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Probably snorting Fisetin would improve its bioavailabilty, but it would take a lot of such snorts to reach the level needed for senolytics. Let's say (as a guess) that putting Fisetin powder in contact with the rich blood vessel network back in the nose would increase bioavilability by a factor of 5. Still, to get to the equivalent of swallowing 2 g of Fisetin powder, you would need to snort about 400 mg, which is a lot. However, if snorting is your thing, give it a try. It should be safe (except for all the yellow snot).
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I get great results from oral fisetin and so do many others in this group. You are trying to solve a problem that doesnt exist.
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Fred Cloud I don't understand how you're getting ANY results by taking fisetin orally, since it's well known that stomach acids and the GI tract in general prevent fisetin from entering the bloodstream.
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Robert Uomini
Flavenoids like Fisetin have a very low solubility in water and are disassembled by enzymes in the digestive system. This makes for a low (but NOT zero) bioavailability. That's why for senolytics one takes a few grams of them instead of a few milligrams. The bioavailability of flavenoids (Fisetin, Quercetin, Curcumin, ...) taken orally is thought to be increased by taking 10 mg of BioPerine (a form of Piperine) an hour in advance of the flavenoid. Piperine is known to suppress the production of P-glycoprotein, a protein that the body uses to break down exogenous compounds found in the body and that leads to short half-lives for flavenoids in the blood stream.
Also, I note that Life Extension sells BioFisetin, a form of the flavenoid that is coated to reduce digestion. This is claimed to increase Fisetin's bioavailability by x25. The last time we did senolytic sessions, we took BioPerine and 80 mg of BioFisetin instead of 2 g of Fisetin powder.
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JGC I take 500 mg per day of fisetin. Since the stuff is so expensive here in France (I pay 84 euros for 60 250 mg capsules), taking more than that would cause me to use up my one-month supply in a hurry.
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JGC I had researched the bioavailability of fisetin when used with Piperine, but I found nothing, although I did see that bioavailability of certain other flavenoids, especially curcumin, was increased. Do you know of any peer-reviewed articles that support the improved bioavailability of fisetin using Piperine?
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Robert Uomini
Do you mean that you take 500 mg of Fisetin every day? Senolytics with Fisetin is supposed to be done in 3-day burst doses of a few grams about every 3-6 months. That way, it works better and is less expensive.
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JGC Where does your protocol come from? Mine comes from a mouse study that, when scaled up to human weight, calls for 500 mg per day for a month.
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Robert Uomini
Our routine is based on the work of the Kirkwood Group at the Mayo Clinic, with the BioPerine added.
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JGC I'm using the same study and converted the 100mg/kg dosage for mice to a human dosage of 8.13 mg per kg of weight.
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Robert Uomini
I meant "Kirkland". Have a look at the interview that Dr. James Kirkland did for the Foresight Institute at this LINK. He discusses the virtue of "burst" doses of D+Q and/or Fisetin rather than daily doses and discusses the mechanism behind the senolytic action.
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JGC Thanks a lot for the link. I just watched the first 42 minutes and plan to continue to the Q&A later today, but I did notice that Kirkland mentioned that he advises us "amateurs" (not his word) to not experiment with senolytics because, in the past, trials that worked fine on animals turned out to be disastrous for humans. Makes one give pause.
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I had researched the bioavailability of fisetin when used with Piperine, but I found nothing, although I did see that bioavailability of certain other flavenoids, especially curcumin, was increased. Do you know of any peer-reviewed articles that support the improved bioavailability of fisetin using Piperine?
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Robert Uomini
No. My assumption is that all flavenoids are chemically similar and react in about the same way to digestive enzymes. Therefore, if taking Piperine enhances the bioavailability of Curcumin by suppressing the production of P-glycoprotein, it should do so for Fisetin and Quercetin also.
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My capsules of Fisetin 100mg are filled with up to 500mg of material. So if you are snorting fisetin, you are also snorting 3 or 4 times as much filler material. You should probably not do that...
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Dan Nave In fact, i never did start snorting the stuff. I did, however, recently start taking it as a suppository. My capsules are 250 mg each, 98 per cent fisetin, so I'm taking two per day.
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