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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  • 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.

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      • JGC
      • Retired Professor of Physics
      • JGC
      • 4 yrs ago
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      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. 

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      • JGC
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      • JGC
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      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.

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      • JGC
      • Retired Professor of Physics
      • JGC
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      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.

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    • 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. 

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      • David H
      • David_Hanson
      • 4 yrs ago
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      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.

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    • 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? 

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      • David H
      • David_Hanson
      • 4 yrs ago
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      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?

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      • JOHN
      • JOHN.1
      • 4 yrs ago
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      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? 

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      • JGC
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      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.

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      • JGC
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      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?

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    • JGC I am interested. Thanks for organizing it.

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      • JGC
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      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.

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    • JGC yes

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      • Dennis
      • Dennis.3
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      JGC I would be interested in the rapamycin purchase also.  Seattle local.

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      • JGC
      • Retired Professor of Physics
      • JGC
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      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.

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      • JGC
      • Retired Professor of Physics
      • JGC
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      JGC 

      Sorry, wrong link.  Here is the correct LINK.

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    • 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.

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      • garland
      • garland
      • 4 yrs ago
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      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...

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      • JGC
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      Dorian Gray 

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

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      • JGC
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      • 3 yrs ago
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      Chuck Frasher 

      It does seem to be the same New Delhi pharmacy.  Their prices seem to have gone up.

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    • JGC  Thanks so much. Your reply leaves much confidence. 😊

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  • 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

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    • Andrew
    • Andrew_F
    • 4 yrs ago
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    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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    • Amaury K
    • Amaury_K
    • 4 yrs ago
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    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

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