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.

    Like 3
      • Iðunn
      • Iunn
      • 1 yr ago
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      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
      • 1 yr ago
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      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
      • 1 yr ago
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      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
      • 1 yr ago
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      Dan Nave 

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

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      • JOHN
      • JOHN.1
      • 7 mths ago
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      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
      • 7 mths ago
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      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
      • 7 mths ago
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      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
      • 7 mths ago
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      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 1
  • 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."

    Like 3
      • Iðunn
      • Iunn
      • 1 yr ago
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      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.

    Like 3
      • Danh Tran
      • Danh_Tran
      • 1 yr ago
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      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
      • 1 yr 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. 

      Like 2
      • Danh Tran
      • Danh_Tran
      • 1 yr ago
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      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.

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    • Mike Almerjanski 
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      • BobM
      • BobM
      • 1 yr ago
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      Mike Almerjanski 

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      • Danh Tran
      • Danh_Tran
      • 1 yr ago
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      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
      • 1 yr ago
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      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
      • 1 yr 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
      • 1 yr ago
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      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
      • 1 yr ago
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      BobM 

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      • Danh Tran
      • Danh_Tran
      • 1 yr 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.

      Like 1
      • BobM
      • BobM
      • 1 yr ago
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      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
      • 1 yr ago
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      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.

      Like 2
      • DIANE B
      • DIANE_B
      • 7 mths ago
      • Reported - view

      JGC  for what its worth I also got a mildly noticible headache (extremely rare) after high dosing fisetin also.

      Anyone who has had a stroke or TSI may want to take note; that it was in same region.  Obviously I decided "ok enuf for now" esp since I took sublingually on semi empty stomach w a ton of my regular early am supplements.  Which are doubtlessly synergystic bio-enhancers!  (Lifelong health nut doing headstands and extreme excercize mere hours before stroke hit... Never any guarantee . Be prepared! 🌻🌼🌳)

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      • Dan Nave
      • Dan_Nave
      • 6 mths ago
      • Reported - view

      JGC Why are you talking the BioPerine one hour ahead of the senolytics?  Why not at the same time? 

      I have seen nothing that indicates that it should be taken one hour before the other supplements.

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      • JGC
      • JGC
      • 6 mths ago
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      Dan Nave 

      I don't have any publication to back it up, but I reason that the drug breakdown-compound P-glycoprotein, which breaks down polyphenols and is resident in the small intestine, needs time to dissipate before the Fisetin or D+Q gets there.  Therefore, we have been taking BioPerine an hour before the flavenoids, on the theory that by providing a delay after the BioPerine shuts down P-glycoprotein production and before flavenoids reach the small intestine, they will have a better chance of avoiding breakdown.  I have no observations to support this idea.  It's just a hypothesis.

      Like 1
  • 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 ! 

    Like 3
      • JGC
      • JGC
      • 1 yr ago
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      Jesper de Meeuw 

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

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  • 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.

    Like 3
    • 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."

      Like 2
      • JGC
      • JGC
      • 1 yr 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.

      Like 1
      • djmichel
      • CDR Phx
      • djmichel
      • 1 yr ago
      • Reported - view

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

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      • JGC
      • JGC
      • 1 yr ago
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      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.

      Like 1
      • Dan Nave
      • Dan_Nave
      • 1 yr 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?

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      • JGC
      • JGC
      • 1 yr ago
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      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.

      Like 1
      • JGC
      • JGC
      • 1 yr ago
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      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.

      Like 1
      • Dan Nave
      • Dan_Nave
      • 1 yr ago
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      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.)

      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. 

      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.

      Like
      • JOHN
      • JOHN.1
      • 7 mths ago
      • Reported - view

      JGC I have done a large senolytic dose with Fisetin twice now but I also take 100mg a day.  I give my wife 100mg a day as well. Do you think it's a waste of money to take a small daily dose?

      Another question for you as well. I am buying some liquid DMSO.  I was thinking about dissolving some Dr's Best Fisetin into it and applying it to my face. Do you know anyone who has done this and if so is it safe and how many 100mg pills should I mix in a 8 oz bottle. Will it have a positive effect on my skin?

      Thanks!

      John

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      • Andrew
      • Andrew_Flint
      • 7 mths ago
      • 1
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      JOHN Be careful with pure DMSO - at minimum you need to dilute.  Personally I wouldn't put DMSO on my face.  Full strength DMSO can cause serious burns and rashes / reactions.  

      Like 1
      • JGC
      • JGC
      • 7 mths ago
      • 1
      • Reported - view

      JOHN 

      I agree that DMSO, while it does dissolve flavenoids, may produce problems on its own.  If you do try it on your face, start with a very small patch.

      As for daily small doses of Fisetin, itwill not trigger the aptosis of senescent cells, but it could possibly have other benefits.

      Like 1
    • JGC 

      Regarding your discussion regarding about the bioavailability of polyphenols. (In the resveratrol thread).  I have done two experiments with fisetin using homemade rectal suppositories. (Fisetin in coconut oil. First 300 mg and then 500 mg.) Though I have not much to say at this stage. But the experiments has made me consider the question: which is the most rational way to get bioactive polyphenolic substances into the bloodstream and then have bioactive substances reach target cells?

       

       And I am not sure how much of fisetin’s actions that can be attributed to the free substance and how much (if any) that can be attributed to metabolites from the metabolism that takes place in the liver when the fisetin absobed and make first pass through the liver.

       

      The oral route is the one that has the science behind it and it is also what the mayo clinic use on both animals and humans. Then again we have reports that “nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice” this indicate that there is potential for bypassing the oral route. (But  not through intraven-injections).

       

      “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.

       

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

       

      The section “2. Bioavailability and pharmacokinetics of fisetin” in the paper below is a good short read and it made me consider that it might not only be free fisetin that gives as the effects we are looking for, but there might be metabolites contributing to the effects we want. How much of those metabolites are produced when using the oral route and how much will we get from using other routes (like the rectal route)

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067175/

       

      “Touil et al. [10] determined the pharmacokinetics and metabolism of fisetin in mice and studied the biological activities of its metabolites. Their studies showed that after an intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 µg/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h. Three metabolites of fisetin were detected including the methoxylated metabolite geraldol. The latter was shown to achieve higher concentrations than fisetin in tumor-bearing mice and appeared more cytotoxic than the parent compound [10].”

       

      When it comes to the bioavailability of fisetin, I still favor the oral route, then the sublingual route and lastly using rectal suppositories. If I  find facts or make experiences that point me in another direction, then I will of course change my mind.

       

      I keep experimenting and when I have something with more substance to report from my experiments I will do it in this forum. 

      Like
      • JGC
      • JGC
      • 6 mths ago
      • Reported - view

      Staffan Olsson 

      The Fisetin metabolites may perhaps play a role in the in vivo results with animal models.  However, in the initial work on human senescent cell cultures that indicated the senolytic effectiveness of Fisetin and D+Q was done in vitro, and essentially no metabolism was involved, in that the cells were cultured in a Petri dish to which the flavenoids were directly added.

      On the question of how to improve bioavailability of Fisetin, I note that RevGenetics in their Nitro Super Micronized Resveratrol capsules suspends the Resevratrol micro-particles in Tween 80 surfactant emulsifier, a commercial product that can be bought by the liter and that has a huge effect on bioavailability.  I am wondering if ingesting Fisetin emulsified in Tween 80 would similarly enhance its bioavailability.

      Like
      • JOHN
      • JOHN.1
      • 6 mths ago
      • Reported - view

      JGC  you seem to have a lot of knowledge on here. I have done a couple of senolytic doses with fisetin and I'm on 1000mg of extended release metformin for longevity. My father in law is in late stage Copd and has some heart issues. Is it safe for a 77 year old copd patient with a weak heart to take senolytics?  Will it help him live longer?   Can there be a benefit or is it too risky?

      Like
    • JGC 

      The cell metabolism in the human body is very complex and the complexity makes it , as we all know, difficult to create specific  and effective interventions.

       

      When it comes to the bioavailability of polyphenols I find this paper “  Molecular Mechanisms and Bioavailability of Polyphenols in Prostate Cancer” being a very compact but good read. It is about prostate cancer. But it highlights the complexity and relates in a meaningful way to research about polyphenols like quercetin, resveratrol, apigenin, curcumin, EGCG etc.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429226/

      Different methods of delivering a substance usually/probably creates different metabolites. This due to metabolism by the mircroflora in the intestine and also during the metabolic passage through the liver and then through metabolism by other metabolic pathways in our cells. we work with a lot of assumtions and partly unknown varaibles, but when it comes to senolytics like fisetin, D and Q  what we have  gained so far is very promising

       

      When it comes to bioavailability of Fisetin I will try a few more experiments with rectal administration but now with higher doses.

      Like
      • JGC
      • JGC
      • 6 mths ago
      • 2
      • Reported - view

      Staffan Olsson 

      That's an interesting article.  Near the end, it discusses techniques for the delivery of polyphenols, and mentions the use of cyclodextrins.  Apparently ß-cyclodextrin, the middle-size cyclodextrin shown below, works well for the delivery of at least some polyphenols.  It's a ring- or doughnut-shaped molecule that looks like this:

       

      The polyphenol to be delivered fits in the hole in the middle of the ß-cyclodextrin.  The outside of the ring is hydrophylic and the center is hydrophobic, so it can dissolve otherwise insoluble molecules in water.  The air freshener Febreze uses ß-cyclodextrin as its active ingredient to trap bad-smelling molecules.   It is listed as non-toxic when taken orally.

      Amazon sells ß-cyclodextrin for $22.95 for 113 grams.   I'm wondering if one should try combining it with our flavenoids of interest, Fisetin, Quercetin, Resveratrol, Curcumin, etc., to enhance their bioavailability. 

      Like 2
      • JGC
      • JGC
      • 6 mths ago
      • Reported - view

      JOHN 

      I'm a physicist, not an MD, so my opinion is not worth much in this area.  However, if it were me deciding, I'd do it, since the only known side effects of burst-doses of Fisetin and D+Q are mild flu-like symptoms that last a few hours.

      Like
      • JGC
      • JGC
      • 6 mths ago
      • Reported - view

      More on Cyclodextrin

           A little further research indicates a problem in what I suggested.  Apparently, ß-cyclodextrin is about x10 less soluble in water than its molecular relatives alpha and gamma cyclodextrin because it is more tightly bound internally.  There are variants of ß-cyclodextrin that are more water soluble and thus better for promoting bio-availability, but these so not seem to be readily available for sale.

           Also, a pill company called Nature's Essentials markets a rather pricey spectrum of products, including curcumin, metatonin, vitamin-C, and resveratrol, that are encased in a liposome and then protected by cyclodextrin for greatly improved bio-availability.  It is not clear which variety of cyclodextrin is being used, but I suspect that it is alpha cyclodextrin.  I note that Amazon sells alpha-cyclodextrin powder at $18.00 for 5 grams, promoting it as a dietary fiber and fat blocker because it passes right through the digestive system without interaction.

      Like
    • JGC I have checked out nature's essentials line of products. I hesitate to try them until they have been tested by a third party. I sometimes check what https://www.consumerlab.com/ has to say about the content of supplements.  They  test supplements and post the results. As far as I can see they have never tested anything from nature's essentials. 

      Like
      • David H
      • David_Hanson
      • 6 mths ago
      • Reported - view

      JGC Nature's Essentials is a great fine regardless whether they have Consumerlab testing or not.  Consumer Labs tests a fraction of what is available in the marketplace so it is not surprising that they have tested Nature's Essentials products.

      Like
    • David Hanson I agree they only test a fraction of what is available. But when learning about a new brand selling products in new formulations, then one want to have some proof of their concept. I hold nothing at all against this company. But I have in mind what some perons in this forum have experienced when it comes to rapamycin.  And I am happy to learn more about Nature's essentials and their products. Do you have any experience of nature's essentials line of product? 

      Like
      • David H
      • David_Hanson
      • 6 mths ago
      • Reported - view

      Staffan Olsson No I haven't used Nature's Essentials (living in SE Asia for 5 months this winter prevents me from buying from t them) yet.  I did write to them this morning asking them for any third party testing.  One thing that they have going for them is that they have a corporate office in Atlanta.  I am not sure where their supplements are manufactured but at least the quality process is being managed out of the USA.  I think this is far better than buying from India or China.  Concerning the Rapamycin discussion, a  product may or may not contain rapamycin and even because it seems to contain rapamycin because it "works" or because of blood levels, how do we know that it doesn't contain toxins because of some faulty Chinese manufacturing process?

      Like
      • JOHN
      • JOHN.1
      • 6 mths ago
      • Reported - view

      JGC in your opinion do you think a couple of synolytic doses would benefit my father in law? Also, Are there medications he is taking that could interfere our interact? 

      Like
      • JGC
      • JGC
      • 6 mths ago
      • Reported - view

      JOHN 

      I think a couple of grams of Fisetin in olive oil taken a couple of times would be good for him.  I'm not aware of med conflicts with Fisetin.

      Like
      • JGC
      • JGC
      • 6 mths ago
      • 1
      • Reported - view

      David Hanson 

      I just ordered their liposome + cyclodextrin enhanced Resveratrol and Curcumin products from Nature's Essentials.  I'll report any observations when I've received it and  taken some.

      On the question of testing, a while back I bought some Lucidias-brand Dasatinib from BonHoa Pharmacy in New Deli, India (at a greatly reduced price compared to Bristol-Meyers-Squibb's $1k per dose).  I provided one tablet from the bottle, and Johnny Adams arranged to have it analyzed high-resolution with liquid chromatography by Echelon Biosciences, as funded (~$200) by his Gerontology Research Group.

      The analysis produced a concentration vs. molecular weight plot that was essentially empty except for a huge peak at just at the molecular weight of dasatinib (488 amu).  There was also a tiny peak (<0.05%) at a slightly higher molecular weight, probably caused by a trace of oxidized or methylated dasatinib.  In other words, the Lucidias product was the real thing.

      I think if we could put together an order for ~100 grams of rapamycin from a selected Alibaba source, Johnny would probably be willing to have a similar analysis done for a rapamycin sample.  Anyone interested?

      Like 1
    • JGC I am interested. Thanks for organizing it.

      Like
      • JGC
      • JGC
      • 6 mths ago
      • 1
      • Reported - view

      Folllowup on Nature's Essentials use of Cyclodextrins

      My order of Nature's Essentials Tumeric/Curcumin just arrived. They are long-ish orange tablets, about an inch long and 1/3 inch wide.  The fine print on the back label of the bottle indicates that the product contains hydroxypropyl-ß-cyclodextrin.   This is a more water-soluble derivative of the ß-cyclodextrin discussed above.

      Like 1
    • JGC yes

      Like
      • Dennis
      • Dennis.3
      • 5 mths ago
      • Reported - view

      JGC I would be interested in the rapamycin purchase also.  Seattle local.

      Like
      • JGC
      • JGC
      • 4 mths ago
      • Reported - view

      Dennis 

      After making an inquiry about a bulk purchase of Rapamycin on Ali Baba and getting the run-around from several potential supppliers, I decided that ordering it this way was too much of a crap shoot.  I had contacted The Antiaging Store about reports that their RapaPro brand of Rapamycin did not show up in bloodwork after taking it.  They sent me a multipage report from a testing laboratory showing assay results of their product that I found to be fairly convincing.  On that basis, I ordered two bottles of RapaPro, which my wife and I are now taking once a week.  Here is the order LINK.

      Like
      • JGC
      • JGC
      • 4 mths ago
      • Reported - view

      JGC 

      Sorry, wrong link.  Here is the correct LINK.

      Like
    • JGC Why not have your batch of Rapa tested yourself?  If AAS was previously exposed for errors or misrepresentation of their product, why would you trust an analysis they provide?  Documentation is easily falsified.

      Like
      • garland
      • garland
      • 4 mths ago
      • 1
      • Reported - view

      Dan Nave I am recovering from the flu or whatever it is going around. Still have reduced symptoms. And yesterday I tried one round of Fisetin along with Quercetin  and Senolytic Activator..... I was going to do it again today and tomorrow until I read your post today. I assume your advise would be to wait til all the symptoms are gone with Flu? I did this a few weeks ago and loved it..felt very energetic... today I feel lethargic. Maybe you are correct...

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

      Dorian Gray 

      The docs (LINK) look authentic, so I don't think it's worth $100 or so to do the redundant test.

      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

    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.

    Like
  • Bonjour,

    Je me présente brièvement j'ai 31 ans, je prends du Trans-reveratrol depuis le 1er janvier 2013.
    J'ai souhaité faire une cure de FISETIN notament pour les propriétés anti-inflammatoire mais également pour l'élimination des cellules senescentes.
    Après de nombreuses lectures d'études et de témoignages j'ai acheté un pot de Fisetin 100Mmg Dr. TheBest et 1 pot de fisetin 100mg. SWANSON. Afin d'être sur d'assimiler la fisetin j'ai pris le produit ventre vide et au cours d'un repas, le matin et le soir et des fois en cours de journée (j'ai tout essayé). J'ai testé la fisetin 500mg au réveil avec Vitamine C + OMega 3 + 30ML d'huile de Noix. Concernant les résultats indéniablement ils existent!!.
    J'avais des douleurs au bas du dos et à l'épaule à cause de la musculation elles ont totalement disparues, je constate plus d'énergie et lors de ma cure qui a duré 5 jours ou j'ai pris en moyenne entre 500 et 800mg par jour, j'ai constaté une véritable sensation de "froid" dans mon corps c'est très impressionnant. Je constate une meilleur humeur et un regain d'énergie, plus qu'avec l'utilisation de précurseur de Nad+.
    Les cellules sénescentes s'accumulent tous les 60 mois. Je vais donc refaire une cure mais cette fois je vais combiner avec de la bioperine. Je tiens à préciser que j'utilisais la FISETIN toujours en combinaison avec 250mg de Trans-resveratrol. Les 2 premiers jours de la cure j'étais un peu amorphe.
    Je vous tiens au courant des effets de la FISETIN + BIOPERINE. N'hésitez pas si vous avec des questions.

    Take Care

    Like
  • Hello,

    I introduce myself briefly I am 31 years old, I take Trans-reveratrol since January 1st, 2013.
    I wanted to do a cure of FISETIN notament for the anti-inflammatory properties but also for the elimination of senescent cells.
    After many readings of studies and testimonials I bought a pot of Fisetin 100Mmg Dr. TheBest and 1 pot of fisetin 100mg. SWANSON. In order to be sure to assimilate the fisetin I took the product empty stomach and during a meal, morning and evening and sometimes during the day (I tried everything). I tested the fisetin 500mg waking with Vitamin C + OMega 3 + 30ML of walnut oil. Regarding the results undeniably they exist !!
    I had lower back pain and shoulder pain because of bodybuilding they totally disappeared, I consume more energy and during my treatment that lasted 5 days or I took on average between 500 and 800mg a day, I found a real sensation of "cold" in my body is very impressive. I consume a better mood and a boost of energy, more than with the precursor use of Nad +.
    Senescent cells accumulate every 60 months. So I will do a cure again but this time I will combine with bioperine. I want to clarify that I was using FISETIN always in combination with 250mg of Trans-resveratrol. The first 2 days of the cure I was a bit amorphous.
    I want you to avoid the effects of FISETIN + BIOPERINE.

    Do not hesitate if you have questions.

    Take Care

    Like 2
  • Regarding the availability of fisetin in oil, see my recent posts on the "Fiestin to Clear Senescent Cells" section. I can say with certainty that fisetin in coconut oil (MCT) has powerful and rapid effects on the body!

    Like 2
  • Repeating *sublingual* advantages and questions ... greatly increases most substances enter direct into bloodstream minus digestive deterioration.   Please correct me? Have been seeking more info.  Thanks.

    Like
      • Ajax
      • Ajax
      • 7 mths ago
      • Reported - view

      DIANE B Sure, sublingual administration avoids the liver's first pass. The basics seems to support that fisetin could be taken sublingually; the molecular weight is less than 500 (286) and it has a logp value of less than 5 (2.5).

      I can't seem to find the ph, which you'd want to know in case it's harmful to tooth enamel. Even if the ph is fine, I expect sublingual fisetin would still stain your teeth yellow, and really it tastes terrible, so I'm not planning on doing it.

      Like
      • DIANE B
      • DIANE_B
      • 7 mths ago
      • Reported - view

      Ajax  thank you kindly! 

      Am still wondering how much to down size by half maybe?  And whether to mix w bit of coconut or olive oil (i dont understand your science details apologies if they answered that!)

      BTW i find it basically tasteless!  Just a trifle chalky.  Definitely conserves money one would think.  

      Like
      • Ajax
      • Ajax
      • 7 mths ago
      • Reported - view

      DIANE B I have no idea how much to downsize by either, since it depends on how much fisetin is absorbed by the liver, and how much fisetin can be absorbed sublingually.

      I am by no means an expert here, but the logp value shows how hydrophillic ("water loving") or hydrophobic ("water hating") a substance is. In this case, the logp value shows fisetin should be soluble "enough" in saliva for sublingual delivery. My understanding is the fact that fisetin is more fat soluble than water soluble would be a good thing for sublingual delivery. So that all makes me think you don't need a carrier (oil) for sublingual delivery.

      It's standard supplement industry practice to say a product is 100% pure, but put fillers into a capsule. Mostly this is done to ensure a full looking capsule for a certain mg amount of product. These fillers won't dissolve sublingually, so you may wind up with a bunch of wet powder under your tongue, even if the fisetin does get absorbed sublingually.

      Like
      • DIANE B
      • DIANE_B
      • 7 mths ago
      • 1
      • Reported - view

      Ajax hi again thanks for reply about absorption.  I've been reading thru this new-to-me forum and sorry for redundancy!  We all have Soo much information and Soo many questions to share.  Great group.  I think I will be hanging out awhile and much appreciate your feedback. 🍓🍓🍓🍓🍓

      Like 1
      • Ajax
      • Ajax
      • 7 mths ago
      • 1
      • Reported - view

      DIANE B you're welcome!

      Like 1
      • RAW
      • Ancient Sage
      • Robert_Weinhardt
      • 6 mths ago
      • 2
      • Reported - view

          Fisetin is known to dissolve best in oils.  The question is how much of the oil/fisetin mixture transfers through the intestinal walls into the blood stream?      Another question is what benefit does Quercetin provide when taken with Fisetin.    The combination seemed to be beneficial when tests were being conducted with Dasitanib but now that Fisetin has been discovered to be more effective,   I don't see any benefit in adding Quercetin.   I anyone aware of any reason for using the two in combinaton?

      Like 2
  • I found this report from 2016. Some are obviously trying to increase bioavailability through nanoencapsulation. I hope someone soon has an efficient route for placing fisetin in the bloodstream.

     

    Some have proposed using suppositories. Suppositories can be ok if the only purpose is to do intermittent senolytic therapy. But for daily use I prefer the oral route. I have not heard about any experiments with homemade fisetin-suppositories. I guess we have to see if anyone is up to it.  

     

    https://www.tandfonline.com/doi/full/10.1080/10717544.2016.1245366

    Like 1
  • One suggestion is to add lecithin to the dose of Fisetin.   Lecithin is well known as an emulsifier so it should help mix Fisetin with water and increase absorption.     I tried it with my last course of senolytic meds using approximately 2 grams of Lecithin with each 2 gram dose of Fisetin.   I also take Echinacea as an immune system stimulant on the assumption that Fisetin exposes senescent cells but it's the macroglia that actually remove those cells.   It seem logical that temporarily stimulating the immune system to produce more macroglia and increase their activity level would make better use of the Fisetin while it's effect lasts.  

    Has anyone seen / heard of a simple test to determine what concentration or percentage of senescent cells are present in a body or some indicator of how much have been removed?    Without some metric to measure the level of senescent cells in a living body it's hard to judge how effective any senolytic treatment is.    

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

      RAW 

      You asked "Has anyone seen / heard of a simple test to determine what concentration or percentage of senescent cells are present in a body or some indicator of how much have been removed?".  The answer is no.

      It is possible to take a biopsy (i.e., a  slice of flesh) and do an assay of the degree of senescence in that sample by looking for the presence of beta Galactosidase (a senescent cell marker) using staining and microscopy.  This is not something for self-experimenters.  There have been some consideration of doing a count of senescent cells of a particular cell-type in a blood sample, but this raises the question of how closely senescence in that cell type is correlated with senescence in other parts of the body.  The in vitro cell culture experiment indicate that different cell types are affected differently by Fisetin and D+Q.

      The bottom line is that we are "flying blind" in doing self-experiment senolytic sessions with Fisetin and/or D+Q, because we cannot measure how much senescent cell clearance is being achieved in the different cells of the body.  We are stuck with subjective measures of whether we feel better or experience fewer age-related aches and pains after a senolytic session.  I can testify that I do feel better and have fewer body aches.

      Like 1
      • RAW
      • Ancient Sage
      • Robert_Weinhardt
      • 4 mths ago
      • Reported - view

      JGC

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