Not all grapefruit juice is the same for the purpose of Sirolimus enchancment

Yes - I like the standardized dosing as you mention. Do we have any idea on the actual effect on blood sirolimus levels? Have you done any testing after dosing?

2 Likes

I have no clue, I have the desire to learn, but lack the motivation to actually follow through. :grinning:

2 Likes

I read somewhere that white GFJ is preferable (in terms of efficacy) to ruby red. Has anyone heard this?

1 Like

Yes, I looked up the Florida citrus report, and the white more bitter Grapefruit has more of the essential flavonoids

2 Likes

I’m not sure - here is one study suggesting similar outcomes with both:

and another article/paper:

4 Likes

Interesting, white grapefruit is yucky anyway

2 Likes

Yep. I get 6xs to 7xs increase of my rapamycin dose on Red Grapefruit. Goes down smooth-ish.

4 Likes

Red/pink or yellow - Duncan (yellow) apparently has the highest levels of most of the four furocoumarins .
Variation of bioactive furocoumarins and flavonoids in different varieties of grapefruits and pummelo | SpringerLink

Full Paper / PDF Below:

s00217-007-0654-4.pdf (483.1 KB)

4 Likes

Forget that grapefruit juice deal - crap ! Do ketoconazole instead as it is more effective and u know what u are getting.

1 Like

Why keep on promoting something that is much more dangerous than grapefruit juice?
“Ketoconazole may cause liver damage, sometimes serious enough to require liver transplantation or to cause death. Liver damage may occur in people who do not already have liver disease or any other conditions that increase the risk that they will develop liver damage.”
Ketoconazole: MedlinePlus Drug Information.

4 Likes

I pointed out previously that grapefruits being a natural product, they will vary in their content of these natural products by variety, season, and weather.

2 Likes

This is notable. AFAIK, grapefruit inhibits CYP3A4 but is not known to inhibit P-glycoprotein. And:

Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.
https://www.pfizermedicalinformation.com/en-us/rapamune/drug-interactions

AFINITOR® (everolimus)
CYP3A4 and/or PgP inhibitors: Avoid the use of strong CYP3A4 inhibitors. If patients require co-administration of a moderate CYP3A4/PgP inhibitor, reduce the AFINITOR dose to 2.5 mg daily. An AFINITOR dose increase from 2.5 mg to 5 mg may be considered based on patient tolerance. Resume dose administered prior to inhibitor initiation, once the inhibitor is discontinued for 3 days
Dosing & Administration - AFINITOR® for Renal Angiomyolipoma

So quercetin would be expected to have a dual mechanism of increasing cellular levels of rapalog, both by inhibiting degradation by CYP3A4 and inhibiting efflux by P-gP.

4 Likes

The full paper of this study is available:

. For the sirolimus plus grapefruit juice study, sirolimus was administered alone in week 1 and with grapefruit juice starting in week 2, one day before sirolimus. Grapefruit juice (supplied by Florida Department of Citrus), 240 cc, was administered once daily without interruption. This dosing was based on research showing that the half-life of intestinal enzyme inhibition of grapefruit juice is 12 hours ([21](javascript:;)), thus providing time for modulation before sirolimus dosing.

Very useful, though I wish they had tested it with lower doses. It seems like there is a possible plateauing of the effect, where at higher rapa doses the relative increase of rapa absorption is attenuated.

I’m sure they were not using some special, organic, high-furanocoumarin variety harvested by pixies and airlifted to Chicago. There is certainly variation in furanocoumarin content from one variety, crop year, and farm to another, but it’s never zero. In a paper on variability of grapefruit furocoumarin content I’ve linked before,

4 Likes

:laughing: I couldn’t find that in the store so I just bought the same bottle Agetron had posted a picture of in one of his threads. Since he looks younger than my 50 y/o husband I figured it must work!

2 Likes

Yes… the brand Simply Grapefruit (which is red grapefruit) even though it is pasteurized has as strong a multiplying effect… as fresh red grapefruit from my Labcorp tests. It works!


Taken yesterday… lol… thanks!

4 Likes

Thats good to know. But I’ve found it best to just buy the fruit and put it in my refrigerator. The problem with these big containers of grapefruit juice is that you really only use a few cups of the stuff dosing once per week - so it tends to go bad before I use it all.

Easier just to buy a grapefruit or two that you will use over a week or two, and just eat the full grapefruit (or two) before dosing.

3 Likes

If only I could get my husband to cut a grapefruit and eat it….Unless I’m off work to do it for him it isn’t going to happen unfortunately.

2 Likes

My results from taking rapamycin with and without ruby red grapefruit juice suggest it’s doing some multiplication.
It takes ~ 20mg with EVOO to produce diarrhea and ~8mg with EVOO+ruby red grapefruit juice to produce diarrhea.
I use the Florida Ruby Red Grapefruit juice because I like it, not because it is the best, and I don’t like raw grapefruit.

3 Likes

Agreed RapAdmin… I like the fresh red grapefruit… just did my Labcorp trough a few hours ago… and 2mg and 1 fresh red grapefruit.

Will have my results to share on blood panel… and Labcorp results. Also, I sent in a new GlycanAge test this morning too.

I have been on 12 ng/mL Rapamycin for 4 months… curious to see what this dose is doing. Blood and biological age. More soon.

4 Likes

I am among the ruby red whole-fruit crowd, because I believe whole fruit is more potent, no matter how you slice it (heh.) I nibble the rind as well. Organic, you betcha.

Also, to even out possible variation between one fruit and the next, I take two, divide them in halves, swap halves, consume one the night before, and the other the next morning an hour before the rapa dose. Seems to be working well.

4 Likes