How to increase the bioavailability of Fisetin

I'm preparing to do a Fisetin senolytic experiment, but I've read on the article from Mayo Clinic ( https://linkinghub.elsevier.com/retrieve/pii/S2352396418303736 ) that the administration mode was done through a mix of phosal and other stuff :

100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol

So the bioavailability of the Fisetin should be a key step for the treatment. I am looking for some information on how to increase the Fisetin bioavailability. Does anyone know of some methods to do this ?

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    • JGC
    • Retired Professor of Physics
    • JGC
    • 5 yrs ago
    • Reported - view

    It is claimed that taking 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids and other supplements, along with a dose of Fisetin will greatly increase its bio-availability.  In our last session of taking a massive dose (5 g) of Fisetin, my wife and I took 10 mg of BioPerine with each of ten 500 mg doses of Fisetin.   This did seem to produce some magnifying effect, because I experienced a mild side effect (vertigo) that I had not experienced with a previous large Fisetin dose.

    Like 3
      • Iðunn
      • Iunn
      • 5 yrs ago
      • Reported - view

      JGC Bioperine certainly increases the absorption of curcumin, although maybe not of the parent compound, but I don't think there's any evidence that it increases absorption of flavanoids across the board, or fisetin specifically — can you cite any?

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      • BobM
      • BobM
      • 4 yrs ago
      • Reported - view

      JGC 

      I lease let us know about your success with dissolving this product in warm olive oil.

      I was not successful in doing it with the Dr’s Best capsules...

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      • Dan Nave
      • Dan_Nave
      • 4 yrs ago
      • Reported - view

      BobM 

      I had absolutely no problem in dissolving my Swanson Fisetin (Novusetin), 1 gram in 1 Tablespoon of room temp olive oil.  I also dissolved 1 gram each of Quercetin and Curcumin in the same oil.  Why are people having problems with this?  Yes, if there are fillers, they won't dissolve.  Both Swanson and Dr's Best should be the same Fisetin (Novusetin), unless they are adding fillers.

      Like 1
      • BobM
      • BobM
      • 4 yrs ago
      • Reported - view

      Dan Nave 

      This is very interesting Dan. I will have to try Swanson Fisetin!

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      • JOHN
      • JOHN.1
      • 4 yrs ago
      • Reported - view

      JGC I did a large dose Fisetin last Saturday and Sunday. I did the Mayo Clinic dosing guide and added Bioperine and olive oil.  On Wednesday I had a blood workup.  Nothing fancy just a liver/kidney function test with Auto Differential.

      My total WBC is low measuring 2.5 plus high Eosinophils at 9.3% (indicating Eosinophilia) and high Lymphocte at 45.5%. I do not have an infection that I am aware of so these numbers could point to serious diseases like leukemia, cancer, or an autoimmune disease just to name a few.  Can a Senolytic dose cause these values?

      My doctor ordered a redo but I need to wait a couple of weeks.

      Thanks

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      • Ajax
      • Ajax
      • 4 yrs ago
      • Reported - view

      JOHN one of the common side effects of another senolytic, dasatinib, is low WBC. It's probably the same for fisetin at critical doses; I believe the white blood cells are depleted due to dealing with senescent cells. Some people get flu-like symptoms from senolytics, so your body is probably reacting like you have an infection.

      Definitely do the follow-up test, but I wouldn't be surprised at all if your numbers are fine the second time around. If you're comfortable with sharing those results, please do, as it would be interesting to have confirmation.

      Like 2
      • JOHN
      • JOHN.1
      • 4 yrs ago
      • Reported - view

      Ajax My follow up labs are as follows:

      total WBC: 3.7

      Eosinophils : 4.1%

      Lymphocte: 33.7%

      A little low but I have historically tested low for WBC in some years previous.  The Eosinophils and Lymphocte's have never been so high though. 

        9/4/2013 5/30/2014 5/21/2015 5/27/2015 6/19/2015 10/26/2016 12/28/2017 8/3/2018 11/13/2019 11/27/2019
      WBC 4.7 4.6 2.3 3.1 3.8 3.9 6.7 4.3 2.5 3.7
      4.4 - 10.7 x10E9/L
      Like 1
      • Ajax
      • Ajax
      • 4 yrs ago
      • Reported - view

      JOHN Yeah, both Eosinophils and Lymphocytes are toward the upper end of normal, though obviously things improved quite a bit since the first test. I'd expect any fisetin effect to be gone by the second test, so I'm thinking you may have some other low level contributor. e.g. inflammation, asthma, low vitamin d. It's also entirely possible it takes longer to return to a normal white blood cell balance after a senolytic treatment, compared to a typical infection.

      Thanks for sharing the results!

      Like 2
    • JPA
    • JPA
    • 5 yrs ago
    • Reported - view

    Thanks for the the tip! I was reading the topic about your experiment right now, it's valuable to know there's a simple way to boost bioavailability without having to dissolve the Fisetin in more complicated formulas that require lab equipment.

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    • JGC
    • Retired Professor of Physics
    • JGC
    • 5 yrs ago
    • Reported - view

    I refer you to https://www.isotrope.com/bioperine/ .  It says that: "P-glycoprotein is a protein the body uses to break down exogenous compounds found in the body. This protein inhibits the action of many medications, and also regulates the degree to which certain nutrients are absorbed by the body. This protein actively controls the permeability of the blood-brain barrier, which directly impacts the overall effects seen by many compounds such as curcumin—the active compound found in Turmeric. Piperine inhibits the action of this protein."

    Like 4
      • Iðunn
      • Iunn
      • 5 yrs ago
      • Reported - view

      JGC I think a person should be very careful about doing anything that will increase the permeability of the blood-brain barrier.

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    • JGC
    • Retired Professor of Physics
    • JGC
    • 5 yrs ago
    • Reported - view

    @iunn

      It isn't clear to me why you think that suppressing the production of the drug breakdown-compound P-glycoprotein should be related to the permeability of the blood-brain barrier. 

      For what it's worth, except for a mild headache that lasted a few hours my wife and I experienced no subjective brain-related effects after taking 10 mg of BioPerine one hour before taking several large doses of Fisetin or of D+Q.

      In my opinion, clearing the senescent cells in the brain and central nervous system is a beneficial thing, and it is good that the Fisetin molecules are small enough to reach the brain.  In fact, it is a concern for me that the very promising new general technique for clearing senescent cells that is being developed by Oisin Biotechnologies, which involves using p16-targeted designer-DNA plasmids delivered to cells by special lipisomes, has problems in penetrating the blood-brain barrier because the lipisomes are so large.

    Like 3
      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      JGC  Hi, do you have any updates on your experience taking Fisetin? I got some DMSO and looking for to use it with the Fisetin and maybe black pepper too, this should increase absorption. Will report back, but will take awhile.

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      • JGC
      • Retired Professor of Physics
      • JGC
      • 4 yrs ago
      • Reported - view

      Danh Tran 

      My wife and I did three senolytic sessions involving about 5,000 mg of Fisetin each last October/November (as described elsewhere in this Forum), and we have taken none since.  In the last two session we took 10 mg of BioPerine (the equivalent of your black pepper) an hour before the Fisetin capsules to increase bio-availability.  I experienced only a few minor side-effects in the 24 hours after the doses.  We both felt well after the sessions, but our bloodwork showed only fairly small improvements.

      We plan more Fisetin (and D+Q) sessions in the near future, but this plan has been delayed because I have recently had cataract surgery and lens replacement in both eyes (I'm now 20:15 for distance vision).  It is well known that senescent cells play a role in healing, and senescent cell clearance interferes with and delays healing from surgery.

      After I suggested dissolving Fisetin in DMSO, I received comments from some bio-experts saying that while it had not been tried, but it probably wouldn't do much.  However, I think it's worth a try, and I will be interested in your experiences.  I note that others have found that one can break open the Fisetin capsules and dissolve the power in olive oil before tasking it orally.  I have just ordered some >98% pure Fisetin powder from VitaSpace, and we plan to take that powder dissolved in olive oil in our next sessions. 

      Like 2
      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      JGC I read up DMSO and HGH, I was interested in HGH without having to needle myself. Found this article, which has interesting information which could also work for Fisetin. http://www.youngagain.org/d6.html

      Basically HGH dissolved in DMSO will not absorb thru the skin but will if place under the tongue. 

      I take B12 and this is how they tell you to take it on the label (place under tongue).

      Like 2
    • @JGC Danh Tran 

      Yesterday I added DMSO to my dose of Fisetin, held it in my mouth between gums & cheek for about 30 seconds, then swallowed.  No problems.

      • Fisetin, 400 mg - Doctor's Best capsules -- opened to remove powder
      • Bio-Perine, 10 mg, capsule -- powder mixed with the Fisetin
      • Coconut oil, liquid, about 20 ml, to dissolve the powders
      • DMSO, 10 drops

      Mixed together with a wooden chopstick in a tiny shot glass (whiskey glass, but no whiskey).   I read somewhere that DMSO will dissolve metal or plastic, so I am using glass and bamboo.

      No problems, so I'll do the same this evening, increasing Fisetin to 500 mg.

      I read above on this thread about reactions to large doses of Fisetin, so I decided to determine my dose by increments.  Started five days ago with 100 mg, adding 100 mg/per day.  Today, day five, will be 500 mg.  Then will pause for a month before the next round.

      Like 3
    • Mike Almerjanski 
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      • BobM
      • BobM
      • 4 yrs ago
      • Reported - view

      Mike Almerjanski 

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      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      Mike Almerjanski That's great. My method will be to dissolve black pepper w fisetin (99%) in DMSO and use a glass dropper to put it under my tongue. I think this is the best area for absorption. I'm  going for 3g at a time for 3 days. I'm waiting for my calendar to be clear. Should be soon.   Actually mnight not need too much pepper or at all, since it's going directly into the blood bypassing the stomach.

      Will report what happens. Will kick it up to 5g next time, if everything goes well. Read some posts where that was how they got the best results.

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      • BobM
      • BobM
      • 4 yrs ago
      • Reported - view

      Danh Tran 

      can you update us on how Fisetin dissolved? How much were you able to get dissolved, in how much solution? How?

      thanks!

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      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      BobM  ok. I definitely will. I'm traveling now. I think it's not even any kind of risk if you take as much as you can to get results. Safer than most "approved" drugs. It's not even a drug, so who cares. Oxy etc. That is 1k times more dangerous. Can you die or get addicted to fisetin. NOT

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      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      BobM I easily dissolved 2 grams in 8ml of DMSO. I think I could have used 5ml. It tasted horrible in my mouth. I chased it with carbonated water, not much help. Milk w a bit of sugar worked pretty well. 

      Like 1
      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      BobM 

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      • Danh Tran
      • Danh_Tran
      • 4 yrs ago
      • Reported - view

      Danh Tran one pile is 2grams. Could dissolve in 4ml of DMSO. When I mixed it with 1/2 cup of milk the fiseten absorbed the milk like a sponge and it almost became solid. I sucked it down without mixing it too much. Today I just did a shot of 4ml w fisetin straight down with a chaser of juice. This was a lot easier than swishing in my mouth, which tasted so bad and was unbearable.

      Like 1
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