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.
New Fisetin Senolytic Session
It has been about 30 weeks since our last senolytic sessions, which were done last January. This morning my wife and I each took 10 mg of BioPerine, followed in 90 minutes by 2.00 grams of 98% pure Fisetin powder "dissolved" in olive oil. I put "dissolved" in quotes because I am not able to distinguish fully dissolved Fisetin from undissolved Fisetin in a colloidial suspension in the olive oil.
I put room-temperature olive oil in a 1 oz shot glass, then added 2 grams of yellow Fisetin powder, as measured on a digital scale with a precision of 0.01 grams. I stirred until I had a smooth liquid that looked a bit like French's mustard. It did not become clear, which may be an indication that lots of undissolved Fisetin granules were still suspended in the oil. The taste was acceptable, but not great. I noticed a slight burning sensation in my throat as I was swallowing the liquid. We used pieces of bread to soak up the mixture remaining in the glass, to make sure that we got it all.
That was three hours ago, and so far we have experienced no observable effects. We will repeat tomorrow, and then I plan to warm the olive oil in the microwave a bit before adding the Fisetin powder, to see if it dissolves better.
Unpleasant Side-Effects from a D+Q+F+P Session
Yesterday morning, my wife, daughter, and I did D+Q-based senolytic sessions. I took 10 mg of Bioperine, followed in 2 hours by 200 mg of Dasatinib, 2,400 mg of Quercetin and 1,700 mg of Fisetin. About 3 hours later I experienced a bout of mild diarrhea and a mild headache, but these passed and everything seemed fine.
In the late afternoon we all went to a Shakespeare-in-the-park performance of The Winter's Tale. Later that evening my daughter and I went to the cast party, at which I had three beers (she was driving). I went to bed about 10:30 PM feeling fine.
About 2:30 AM I awoke with intense abdominal cramps. I couldn't sleep for the rest of the night, so I got up and did computer things. At one point I became nauseated and vomited a bit of yellow fluid. The cramps were very intense and persisted until about 9 AM the next morning. Later, I took a long nap, and now I feel quite well and even a bit energetic.
I guess the moral here is, don't follow a senolytic session with beers. Live and learn.
98% pure Fisetin powder is available on Ebay in 10g ($22) or 25g ($49) quantities. The listing provides additional information, and suggests an EZ way to take it by just stirring the fisetin into a standard 1 oz. shot glass of warm water to form a milky yellow suspension, and then quickly gulping it down before the suspension has a chance to settle. You could say it has a 'chalky' taste, but it is basically tasteless. I've taken 500mg 'shots' this way. It's possible more than 500mg could be taken this way in a single shot, but I limit myself to 500mg. This is a very easy way to take it.
I personally do not like capsules (they seem to 'float' in my esophagus a while), but out of curiosity I made a few capsules containing approx. 500mg of the pure yellow powder. Using a size "00" empty capsule (empty wt. 110mg), I packed the big part of the capsule by pressing it down into the powder a few times until it wouldn't take any more, and then I put the smaller 'cap' part back on. The filled capsule weighed 610mg. Subtracting the 110mg wt. of the empty capsule, the content wt. was right around 500mg.
If doing this, keep in mind that the fisetin will dye fabrics a bright yellow, so avoid getting it on your clothing and wash your hands afterwards.
I've been lurking on this post and just signed up so that I could comment on the use of EGCG/Green Tea. My interest has been in the prevention of Alzheimer's and other dementias and depression. For those that do not know, EGCG is a powerful anti inflammatory that easily crosses the BBB. It acts on the same cytokines that present in the inflammatory process of brain issues mentioned above, notably TNFa, IL-6, and IL-1. So far it all seems to be of theoretical benefit.
My reasons for interest in this subject is that I have someone in my life with APOE4-4 and a long history of bipolar2, and intense depression. In my studies over a number of years I have come to accept that depression is the result of brain inflammation, which is becoming more widely accepted.
The practical application of this theory was tested one cold winter at about 3 am when the person in question decided to just walk away from life, not knowing where to go .. just trying to escape the depressive episode they were stuck in. I intervened about half a block away and returned them to the house with fair amount of resistance.
Maybe it sounds stupid but I had been studying the effects of EGCG on brain inflammation so I went to an all night grocery and bought up a bunch of green tea extract. It literally made a night and day difference in this person the same day.
Since then we have settled on 700 mg of decaf Green Tea extract from LEF 3 times a day. It's important to spread out the dose because EGCG has a short half life of about 5-6 hours. This event was years ago, BTW. My point? EGCG DOES work on an acute level in high doses. You do not need to theorize it's effects.
There is some speculation that EGCG can be tough on livers. We have not found that to be the case and early we did get liver enzymes tested a few times.
In your use with asynolitic treatment it's anti inflammatory effects alone might minimize the stress of the treatment and would likely improve the treatment IMO.
BTW, here's a link discussing the properties of green tea and EGCG in particular. It is much more than just an anti inflammatory but I cannot directly speak the many other benefits of it.
I will likely be trying out my own synolic testing with Q and F, and it will always include EGCG.
For those affected by APOE4 I do have a considerable amount of info to share which I am sure would be useful. When I get time I may search out any APOE4 posting on this site and contribute there. For now I am following this post and if this site allows it you could send me a message and I can share what I do know. I won't be polluting this fine post with that subject matter.
Hello, again. I take 500mg daily of pure theannine in capsule form., it is an important derivative of green tea. It has transformed the major stresses out of my life. I've taken it almost daily for 4 and a half years to help deal w a 4 1/2 year old child. It was recommended by my naturopathic physician. I know quite a few others who successfully use it also. Thankyou
I have been looking for a dasatinib mimic. In other words a Bcr-Abl tyrosine kinase inhibitor. If we can find this kind of substance then this substance could potentiate the combinations that we already experiment with. (fisetin, curcumin, quercetin and others) There are quite a few natural BCL-2 and BCL-XL inhibitors. Since dasatinib is a potential companion to fisetin I post this here.
Dasatinib is a BCR-ABL tyrosine kinase inhibitor and has, as far as I have seen, few similar natural substances. Until recently I have not found any interesting candidates that mimics dasatinib. What I have found out now is that chlorogenic acid might be a theoretical candidate. And I like to share this theory with the rest of you and those that are curious about finding a potential partner to fisetin + quercetin.
This indicates that chlorogenic acid has potential for being a dasatinib mimic. It is a long shot, but this is a far I have come. Future studies are of course needed but I have not found any other than the above mentioned study. The question is if we will see increased senolytic activity when Chlorogenic acid is combined with fisetin or quercetin or both? Or if it is combined with curcumin or theaflavins?
Since science (most likely) not will go in this direction it is up to us to do self-experiments. There are of course very many questions. How much chlorogenic acid is needed to reach therapeutic levels in plasma? Is it even possible to reach therapeutic levels? What do you think?
And does anybody here know of other Bcr-Abl tyrosine kinase inhibitors that are widely distributed substances.
And also, what relevance does this recent article in fight aging has on this theoretical discussion?
It is a long shot from the deletion of p38α in Neurons to triggering p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells.
Yes I know, This is a speculative theory but this is were we are right now. (Flying low and flying short, like the wright brothers did at kitty hawk).
Swanson Vitamins has Their own Fisetin supplement out - equivalent to Dr Best. lots cheaper!!
$10.39 / 100
Free shipping with $50 order...
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.
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.
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 :-)
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 :-)
Hello everyone I wanted to give you a breakdown of my fisetin experience over the last year.
I went in fairly hardcore trying to emulate the experiments done with mice only in humans. And I also repeated the treatment routinely.
I think the math worked out 100mg for every 15 pounds of weight. I did the math back then. Suffice to say I was around 220 lbs and I took 18 tablets (100mg each).
Me: 43 years old, male, 220lbs
The specific amounts I took were:
DAY 1: 18 x 100mg tablets (Swansons Brand)
DAY 2: repeat
DAY 3: repeat
Initial observations where that by day 2 I was a little jittery, not a lot, but I had amazing strength in my legs and a firmness throughout all muscles. By day 3 I was feeling fantastic and this feeling became more intense for a week after and even was noticeable 3 weeks out.
I suspect that fisetin raises hormone levels as well. Because I felt 20 years younger and full of strength, Mentally I twice as sharp. I remember distinctly that when walking around during week one I could hear every thing brilliantly, the world was crisp and alive. So there is definitely some kind of hormonal effect or other stimulation than just senescent cell clearance. These effects were much too fast to be a result of that.
I repeated the treatment at 2 weeks, then at 4 weeks, then at 6 weeks, and 8 weeks again and then gave it 5 months or so and now I am doing a repeat but at a slighty higher dosage.
In each iteration I noticed a powerful effect for the first week, and a great 2nd and 3rd week. And then I still maintained much of the muscle density and firmness and increased energy thereafter. I decreased the frequency I was taking fisetin due to my concerns that it was spiking testosterone somehow. After all the goal was to clear senescent cells not mess with hormones.
I can say that in the year since I started, I have maintained a stronger physique, my posture is better, my abs and chest are firmer, I don't look my age, but I kinda was that way before to an extent. If I shave close people will honestly think I am in my late twenties.
My view on this is the following: Any senescent cell clearance benefits will show up slowly, just like the negatives of having them in your body to begin with. I would use hormone therapy for gender reassignment as an example. If you see how long HRT takes to have real results its about 6 months to a year with the most dramatic results at the 2 year mark. So quickly making assessments about fisetin is likely foolish as the body needs time to regenerate lost cells, and cells which were antagonized by senescent cell signalling need time to adjust back into equilibrium.
Additionally fisetin is shown to be more effective in certain tissues. I think more so in muscle tissue, and some organs.
Overall I am seeing and experiencing good results. My energy levels have remained high ever since dose one. I still remember myself a year before starting and even 4 years back. I was dead tired after work, hard to stay focused on anything mentally and lethargic. That is no longer the case and my new norm is lots of energy and focus, and I can stay up till 2 am if I want.
My current regime is 25x 100mg tablets. I will do this for 3 days. The main thing is I noticed no side effects. A little jitterness in the first few days when doing a treatment and then that goes away. I was worried about my hairline but it does not seem to have a lasting effect though I suspect if you dosed constantly it could so something there. All in all I suspect this is effective in humans just as in mice, but we have to look 2 years out to see results and then compare ourselves to our no longer existing former selves who did not take the treatment.
If there are any questions for me I can answer. I will say this, fisetin works, it's safe, and likely it does exactly what it does in mice, only in humans. Fairly exciting stuff.