has on your rapamycin absorption to take it under different circumstances you have to measure rapamycin after at least 24 hours after dosing, when it has dropped down from the peak level. This has been mentioned in several other discussions on this forum.
Do you have any comments on the “dose” of grapefruit juice?
And I’ve just started taking Rapamycin (only 2-3mg per week), but I take it at night, after dinner, with a shot of EVOO. Then I don’t eat until dinner time the next day, so approximately 24h.
My theory is that the EVOO helps absorption, and by not eating anything for a while I am helping with mTOR inhibition and activating some autophagy. It seems a little counterproductive IMO to take Rapa alongside carbs (thus insulin, PI3K, AKT, mTOR) or protein (GTPases, mTOR) which will go ahead and try to activate it again.
The dose is very important. Some people may have little to no increase in absorption if they only take 200 ml of grapefruit juice so I would aim for 300-400 ml if you want a good increase in rapamycin absorption. Also note that while the average increase in absorption when taking grapefruit juice is about 3.5x, it can vary greatly between individuals. It can be anywhere from 0x to 8x increase depending on things like your genes.
That’s what Dr. Greger also emphasizes: GF and increased ACM. In general he’s extremely pro-fruits and vegetables, but makes an exception in the case of GF.
I used to eat quite a bit of GF, but have cut back substantially.
Its an epidemiologic study. Correlation doesn’t equate with causation.
Moreover, the participants were habitually consuming GF.
What if you are consuming GFJ once a week (for Rapa) plus if you are fasting and rest of the six days you are devouring berries, green tea and nuts!
Classic example, Framingham Heart Study in 1960s: coffee drinkers had higher incidence of CVD. It turned out coffee drinkers were also smokers. Smoking was the cause and not coffee.
I just discovered I need 8mg of rapa to have a level of 3.1 ng/ml at 50 hours. (It’s shocking!)
Now that I’m at 8 pills, I’m intrigued by the grapefruit or EVOO trick, but I have wondered if once you know your dose (x amount of evoo or gf juice) is it consistently accurate?
Because I’m petite, my main worry is if that trick could cause my levels to go up in an unpredictable way that winds up being too high during some weeks. Is this worry valid?
When I get the rest of my labs back, I’ll be running this question by my doc, but in the meantime…. ???
One can speculate, but without measuring there’s no way to know.
Regardless of the level, what matters is how a given level affects you. You can and should run some blood panels to see how your biomarkers are affected compared to optimal values. And how do you feel, what are the side effects, if any.
GF can affect the levels. But how consistent and repeatable is every dose from week to week?
I would try it out with GFJ and get your blood tested. That’s the only way to know for sure. I’m assuming 3.5X with GFJ and EVOO but I haven’t had it tested. I use my side effects to dial the dose up or down. I don’t see any real downside to being too low or too high as long as I am in the ballpark.
I just took 4 mg with GFJ and EVOO this morning for my weekly dose.
I imagine you don’t want to be on such a high dose that it’s still in your system by the time you take your next dose, so I’m surprised you only let side effects guide you.
Is there something I’m not understanding? (This is extremely likely!!)
That’s a great question. My guess is that it’s fairly consistent if you consume enough grapefruit juice. If you consume just barely enough grapefruit juice to increase the bioavailability then the bioavailability could vary quite a bit because maybe you drank x amount of grapefruit juice one week, then next week you drink again x amount, but maybe the juice you drank the second week is from a different batch of grapefruits, or is of different age or source. There are many variables that can influence how much of the compounds that improve bioavailability are in x amount of juice. Therefore, if you want more consistent effects it’s wise to drink a bit more than the minimum you would need.
This is the case because there is a threshold effect whereby x amount of grapefruit juice of a particular batch will lead to almost maximal increase in bioavailability. Consuming more than that will not increase the bioavailability significantly more. Lets say that for one batch of grapefruit juice the amount that leads to maximal inhibition for you is 200 ml. It would be good idea to consume 300 ml each time, instead. That would make sure you’re likely to still get close to full inhibition even if the juice you buy next time contains 50% less of the compounds that improve bioavailability.
One more important thing. Regarding the predictability. If you drink a high dose of grapefruit juice every time you take rapamycin the amount you absorb might actually be less variable and more easily comparable to that of other people. One of the main reason people get different levels of rapamycin after ingestion is that they have different amounts of the CYP enzymes in their digestive tract. But two people drinking a lot of grapefruit juice will both have much lower levels and therefore will likely have more similar bioavailability. So I think drinking grapefruit juice with rapamycin will tend to reduce the variability between individuals in absorption.
Consuming more than that will not increase the bioavailability significantly more
This is fascinating and very informative, thanks for the lesson! I had incorrectly assumed if, for example, 20 ounces of GF turned 1mg of rapa into an effective dose of 5mg, that 40 ounces would turn it into 10mg, and so on… that it would keep multiplying vs hitting a ceiling.
So, once I have to have 300ml of gf juice to make sure I get a fairly consistent dose from week to week, I guess at that point I might as well just have the 8 pills instead (because my rx from CVS is really cheap).
That makes sense. The average person that drinks grapefruit juice is not doing it purposely to increase the absorption of a specific drug while simultaneously being careful to not consume other things that are metabolized by the CYP3A4 enzymes. The average person is ingesting it habitually and is not likely to be aware of or be careful about things ingested around the grapefruit intake. I bet many people eating grapefruit are taking some drugs whose absorption is increased with the intake, while not realizing they may be getting a much higher dose of that drug than they are intending. To use grapefruit more safely you really have to look into how it effects things and which things it effects.
I tend to be fasting and halt my Taurine supplementation the day before and during the day of taking Rapamycin.
Another don’t is - don’t take it too frequently (allow sufficient time for previous dose to wash out). Most people go with 1x weekly dosing. I go with a higher dose, but 1x fortnight frequency.
Taurine is an MTOR activator and could possibly blunt the effects of both Rapamycin and Taurine, canceling each other out.
Yes, it’s also probably a good idea to get all of the Rapamycin out of your system by waiting a week or two for it to clear before your next dose. My dosing schedule is a hybrid. 2 weeks on and one week off of 4 mg + GFJ + EVOO. However, I may just do it every 2 weeks due to side effects. I’m constantly trying new routines. The problem is that my body is adapting and the side effects keep changing - the good and bad both.
I was under the impression rapamycin was so effective at suppressing mTOR that other things wouldn’t be able to touch it. I will try to remember to avoid taurine the day before and day of rapamycin dosing.
I just started last week so I’m unsure if I want to do weekly or fortnightly dosage. I am going to be taking it on an exercise rest day however, does this sound like a good idea?
I wonder if I could do a naringin supplement with rapamycin to increase potency? I’m looking at a study, it isn’t as effective as GFJ, but it still has an effect and is easier to keep on hand than grapefruit.
You are probably correct. So don’t waste your taurine. I think there was one study that showed taurine reduced the effectiveness of Rapamycin a bit.
Rapamycin can affect taurine:
Rapamycin may also affect taurine transport and release, although the specific mechanisms and effects are still being investigated, according to the American Physiological Society Journal.