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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Ajax would you mind sharing your bodyweight. Would like to know the mg/kg. Thanks!
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Ajax I'm one of those who had no reaction from fisetin and great results form D&Q. I will try your protocol, thanks.
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Mel Always a question people enjoy answering. 😉 I'm 110kg.
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Ajax How old is your aged mother? My mother is 93 and cannot walk anymore. My father has Alzheimers and is 88. I have asked their Dr if I can give them Fisetin becuase they live in an assisted living home and I cannot just hand them pills. The Dr. said there was no indication for giving them Fisetin. I may fight it. But I'm really interested in how your mom fared and how old she is , etc etc....
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JOHN My mother is in her early 80s.
It's hard for me to pinpoint any beneficial effects specifically to fisetin (aside from the disappearance of the scar and skin tags) because we've also been taking NR.
That said, she reports a great improvement in her gluten sensitivity (which showed up in her later years), a reduction in fine wrinkles (I see the same in both of us), a thickening of her hair, and an overall increase in energy and well-being. Relatives have recently asked her if she had "work done".
Prior to taking NR we both had chronic fatigue, and what NR did to combat that was amazing. However, these last few months if I miss a few days of NR I don't notice the same return to fatigue. I'm not entirely sure if it's the fisetin treatments that have done that, or if I've just managed to bank up a lot of NAD.
Doctors will never recommend any of this stuff. They don't follow studies, and the studies that do get brought to their attention are via the drug companies.
For your Dad, I'd actually make NR more of a priority than fisetin. It's been shown to help with an Alzheimer’s model in mice, and NADH (reduced NAD) has been shown to help Alzheimer's in people.
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Ajax thanks Ajax. Can you send me a link to the nad you take? There's a lot of stuff out there, precursors, nmn, etc so I'm not sure which one to take. I have taken a high dose Fisetin regimen once and I'm in the middle of my second one now. I did 2100mg with 850mg quercetin, 165mg bromelain. 10mg BioPerine and a tablespoon of olive oil. Day two it today. I haven't noticed much from the first one which was a much lower dose 800mg over 3 days. I take 100mg a day as well. Still waiting on results. Thanks for your input. I'm 51 old male by the way.
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JOHN
I've been taking Tru Niagen (NR) which I order through amazon. My reasoning for using NR is because it's the most studied in humans, and overall cost. It has an FDA GRAS (generally recognized as safe) designation, so it's probably easier to get the assisted living staff to give it.
The recommended amount on the label is two pills, but it's better to start off with one and see how it goes. Also, best to take them early in the day, as they can disrupt sleep in some people if they take them too late in the day. (NAD influences circadian rhythms)
Good luck with your folks, John.
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JOHN
Fight that Doctor. Make him justify why not and what the risk is. I would want my advocate to do this for me.
Many of these elderly care doctors are SO out of touch, IMO -
BobM I don't know if I could ever live with myself if I ended up giving them high doses of Fisetin and they ended up getting sick or drying. Unfortunately it's not as easy of a decision when it involves somebody else.
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BobM yes, we’re so out of touch.
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Do you know anyone that is also taking Apocynin along with the Fisetin? If so, what is the dosage they are using?
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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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Koo I've posted some interesting inflammatory cell count results from a blood test recently, which credit to fisetin. Have a look at my post in the "Test results" category.
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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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Koo
That's very interesting. My wife and I had used 2000 mg in warm olive oil for 2 days. We didn't notice any symptoms as extreme as those you describe.
Does anyone know if there is a chemical reason why coconut oil would do better at producing fisetin bio-availability than olive oil?
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That's a good question! If I remember correctly other people have taken fisetin in coconut oil and not noticed significant side effects, maybe a burning throat was mentioned. If I feel brave I might take fisetin in olive oil next week :-)
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Koo
Milk takes up to 4 hours to digest. When it hits the stomach it immediately curdles and forms a mass which slows its digestion. Anything taken with milk or mixed with milk will likewise take a long time to digest or be absorbed as it will be surrounded by the slowly digesting milk proteins, etc. Don't take anything with milk if you want quick digestion.
300 mg of fisetin is not a particularly high dose. I suspect you are experiencing a food sensitivity or intolerance (similar to an allergy, but limited to the digestive system) to either fisetin or the plant from which the fisetin is extracted. The burning throat is a good clue, not to mention the really bad diarrhea for 3 1/2 hours which you reported.
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Dan Nave
I don't think it's clear that milk is problematic for fisetin delivery. Milk is used to increase the bio-availability of fat soluble vitamins (fortified milk), and unbound fisetin has a half life of 3h in the blood (in mice, with their fast metabolism), so there's likely a bit of time to get to that critical dose.
I used cream with fisetin, mainly because the salicylates in coconut oil and olive oil makes me extremely nauseous and gives me the runs. It was my hope that some of the cream might act as a crude liposomal coating, but either way it worked very well for me. I had clear signs of senolytic action. (mentioned earlier in this thread)
I do agree that the dose here seems low. I think even the Mayo protocol dose is conservative, and it's much higher.
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Ajax Thanks again for your feedback on having salicylate sensitivity. I finally plucked up the courage to try the coconut oil on its own yesterday, about 1/4 cup, and it wasn’t pleasant hehe. I have discovered an interesting fact about myself – I appear to be sensitive to salicylates! As before, my heart rate and blood pressure shot up soon after taking the oil, and a little later the diarrhoea started. OhBoy!
If you hadn’t mentioned it I wouldn’t have had a clue what was going on. On the bright side, it means I’m feeling a lot better about taking the fisetin! And the interesting thing about salicylate sensitivity is that it arises from the COX genes/enzymes not functioning properly, and I have a condition associated with chronic inflammation. So there is potential for treatment.
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Koo I'm glad you figured it out, and that my post was helpful!
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Ajax I would love to hear from anybody who dissolves fisetin in oil. How much oil are you using? I want to know if I was using way too much, it was around 60 mL, or if others use this much without any problem.
Thanks.
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Koo I was using a bit less than that - about a shot glass worth - so maybe 45ml.
I don't see smaller amounts being used. Even at these amounts, it looks like the fisetin is suspended, rather than dissolved.
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Ajax Thanks very much, that's good to know.
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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 :-)
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Another thought, I wasn't paying any attention to my coffee drinking, so maybe there was an interaction between the fisetin and caffeine, which caused the heart effects. It might be a good idea to drink decaf on the days I take fisetin and probably quercetin.
