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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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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garland Anything that is in quotes is quoted. You can take a unique portion of the quote or all of it and do a Google search to get the source. I have stopped including urls as it is easy enough for you to Google it if you want to.
I am not overly concerned with Quercetin or Fisetin as being a problem. I am concerned with Dasatinib. If you take Dasatanib with a lot of these substances over and above what has been used in the trials, you are potentiating the Dasatinib, and that could be a problem. That is the point that I am trying to make.
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Dan Nave Ok now I see what you are saying... but does it make it that much more potent then 100 mgs? I will check out the quotes and see what they are saying. Again LE had much higher doses that I was using so I felt safe with this dose especially after reading about the research on Dasatinib which showed the safety of 100mgs of Dasa... however it potency increases dramatically then yes it can be an issue... thanks
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Dan Nave I guess I am confused as to the amount of DASA to use now... I had thought that the LE people researched this. Sounds like I should use closer to 50 mg of Dasa when i use the flavonoids... I saw some substances would increase DASA by four or 5 times.... wow.... which researchers should I look at or should I take it at different times. But what about all that research that shows that Dasa and Quercetin should be taken together...
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Dan Nave Hello DAN....
I checked out some of the things that you mentioned. The link below summaries all the research as of May 20th this year . It seems that most studies looked at 50 or 100 mgs of Dasatinib with Quercetin for either 1 day or 3 days or 5 days. The quercetin is usually heavily dosed. I did not see any studies mixed with Quercetin and Fisetin together however. I think the peperine is something that may put this over the limit, and you maybe correct that the Fisetin may also take this over the limit. The good new is that in none of these studies where Quercetin is combined with Dasatinib. were there any negative side effects related to Dasatinib. I do know one thing that I am feeling better and better and more strong and alive and mentally aware. Next year according to LE they are going to be giving us some new senolytics that we all are looking forward to. So I hope to replace the Dasa with something better. I think that using every 3 weeks or so seems to be canceling out whatever possible negative effects. You are right they suggest 100 mgs not 200 mgs because side effects go down appreciably with 100mgs a day. So not sure what this means.... so for sure I am getting rid of the Peperine.
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garland The clinical studies I saw for D+Q used from 50 to 100 mg of Dasatinib with about 1000 mg of Quercetin a day. One of the studies divided up the Quercetin into 2 doses per day. Taken for either 2 or 3 days. I think this is realistic for average weighted people. In my opinion, there should be no attempt to potentiate the D or Q in this protocol.
When I take Fisetin and Quercetin I take 1000 mg each and potentiate the hell out of it by mixing it with oil, including Bioperine, and taking it on an empty stomach. Fisetin could go up to 1500 mg if you are heavier, or if you want a heavier dose. I take this for 3 days. I find that one feels achy, headachy, under the weather for about a week to a week and a half. After that one feels better than the baseline. This effect seemed to be lasting. On the other hand, some people report absolutely no negative or positive effects. Two other people here have done this, one falls into the former category and one into the latter.
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Dan Nave thanks I have decided to not use the pepper and may take 50mg of dasatinib
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Dan Nave I meant that I will take Dasatinib of 50 mgs in the middle of the three day run thanks to your warnings. Still take it 100 first day and last. I also did the same procedure as yours with Fisetin and the Quercetin with Peperine mixed with OIL.. And I also had some down days but really those have become less and less. Usually just the first day or two. Compared to the positive changes I get far more of those now. I have done Fisetin regularly for months now usually every 3 weeks and sometimes 2 weeks. I have added the Dasatinib in the past 3 months and again the first few times I did it I had more negative then I do now.
There have been so many positive changes ... My prostate problems are far less. Also I am far more limber for yoga and have more energy and clarity of mind. It is almost like I am high in non drug way. So count me as someone who has had very favorable results. I have done Fisetin maybe 15 or more times with Quercitin and
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garland Tnx for that dasatinib / quercetin risk assessment meta study. Interesting risks of both. Q may enhance cancer growth, D has water on the lung etc sides. Any longer term taker of D+Q have comments re their more negative side effects? I've read re feeling bad as a potential.
Another issue in play with listing luekemia study side effects is they take D continuously (?) and may be higher doses (?). This senolytic oriented meta study didnt list the doses and duration from the studies they pulled the side effects from.
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Curtis Smith It says Q could be preventative, but in other studies that it could enhance tumorigenesis. Quercetin has been listed by many doctors as a possible prophylactic for Covid-19, but maybe it's not a good idea
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Is it best to take the fisetin on an empty stomach? is there a specific diet to follow that is best to be on while taking the fisetin?
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LCM
Good question without a good answer. The published research on Fisetin senolytics is on mice, with the Fisetin added to their mouse-chow, and on human cells, with the Fisetin infused into the cell cultures.
My wife and I have done 3-day Fisetin sessions in the morning, taking Bio-Perine first (to temporarily shut off digestive enzymes) and then an hour later taking 2 g of Fisetin powder suspended in warm olive oil. This procedure, however, is not based on research, but is just an educated guess as to how to achieve the best bioavailability.
I note that Life Extension is now selling Bio-Fisetin, which has been treated with a protective coating (developed in India to boost Curcumin) that is claimed to boost the bio-availability of Fisetin by up to x25. That can probably be taken any time with water. We plan to do a 3-day senolytic session with Bio-Fisetin soon.
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JGC What do you think about mixing regular fisetin with, say, Guar Gum which is a galactomannan containing gum to simulate the Bio-Fisetin? Or are they doing some special process to combine them?
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Dan Nave
I ran down the published paper by researchers in India on which the Life Extension technique for increased bio-availability of flavenoids (curcumin, fisetin, quercetin, ...) is based (J Funct Foods. 2015;14:215-225.). It involves an elaborate procedure for coating the flavenoid granules with the galactomannan from fenugreek powder. Therefore, I don't think just mixing fietein with guar gum or fenugreek powder would work.
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JGC Thanks for this. I spoke out against senolytics previously but I've been trying novusetin and just ordered Bio-Fisetin to try.
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JGC Thanks JGC!
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JGC My first session of 3 days was 1.5 grams fisetin in olive oil, somewhat similar to your technique a month ago. I noticed nothing either good or bad. My second session, just finished, was mixing 1.5 grams with real butter (no salt) and blending it into my keto coffee. It mixed well and tasted fine, but no side effects either good or bad this session either. Any thoughts on the use of butter?
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I have made a similar experience. Based on nothing but my own personal experience I prefer to take Fisetin on empty stomach in the morning (after having taken some black pepper or piper longum extract)
Occasionally I have used other substances a few hours (1-3h) after ingesting fisetin. I have used the senolytic activator and curcumin. And those times I have experienced what can be called side effects in the form of Headache.
Next I will order sublingual fisetin gel.
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Staffan Olsson
regarding the above mentioned product it is important to read their webpage. The research that has been done on sublingual liposomal fisetin is done by comparing administration of intravenous and intraperitoneal free fisetin VS administration of intravenous and intraperitoneal liposomal fisetin.
The bioavailability study does not include the oral route. That said I still have an interest in the product.
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Staffan Olsson Ding ding! There's a lot of sleight of hand in this company's marketing.
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Staffan Olsson As a livestock producer I use several medications off label and oral dosing of an injectable is VERY common. I will be looking into this product as well. For now I chew it up (on buttered toast) and swallow my fisetin.
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New study at Mayo using heavy dose of Fisetin on women to study aging bans sirolimus users from participating. ... Very interesting. So they feel that sirolimus interferes with some of the effects of Fisetin....
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garland No, it doesnt interfere with the effects of fisetin, that is not the concern. Rapamycin can suppress sasp like fisetin so you wouldnt be able to tell if it is the fisetin reducing sasp or the rapamycin.
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Fred Cloud wow that makes sense
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garland That doesn't necessarily follow. They may be concerned that a beneficial effect of rapamycin (Sirolimus) may be mistaken for a beneficial effect of fisetin.
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