Fisetin - The Mayo Clinic Senolytics Protocol?

There are limited human studies using fisetin.
From the animal studies I have read, the benefits are dose dependent much like rapamycin and pulse dosing is effective as it is with rapamycin.

Also I take fisetin because quercetin doesn’t agree with me.

I would never recommend to anyone else to take the dosages I am taking especially to someone that is relatively young.

My rational is: I am old. I have more senescent cells to get rid of.

If I were taking liposomal fisetin I would certainly reduce my dose.
“In vivo, liposomal fisetin allowed a 47-fold increase in relative bioavailability compared to free fisetin”

“fisetin did not need to be continuously fed to the animals to suppress markers of senescence consistent with a senolytic mode of action which would result in the elimination of senescent cells.”

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Can anyone recommend a brand of liposomal Fisetin? Thanks!

I am having this one: MCS Formulas. So far so good.

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In USA there seem to be only 2 reputable manufacturers of Liposomal supplements, with scientific studies to back their product’s effectiveness : LivOn and Valimenta. LivOn only makes liquid liposomal products in pouches and does not make Liposomal Fisetin. Valimenta makes both liquid and powdered liposomal products, but sells most of them as a contract manufacturer to various other brands. You can recognized those liposomal products based on their use of Cellg8 technology. Renue By Science is one such brand that resells Cellg8 based liposomal supplements, including Fisetin. I take 10 capsules of their 150mg Liposomal Fisetin 3 days every 28 days, targeting around 20mg/kg body weight per day.

Update : Corrected spelling of Cellg8 manufacturer Valimenta

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Have you noticed any changes, good or bad, from taking liposomal fisetin?

Not yet, but I plan to ran two NAD+ blood tests before and after a 3 day treatment, since Senolytic cells are believed to be the main source of rising CD38 as you age which in turn depletes NAD+. Rapamycin acts like a Senomorph and reduces the SASP signal, and would also reduce CD38 (and increase NAD+), so I will take the Fisetin in between my every other Friday Rapamycin doses.

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Please let us know your results! It will be interesting to see how effective it is in humans!

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You mean 10 capsules every day for 3 days - as 10 is undivisible by 3, so in other words, 3x10 = 30 capsules = 4,5g fisetin?. Liposomal supplements are suposed to be absorbed up to 20 times better than regular supplements. Even if that claim is, let’s say, 100% over estimated, so ‘only’ 10 times better absorbed, you are then taking 45g. fisetin, right?.

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Yes, I am taking 1.5g/day or 4.5g liposomal fisetin over 3 days, once ever 28 days.

While some Liposomal supplements may be 20 times better, that only applies to supplements with normally very poor bioavailability. Liposomal supplements have 70-95% bioavailability, so to be 20x better the regular version must have 4% or less bioavailability. Fisetin is estimated to have 30% bioavailability, so you are getting at most 3x better absorption with Lipo Fisetin. But the other benefit with Lipo Fisetin is that it seems to increase the half life to 12 hours, which I am hoping will even out the plasma levels, effectively turning it into an extended release version.

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I know it is a little off topic, but I ordered some fisetin online from GB and it is being held by customs in EU on claim that is is possibly a medicine. Does anyone know how is fisetin regulated in EU? I could not find anything, but noticed that Swanson and Life Extension do sell it on their EU sites, Doctor’s best is also widely available. I mainly ordered it from GB as the price was good, but also the dosage was much higher and seller has GMP certificate, which in my opinion is (the only) good option when buying supplements.

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Hmmm…it is an over the counter supplement… strawberry seeds basically. Can buy on Amazon.

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I use the Life Extension brand. They claim up to 25 times greater bioavailability.

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FWIW

Any company/individual can make claims.

The only way to know is to measure!

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Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study

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Making claims? Yes, and they use “up to” which gives them a lot of leeway. That’s how the supplement industry goes. I’ll accept that rather than having the government getting involved. That said, Life Extension has been around many years so I use some of their products.

Review

"Molecular and Therapeutic Effects of Fisetin Flavonoid in Diseases"

Attached is a PDF copy
Molecular and Therapeutic Effects of Fisetin Flavonoid in Diseases.pdf (131.7 KB)

In Killifish…

A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish

The young African turquoise killifish has a high regenerative capacity, but loses it with advancing age, adopting several aspects of the limited form of mammalian regeneration. We deployed a proteomic strategy to identify pathways that underpin the loss of regenerative power caused by aging. Cellular senescence stood out as a potential brake on successful neurorepair. We applied the senolytic cocktail Dasatinib and Quercetin (D + Q) to test clearance of chronic senescent cells from the aged killifish central nervous system (CNS) as well as rebooting the neurogenic output. Our results show that the entire aged killifish telencephalon holds a very high senescent cell burden, including the parenchyma and the neurogenic niches, which could be diminished by a short-term, late-onset D + Q treatment. Reactive proliferation of non-glial progenitors increased substantially and lead to restorative neurogenesis after traumatic brain injury. Our results provide a cellular mechanism for age-related regeneration resilience and a proof-of-concept of a potential therapy to revive the neurogenic potential in an already aged or diseased CNS.

https://www.nature.com/articles/s41536-023-00304-4

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Unfortunately I think you are double counting by dividing the basic stuff by 3 and multiplying the lipo by 3. You can’t do both; it’s one or the other.

8mg is just that. It can’t turn into 24. It just isn’t diluted like the other one.
That’s just the way I see it.
I’m no expert on fisetin so I’ll let tananth take over from here and be the arbiter.

Update: A study states fisetin’s low bioavailability is 44,1%, not 30%. So BioFisetin’s enhanced bioavailability must be around 2x., following tananth’s calculations above.