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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've done two courses of Fisetin treatment (I'm 50) along with my wife and aged mother, and we all saw fairly obvious symptoms of senolytic action. During the first round of treatment, I had a brief runny nose, my Mother had full-on cold symptoms, and my wife didn't notice any change. Also a scar/mole on my stomach started weeping from the edges. I noticed a week later that my stomach scar had shrunk greatly in size, and another scar on my shoulder that I had been keeping an eye on had completely disappeared. My occasional aching knee has stopped aching, and feels much looser. My mother and wife both had some skin tags that have now disappeared.
I see a lot of "fisetin does nothing" posts on the net, with people saying to try D+Q instead. I have a feeling people are using a sub-optimal protocol, sub-optimal fisetin, or don't have a great senescent cell burden, if they're seeing nothing.
The protocol I followed was to take 3g per day split over in 2 doses - one in the morning and one a couple hours later around noon, repeated 3 days in a row. To improve bioavailability, I took bioperene first, and unlike others here, I mixed the fisetin with cream. I seem to be one of those people that react badly to the salicylate in olive oil, and found the stuff would stir into table cream fairly easily, which covers the fat-soluble requirement. Two days prior to the protocol I dropped every supplement I was using, which at the time was just NR. I will say that none of us stopped drinking coffee.
The fisetin was 50% pure fisetin in bulk powder form. I used 6g of the product, to obtain a dose of 3g of fisetin. I mention this in case some of the other 50% product in the fisetin source (Cotinus Coggygria P.E.) has an impact on the effect.
Anyway, I tried this out mostly thanks to the information here. A big thanks from me for this great resource.
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Hi,
Thanks for all the great posts and research, they have been very useful! I have some age-related conditions even although I'm not 60 yet and have always had a healthy diet and been very active. So I'm keen to try senolytics to get some quality of life back.
First I tried 100 mg fisetin in the capsule, that was fine, so I a few days later I tried 600 mg dissolved in MCT coconut oil, on an empty stomach. That caused a burning throat and really bad diarrhea for 3 1/2 hours! I had to stay very close to the toilet, the visits there were only about 5 minutes apart for the first couple of hours. I think I must either be really sensitive to fisetin, or have a lot of senescent cells.
I noticed the first effects 20 minutes after taking the fisetin, my throat started to burn and my tummy started to grumble. I was quite surprised and thought maybe it was all in my head, until I had to bolt for the toilet 30 minutes after taking it.
The good news is that it seems quite a lot of fisetin dissolved in the oil and was bio-available, because it could not have reached the large intestine so rapidly. I also got a couple of quick fevers that only lasted a few seconds, and chills while on the toilet.
So after waiting a week I’ve just done two days of 200 mg fisetin in warm milk, after a meal. The first day I got some tummy grumbles and burning throat but nothing more, and the second day nothing at all. Next week I’ll try 300 mg and see how that goes. If I can gradually increase the dose then I think that could be a sign that the load of senescent cells is reducing.
Each time I have stopped taking all other supplements the night before, the morning of, and the night after taking fisetin, and reduced the metformin to 500 mg.
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An update on my fisetin trial (above). This week I tried 300 mg of fisetin (Dr's Best) in warm milk, after a protein shake. There were no effects. The next day I decided to see what would happen if I dissolved the fisetin in MCT coconut oil again, like I did before, but this time I only used 300 mg fisetin and took it after I had a protein shake. And unlike when I put the same amount in milk, I did notice effects! 10 minutes after taking it I started to sweat, and felt unwell. But I didn't get a burning throat like before.
20 minutes after ingestion I decided to take my blood pressure, as I could feel my heart going. My blood pressure had gone up to 143/86, with a heart rate of 95. I kept monitoring it, and it went to 142/90, HR 101 before it started to fall. At 30 minutes post ingestion my blood pressure had returned to normal and HR was down, but still a little elevated. Later that evening it was 123/88, HR 85, so my blood pressure was almost back to normal but I still had a slightly elevated HR. This morning everything is back to my usual, 110/67 HR 72, and I feel good.
I don' t know if the heart effects happened last time I took fisetin in oil because I was too busy running to the toilet, and didn't check my blood pressure! This time I had to go to the toilet at 30 minutes, it was normal consistency, then I slept for several hours. When I got up again I had diarrhea but only once. I did drink coffee every time.
So it seems that fisetin can have dramatic effects when dissolved in oil, but I don't know if the difference between being dissolved in oil and milk is because less of it dissolves in milk. Or maybe the oil has some other influence on the way fisetin is processed by the body. In any case I can confidently say that fisetin in coconut oil is bio-available and rapidly and powerfully influences the body.
Maybe to test the amount dissolved I could leave the two mixes for 24 hours and see if there is a similar amount that settles to the bottom of a glass. I'm not keen to try fisetin in oil again :-)
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Thanks Dan, that's interesting about milk. It's also 90% water, so probably a lot of the fisetin doesn't dissolve.
Yes, it seems that I'm unusually sensitive to fisetin. I'm curious to see if I can gradually build up the dose, and it is interesting that I didn't get the burning throat the last 3 times I took fisetin. But maybe the thing to do is to try quercetin next week at a low dose and see what happens with that, it might provide some clues. I hope I can take something!
Anyway, at least I can assure the people who are taking fisetin in oil that it is bio-available in purified coconut oil :-)