@McAlister Great thought-out reply. Thanks for your informative response and glad to have you here!
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Thanks for this. I did see some of those articles in my amateur digging. One thing I learned is there are two types of inhibition: there’s inhibition of the initial production of the enzyme (I forget the term) and this is what grapefruit juice does. One paper btw showed that the maximum inhibition effect peaked about ten hours later. Something to experiment with, drinking GFJ earlier in the day before taking Rapa in the afternoon (the curve was gradual, suggesting precision in timing wouldn’t be important)
The other inhibition effect was termed “mechanical” and this was an immediate inhibition or blocking of the enzyme already present. Ginko was one substance that did this for CYP3A4 - there were several. So taking one of these “mechanical” inhibitors WITH the Rapa dose might also amplify the effect. If that’s what’s wanted of course.
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Yes - I’ve seen people who take rapamycin and GFJ take the GFJ the night before, (or eat the fruit) then again an hour or two before taking the rapamycin. I’ve not seen any blood/sirolimus testes comparing these approaches though.
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Hello everyone,
I’ve been taking rapamycin at a dose of 6mg/week and wanted to inquire about any potential interactions or side effects when combining it with the following supplements:
Fish oil
Magnesium
Vitamin D
Creatine
Collagen
Acarbose
Betaine
Additionally, I occasionally take the following supplements but avoid them 1-2 days before and after taking rapamycin:
Spermidine
Quercetin (CYP3a4???)
Sulphoraphane
Bergamotte
Red rice monacoline-k
Metformin
Psyllium husk
For context, I typically consume all the supplements together in the morning, with the exception of acarbose and psyllium husk, which I take with meals.
Has anyone here experienced any side effects or interactions when combining rapamycin with any of the above supplements or drugs? I’d greatly appreciate any insights or experiences you can share.
I gather its better to take it with food than without.
Thank you in advance!
Thats a big list… the only obvious issue I see is this one.
You do have to watch Quercetin for sure:
Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A .
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With regard to ginger, which I tend to partake in quite often, is there any scientific data to substantiate the intake of ginger and its associative effect on the efficacy of Rapamycin?
Thanks!
It seems that there is moderate inhibition of the CYP3A4 enzymes, so a moderate effect on increasing bioavailability of rapamycin (ie. increasing the effective dose). What exactly that translates to in terms of multiplier effect I don’t know.
You can just search on “Ginger CYP3A4 inhibition” to learn more.
All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4
Source: Pungent ginger components modulates human cytochrome P450 enzymes in vitro - PMC
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I appreciate the response and additional resource suggestions. I will dig a little deeper and see what I can glean. All in all, not a big deal as I can refrain a bit before and after taking my weekly Rapa dose.
Thank you!
Jeff
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Happy Holidays - I want to point out that there is more concern than interactions with certain supplements. Natural mTOR inhibitors such as Curcumin and LEF’s autophagy renew (mentioned earlier) - while excellent supplements - should not be used while on Rapamycin. The reason being that you can suppress mTOR TOO MUCH. I quote from Ross Peltons recent book " Rapamycin The Most Promising Life Extension Drug" page 94 - “Various other compounds and lifestyle factors are classified as Mtor inhibitors. Too much of a good thing can result in bad outcomes. Let’s imagine an individual who is taking 6mg of Rapamycin weekly. If this individual decides to take metformin, engage in intermittent fasting and strength training and take one or more of the nutritional mTOR inhibitors, one could begin to develop side effects such as excessive loss of body fat, muscle, and bone density. The bottom line is to avoid overusing and excessively inhibiting mTor.”
My thoughts are - which of us biohacking types don’t do and take all of those things?? I’d like to see a comprehensive review/list of mTor blocking supplements that we should likely avoid as well as a list of redundant supplements that we can toss because we are on rapa once a week because they are now unnecessary. I doubt is of extra benefit to keep taking 30+ supplements while on rapa.
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I am not sure there is solid research in interactions that you can use to guide what you do with that much precision. I tend to think careful experimentation is the order of the day.
Keeping a lot of notes is important. (notes as to what you take and what the outcomes are).
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I disagree, because I think these natural mTOR inhibitors do not cause significant mTOR inhibition in vivo. Pretty much the only things that really effect mTOR aside from rapamycin are fasting and calorie restriction.
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Thank you for responding! I love curcumin for all of its other benefits so this in vivo study information is very good and important to know. I will resume tsking it.
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Agreed. Polypharmacy There’s lots of reasons to be cautious about taking 30 supplements all the time regardless of rapamycin. I now limit myself to 10 chemicals (meds or OTC meds) per week. I don’t count dried, ground up food powders (protein powders, spices/herbs actually added to food, etc). And I enforce a chemical fast every weekend (no supplements).
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Having just started rapamycin, I am also concerned about statin interactions. Looking at specific statins, however, it does appear that there is some interaction.
I’m currently taking 10mg of atorvastatin, which is listed as a moderate interaction with rapamycin due to P-glycoprotein inhibition and suppression of MDR efflux.
From what I’ve read, it seems that p-glycoprotein transporters are predominantly in certain tissue like the liver, intestine, kidneys, and BBB. So, I’m wondering if this interaction would be akin to increasing rapamycin levels using CYP3A4 inhibitors, but only in these organs?
I’m assuming it would just be simpler to switch to a different statin? I’m titrating up slowly and starting at 1mg of rapamycin, so I’m not overly concerned. But, I’m still curious on thoughts or if anyone else has been on this combination.
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I believe Rosuvastatin has the least interaction with grapefruit juice and Rapamycin. You could try that. Or switch to Bempedoic acid.
Unless you have only just started on Atorvastatin in the last few months I really wouldn’t worry on that dose. The maximum dose for Atorvastatin is 80mg. You would probably notice if your kidneys are having any trouble because your urine will darken.
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Another reason to consider a different statin is that Atorvastatin is fat soluble so it will have greater access to inhibiting cholesterol synthesis in the brain. A common viewpoint given the research on the relationship of ApoE alleles and Alzheimer’s is that you don’t want to limit Cholesterol synthesis in the brain and you want to maximize your inhibition of cholesterol synthesis in the periphery for the cardiovascular benefit. So ideally, if you have concerns about Alzheimer’s or know your ApoE allele status you should choose a statin that is water soluble so that it will have minimal impact on brain cholesterol synthesis. Rosuvastatin is probably best.
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No it doesn’t matter, and atorvastatin is considered the superior statin because of fewer side effects like diabetes. Two large trials are actually investigating if atorvastatin can reduce risk of dementia right now, too.
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Atorvastatin is safer for those at risk of diabetes.
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What does ‘at risk of diabetes’ mean and who does it include - and how do you know if those that got diabetes in the LODESTAR trial from rosuvastatin compared to atorvastatin is because of this?