Grapefruit interaction with longevity meds?

I was just about to augment my fasting mimicking diet with canagliflozin, rapamycin + grapefruit, and acarbose. And then I realized that grapefruit might be interacting with the other two as well. I couldn’t tell definitively by googling about whether they interact or not, even though it seems like it shouldn’t be a problem.

So I wonder what you think (?) Do you know which other commonly used meds in longevity protocols that it interacts with?

I think Statins (at least some of them) are probably the most popular medication you have to be careful about using with GFJ:

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Epocrates is a free app that gives info on drug interactions. Since grapefruit isn’t a drug per se, you can look at a drug’s “pharmacology” section and see if it’s metabolized by CYP 450 3A4, as per the listing for atorvastatin:

It the drug is metabolized by this enzyme, it’s safe to assume its absorption will be increased by GF, potentially to a very unsafe extent in the case of atorvastatin.

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I read that 6mg rapamycin + grapefruit equivalent to pure 20 mg rapamycin, due to 350% bioavailability.
when we calculate rapamycin half live, should we use 20mg or 6 mg as the starting point?

Davin8r, there are actually no 20 mg worth of rapamycin molecules around, the maximum amount of rapa in your body is only 6 mg.

You only absorb a fraction of the 6mg dose. If you absorb 350% of that, it’s the equivalent of taking a 20mg dose.

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let’s do the calculation: if you take 20 1mg pills, 20mgx27%=5.4mg absorbed. Using drug half life calculator, after 7.5 days, only 0.68 mg left in the body. But if you don’t consider bioavailability, it would be 2.5 mg left. which one is right?

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Oh, I see what you’re asking. It only makes sense if those half life calculators are based on the drug concentration in circulation (post-absorption). Otherwise you’d have the large variability in drug absorption as a huge confounding variable in half life calculations.

So, my earlier answer was incorrect (post deleted!). Half-life calc should start at 5.4 mg if that’s the amount theoretically absorbed in your example. Hopefully one of our local pharmacists or pharmacologists will chime in on this if I’m missing something.

thanks, in conclusion, to save on the expense of Rapamycin and to achieve 20 mg/biweekly like others do, we can take 6mg with grapefruit juice. After five half lives (12.5day), only 0.19 mg remains in the body.

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quote from a post in LongeCity
“The whole point of using intermittent rapamycin dosing is to get a high Maximum to knock down mTORC1, but a nice low Minimum to avoid knocking down mTORC2. So, for example my dose of 2mg a week assuming a 65 hour half life gives you a Maximum (after repeated dosing) of 2.4mg and a Minimum of 0.4mg. Alan Green takes 6mg a week, so that gives you a Maximum of 7.2mg and a Minimum of 1.2mg. Grapefruit juice will not improve the Maximum, but will raise the Minimum by some unknown amount, increasing the chance of side effects.”

Can someone explain how he got the Maximum and Minimum of 2.4mg and 0.4 mg?

I can only assume he’s talking about blood levels of rapamycin but using the wrong units (which should be in ng/mL or similar units, not mg). I don’t know the typical peak levels after weekly dosing (planning to get my peak tested this Tuesday after 6mg dose).

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Have been taking all 3 of these drugs for longevity, glucose control, and to get lower inflammation in my body for 6 months now without any problems. I also checked for interactions and found none except for statins. I take 5 mg. Crestor and just skipped that dose for a day when taking rapa with GFJ. I would suggest you weigh your GF juice and pulp before taking so you can be more consistent in how much of the CYP3A4 your getting. I personally take 400 grams. 200 grams night before, and 200 grams 30 min., before rapa next morning. Been on Rapa for almost 5 years. As we learn more we can add additional interventions to slow down ageing. In my opinion, 90%+ of most studies will not actually extend life. Wait for proof, before adopting.

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You are way behind. Dr Green takes 20 mg every 14 days, and has for 3 months. Cancer patients have been using GFJ for many years in order to control costs on there Sirolimus. Why try to reinvent the wheel, the science is solid, just follow. We all know that only a fraction of dose is taken up in the body, so what that fraction works.

Dr Green has changed to 12 mg per week

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Did he give the reason why he changed back to 12mg per week?

Thanks all for the responses! Btw, do any of you have an idea of the minimum amount of grapefruit juice or grapefruit approximately needed for 3x bioavailability? I always feel uncomfortable breaking my keto or FMD with a bunch of fructose just for this purpose.

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You save a lot of money if you take 6 mg with grapefruit juice, it is equivalent to taking regular 20 mg pills. Cancer patients take up to 45 mg twice per week, beyond that, they get gastrointestinal side effects.

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i read you should take 8 ounces of white grapefruit juice, not pink colored one.

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Blagosklonny indicated a 8 ounce glass as the amount:

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Wouldn’t the enzyme be present no matter which color grapefruit juice one uses?