#103

I was seeking for specific compounds in Grapefruits to build a mixture to inhibit Cytochrom P450 3A4. But in short, its really complicated - Grapefruit is best.

“The available evidence indicates that, at commonly recommended doses, other selected herbs including Echinacea, Ginkgo biloba, garlic, goldenseal and milk thistle do not act as potent or moderate inhibitors or inducers of CYP enzymes.”
There are some effects, but in my opinion, not what we are looking for.

Here is an interessting study about the Coumarins found in various citrus fruits. After reading this, I thought my Citrus hystrix could be a good candidate for inhibiting CYP3A4. But in short: no.

findings: Naringin and 6’,7’-dihydroxybergamottin are not the major active ingredients.
Naringin itselfs is absolutly useless besides you want to sanitise something or maybe if you want to cure mouth sore.

they found out that Grapefruits have more Coumarins with fancy Furan-rings.

the newest one, seems like Grapefruit is the anwser: its the specific combination found in Grapefruits that inhibits CYP3A4.
If anyone is interessted in adulderating a mixture, this is what you are looking for.

Compounds are:

And even if it was in vitro:

is intressting to know. Search for: salvage pathway.

I am wondering if NMN, a nicotinamid derivate with 3 phosphate groups, could increase this process. But the salvage pathway isn’t about my intestinals and I am not a petri dish.

So I decided not to worry about it. I just keep calm and eat grapefruits.

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Introduction // Ritonavir for rapamycin-boosting
#104

Just to be complete I forgotten to write the real reason I dont want to brew a potion by myself:
See wikipedia, Phototoxicity

The effect caused by furanocoumarins found in varios plants including giant hogweed, st. johns wort, citrus fruits and so on. I dont have the equipment to mix a nontoxic dose.
My first thought to mix a herbal essence is not a good alternative: goats can get a phototoxic burn just by eating to much jt. johns wort. But it might be possible.
If you still want to, the phenol explorer could be an interessting tool to search for polyphenols in various plants. But it has barley a complete listing of polyphenols.

1 Like
#105

Greetings, Some blood testing and absorbtion experiments to report. Good news!

Back ground; I can’t swallow pills even the small sirolimus pills, so I grind everything in a bullet grinder with water. I have blood tested for actual sirolimus blood levels about 6 times now. The test is only $99 via LEF.org, have to call customer support and ask for the blood dept THEN tell you want a sirolimus blood test and for some reason, still, they put me on hold to figure out how to sell you that test. I buy 2 at a time or more. They take your CC over the phone… I strongly suggest for those who can actually buy this test and have labcorp draw location near by that you actually test. Rapa is expensive enough to know for sure you aren’t wasting it.

The rapa I have in the freezer: 30x10mg doses of Sirolimus (sirokem buy kachhela (Indian), 20x10mg doses Sirolinmus (rapacan by Biocon (Indian), 3 grams of Chinese rapa 99% powder cut down per helps here which equates to 300x10mg doses (Chinese Whuhan labs ?? found on this site).

All of the above was bought last year and year before and stored in the freezer. So some suppliers may not be findable today. I tried to find the Chinese Whuhan source on the alababa or some other company specific site and it seems they where forced off the internet… I forgot my ave cost per 1mg. What ever it was in 2020/21.

Should I stick to 14 day periods and dose size to arrive at a desired blood level (see below) and IF that does is 10mg of 1mg pills + 6mg of chinse cut down powder (to use all sources up in parallel as a strategy) then I have 50 doses at 2 weeks or approx 2 years and then I’ll have 250 doses of powder left (in theory).

Important question: What blood level is considered that target for anti-aging pulsed dosing?? Yes I agree the target will vary per the periodicity; 7 days, 14 days, etc etc.

My testing results history and how I dosed, ending on a success (IMO but TBD). If I hadn’t blood tested I would have never known I was wasting rapa!

Early dosing: 20mg 1mg pills CO-TAKEN with freeze dried GF powder blended in water. 2 days running then on the 3rd day blood test. This resulted in poor blood levels;

Early dosing; every 14 days; 2 day dosing; 10mg taken at the same time with 1t of freeze dried GF juice (spoiler; this didn’t work). Tested blood level; 2.2ng/ml sirolimus level (low)

Most recent dosing experiement results: every 14 days; 1 day dose steps:
(all the compounds mentioned above that suppress (??) enzyme (??) to allow higher absorbtion:

  • 1g berberine, 1g Fiesitin, 1g quercetin, 1/2 can frozen GF concentrate.
  • wait 2 hrs
  • 10mg sirolimus/rapa; put into a blender, drank with water. I can’t swallow pills.
  • wait 4 hrs+/- get blood tested
  • blood results: 23.1ng/ml (labcorp says this is high; 3.0-20.0 range). SUCCESS

OK OK success. I’ve figured (for me) how to get my rapa into my blood in a reproducable protocol.

BURNING QUESTION: now what?? What blood level should I be targeting?

  • Note; the above 2hr prior dose to increase absorbtkon is 90% of the senolytic mix. So I just add Dasinitib (100mg +/-) to the initial dose to double up senolytic with the rapa dose since there’s 90% overlap. I was trying to alternate weeks rapa week then senolytic week alternating and it was driving me crazy. Now blood testing finds value in doubling up senolytics WITH rapa absorbtion at the same time.

Fair questioons; does dasinitib thwart the function of rapa? No idea. Too much DIY here at present.

Thanks 5000% to this group and the sharing of fantastic helps! Best wishes to all.

7 Likes
#106

Correction; I said I take 10mg above, but its actually 10x1mg rapa (Indian) plus 6mg of chinese titrated down powder. I mix the 2 just to be using both sources of rapa up approx in parallel. So 16mg dose with the above pre-dosing 2hr prior results for me in 23ng/ml blood level.

Best to all, curt

2 Likes
#107

Would taking rapa with a tablespoon of olive oil after my morning banana oatmeal breakfast qualify as improving bioavailability ?

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#108

Just an observation. I have been taking Rapamycin for approximately 3 months and have been wearing a cgm the entire time. First month 3mg weekly, no noticeable physiological effects. Second month alternated between 6mg and 9mg weekly with again no noticeable effect. Last Saturday I took 6mg with two capsules of turmeric that contained piperine. Sunday my fasting glucose which typically hovers around 100 mg/dl was 140’s and has been elevated ever since. I am aware of the cyp interaction of piperine but has anyone else experienced this dramatic of a change in blood glucose from just adding piperine to their Rapa?

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#109

Yes. Olive oil is high in fat, and high fat meals increase the bioavailability of Rapamycin.

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#110

Odd as turmeric is supposed to reduce bioavailability of Rapamycin.

#111

Odd, I agree. I have also read about curcumin activating cyp3a4 enzymes. I was curious if anyone has had this experience with piperine as that is mixed with the curcumin to inhibit cyp3a4. I have previously drank GFJ 20oz with the Rapa and did not notice prolonged elevation in glucose. As of today my average glucose has trended down to the upper 120s but still 20% higher then my base line. Again just an interesting observation.

#112

Are you sure there is no other changes that you have made to your diet that could affect this? It seems a little too dramatic of a change to be caused by piperine.

#113

Thanks for the reply. My point exactly, strange, which is why I was wondering if anyone else has seen an effect like this. And no there has not been any dramatic change in any supplements, exercise or food.

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#114

unsure! in the related study above it was a high fat meal with 840kcal. There are more factors than a wee bit fat. Dont rely to much on it.

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#116

Thanks! And yes, this explains why my use of the juice of one fresh Red Grapefruit to down my rapamycin dose multiples my ng/mL up to 5-6 times not the 3 - 3.5 as often stated.

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#119

No, there are lots if GI effects of high dose rapamycin. You may have read about people getting diarrhea as they ramped up dosing. In the cancer studies with high dose rapamycin they found better side effect profiles for Rapamycin plus gfj than equivalent dose of rapamycin alone.

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#121

Nobody has yet done high dose weekly rapamycin in healthy humans, so we don’t know.

Here is that study on high dose rapamycin for cancer, with the side effect comparison:

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#122

Did you ever ferment the Grape fruit juice with the help of a kombucha mushroom or a water kefir? I also don’t want to drink the fructose, so why not letting other microorganisms eat it first?

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#123

Sweet, good to know. Thanks!

1 Like
#124

I nearly never have milk products and I really never combine them with supplements. Milk binds polyphenols and according to ChatGPT, it also decreases the bioavailibility of rapamycin.

Milk decreases polyphenol bioavailability.

Does milk decrease the bioavailibility of polyphenols

Yes, consuming milk with polyphenol-rich foods or beverages can decrease the bioavailability of polyphenols.

Polyphenols are a group of plant compounds that are known for their antioxidant and anti-inflammatory properties. They are found in many foods, including fruits, vegetables, tea, coffee, and red wine.

Milk contains proteins called caseins, which can bind to polyphenols and form complexes that are not easily absorbed in the body. This reduces the bioavailability of polyphenols, which means that less of them are available for the body to use.

Several studies have shown that consuming milk with polyphenol-rich foods or beverages can decrease the absorption and availability of polyphenols. For example, a study published in the Journal of Agricultural and Food Chemistry found that adding milk to black tea reduced the bioavailability of tea polyphenols by up to 64%.

Therefore, if you want to maximize the health benefits of polyphenols, it’s best to consume them without milk. Instead, you can try drinking black tea or coffee without milk, or adding polyphenol-rich foods like berries, dark chocolate, or nuts to your diet.

Does milk decrease the bioavailibility of rapamycin

There is limited research on whether milk affects the bioavailability of rapamycin, but some studies suggest that it may decrease the absorption of the drug.

Rapamycin is a drug that is commonly used to prevent organ rejection after transplant surgery, and it also has potential uses in treating certain cancers, autoimmune diseases, and aging-related conditions.

Milk contains calcium and other minerals that can form insoluble complexes with rapamycin in the stomach and intestines, which may reduce its absorption and bioavailability. In addition, milk also contains proteins that can bind to rapamycin and reduce its absorption.

One study published in the Journal of Pharmaceutical Sciences found that the presence of calcium in milk decreased the absorption of rapamycin by up to 50% in rats. Another study published in the International Journal of Clinical Pharmacology and Therapeutics found that consuming milk with a single dose of rapamycin in healthy volunteers decreased the drug’s bioavailability by approximately 30%.

Therefore, it is recommended that rapamycin should be taken on an empty stomach, at least one hour before or two hours after a meal, and should not be taken with milk or other dairy products. This will help to ensure optimal absorption and effectiveness of the drug. However, it is important to consult with a healthcare provider before making any changes to your medication regimen.

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#125

I wouldn’t trust ChatGPT on this kind of stuff yet… I’ve played with it and when I try to get it to tell me the exact papers that its referencing in “studies”, they don’t exist. ChatGPT makes shit up all the time.

Plus, its likely complex. High fat milk might increase the bioavailability of rapamycin due to the fat content…

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#126

I’m still trying to arrange a blood test for Rapamycin from Life Extension but they don’t know anything about the blood test, lab Cor does it but they need an order for it , any help would be appreciated
Thank you