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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  • 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.

    Reply Like 3
      • Iðunn
      • Iunn
      • 8 mths 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
      • 3 mths 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
      • 3 mths 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.

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      • BobM
      • BobM
      • 3 mths ago
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      Dan Nave 

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

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  • 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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  • 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."

    Reply Like 2
      • Iðunn
      • Iunn
      • 8 mths 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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  • @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.

    Reply Like 2
      • Danh Tran
      • Danh_Tran
      • 5 mths 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
      • JGC
      • 5 mths ago
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      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. 

      Reply Like 2
      • Danh Tran
      • Danh_Tran
      • 5 mths ago
      • 1
      • 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).

      Reply Like 1
    • @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.

      Reply Like 2
    • Mike Almerjanski 
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      • BobM
      • BobM
      • 5 mths ago
      • Reported - view

      Mike Almerjanski 

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      • Danh Tran
      • Danh_Tran
      • 5 mths 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
      • 5 mths 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
      • 5 mths 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 mths ago
      • 1
      • 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. 

      Reply Like 1
      • Danh Tran
      • Danh_Tran
      • 4 mths ago
      • 1
      • Reported - view

      BobM 

      Reply Like 1
      • Danh Tran
      • Danh_Tran
      • 4 mths ago
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      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.

      Reply Like 1
      • BobM
      • BobM
      • 4 mths ago
      • Reported - view

      Danh Tran 

      I tried DMSO, A drop on the tongue.  Taste is awful. I think my body is telling me no way. Dissolving some fisetin in it and rubbing on my skin left a yellow stain.  DMSO is going in the trash can. In researching further, there are to many things not known about this. Not sure any benefits outweigh risks. 

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      • Danh Tran
      • Danh_Tran
      • 3 mths ago
      • 2
      • Reported - view

      BobM Yes! taste is horrible but DMSO is not toxic and really safe from what I've read.  Study, experiment and learn, we can't rely on big corporations to really help unless there's big money involved. I'll keep learning to find a less gross tasting way to take it.

      Reply Like 2
  • Hi there, i’m also interested! But i just got the band together. Fisetin, phosal, bio ethanol, peg 400. Next week i’ll send the Fis and phosal 50 to a lab to analize ! 

    Reply Like 3
      • JGC
      • JGC
      • 5 mths ago
      • Reported - view

      Jesper de Meeuw 

      Where did you get the Phosal 50?  A quick web search showed some information but no sources.

      Reply Like
  • JPA, check out the Bulletproof Radio podcast where Dave Asprey interviews Joe Mercola -- episode 588.  They discuss creating a customized suppository to supplement with things fisetin and NR specifically, which are apparently absorbed 10x better that way than via digestion.

    I'm NOT doing this because it's gross, but apparently it works.

    Reply Like 2
    • Paul Tozour JGC Jesper de Meeuw  I am also trying to find ways to increase bioavailability of Fisetin besides spculative use of oil and piperine. I am thinking of ordering liquid phosphatidylcholine and PEG400 both can easily be bought on amazon. And of course ethanol (which I think I know where to buy :)

       

      Phosal is hard for me, as consumer in Europe, to find a good place to buy. I wonder if it will be very differnt to use liguid phosphatidylcholine instead of PHOSAL? What do you think?

       

      http://www.lipoid.com/en/phosal

       

      "The Lipoid PHOSAL® brand name encompasses unique liquid compounds based on phosphatidylcholine. They can act as solubilizers for components that are either insoluble or barely soluble in aqueous solutions or function as a source of phosphatidylcholine with essential fatty acids. The PHOSAL® products can be incorporated directly into oral or dermal formulations."

      Reply Like 2
      • JGC
      • JGC
      • 4 mths ago
      • 1
      • Reported - view

      Staffan Olsson 

      Phosal 50 seems to be a mix of 50% phosphatidylcholine and 50% propylene glycol, both of which can be ordered from Amazon.  In particular, they sell phosphatidylcholine  for $14.09 for 100 x 420 mg liquid-filled gel caps and propylene glycol for $14.47 per quart bottle.  Therefore, you should be able to mix up your own equivalent of Phosal 50, if that's what you want.  I think I'll try olive oil first.

      In June, my wife and I plan to do another Fisetin senolytic session, and for this I have purchased 100 grams of >98% pure Fisetin powder.  I also bought a $17 digital scale that reads in milligrams.  I'll put a small glass of warm olive oil on the scale, zero it, and add the Fisetin powder until I get the desired dose, then stir and drink.  We will first take a 10 mg capsule of Bioperine.  An hour later we will dissolve 2.0 grams of Fisetin powder in warm olive oil and take that.  We will do this in the morning for three consecutive days.

      We are shooting for a total 6 gram dose because we previously experienced no ill effects from 5 grams taken over four days and because there seems to be a threshold effect with the senolytic effects of Fisetin and we would like to be over that threshold for as many senescent cell-types as possible.

      Reply Like 1
      • djmichel
      • CDR Phx
      • djmichel
      • 3 mths ago
      • Reported - view

      JGC where did you purchase your Fisetin powder? Thanks in advance.

      Reply Like
      • JGC
      • JGC
      • 3 mths ago
      • 1
      • Reported - view

      djmichel 

      I bought the 100 g of Fisetin for $196 including shipping from vitaspace.com, which seems to be located in New York. I was dealing with a person named Peter. The URL is https://www.vitaspace.com and the phone number is (631) 342-1883.

      Reply Like 1
      • Dan Nave
      • Dan_Nave
      • 3 mths ago
      • Reported - view

      JGC How do you plan to use the Fisetin?  That is an awful lot for senolytic doses.  Will you also take smaller doses daily?

      Reply Like
      • JGC
      • JGC
      • 3 mths ago
      • 1
      • Reported - view

      Dan Nave 

      Senolytic research with mice indicates that there is a threshold all-at-once dose of Fisetin, below which there is not much action in clearing senescent cells, so small daily doses probably have no senolytic effect.  Further, a big unknown is whether that threshold level varies significantly for different cell types.  Therefore, we are taking doses on the large side (2 g) for several days, then nothing more for 6 months.

      We had planned to start this session last week, but there is a significant bruise on the back of my hand from competing at a dog agility trial (my hand accidentally hit a jump post).  I am waiting for that to fade before starting the session.

      In response to another question, I have not yet personally determined whether 2 g of my Fisetin powder will easily dissolve in warm olive oil, but there is a post here somewhere saying that this works.  I will report my own experience, one way or the other, probably next week.

      Reply Like 1
      • JGC
      • JGC
      • 3 mths ago
      • 1
      • Reported - view

      Paul Tozour 

      Yes, apparently Amazon sells suppository molds, and one can fill these with coconut oil sandwiched with the supplement of interest, solidify them in the freezer, and insert away.  This is reputed to be a good way of getting fragile supplement molecules into the bloodstream while avoiding stomach acid and breakdown enzymes in the intestines.  It's worth considering, but I think I'll hold off for now.

      Reply Like 1
      • Dan Nave
      • Dan_Nave
      • 3 mths ago
      • 1
      • Reported - view

      JGC 

      That sounds good.  

      I had absolutely no problem dissolving my Swanson (Novusetin) Fisetin in room temp olive oil, and also it worked with another kitchen/cooking oil I had when I ran out of olive oil.  If there are fillers in your product they may not dissolve.  However, mine looked well dissolved, as well as the Quercetin and Curcumin I had also gotten from Swanson Vitamins.  Didn't really taste too bad either.
       I think you are wise to wait until you heal up from anything going on in the body before taking the senolytic dose.  From my experience, I feel that it slows/stops healing for a week or two.
      Also, I feel that a wait of 6 month between doses is also wise.  When I took a second dose in 1 month after the first (F+Q+C) it really seemed to hit me hard, and took 2 1/2 weeks to 3 weeks before I was feeling normal again.  (I took 1 gram each of F+Q for three days.  The second month I did the same with F+Q+C. This dissolved in olive oil, and also took approx 1/2 teaspoon freshly ground black pepper at the same time, no waiting.)

      Reply Like 1
    • Dan Nave Dan Nave

       

      Today I had my first dose of fisetin. To enhance bioavailability I made my own PHOSAL (I mixed 50% phosphatidylcholine with 50% propylene glycol) and then I added Polyethylene Glycol (PEG 400). Then I mixed it all with Fisetin.

       

      The Fisetin dose I took today was slightly over 20 mg/kg. My weight is 78 kg and I used 1600 mg.

      I have been ok all day. No negative feelings.

      Maybe i slight feeling of increased wellbeing during the day. But that can be placebo.

      I am not sure ithat acute and short term effects is something to aim for or if short term effects should be seen as an indication of Fisetin doing a good job. But it can be an indication that I have not got any acute negative reactions. 

       

      Tommorrow I aim for 35 mg/kg. 

      Reply Like 1
    • Dan Nave JGC

       

      When it comes to bioavailability there is research going on with a nanoemulsion. It works fine with mice. If it is well tolerated by humans and is as effective in humans as in mice it will be a very attractive product.

       

      “Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin. Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of fisetin and have shown that it could improve its relative bioavailability and antitumour activity..”

       

      https://www.ncbi.nlm.nih.gov/pubmed/22387278

       

      ta take it intraperitoneally is not an option for us but at least this gives us an indication that the issue with low bioavailability can be handled in creative ways.

      Reply Like
  • i think you cant add enough alcohol etc to keep it dissolved in the stomach without having an overdose of etoh or dmsiô. as in chem laboratory you put an etoh soluble , water insoluble product together in water, the water product will seperate and go out via large intestine.? or mabe not

    Reply Like
  • I'm on day 4 of a 5 day x 1200mg fisetin regimen (planned for every 2 months per my doc), and both yesterday and today added 100mg 7,8 Benzoflavone, 100mg resveratrol + 10mg black pepper + 240mg r-lipoic acid + 290mg PS to the 1200mg fisetin.  Detox reaction / headache & vertigo for the last 3 hours, although yesterday wasn't as much of a headache.  Also consider the deep tissue massage received shortly after today's dose.  Also on 6mg rapamycin / week + 500mg Metformin ER x 2.

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