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.
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...
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)."