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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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.
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JGC
I can show you who it looked like. Your question made me curious so today I used two oils. Olive oil and avocado oil.
In the picture the avocado oil is to the right and olive oil is to the left. Not much difference. The mouthfeel was very much the same. And not any of them became a clear fluid. I used my regular kitchenoils and they are unflitered. But that goes for both of them. The avocadooil to the right has a tiny bit darker color.
Today I had 30 mg/kg fisetin and without any piperine/black pepper/piper longum. The larger dose of 30 mg/kg and yesterdays headaches made me cautious. The experience I have today is milder. I have not experienced any headaches today. But the day is not over yet. Compared today with my experiment 4 weeks ago when I only had 20 mg/kg but then with piperine/piperlongum, then I must say that todays session is much milder.
At this point my very own and subjective experience is that fisetin should be a part of a combination with piperine + some other senolytic substance.
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Thank you for documenting and sharing your data
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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.
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JGC
Thank you for sharing! A few questions-
So your wife and daughter had no such signs?
Did they take the same dosing per body weight?
How long ago was the previous dosing?
Was it the same?
thanks!
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BobM
My wife and I have close to the sam body weight and had done three sessions of Bioperine (10 mg/day) and Fisetin (2,000 mg/day in olive oil) about August 15-17, and my daughter had done three sessions of Bioperine (10 mg/day and Fisetin (1500 mg/dy ) last week. This was our last session and the only one with D+Q. Before that, all of us had done similar senolytic sessions around the first of the year. We had intended a 6 month spacing, but we were a bit late.
Neither my wife nor daughter experienced my symptoms from the D+Q+F+P, but my daughter reported muscular aches resembling the flu.
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JGC
Thank you for sharing. I speculate that dasatinib + alcohol can put to much stress on the liver. but a recommendation to avoid alcohol when doing senolytic treatments seems like good advice.
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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.
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There's no point in taking Fisetin with water. Mix it with oil, or a fatty meal.
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I've been mixing 2g of fisetin with 2tbs of MCT oil and 2sbs of ghee. Blended it quickly with a double espresso. This is my third day and I've had no negative symptoms. I plan to do two more days and then get blood work done in a month.
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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.
https://www.degruyter.com/downloadpdf/j/tnsci.2013.4.issue-4/s13380-013-0137-y/s13380-013-0137-y.pdf
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.
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John Whitling
Thank you for your report. Based on your experience 3*700 mg is needed to get benefits. That is a useful information. I think insufficient dosing (or wrong dosing) is that factor that make quite a few products fail to help people. Nowadays I use green tea max. it is supposed to be more bioavailable and to remain longer in the body.
https://www.lifeextension.com/Vitamins-Supplements/item02305/Green-T-Max
After reading quite a few scientific reports I have found out that we might have to drink at least 1 – 1.5 liter of green tea to be sure to get its preventive and disease delaying effect (at least when it comes to the onset of many cancers).
When it comes to EGCG and dementia and other diseases of the brain there are interesting reports from japan when EGCG is used together with ferulic acid. Promising results on dementia.
https://www.sciencedaily.com/releases/2019/03/190306133414.htm
we have a section on this forum that is dedicated to Green tea extracts.
https://forum.age-reversal.net/t/m2cwax/green-tea-and-green-tea-extracts
If you like to share more information from your experience and knowledge of EGCG the above mentions forum might be a good place for future posts. Thank you for your information about the dose that is needed to achieve benefits in a AD affected brain
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Staffan Olsson Thank you for the lead on ferulic acid. I will look into that. Also the forum links are quite helpful as well. Given it's effect on aging I am a little surprised that you do not have an APOE forum. I couldn't find one anyway and the site doesn't have a search tool that I could find. APOE status effects cardio as well as neuro health .. it creates advanced aging in it's APOE4 status and it changes the way that cells create and process energy. APOE2 actually extends life.
Just to be clear the dosing of 3x700 mg EGCG is just what works in our instance, and it's not just about AD, it's really about any chronic brain inflammation. Brain inflammation is common in head traumas, bacterial infections, etc. I believe that it is the the primary cause of the spike in medical workers suicides, though that is only speculation on my part. More and more, research shows that real physical depression is also due to brain inflammation as well.
When you consider how often medical workers are around infections and bacteria is reasonable to theorize that they could be picking up the same kinds of things their patients often have.
One other thing .. we found Green Tea Max to be pretty useless, perhaps because of dose, but it seems that more likely that it's missing some critical poly phenol or something. Within a few days it was evident that it didn't measure up so we bailed on it then. I have a few bottles sitting around.
In a similar vein LEF makes a product called Cytokine Suppress. We tried that for bed time hours but the performance was the same and the half life seemed equivalent. I was hoping for a longer half life but no luck. It's much pricier than than Mega Green Tea Extract.
Thanks again!
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John Whitling
Thank you for your respons. When it comes to brain inflammation. I remember being at a stroke conference some 10 years ago. At that time they had brain inflammation after stroke as one of the subjects. (Depression is common after stroke). And one of the doctors proposed that brain inflammation also should be targeted in other forms of depression than just poststroke depressions. I have not really followed up on that lead. But it is always great to remember persons who are decades ahead of the mainstream folks. "I hope we have quite a few in this forum".
And Systemic inflammation as well as brain protection are two of my targets when it comes to anti aging. (Targeted with Omega 3, curcumin, Senolytic treatments and more).
It is interesting to hear about your experience of green tea max. Liposomes have a much greater availability then standard green tea. But it might not be metabolized in ways that makes it equivalent to regular green tea. Sometimes it is the metabolites of a substance that are responsible for the major effects that we can get from a substance.
BTW, when it comes to Ferulic acid and EGCG they used quite small doses. Good luck with your research.
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John Whitling Maybe you should try a Senolytic on your friend. Dasatinib and Quercitin are cheap and with the latest study shown to be safe in humans. Look at this study:
Scientists at the University of Texas have implicated a type of cellular stress for the first time as a player in Alzheimer's disease. And their discovery could lead to treatments for more than 20 human brain diseases including Alzheimer's and traumatic brain injury. One author of the study went as far as to say the treatment that researchers used on mice to rid them of the stressed cells actually stopped Alzheimer's disease "in its tracks."
After three months of treatment, UT Health said their findings were “exciting.” Orr said in a statement that the Alzheimer’s mice were 20 months old and had advanced brain disease when researchers started the therapy. “After clearing the senescent cells, we saw improvements in brain structure and function. This was observed on brain MRI studies (magnetic resonance imaging) and postmortem histology studies of cell structure. The treatment seems to have stopped the disease in its tracks,” she said.
Senolytic drugs only target and only kill senescent cells. They are cleared quickly by the body, and researchers saw no side effects.
Mice were treated with a drug combination including Dasatinib every other week. "So in the three months of treatment, they only received the drug six times," Orr said. "The drug goes in, does its job and is cleared. Senescent cells come back with time, but we expect that it would be possible to take the drug again and be cleared out again. That's a huge benefit -- it wouldn't be a drug that people would have to take every day."
Musi said he anticipates many further studies to understand the process using senolytic drugs. “Because these drugs are approved for other uses in humans, we think a logical next step would be to start pilot studies in people,” he said.
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Larry D&Q appears to be safe and effective in humans (small study but larger studies are ongoing)
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Larry That is my plan. That's why I've been lurking on this post for a few months. As for D being cheap and available, I am clueless about that. I saw the write up where you could get D without a prescription but only in FL and only to FL residents. Before my readings here on this post I was not aware that it was high acute dosing.
Where can I get D. I am in Ohio, BTW, if it matters. I understand that the dose is small in comparison to Q .. maybe a 10 to 1 ratio.
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John Whitling John Whitling I got mine here: https://www.dropshipmd.com/
I had quick and impressive results so I am confidant it is real. I also used them for Rapamycin. Use Western Union.
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Larry Thanks!
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Larry FYI, they say that cannot ship generic dasatinib to the USA. They mentioned sprycel ( a generic version) but said they were out of stock on that too.
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John Whitling They must have got pushback from the USA. You can try this Doctor. He started a new practice called Qalytude. I'm not sure if he is writing prescriptions now but he says he will in the future. https://www.youtube.com/watch?v=pRhOYL_n9lk
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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
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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).
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For those interested in dosing of chlorogenic acid. They studied the metabolism of chlorogenic acid by giving 2000 mg to the participants. So that (2000 mg) is defintely a tolerable dose. if (and a big IF) chlorogenic acid t can be used as senolytic the dose would probably be much higher.
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Swanson Vitamins has Their own Fisetin supplement out - equivalent to Dr Best. lots cheaper!!
$10.39 / 100
https://www.swansonvitamins.com/swanson-ultra-fisetin-100-mg-30-veg-caps
Free shipping with $50 order...
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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.
