Bio-Fisetin, a x25 Boost in Bioavailability?
One of the big problems with senolytic flavenoids like Fisetin and Quercetin is that they have a very low solubility in water and poor survival in the digestive tract, leading to very low bioavailability. Therefore, one must take large doses, e.g., several grams, of the supplements to have any presence in the bloodstream.
This weekend I have been watching RAADFest 2020. This morning (Day 2) Bill Faloon gave a very nice age-reversal overview talk (his 153 slides are available HERE). It included a mention of a new LIfeExtension senolytic supplement called Bio-Fisetin. I looked it up on their website. In the description, they say: "We’ve combined fisetin with special galactomannan compounds from fenugreek seeds. Doing so protects fisetin during digestion, a technique we pioneered with our flagship Curcumin Elite™ formula. The result: better bioavailability—up to 25 times better than unformulated fisetin—so your body gets the maximum health benefits."
Bill's RAADFest slide (reproduced below) has a note about one "Akay" at the bottom and references an in-press study with human volunteers comparing the Fisetin blood levels when given 1000 mg of pure Fisetin vs. 200 mg of the mixture. (A web search didn't find a preprint of this to-be-published paper.)
One bottle of LIfeExtension's Bio-Fisetin costs $11.25 and contains 30 x 44.5 mg capsules, each with 8 mg of Fisetin [from wax tree extract (stem)] and 15 mg of Galactomannans [from fenugreek (seed)]. It is claimed that this combination increases the Fisetin bioavailabity by a factor of 25 (so that taking one cap would be the equivalent of taking 200 mg of pure Fisetin.
Judging from the label, one is supposed to take one cap daily, and the 30 caps are represented as a 1 month supply. In other words, take one every day. This dose pattern differs from the senolytic animal studies, which indicated that low doses like that don't do much. To get above the senolytic threshold and actually induce apoptosis in senescent cells, one should take a dose about 10 times larger than that above for three days, and repeat this only about every 3-6 months. In other words, to reproduce the animal studies, one should take 10 caps every day for three days, thereby consuming the contents of the bottle.
I note that BulkSupplements sells 500 g of Fenugreek Powder for $19.96 on Amazon Prime. If one already had the Fisetin powder and wanted to go the do-it-yourself route rather than buying Bio-Fisetin, one would take 80 mg of Fisetin combined with 430 mg of Fenugreek Powder per day for three days instead.
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I think he said he wanted to get to a state that's more like a young person, who's having continuous death of senescent cells.
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T F
Yes, BF did say that. However, there seems to be a threshold effect in the mouse study. I seriously doubt if you can just take 10% of the dose and clear 10% of the senescent cells that you would have cleared with the larger dose. Perhaps I'm cynical, but I think LE would like to sell you a bottle every month rather than 2 times a year.
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T F I wish B F had explained how much Bio-fisetin to ingest to make it work as a senolytic. I bought 12 bottles today at $10 each. Last time I took regular fisetin as a senolytic I took 3 grams each day of the treatment.
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David H
I think to get the equivalent of 3 g, you would take 15 caps.
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JGC My calculation is the same - 8 mg x 25 = 200 mg per capsule 3000mg / 200 mg per capsule = 15 capsules. Cost of a 30 capsule bottle is $10 if you buy at least 4. So cost of 3000mg equivalent would be only $5. But the cost of Double Wood fisetin isn't that bad either $23 for 60 100mg capsules or $11.50 for 3000mg. I think I would use more than 15 capsules of bio-fisetin just in case the 25x is too optimistic. I ordered a dozen bottles the other day.
I haven't been using fisetin as a senolyic for the past few months as I did D&Q 3 or 4 months ago and have been doing Fasting Mimicking Diet monthly - and 6mg rapamycin each week (except the week after the FMD week). I am not sure it is wise to any more protocols than these. I do take 600mg regular fisetin daily. Plus I take supplemental spermidine daily to induce autophagy (in addition to spermidine containing foods daily - natto and lentils). And I almost forgot 2000 mg metformin daily except during the FMD week.
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JGC LE’s website says “
- Maximizes fisetin bioavailability with special fenugreek fiber coating“
Mixing the two together may not have the same effect.
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David H
You are correct, David. LE's Bio-Fisetin page references their Curcumin Elite page (which uses the same bio-boost trick), which in turn gives journal references. Chasing these references down two levels in the Journal of Functional Foods yields the following description of how they combined Curcumin with Fenugreek Powder to boost bioavailability:
"Various percentage CGM were prepared by ultrasound mediated gel-phase dispersion of curcuminoids in fibre matrix. Briefly, 1 g curcumin powder was uniformly suspended in 100 ml of water containing 0.1% weight of hydroxypropylmethyl cellulose and 10% (w/v) glycerine under sonication for 20 min, at 60 C. Soluble dietary fibre powder (2.5 g) was separately dissolved in 100 ml water with sonication to a homogeneous viscous solution. Curcumin solution was then slowly added to the fibre solution. Care was taken to keep the temperature below 50 C during ultrasound-mediated mixing. Cloudy yellow aqueous solution thus obtained was dried under vacuum at 60 C and the resulting yellow flakes were
milled and sifted to produce uniform microgranulates of 150 ± 20 lm in size. The procedure was repeated to produce CGM containing various percentages of curcumin, ca. 20, 40 and 60."It appears that the do-it-yourself route would require some rather formidable lab work.
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JGC On the RaadFest 2020 website (it is only open to those who paid the registration fee), Mr. Faloon was asked about using Bio-Fisetin as a senolytic. He answered "Dasatinib + quercetin is currently the best validated senolytic, but we have reason to believe that the new bioavailable fisetin may induce better systemic “on-target” senolysis. I talked about the senolytic options during my presentation and we will be doing a lot of research over next 12 months to identify the best senolytic protocol, but in the meaintime, we should all be on some program to reduce our senesecnt cell burden."
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David H
That sounds great, but it has the ring of emptiness. There is already much research on the senolytic effects of fisetin on aging mice and on human tissue cultures that demonstrates its high effectiveness when given in large "burst" doses for a few days. Human fisetin senolytic trials with N>100 would be expensive and pointless, until such time as we have a good method of doing senescent cell counts with some method other that staining a biopsy and counting the blue cells as seen in a microscope. Therefore, I'm doubtful if LE's 12 month research program could lead to much that we don't already know. And our present understanding is that while small doses of fisetin may have other benefits, their senolytic effects have not been demonstrated. Everybody taking one Bio-Fisetin cap per day will sell lots of pills, but it probably won't clear many senescent cells.
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JGC "...Everybody taking one Bio-Fisetin cap per day will sell lots of pills, but it probably won't clear many senescent cells."
Well maybe they will or maybe they won't hence the internal (it seems) time to get true picture from peer-reviewed, double-blind, human trials. I lament that we likely are in the pre-penicillin age equivalent of age research.
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From a new comer to these Kaufmann et al nutrical protocols, but not a slow learner.
Fisetins senolytic efficacy in humans I feel/felt is demonstrated prior to LEF's fancy pills (I'm a LE long time buyer and was on RAAD's videos), so what is THE source of fisetin? Sure at 10x or some x (vs LEF), it works right? What are your std fisetin sources?
Ebay has 98% fisetin $22/10g = $2/g , another at 50% fisetin... ;(
At the Mayo does of 20mg/kg at 180# that is 1700mg rounding call it 2g per dose or $4 for Mayo protocol once daily for 3 days qtrly. I heard Dr Green reco's for over 60yo one round a month.
I see Fisetin on ebay, some at 50% some at 98%. Then the LE fancier stuff but if scaled up per the 15/17pills per does and $10/bottle (30) you'd be in for about the same cost but per here questionable efficacy vs just taking plain old fisetin 98% powder at larger does (2gm ish).
Yes re per others plus Kaufmann stacking with; Dasatinib, quercitin and the new kid spermidine.
Recapping; from those who have had efficacy from fisetin (plus etc) where do you buy it?
And given the same absorption issue is in play with quercitin, there's nano-quercitine etc. I'm buying Now (cheap generic brand) quercintin + bromelain 2x = 800mg of querctin so I'll have to take a few of these too...
Tnx much.
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What are your thoughts on the following from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/
"It was thereby concluded that fisetin acted both as an aneugen (affecting cell division and mitotic spindle apparatus resulting in the loss or gain of whole chromosomes, thereby inducing aneuploidy) and a clastogen (causing breaks in chromosomes, leading to sections of the chromosome being deleted, added, or rearranged). At low doses, fisetin was capable of interfering with proper chromosomal segregation and acted as an aneugen, whereas at higher concentrations, fisetin through effective inhibition of topoisomerase II inhibitor exerted clastogenic effects causing double-stranded DNA breaks in the cells (52)."
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This section of the paper refers to lymphoblastoid cell types, which are a type of white blood cell line infected with a virus...and not a normal healthy cell.
