Fisetin to Clear Senescent Cells
Following studies with mice that showed significant senolytic clearance of senescent cells following large doses of the readily available flavenoid supplement Fisetin, my wife and I (ages 79 and 84) decided to try it. We have just completed two sets of massive Fisetin doses.
We had Life Extension blood-work done in October before the start, and we will have more again next week to observe any changes. The first set of Fisetin doses was on October 22-25 with 800 mg/day for three days followed by 600 mg on the fourth day, for a total of 4 g. I didn't notice much in the way of effects. Perhaps some reduction of small aches and pains and some increase in energy and mental acuity.
For the second set of doses done November 22-26, since we experienced no negative side effects in the first set we decided to increase the dosage a bit and to add 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids. For five days starting on Thanksgiving we took 500 mg of Fisetin and 10 mg of BioPerine twice per day, for a total of 5 g of Fisetin.
This time. I did experience one negative side effect. A few months ago, about 2 AM in the morning I awoke from a deep sleep and experienced a severe episode of vertigo. I turned over in bed, and the the whole room seemed to tilt. Suddenly, I didn't know which way was up. I staggered to the bathroom and vomited. The symptoms tapered off and disappeared in a few days, but it was a very distributing experience.
On the 2nd day of our 2nd Fisetin series, I experience a recurrence of that vertigo in the middle of the night, not as bad as my initial experience but still rather disturbing. I tolerated this mild vertigo and continued the treatment. My wife had no similar symptoms, and after my last dose I experienced no further vertigo symptoms.
On the positive side, following the second set of dosages I did feel very well, and very sharp and alert. This past weekend I ran my Shetland Sheepdog Taliesin in an AKC Canine Agility Trial in Mt. Vernon, WA, and we did very well, qualifying in 7 runs out of 15 and getting various colored placement ribbons. I was feeling quite sharp, and I even invented a new dog-handling technique that fixed an ongoing problem we were having.
Next week we will do the blood-work again, and I'll report any changes.
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I believe it's been discussed but with so many thread...........What is a good brand for Fisetin 500 mg tablets or capsules. I was looking at on on amazon and the comments said it was false advertising and it was in reality only 250 mgs.
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Just received my order for Fisetin 50 grams and Dasatinib 5 grams from China. No problems with Customs was shipped via Fedex. Fisetin was $2.50 gram including $25 Fedex. Dasatinib was $20 gram + $25 shipping. I received exactly 50 grams of Fisetin, and 5.6 grams of Dasatinib. Over paid for Fisetin, better to order online. Dasatinib and Rapamycin also are such small amounts that they can ship in an envelope and less likely to have a problem with customs. Dr. Green is now recommending to take Fisetin and Dasatinib together and you can skip or not quercetin because Fisetin works better. Green recommends 1500 mg Fisetin x 3 day x quarterly for anti ageing. I prefer to use Mayo clinic's formula of 20mg/kg. On July 01, 2020, I will take Fisetin 1700 mg x 3(with olive oil) + Dasatinib 100 mg x 3.(quarterly) The next week will take 250 mg Zithromycin x 6 days (quarterly) Will try taking Vitamin C, 500 mg with all of the above. These 3 drugs target 3 of the 4 senescent putrid cells, (aka, zombie) WIll be waiting for a treatment for the 4th. cell type.
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Van
What is the contact link for the Chinese firm you dealt with?
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RAW said:
As I understand it, Fisetin does not attack cells of any kind, it simply removes the covering or "camouflage" coating that hides senescent cells from macrophages and prevents them from being removed by normal autophagy. ... [I]t seems logical to ingest a large dose of Echinacea to stimulate our immune system about a day in advance of starting a course of Fisetin + lecithin. Reports indicate that stimulating the immune system causes it to produce more, new macrophages (or microphages in the brain) which should increase the probability of senescent cells being removed during the brief period while they're exposed.There's a lot of misunderstanding here. I don't know where you got the idea that fisetin removes some kind of covering or camouflage from senescent cells, or that it involves the immune system; it is generally accepted that it works in a similiar way to other senolytic compounds: by inhibiting cell-survival pathways that are ramped up in senescent cells. Several such potential pathways have been identified, although none has been shown to be the one (or the main one) responsible.
Separately from senolytics, the immune system does eliminate some senescent cells, but macrophages aren't the cell type that does it: natural killer cells are. And autophagy doesn't remove cells: it removes components of cells, such as used and damaged proteins and organelles.
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Has anyone seen any information that Curcumin and Fisetin counteract each other when used as a senolytic, or their different modalities of actions nullify each other? I have seen several comments to this effect, but have never seen any literature that cleared this up in my mind. Any references or thoughts would be welcome.
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Dan Nave
Hi! I have this link to a paper from 2010 that discuss how to Improv the oral bioavailability of beneficial polyphenols through designed synergies. it is a general paper and not specifically about fisetin. But personally Learned a few things from it. Curcumin is a BCRP inhibitor which also goes for Quercetin. But I don’t have any specific paper about fisetin.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820202/
I take curcumin a few hours after the Senolytic agent.
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Staffan Olsson I have been taking Quercetin along with Fisetin... when I do my senolytics... should I not combine them?
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@garland Metabolism is a very complex process and at this stage it is not possible at this stage to say something certain about how fisetin and quercetin influence each others biological actions when they are co-consumed. But so far the science regarding quercetin seam to favor co-consumption with other substances. if the question is to increase the senolytic effect of fisetin I find that co-consumption with piperine/black pepper is a safer bet.
But then again one has to be humble about this. There are many here who co-consume fisetin with quercetin and report positive effects.
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Staffan Olsson Thanks.... am doing bio-peperine with it and it seems to help...
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garland The question here was whether to take Curcumin and Quercetin together. My feeling is *no* for C + Q, or C + F.
I would take Quercetin together with Fisetin though.
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Does anyone have an opinion on the new Life Extension product Bio Fisetin? They claim (up to) 25 times availability, which suggests that one capsule with 8 mg of fisetin would be equivalent to 200 mg of plain fisetin. So, potentially a 4 tablet dose for 3 days might have senolytic effects???
Here's a link to the product page: https://www.lifeextension.com/vitamins-supplements/item02414/bio-fisetin
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Michael Avenoso I am trying 10 tomorrow to get a dose that seems close to Mayos... I always do at least 2300 mgs when I do senelytics every 2 or 3 weeks. I the past I mixed the Fisetin with olive oil and took it with bioperine pepper. I also took Quercitin and 100 mgs of Dasatinib. The Quercetin was the highly absorbable form from LE> I also took Senolytic Activator from LE each day. So I am excited to try the new formulation of Fisetin out to see if I notice any difference with it. After all Fisetin is supposed to be the most powerful of them all. I notice all kinds of good effects at high doses from what I did in the past. I am more limber and get in yoga positions i could not get into for years. I have no pain in my body... I feel more clear and alive for sure. Kiind of high on life.... high doses are where it is at if you are not allergic and always talk to your doctor first> I would not do this unless you are under doctors care.
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Michael Avenoso They don't present any studies showing this improved absorption; I would phone them and ask them for their evidence before taking this statement at face value. JGC 's post above seems to suggest they're just guessing based on a rodent study involving curcumin, not fisetin. In any case, even if it really has 25 times availability, it's more than 25 times more expensive per milligram, so not really an advantage.
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Iðunn
I don't think LifeExtension is just guessing based or rodent studies. As I recall the account I read somewhere, they used the same bio-enhancement coating trick that had been used on curcumin, gave the coated fisetin orally to several human volunteers, and tested the resulting blood-levels of fisetin. That's where they got the x25 value. As I recall, when LifeExtension tested the coated curcumin the same way, they got a much bigger (x80?) bioenhancement.
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JGC Hm. It'd be great if you could track this down...
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Iðunn Ah: I see you posted it here. Thanks, JGC .
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garland Thanks for your response. I am waiting on the product to arrive. I am going to take a small dose to rule out an allergic response and then try the 4 caps for 3 consecutive days. If I survive that, I'll attempt your heroic dose. :^). I will also take some of the LEF Bio Quercetin with it. If I see any obvious benefits, I'll post them here.
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That sounds like a good way to start... give it time to make sure. Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one. I have done Fisetin at least 15 times usually about 2,300 mg... so I started with 8 of the capsules and feel it is very powerful. I feel unbelievably clear headed and full of energy and kind of 'high on life' type of feeling. But again I have done this many times and also with Dasatinib and Quercetin so go slow. You can always wait a couple of weeks and redo at a higher dose. Getting rid of old cells can be very taxing and draining and uncomfortable. But now I am sitting up straight and walking tall with a spark... but I feel this way after doing fisetin each time but this definitely feels more intense and more complete. I will know more after tomorrows when I take another dose.... and after what I feel like in a few days coming down from this session... dont ever over do it... it is not worth it.... there is always time to do another round in a few weeks...
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garland Sounds like strong effect. Did you take fisetin alone or did you take it with quercetin?
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Staffan Olsson see below for a report of my latest experiences. I had a difficult time sleeping last night ... I take it with Quercetin, Dasatinib and Senoytic activator from LE..with bio peperine .... awesome combo feel alive but it is intense so be careful when you are starting out with Bio Fisetin
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garland said:
Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one.I wonder if we couldn't do this ourselves by mixing regular fisetin with, say, Guar Gum which is a galactomannan containing gum.
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Supplement Facts
Serving Size 1 vegetarian capsule
Amount Per Serving Proprietary Blend: 44.5 mg Providing 18% fisetin (8 mg) [from wax tree extract (stem)], 35% galactomannans (15 mg) [from fenugreek (seed)] Other ingredients: microcrystalline cellulose, vegetable cellulose (capsule), silica, vegetable stearate, soluble fiber, sunflower lecithin.
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Dan Nave Maybe but it would be a totally blind experiment... at least with the LE mixture they did some research on it. I also include Bio-Perine with the mixture of Bio-fisetin.... that may help it get into the blood stream as well. But at 10 dollars a bottle with 3 doses per bottle why take a chance. I will be taking 10 capsules for 3 days equivalent to 2000 mg per day... Word to the warning the Bio-fisetin is far more powerful then the regular one according to my experience. So go slow... I started at 8 capsules but i have done these probably close to 15 times in past year and a half... I mix it with 100mgs of Dasatinib and Quercetin..... So if I was starting new I would probably just do 2 or 3 per days to see how I adjust... then the second time increase slightly.
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garland I'd be more concerned with the Dasatinib. Anything you do that increases the bioavailability of the polyphenols, including taking more of them, increases the bioavailability of Dasatinib, as they act like CYP3A4 inhibitors themselves.
"Dasatinib is a CYP3A4 substrate. Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 may increase exposure to dasatinib and should be avoided."
"Quercetin, a flavonoid, is an inhibitor of P-glycoprotein-mediated efflux transport, and its oxidative metabolism is catalyzed by CYP enzymes. ... Quercetin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC(50)) of 1.97 μM."
" In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4."
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Dan Nave thanks for the heads up... . However i wonder about that specifically with the Quercetin. I know last year LE suggested heavy doses of Dasatinib (225 mgs) along with heavy doses of Quercetin (2200 mgs).... once a week for 2 weeks to be repeated every 3 to 6 months. I have seen many research studies that have found that Quercetin works much better with Dasatinib then without it. And the combination is better then isolating them. I decided once i was able to finally get DASA to limit it to 3 days of 100 mgs of it because I looked at the research on DASA and found that the 100 mg dose once a day had far less side effects then 200 mgs a day. I am following doctor Green from New York protocol with this combination. Plus I stay away from this for a few weeks. So maybe once every 3 weeks I do this. There is too many unknowns here about Fisetin. Maybe one should not mix it with Quercetin at all. Who knows. What we do know is that researchers have found that Fisetin appears to be the best flavonoid for Senyletics so far. And I do know that the Quercetin/Dasatinib is the most researched.... so there is something to that combination as well and it is a very powerful combo. By the way I notice that you had quotes around your post ... were you quoting from some source? if so what was the source. I am not disagreeing with you and perhaps one solution is to get rid of Peperine. I added that last year to help absorb fisetin but now with BioFisetin i do not think it is so necessary.
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