Rapamycin Dosing Day - Dos and Don'ts

Hi all, Im hoping to tap the crowd wisdom on dos and don’ts for Rapamycin dosing day.

Is there anything you avoid (supplements, foods, timing) or specifically do on the day you take rapamycin?

I avoid all other supplements on dosing day, out of cautious ignorance. And I try to avoid sugar.

Any insights welcome

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This may be controversial, but I usually fast on dosing day. Mostly to avoid the potential complication of elevated glucose, but hopefully the diminished calorie intake provides a little additional downward pressure on mTOR activation.

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If you use search function here you will find extensive discussion and collective insights of the discussants on do’s/dont’s along with their reasonings.
However, I do pair my dosing with 24 hour fast for the same reason. I do cycle.
I dont take taurine, lysine and glycine as discussed elsewhere.
I will do serum insulin, IGF and lipids levels since Institutwd new protocol.

If you take grapefruit juice 1-4 hours before you take Rapamycin, it will increase the dosage by 3X. Some people, like myself, like this as I need fewer pills. Some others may not like this.

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Do pair it with a blood sugar lowering intervention such as metformin, berberine, acarbose, or sglt2i.

Do pair it with an LDL lowering intervention such as berberine, black cumin seeds, flax seeds, or statin.

Do know that pairing it with a CYP3A4 inhibitor such as grapefruit juice, pepper, or berberine will increase the absorption and effective dose. Taking it with fats will also do so.

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Don’t take it if you are sick or at risk of bacterial infection

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I take Rapamycin on a totally empty stomach first thing in the morning with water. I don’t have anything else (drinks, food, supplements, medicine) for 1 hours after the dose.

I’ve done the sirolimus blood test several times after taking the rapa dose. Usually 2 hours post ingestion and have found that many things can interfere with absorption. Taking the same 7 mg of rapamycin, I’ve had results from 0.9 ng/ml to 20 ng/ml. The difference being (drinks, food, supplements, medicine) before or with rapamycin vs on an empty stomach. I haven’t bothered to identify exactly what blocks the absorption but something with the (drinks, food, supplements, medicine) totally kills absorption.

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I believe that concurrent administration of curcumin especially in highly bioavailable form like theracurmin can potentiate effect of m-tor inhibition. Which can be a desired or an undesired effect, depending on the approach.

I don’t think it’s necessary to stop ALL supplements, I don’t see how your Vitamin B complex or hyaluronic acid would affect the rapamycin intake.

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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.

YMMV.

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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.

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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.

EVOO increases the dose by 50%. GFJ increases it by 300%.

I eat two fresh whole grapefruits before taking Rapamycin. I like it better than just the juice.

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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.

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Grapefruit is associated with increase in all-cause mortality:

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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.

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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.

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@Olafurpall, @relaxedmeatball, @DeStrider, @CronosTempi, I’m glad you are discussing this topic.

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…. ???

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  1. One can speculate, but without measuring there’s no way to know.

  2. 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.

  3. GF can affect the levels. But how consistent and repeatable is every dose from week to week?

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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.