Fight Aging!

Powerful senolytic with apparently no adverse side effects, easily attainable and inexpensive, what are we waiting for? It's amazing something so simple could have such a huge impact on world life expectancy.

Check clinicaltrials.gov for the Mayo human trials of fisetin. Dosage is 20 mg/kg/day for 2 consecutive days. I've already done my trial.

@Proud Daddy
What brand of Fisetin supplement did you use?

From what I hear most of the human senolytic trials are using higher doses that you'd get by the usual method of scaling up from the relevant mouse studies. I haven't had a chance to chat to someone who knows why this is the case.

I am hoping to be using Senolytics within 2 years. Would anyone hazard a guess when data would show the safety and effectiveness of Fisetin? This sounds like an effective 1st gen (and low cost) Senoytic treatment. I am hoping we are talking months and not years for some definitely data results.

BTW, I looked on Amazon for what is available and cost for Fisetin.

@Robert
The safety is kinda already proven. It is a widely available supplement and it is considered to be a neuroprotector without proven ill side effects, if taken in moderation. Probably you will need to take a cocktail of different weak senolitics including dasatinib and navitoclax to get a detectable effect. I am not sure whether fasting for 2 weeks, can give a better effect than the weak senolitics, but that's the poors man autophagy booster that is available even now...

I waiting for OISINs mice study to finish. p53+p16 targets seem to be doing much better than the control group. My hopes are high on their approach. And i am rather skeptical about finding a strong senolytic within the existing supplements. If it was available, somebody already should have seen the remarkable effects by now.

Hi there, hoping this pans out into something tangible (in humans). I think we should curb our enthusiasm (not to be pessimistic) but because mouse study results don't always translate 1:1 to human (more often than not, they don't translate at all because we have different 'specie master plans/blueprints'), with that said a 20% extension in mice might give us a 5-10 year boost in health and lifespan. I'm saying this because we already get some (though not much in general) senolytics in the food we eat or beverages drunk (red wines/red grapes, certain fruits and vegetables). This means that it may be end up being redundant (or it may synergize but I doubt it because of pathway redundancy (i.e the therapies are just emulating what these senolytics are already doing), long lived people drank (and thus consumed senolytic mimics) red wine, like centenarians (yet other centenarians did not drink once ounce of wine and ate plenty of crapfood (that kills everyone else) and Still lived to centenarian. Demonstrating, clearly, that its 'some placebo' effect there and 'mild' improvement in health - but it's genetics (epigenetics specifically, which act in concert with/to damages but superced damage as a signature you cannot just erase by removing damage/even reprogramming proved it you can't erase cell age memory) that determines if you reach a 100 or not (you inherited family genetic is also behind this, it touches the intrinsic genomic epidevelopment; which is different than the extrinsic one molded by external factors). Taking senolytics will improve external epiaging, which relates to health status (senolytics reduce SASP/p16p53/IL6/TNF, basically reduce inflammation and general stress, oxidative stress too. But, this is still something different than your DNA intrinsic epigenetic aging clock which relies on cell passaging (something uncoupled from replicative senescence/Hayflick limit and telomeres attrition; they are just independent measures of your health but the one that dictates chronological lifespan is in the methylome landscape; damages just accelerate that (as seen in Hutchison Gilford Progeria) but 'regular' 'healthy' aging is dependent on cell passaging (can be uncoupled from senescence); unlike accelerated aging (HGPS/Werner) which relies on replicative senescence acceleration). In my mind, the cell 'age memory' is what determines longevity, this signature is (so far) irreversible/permanent once written (the cell Never forgets its age and thus 'act' appropriately to its age despite being reverted to immature state ('Age 0')).

I hope they make these therapies available soon, we have been talkinb about SENS since....god knows whwen, sh*T needs to happen, we are aging and people don't give 2fcks about these therapise, they prefer botox and beautiful cremes (or even, goodness sake, surgery (f...!) of their face), face lift, and look 20 again in the mirror; who doesn't?

There is a saying (I.Newton i think) :

''Work expands as it completes itself and 'fill its time' to be made/accomplished''

which basically, means, it could take long(er), still. And we ain't gettin younger. I know we still have time and have to 'tough' it but the more time passes the more I realize we were too eager/too optimisic/too innocent, there are so many obstacles, people that don't want longevity extension, peoplpe who love to 'die' (aka fatalists) and force us 'to accept our fate and be good person with a conscience not selfish', people screaming 'overpopulation' and bs, FDA/health regulation hurdles and sh...I fear we will wait AT least another 15 years before we see ANYthing remotely 'good'. The 'news' you hear are falling on deaf tone ears and they baby steps - that scientists have been making for what? like 40 years now, baby baby babysteps one after another...- you're dead (too late), missed the boat.
It is excrutiatingly slow AF. We don't have much time (those say, hey we have 30-40 yaers ahead of us, keep on saying that, and times goes, 'you said that 10 years before??'...OK, I'm exaggerating and going on a ranty tangent a bit (sorry)). I just feel that the biogerontology domain is both its own accomplishment and its bane. Its accomplishing Great Things, yet at the same time, not much either 'in real time'; in very long time yes, not in short 'real time'. I know that thatis the 'speed' we can get and it takes huge efforts hence why so slowmo, but it's also normal for people to get fed up and just say fck it...and leave it all altogether. It,s like this Grand Project, that may never happen, when we are older, and then...sh*t..(then) what? (we're fckd/we thought all along that this grand project would save us). That is why I try to curb enthusiasm and be more real in terms of advancement with this (I am now thinking 20 years sounds about right before anything super duper big happens/ultrastagnation the name of the game (small development don't count much if they are not marketed to public and Happen tangible/be sold to humans after trials), 20 years, in 20 years I will remember I spoke about that 20 years BEFORE...and still to same point roughly).

Just a 2 cents.

@Cuberat
Regarding the idea that the beneficial effects of fisetin should have already been seen, I have been wondering about this myself.

If we assume that the effect size in humans is a ~10% gain in longevity, and then only after years of regular use starting at least in mid life - this effect might not be evident from uncontrolled anecdotes alone. And it would take a long, decently powered study to observe this in the clinic - one that as far as I can tell hasn't ever been attempted. There are a mere 5 results on clinicaltrials.gov for "fisetin," 3 of which were just started at Mayo and all of which were posted after 2016.

Now if we were talking about curcumin (183 results spanning many years) then I might be more skeptical...

@CANanonymity - a lot more impassioned than usual, I gather you feel time's running out. I'm 55 - are you older than that? I agree that humans aren't two-legged mice - we need to find much better testing methods. Now go and put some of those 2c coins in the Swear Jar :) :)

This is a pretty cool, slam-dunk of a paper and a great 'low-hanging' fruit given fisetin's low cost and availability.

Assuming bioavailability issues can be overcome and this is translatable, fisetin alone seems to be able to reduce senescent cell load in many tissues by ~25%. It will still rise with age, even with treatment, but the burden will be less.

No doubt combinatorial therapies will be even better.

Fisetin might be a winner.

Fisetin is found in strawberries in higher levels than other foods and a clinical trial with 60g/day freeze-dried strawberry powder reversed pre-cancerous lesions in humans.

https://www.ncbi.nlm.nih.gov/pubmed/22135048

Re dosage and brand. I'm using Doctor's Best fisetin via Amazon. Dosage for me is 1/2 BOTTLE each day for 2 days using the Mayo clinical trial dosage. I doubt that anyone has been taking fisetin in this manner, so it isn't surprising that nobody has experienced profound benefits from regular use.

@Will
A significant reduction in the senecent cells count should bring immediate and quite measurable health benefits. If fisetin was that good you would be witnessing major health improvements in the users. We can have several explanations what it is not the case

1. Fisetin doesn't work for humans very well 2. The bio availability is low 3. It comes with toxic sure effects. The first option basically gives no hope with this compound. The second one, requires research to improve the bioavailability (there's room for patenting medications that improve the bioavailability and that enhance the effects). It would take years for human results. The third option in a way, suggests immediate benefits. The toxicity world imply that the effects are there but not very targeted. With proper protocol the poison can become a cure. Again, they're options to patent compounds that protect non- senecent cells

And there is one more explanation that nobody noticed so far. I am not holding my breath on this. I would be glad to be proven wrong, though

@CANanonymity
Alas, what is needed is not aligned with way
What is happening. We might be on the teaching of rechuing LEV in 10-15 years. Or cold be 50 years away. And acceleration to LEV Aaron be quite uneven. People with more mean it knowledge could be 10 years ahead of the general public. For example, we (at FA and related forums) know that dasatinib should work, and the moment we have a credibile confirmation for humans, we will find a way to obtain the compound, nevermind that it costs 200$ a a gram and requires prescription. Of course, we don't know the good protocol and it is very hard to Measure the count if cenecsent cells.

@Reason: from what I can tell, Human Equivalent Dose is both inexact and controversial. It's main purpose is to start human trials without killing anybody. Effective doses are often much higher than the 1/12th of mice mg/kg HED would be.

HED is based on relative surface area. The relative rate of metabolism of a drug would seem to involve a lot of other factors.

@Reason

Do we have a theory of the damage level caused by the cenecsent cells concentration? Does it go up linearly, exponentially, less stat linearly, or does it have a more cold l complex dependency?

Is a 25% refuction enough to increase the health span? I would guess that the improvement would be more for the general population and spectacular for some isolated cases

what is the right dosage for humans?

@proud daddy are there any adverse effects from hugh dosages of fisetin?

When purchasing some long pepper peppercorns on Amazon (after giving up on finding a good source of the root), the section titled 'Frequently Bought Together' showed a fisetin supplement; apparently people have been trying the combination.

The shipment finally arrived yesterday; I literally can't believe how good it smells. I'm hesitant to ingest it since it smells like they dunked the peppercorns in patchouli oil.

~
Strawberries deserve their reputation as a functional food; strawberry consumption is associated with reduced all cause mortality:
https://www.ncbi.nlm.nih.gov/pubmed/?term=28606222

~
I'd be happy to contribute to a crowdfunded well-designed human trial, if such a thing is possible.

@Scott. Adverse effects of high dosages are possible but unlikely. I doubt that the Mayo Clinic doctors would use them in a trial without a high degree of certainty that they're safe. I've used the half bottle dosage for two days twice now, and noticed no I'll effects.

Also, remember that maximum safe usage doses are based on continuous use, so no current guidelines would apply.

This story is eerily reminiscent of the Phenoxodiol saga, from the Australian company Novogen, back in the late 1990s-early 2000s

Structured off another of the 6,000+ flavanoid polyphenols, it looked great in animals and cancer models, but failed to do anything meaningful in the clinic

Turned out to be a very weak chemo-sensitizer, as most of these substances end up being in humans

Probably best to save your money and eat a lot of dietary sources of these things, or which their are 000s

@proud daddy when you say 2 days do you mean 2 days every week or something?

@Scott. Please go to clinicaltrials.gov and get the details. So far, I've repeated the 2-day regimen once - 4 months later.

Here's the entry:
https://clinicaltrials.gov/ct2/show/NCT03675724?term=fisetin&rank=1

@proud daddy
Are you monitoring any biomarkers?

I want to thank Proud Daddy for the info, and CD for the link. Looks promising and looking forward to the clinical study results. Also, it would be nice to hear from you Proud Daddy over the course of next couple years as well for your results as well.

@CD. I'll be getting A1C and hsCRP in November. I'll try to remember to post the results here, but I'm 77 so...

Over and over again, treatments that work well in mice have shown to be useless in people. We, as a species, are probably close to bumping up against intrinsic age barriers, unless we develop mutations such as the antitumor mutations found in mole rats, or the multiple copies of the p53 gene found in elephants.

We had been breeding ourselves, slowly, for longevity, by having older males have children with young females. That process has pretty much stopped, but clearly we did have a drive for longevity, whereas many other species, like mice, do not have any similar longevity driven (living longer would not benefit them reproductively), which makes increasing their life-spans "low-hanging fruit."

I take care of the very elderly, and looking at their skin, muscles, etc., probably the only thing holding them together at all are those senescent cells (and the foamy cholesterol in their arteries).

I suspect that, as mammals passed through the evolutionary bottleneck at the end of the Mesozoic, we lost crucial cellular DNA repair gene complexes. We need to examine other life forms, probably aquatic ones, to find the gene complex that repairs genes better than the existing, somewhat simple-minded ones, we have now, and find some way to integrate it into our genome.

@Benjamin Wade: What if we with biotech could end menopause and older women got children with younger men. Would that be the same effect?

@Benjamin Wade: Im not sure that the effect has stopped. Today I saw a women 30 with a man 40 buying an apartment. He were so much older because that were in the age segment she could find anyone with a sufficient income. Its easier today to get jobs for women (nurses), then for men, which jobs get automated. I think the effect can speed up. There should be research on it.

@benjamin wade "what works in mice are always useless in people?

not true, there have been things that have had just as good effect in humans like in mice. i agree with the caveat, but you can never tell for sure until a propper human trial has been conducted.

lets try and be open minded before jumping to conclusions

@Norse
the funny thing is that the stronger the breeding effect is the slower the progress would be since postponing childbirth till older and older age will make the generations longer and longer. And dilate the periods. So for that effects to have a strong difference we need to wait a few generations. Say the first child is at the age of 35. 5 generations are already 150 years.... And probably there the effect would be to shift to having the first child at 40....

Looking at the clinical trial that was linked by CD, I see that it's phase 2, but I can't find the phase 1 trial. Has anyone seen it or know the results?

@Benjamin Wade & Norse : Interesting idea about the age differences in relationships being a factor in life expectancy. Now that men are considered creepers if they date a women more than 5 years younger than themselves in the West, I wonder what impact this will have on life expectancy in a few generations time?

I'm speaking as more or less as a layman, but to the objections that this wont work on humans, in particular because we already likely get enough of these natural senolytics in our diets from various foods already, the following is from the Newsweek article on the study :

"The team also tested fisetin on human fat tissue in the laboratory, to see how the drug would interact with human cells, and not just mice cells. Since they were able to reduce senescent cells in the human fat tissue, the scientists think it's likely fisetin will work in humans. However, the amount of fisetin in fruits and vegetables isn't enough to have these benefits-scientists still need to work out the best dosage."

https://www.newsweek.com/fisetin-natural-fruit-vegetable-slow-aging-1151304

In a few generations I should hope we are no longer relying on the genetic crap shoot for reproduction. Longevity can be engineered in. Deciding to create a new life has always seemed to me to be more than a bit hubristic. Petulant teens do have a point - they never asked to be born. Even if a parent can guarantee a good genome, they can't guarantee that their child's life will be mostly full of joy versus suffering, if the good will outweigh the bad. In a post-singularity future, if someone wants a new person in the world, it will be possible for them to redesign themselves and they will be the only one to have to live with the outcome of their decisions. If they want another being to adore them unconditionally they can get a (possibly augmented) dog.

@Transhumanist Runner

Unfortunately, it's never just about dose, but complex pharmacokinetic and pharmacodynamic differences between species

As I said above, study the history of Phenoxodiol (one of thousands of similar compounds that have been in large scale clinical trials) to see the inherent issues of this approach

http://www.touchoncology.com/articles/phenoxodiol-chemosensitizer-midst-cancer-chemoresistance

Perhaps it may have benefit as a "seno-sensitizer"

I just took 3,000 mg of Fisetin, along with 1,250 mg of Quercetin. In a few days, if I've suffered no ill effects, I plan to take 1,200 mg a day for five days. If I live, I shall write a follow up comment. I know this is foolish, dangerous and urge others to use caution.

The Mayo study cites 20mg/kg/day for their study. This translates into 1400 mg per day for a 70 Kg human. Is the study using Fisetin in pure form, or the version you can buy off of Amazon. How may days does one it for? A week? A month?

Someone here is using "Doctor's Best". Any others?

Any more thoughts on this?

I was planning to wait a couple of years before diving into the senolytics. But I'm now thinking I might want to give this a try.

The problem I have with the D & Q combo is that the Dasatinib is not specific enough and will kill functional cells that you don't want to kill and the Quercetin is essentially useless on its own.

@scottalias
While your are taking much higher dose than what is usually recommended , it should not be life threatening, unless you have some serious kidney/liver/metabolical problems. Now there might be some harmful side effects but I am not sure that taking it orally ensures such a high bio availability. So, of you don't do the overdose now than a couple of weeks and don't have some serious problems already, you shuold
be ok... And have some more expensive pee ;)
Of course, your milage will vary...

@Abelard Lindsey
That's the catch 22. You want to kill the senecent cells, therefore you need to use something toxic. The less toxic the compound is the fewer cells it will kill. So a generally available medicine cannot be a strong senolitic without being a portion.
If the compound is highly targeted, then you limit the effect to the senecent cells. We are not there yet. Even Oisin platform is not strong enough. At least it seems to be very targeted...

So there will be some collateral damage. And here we are threading uncharted waters. We care about the senecent cells with harmful secretion. Penally killing 1 good cell for every cenecsent one is a good tradeoff. ( I don't know about the brain, though)

As for should you try it ... It is a cost versus benefit decision. If you don't have a measurable inflammation that can be blamed on cenecsent cells then I don't see much benefit. You might have some inflammation without notifying it, though.

Dasatinib has well documented side effects and the risks should be more or less clear. We don't know so we'll what will be the side effects of the d+q combo. I would err on assuming that adding quercetin is as bad as increasing the dasatinib dose. So if you are young and healthy you could easily tolerate d+q but then there will be no benefit. While I want to see human results of this combo I cannot advise you on trying it...

Abelard Lindsey
I'm using the Doctors Best brand, from Amazon.

Cuberat, I am in good health, I appreciate the concern. The supplement is quite affordable. The high dose was an impulse, but I see Proud Daddy has survived essentially the same dose split over two days.

It's been nearly twelve hours and I feel fine, quite well, in fact. No negative side effects, so far, and I feel like something is happening. Don't try this at home.

@Benjamin Wade

" ... clearly we did have a drive for longevity, whereas many other species, like mice, do not have any similar longevity driven (living longer would not benefit them reproductively), which makes increasing their life-spans 'low-hanging fruit.'"

It would seem to me that some of it has to do with kin selection dynamics in our ancestors -- i.e., grandpas and grandmas made significant contributions to the reproductive success of their close relatives (children and grandchildren) and thus increased the frequency of their own longevity-promoting genes in the population. Not as strong an effect as we would all like (too much death by predation, accident and infection), certainly. Mice don't help their adult offspring, at all.

I redid the calculation. The appropriate amount of fisetin for a 70Kg person is around 700mg/day, not the 1400mg/day I cited earlier. I found the paper this blogger linked to in a previous posting about animal to human dosage calculation and have downloaded it. I am using it to calculate appropriate dosages for various senolytics as well as other stuff that may or may not remove lipofuscin. Needless to say, the next 8-12 months will be interesting for me.

I took 1400mg of the Amazon "Doctor's Best" Fisetin last night, about 2 hours before bedtime. I weigh approximately 70 Kg and my age is early 60's. Administration (rather than choking down 14 pills) was to open each pill into a glass holding approximately 8 oz, then add cold water. Very little taste, not unpleasant, a little chalky.

I plan to take an additional 1400 mg tonight about the same time, then nothing more until about 3-4 months from now.

I did notice about an hour after taking it that I had a slight burning or itching on my forearms which passed quickly.

I slept well, as usual. When I first woke up this morning, I was feeling a bit hot, like I had a mild fever. That also passed quickly.

On the positive side, for quite some weeks, I've had constant inflammation/stuffiness in my nose, particularly on the right side, which is now much improved.

I do seem to have more energy this morning, but it's too soon to tell if that's real or just my imagination.

Day 2, second 1400mg of Amazon "Doctor's Best" taken last night, about 4 hours before bedtime.

It was taken a couple of hours earlier than the night before, so I got to see more of the immediate effects. No burning or itching on my arms, just a little on my face. I did get the hot and feverish feeling again, however. I checked my temperature by mouth, and it was only up a couple of tenths of a degree. I did, however, have some shaking/trembling of my hands.

I woke up this morning after a good night's sleep, still feeling a little hot/feverish. I also had a headache, but no more shakes.

One strange effect - I could taste the fisetin again very clearly about a half hour after getting up.

By now, two hours later, it has all passed, and I'm feeling good, with a high energy level.

I plan to wait 3 months or so before taking any more of it.

It's been six days since I took 3,000 mg of Fisetin and I've noticed a reduction the symptoms of my BPH (Benign prostatic hyperplasia). I Googled BPH and senescent cells and found a wealth of information suggesting cellular senescence is implicated as possible contributing factor to BPH, and considerable research into polyphenols in general and Fisetin in particular for treatment of BPH.

It's been about a week since I took 2800 mg of Fisetin across two days.

Sinus inflammation is still much reduced from what it was prior to the dosage.

Mental acuity is hard to judge, since it's affected by so many different factors (tiredness, stress, amount of sleep, etc. etc.) but I do think I'm sharper - less episodes of searching for a word, for example.

FA says ". Consider a combination of fisetin, dasatinib, quercetin, piperlongumine, and FOXO4-DRI - multiple different mechanisms to provoke apoptosis that are all hitting senescent cells at the same time" The study being conducted on humans will use 20mg/kg of Fisetin for two days.

Opinions needed! for a two-day zombie cell clearing:
Should fisetin be consumed on an empty stomach or with food.
Take all 1200 mg at once or in divided doses each day?
Should capsules be taken whole or dumped out and mixed with some type of oil
Should piperlongumine be taken at same time or later in day?
How much piperlongumine to go with 1200 mg of Fisetin?
How much Quercetin to take at same time or later as well?
Stop all other supplements those two days?
Should we try to get FOXO4-DRI as well (hard to do)?

I hope this thread is kept up and the likes of Pete and Scottalias continue to give weekly updates. Maybe Reason should highlight it in the sidebar or something?

I notice that fisetin quickly sold out on Amazon UK. There doesn't seem to be any way of getting hold of it now in Britain other than ordering from the USA.

I would love to perform my own self-trial. As an aging runner suffering from manifold inflammation problems that hold me back, I could provide some 'objective' anecdotal feedback if my times were to suddenly improve.

Took 700mg Fisetin for 2 consecutive days about 1 wk ago. The very first day I noted a marked diminution of back pain which has contunued to present. Even if this is placebo effect I'll take it! The question is whether the Mayo study is a two shot deal or is this repeated monthly? Any advice pros and cons to a monthly repeat?

My one concern is if large dose fisetin "purges" senescent cells, isn't it in effect similar to chemotherapy. Could fisetin kill other cell lines such as stem cells? People who undergo chemotherapy and survive their cancer in the long term can have significant side effects.

Any thoughts on why fisetin would cause apoptosis on senescent cells but not stem cells.

Some articles:
Role of Flavonoids in Future Anticancer Therapy by Eliminating the Cancer Stem Cells

Still going strong, sinuses still seem much clearer than they were before fisetin. I do think there has also been an increase in mental acuity, less episodes of "fishing for a word," and the episodes that do occur are shorter in duration.

I'm planning on another course of treatment towards the beginning of the year. I'm shooting for one every quarter (3 months) if I can still find the stuff!

I don't know if my "1400 mg per day, two consecutive days" is any better or worst than 500 per day for 5 days - the total dosage works out to be about the same, and I tolerated the 1400 mg with no problems.

As I understand it, fisetin targets only senescent cells, not stem cells, but then again, that's the risk with self-experimentation, yes?

It does seem to me, however, that senolytics are causing senescent cells to die, which means that they have to be replaced by the division of other cells, which will bring those other cells "close to the brink." It makes me wonder, then, if there isn't a point when senolytics would push organs over that brink in a chain reaction.

I find this paper to be somewhat disconcerting when it comes to using fisetin as a senolytic.

"The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells"
https://www.sciencedirect.com/science/article/pii/S138357180900432X?via%3Dihub

I imagine the structure of DNA topoisomerases I and II are highly conserved between mice and humans being as they're integral to DNA replication, and no side-effects from fisetin (like leukemia or something similar) were seen in the mice to my knowledge, so perhaps fisetin doesn't have such a strong effect in the body. Still, it makes me question the safety of taking fisetin in the large doses that seem necessary for it to act as a senolytic. Maybe the good outweighs the bad though?

Tranhumanist Runner: I had some trouble getting the Fisetin delivered, but finally got it. I have decided on a course of 1,000 mg (1 gram) a day for 15 days, today will be the seventh day. I am taking it on an empty stomach. The reduced symptoms of BPH have continued, hard to say what other effects I'm having. I have no way of measuring the senescent cells in my body, so any anecdote I might relate can hardly be taken as scientific evidence. Recurring pain in my back has dissipated, but that could have any number of causes, including psychosomatic causes. I've had slight trouble getting to sleep while taking the supplement, that happened when I took the large dose and stopped the next night. I have been sleeping, just have trouble getting to sleep, I have a feeling akin to excitement that I have associated with the supplement. Mainly, I've not noticed much of a change and don't expect to for a while, months or years will tell if I have less dementia, arthritis, frailty and other age related symptoms than I would have had if I had not experimented with Fisetin.
Adam Hruby I can find no evidence to suggest that links Fisetin with leukemia, quite to the contrary, Fisetin is thought to have a chemopreventive/chemotherapeutic potential against various types of cancer. Self experimentation is, however, fraught with risks and inadvisable. You should surely wait for FDA approval, which should only take a few decades.
Pete, I am thinking an organism needs a sufficient dose for a sufficient number of days. Five days for a mouse that lives a couple of years and five days for a human that can expect to live eighty years are vastly different time periods.

I have been looking into the dosing in the study which works out to about 20mg per KG equivalent in humans. The one issue I see is that mouse lifespans are so much shorter. In this study, they found that one human year is equivalent to nine mice days. https://www.ncbi.nlm.nih.gov/m/pubmed/26596563/ Sonic nice had this effect in 2 days of dosing, would that indicate that for the same effect in humans we would need to take that dose daily for just over a month? That could get rather costly. What are everyone's thoughts?

I purchased 4 bottles (Rejuvenation Therapeutics) on Amazon after reading the article in Science Daily, thinking to add the 100mg to my daily routine. Now I've read the (above) forum I see that many are mega-dosing for just two days or a week.

Curious how long Fisetin stays in the system, would it build up over time? Can you see any benefit to taking 100mg daily open-ended? Or must one go for the 1400mg for two days?

I took 100mg today, broke open the capsule and let 1/4 the yellow powder dissolve on my tongue (just to make sure no allergens). No taste. 30 min later took the rest of the powder. Had a headache for an hour or so after. I rarely if ever have headaches (once a year?). Maybe just the delivery method (dissolve). Will swallow the pill tomorrow.

Michelle,
We're just guessing on the dosage, and self experimentation is hardly scientific. I've taken a thousand milligrams a day for 12 days, with 750 mg of quercetin a day and plan to continue for 3 more days.

My observations so far: I have less frequent urges to urinate, a symptom of BPH, I have slept through the night couple of times, for the first time in decades, and now get up once or twice a night to pee, a marked improvement which may have something to do with Fisetin.

For a couple of years, I have had an urge to drink a lot of water, over 2.5 liters a day, which my doctor attributed to my pre-diabetic condition. I don't feel the need to drink so much water any more and will be interested in my A1C and fasting blood sugar tests in January of next year. I feel like I may no longer be pre-diabetic. I have been carefully watching my diet and exercising for a few years, so this may or may not have anything to do with fisetin. I've also added a tablespoon of Moringa a day to my diet, which might be a factor.

I'm having some trouble sleeping. It takes a while to get to sleep and I wake up early and this is something I associate with the supplement so I look forward to the end of this experiment. My appetite has increased and this is not good because I am overweight, but I feel like exercising more, and am exercising more. The trouble sleeping is not that bad and if I still feel like this had benefits I'm going to do this again next year. I like to think this experiment may have delayed the onset of arthritis, dementia and a host of other maladies and look forward to scientific testing on humans, which should begin soon.

Transhumanist Runner, I'll try to remember to update this after January 8, when I get the results from my physical, my blood work and all.

Rice, I read on another article that positive results were seen with both daily dosing and intermittent high dosing, so, who knows? I also read curcumin had a similar effect in the same initial test but was not tested in high doses on mice because fisetin killed more senescent cells in the cell cultures, but not that much more. I think I might try curcumin next month, probably with the recommended dosage.

My father took a 1,500 mg dose of Swanson brand fisetin on Saturday and another 1,500 mg on Sunday. He is 72 years old, weight about 170 pounds. The only reported effect on Saturday was a bit of light headedness within 30 minutes of taking the dose that lasted for around 2 hours. Sunday morning he reported fatigue that lasted all day and a bigger appetite. He did not experience the light headedness after taking the 2nd dose. Monday he reported feeling even more tired than on Saturday with the same level of appetite. The only other report of interest is that he feels he can breath better, he has asthma. I'll make follow up posts in the days ahead.

Guys, any success stories?

@Corbin, I believe the reason why your father felt tired may be because of the mechanism of senolytics. They kill off senescent cells, which then must be purged from the body via the immune system. Because of that, they could present like a mild illness (i.e. tiredness, even more appetite to replace energy reserves) until the cells are purged.

When I took my dose, I did feel a little bit "feverish" the next morning. I'm not as old as your father, so I don't have as many senescent cells to purge, so my effects were probably milder.

Just my thinking. I'm not a biologist, but an engineer, so don't take it to the bank.

By the way, still feeling fine, nose still clearer (inflammation much reduced since before the dose), and still feel cognitively smarter.

I plan on taking the next dose in late December or early January. I'm toying with the idea of combining it with quercetin, but don't know if that's a good idea or not.

Fisetin is good for health?

Thanks Pete for the input, that was in line with my thinking too, I took it as a good sign that the fisetin from that company was the actual product. His fatigue lasted on and off until about 4 days after he took his last dose and pretty much returned to normal. There doesn't seem to be any noticeable change in his health or appearance two weeks later, except that he maintains that his asthma has improved and that I noticed he doesn't seem to cough as much. I'll give another update if anything changes.

Very interesting discussions so far!
I'm also planning to do my own personal trial with a 2x 1,300mg dose.
I am still relatively young (38) and in peak physical condition (exercise most days, compete in long distance races, great CV health, no health issues to speak of etc). The prospect of turning old frightens me however, and I want to delay ageing as long as possible so that my body is still "young" by the time truly effective anti-ageing therapies come around.
Is this a foolish idea at my age, or merely likely not to make much of a difference?

I've been on 100mg a day for about 3 weeks. Feeling no different. Maybe you only feel something at higher megadoses. Have added it to my stack and hopefully there will be some long term gain?

It seems to be impossible to buy Fisetin in Canada. Does anyone know a source?

Stephan - Can you order Amazon in Canada?

https://www.amazon.com/Rejuvenation-Therapeutics-Antioxidant-Anti-Inflammatory-Gluten-Free/dp/B07F1J9PDF/ref=sr_1_1_a_it?ie=UTF8&qid=1542977773&sr=8-1&keywords=fisten

@Rice Thanks for the link. Unfortunately, they don't ship this item to Canada.

@Stephen - if you really want it you can sign up for a re-mailer service. Like MyUS.com or USA2ME.com. Have Amazon ship to the address and then have them ship it to you. More expensive - but if you can't get it where you are...

@Rice Cool, thanks again!

Piotr-I don't think that's foolish at all, but this self experimentation with high doses of fisetin might turn out to be ill advised. It is generally recognized as safe, but at a fraction of the dosages we're using. I urge caution even if I don't practice it. I don't feel like I've suffered any ill effects. Recurring back pain has subsided, urges to urinate at night associated with BPH seem to be in remission, and I have less thirst that my doctor associated with a pre-diabetic condition. My sleep has returned to normal since I stopped the fisetin. I generally feel better and feel like exercising more. Whether this has anything to do with fisetin, I couldn't say. I plan to repeat this experiment about six months after the first try, maybe 1,500 mg a day for ten days. I will update this after January 8, 2019, when I have my labs done, and maybe around March if I do repeat the experiment.

I'd rather go with the mouse trial that has had positive results than with the human trial that hasn't yet been conducted! That reasoning led me to take 600 mg of fisetin for each of five days (with no noticeable effects). I'd like to caution our younger readers that the risk versus reward ratio for this protocol may not be favorable for people who haven't at least reached middle-age, at which time they may need "help" in clearing their increasing number of senescent cells.

Most fisetin supplements are derived from Rhus Succedanea, a toxic plant. Presumably, manufacturers know how to remove the toxic substances, but perhaps there could be enough left to cause symptoms at the high doses being tried by some reporting here...? The plant has some similarities to poison ivy, and one of the symptoms associated with it is a rash. So the skin irritation reported by some taking high doses *might* be due to such residual toxins, rather than to the fisetin as such.

I think it is important to read the original paper, which is linked to the synopsis that many of us read on sciencedaily.com. In the paper it clearly states that the results seen in mice were strongly correlated to dosage. One graph they presented showed negligible results at low dosages like the 100mg/day (ignoring body weight entirely) specified on over the counter fisetin supplements. Results improved dramatically at 10-15 mg/kg of body weight. You can also google Mayo Clinical trials to learn more of their current trial to treat frailty in elderly women over 70 and a second one that they currently recruiting patients for. Both seem to be using 20mg/kg of body weight for a couple of days at 30 day intervals for 3 months over a couple of years. I am in my second month using the same protocol as described in the Mayo Clinic trials with no negative side effects observed. Some decrease in facial wrinkles and a decrease in spider veins near my ankles has taken place. (Age 64)

Thanks for the feedback, all.
I have not yet taken the plunge; still debating whether to proceed.
Fully appreciate the point about the risk/benefit ratio being significantly higher for someone in their late 30s than in their 60s or 70s. My thinking is that, rather than wait for senescent cells to accumulate in large numbers and then get rid off them, I would like to stop aging in its tracks (relatively speaking, anyway) and prevent large numbers of senescent cells from accumulating through sporadic administration of fisetin megadoses.
All of this is, of course, highly theoretical at this stage.

Pray, let us keep this very valuable thread alive with current user fisetin experience reportage.

Many thanks and praise to Reason for providing this wonderful site and his informative views.

In the two and a half months since the last dose I took, nothing bad has happened, although the constant inflammation in my nose started to come baqck about two months afterwards.

I did another dosage of 1500 mg two nights ago, and 1700 mg last night (I still had 2 x 100 mg pills left over from October). In addition, I also took "Activated Quercetin complex" each night, containing 1000 mg Quercetin Dihydrate, 645 mg of Vitamin C (not my choice, but it was in the pills), and 500 mg of Bromelain (don't know why they put that in there. Whatever). As before, I opened all the pills and emptied them into a cup and added approximately 12 oz of water. To make it more palatable, I also added half a packet of Crystal Light Pure Raspberry Lemonade (mostly sugar).

Results so far - nasal inflammation has, once again, cleared. Felt a little tired yesterday, and significantly hungrier than usual (also reported by Corbin's father). I also felt a little light-headed the first night.

Today, not tired, still hungry, and have had some interesting sharp pains in various parts of my body. They pop up rather suddenly, last for about 10-15 minutes, then go away. They're rather sharp, and not associated with any activity that would have resulted in sore muscles.

I'll pass on anything notable. In any case, I plan to take another dose in 3-4 months. I'm curious if the nasal inflammation comes back again in a couple of months.

@Pete koziar - thanks for the update. I am thinking of taking 100mg to 200mg of Fisetin per day, not for the senolytic effects, but for the anti allergy effects. Steve Hill's article over at Leaf yesterday had some links to in vitro and in vivo experiments showing that Fisetin inhibited mast cell activation and T cell mediated late phase allergic inflammation (https://www.leafscience.org/fisetin-may-be-a-low-hanging-fruit-for-aging/).

Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice. (2014)
https://www.ncbi.nlm.nih.gov/m/pubmed/24525099/

The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes. (2009)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765609/#__ffn_sectitle

So it is not surprising that Fisetin seemed to have had an impact on your nasal inflammation. I hope will have some impact on my severe chronic allergic rhinitis (CAR).

I took 24g (24000mg) fisetin over a period of 8 weeks, 3 g / week, no adverse effects, all blood laboratory values remained perfect and normal.

3g a day also without any adverse effect.

I am a physician, neurologist, I would say that 6 g / day (6000mg / day) would be a safe dose.

(dr. kirklands trial: 1.5 g / day).

hans

New year came.

Ｉhave a question. Ｉsaw this comment,

＞Fully appreciate the point about the risk/benefit ratio being significantly higher for someone in their late 30s than in their 60s or 70s.

Mouse live more longer by taking fisetin from young age?

Thanks very much for good imformation! I want to know how to check the effect of taking fisetin, how to know the increasing of new cell! I want imformation!

This research about fisetin says,

Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.

So, there is possibly of benefits by taking fisetin from young age.

But it needs long time to prove.

↑sorry. above comment is not about fisetin but another senolytic drug research!

But there is possibly that this above comment is important.

It needs long time to prove.

I been following this post since it started in October. I've done a fair amount of investigation over the last few months on Fisetin. I have concluded that the data supports Fisetin as a senolytic; it's less clear if fisetin can perform its senolytic function when taken orally. The community understand that senescence cells are detrimental as the data makes it quite clear…with little room for argument.

I've started a regiment of 1.4 grams of Fisetin for two days. I've had no apparent side effects from that dosage, meaning no headache, digestive issues, lightheadedness, etc. I feel same as before I took the two doses.

The 1.4 grams matches my body weight appropriately scaled from the studies. I plan to perform monthly ingestions at 1.4 grams (two doses one day apart) for three months. At this time there is no reason to believe I will suffer any unwanted side effects. However if I do I will reassess and let the community know and I'll try to be as specific as possible. I'm a male, 55 year-old aerospace engineer in fairly good shape, not overweight, I don't work out, but I do eat fairly well…just you average "Joe". I also take NR (500 mg), MSM (4 g), Pterosilbene (300 mg),CoQ10 (200 mg) and PQQ (20 mg) every day. I have been taking these for almost a year. I don't believe my current regiment will affect/skew the results.

Currently I have no known aliments (I plan to stay that away as long as I can) so I'm not attempting to treat any ailment specifically. However, I do have slight joint discomfort upon waking and if I sit more than an hour. If you're around my age you know what I mean. I'm curious if the "achenes" reduce in intensity or go away altogether. I have no way to measure other than qualitatively. I will report on this and try to be as objective as possible knowing it could be a placebo effect.

Finally I've taken pictures of my face and spider veins. If I note any changes I will let the community know.

It's been a couple of months since I took 18 grams of Fisetin, spread out over more than a two week period, mostly in 1 gram (ten capsules of Doctor's Best Fisetin, six bottles) doses. As far as my doctor can tell, I have suffered no ill effects. I am no longer thirsty all the time, my fasting blood sugar is 86, my A1C is 5.4. My doctor attributes this to diet and exercise, and I have been exercising more with more intensity. I have felt like exercising more since the course of Fisetin, that could be psychosomatic or just a coincidence. I have less recurring back pain. The real surprise was my testosterone level. I've been using testosterone for nearly ten years and all of a sudden, though I was on the same dose of generic Androgel as I have been using for years, my testosterone level shot up to 1300. A month after that test, after cutting the dose in half, my level is 1049, which is a bit higher than recommended, and higher than it was at the regular dose, but not dangerously high. I have no idea if this is related to the fisetin, I've found no literature suggesting senescent cells can lower testosterone levels. All I can say about the Fisetin is I feel better, I've felt like exercising more, it may have something to do with my healthy blood sugar regulation and testosterone levels, but I take a lot of other supplements, including Nicotinamide Riboside and Pterostilbene (Elysium Basis for 2.5 years), Resveratrol (more than 3 years), Quercetin (6 months), Curcumin (just started my second month) and Berberine HCL (over a year). I'm going to do this again late spring of 2019, a similar dose of around 6 bottles over 10-15 days.

I fasted for 3 days during which I took each day:
900 mg fisetin powder taken from capsules dissolved in 1 tsp olive oil ( delicious when fasting)
2 caps of Life Extension senolytics formula ( high potency querciten with a dasatinib mimic)
1/2 tsp. Piperlognunmine powder dissolved in olive oil.
I am now on day 3 post fast and have felt or seen nothing unusual other than a continuous warmer than usual feeling facial skin, with no temp. increase. Breathing seems improved, like I'm taking in more oxygen. I did not have breathing problems.
I do want to mention that my eyes seemed slightly yellow after fasting day 3 so I've been taking Milk Thistle and that has resolved. LEF specifically stated on the package, do not take more than 2 caps per week, so I may have overdone it. I have no idea whether to expect to see or feel any results from this treatment but plan to repeat quarterly until we learn more.

Eye opening discussion. I've been taking Quercetin 250 mg. and Fisetin 100 mg. daily. Looks like I should be taking higher doses (e.g. ≈750 mg. each for a limited number of days, ≈5 days and then a longer period of none, ≈ 1 to 3 months off to increase efficacy, if I understand correctly what most discussants are saying.

After 14 years of IBD I discovered I had Celiac disease. But 1 1/2 years of gluten free diet had no effect. One dose of d+q and the IBD was immediately gone and has been now for 5 months. My theory is that the Celiac disease built up large quantities of senescent cells in the gut which continued to cause enough inflammation to continue the IBS even on a gluten free diet. For me the d+q was a life changer.

I have Osteoarthritis around my knees. I started taking D+Q three months ago (70mg of D and 1,000mg of Q for three consecutive days / month). For the first two months, I felt fever around the knees a few days after the dosage. Actually, the knee temperature got 1.5 degrees celsius higher than that of thigh. I guess my immune system attacked the senescent cells.

However, my knees are much improved now. I feel no pain anymore when I go down the stairs. I am very impressed by the result.

At 66, I have suffered from severe degenerative arthritis for over 30 years, with both hips replaced, and a knee. Arthritis is in my neck, shoulders and back, although I have adapted to much of the pain, so I don't let it keep me from doing what I want (within limits). I've been on Tramadol for 15 years, which takes the edge off. I have been health-conscious since my early 40s, starting different regimens of supplements, the longest of which has been Krill Oil, CoQ10 and Gingko Biloba. My blood work is excellent and I have no heart-related illness; in fact, I have always monitored blood work closely, since my dad passed at 56, due to heart disease, having had his 1st heart attack at age 36!

Currently, I am on a daily intake of NADH+, Glucosamine/Chondroitin, CoQ10, Krill Oil, CBD oil, Nicotinamide Riboside, Pterostilbene and Nattokinase. I had a noticeable increase in mental clarity with the addition of NADH+ (after 3 days), and I've been taking 100mg/day since mid-December. I am looking to add the Fisetin and deciding on the dosage. I am leaning to a dosage of 20mg/kg, which would be, based on my 50kg weight, 1 gram per day, for 2 days, repeat in 1 month. Any thoughts?

I wanted to add an article regarding Fisetin research: https://www.researchgate.net/publication/327969476_Fisetin_is_a_senotherapeutic_that_extends_health_and_lifespan

@scottalias
Thanks for sharing your experience with fisetin. Would it be possible for you to share your before fisetin lab results for blood sugar, A1C and testosterone? Also, do you have before and after lab results for creatinine, HDL & LDL cholesterol and triglycerides that you can share?

I've had genital herpes for 11 years. I had breakouts pretty consistently whenever there was any damage to my shaft (masturbation, rough sex, friction from gym pants etc). I have been on the exact same vitamin regiment for the last 22 months, same diet, exercise level etc. On average I would get 7 breakouts per year (thanks spreadsheet). Since taking Fiestin I've had exactly 0 breakouts in almost 4 months. This includes during 1 cold, 1 food poisoning, and two episodes of slight damage to my penis (sickness always brings an episode on). I have absolutely 0% proof that it's the Fisetin - just throwing this out there.

I tried Docters best Fisetin at 12mg/kg (600mg/50kg) in 5 days. As a result, I realized clear improvement of cognitive ability after the 2nd or 3rd day. I do not believe that it is a placebo as I am taking supplements to improve cognitive abilities. Clearly it was a clearer effect than other supplements.

On the other hand, I did not feel the effect of removal of senescent cells in particular. The reason may be that I am still 39 years old, or it may be due to dose/usage.

For the latter, I am planning 20mg/kg for 6 days or 10mg/kg twice a day for 6 days.

The problem is whether Fisetin's senescent cell depletion is concentration dependent or time dependent. Does anyone know the literature suggesting that?

This research about not fisetin but another senolytic drug research says,

Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.

So, there is possibility of benefits by taking fisetin from young age.

But no one did experiment about mouse,

and it needs long time to prove for human being.

This is my update from taking two doses of Fisetin. Please see my post above dated January 6th. Physically I see no effect. As some reported, I did have a significant improvement in allergy relief (sneezing, sinus drainage, etc.). Immediately after taking the dosages I had mild, flu-like symptoms, including a slight upset stomach and some lightheadedness, which passed after an hour or two. I also noted an increase in appetite during the two days of treatment. This too was reported by others. Other than that I have suffered no other detectable ill affect. Currently, I plan another, similar dosing in six months. One final note, the first pass I took capsules. The second time I open all the capsules in a small dish and mixed it with MCT oil (C-8 and C-10). Since Fisetin is fat soluble this worked very well. I hope this helps those who are considering self-experimentation. GLTA.

I take fisetin 500mg today.

I felt no sideeffect now.

If I have change about me, I will write this board.

I am a 58 year old male. I have hypertension, mild arthritis and asthma.
I take supplements including CoQ10, DHEA, L-Carnosine, L-Carnitine, Alpha lipoic acid, pycnogenol, Resveratrol, and Elysium Basis.

Last weekend I took 1500 mg of Fiseten + 1000 mg of Quercetin for two consecutive days 1 hour before bedtime on an empty stomach. I skipped all of my supplements both days (but did take my blood pressure medication). I had no noticeable reaction to the megadose of Fisetin. After 1 week I believe that my asthma has moderately improved, but other than that I feel no discernible difference. I intend to repeat this dosing regime the first week in March.

I am 48 year old.
February 9th, I took 500mg fisetin
February 10th, I took 500mg fisetin
February 11th, I took 1000mg fisetin
I felt no sideeffect now.
Fisetin is good taste.

Hi All...latecomer to this conversation, but here because I have a dog with cancer that I am going to give fisetin to. Trying to figure out how much when. But in all the discussion about inflammation, I see no mention of Omega 3's. They are the top anti-inflammatory in my book (I am 74, take a lot of krill oil and test CRP often so I know they work with CRP scores <.2). Anyhow, it just seems so obvious to me and I hear nothing from others re Omega 3's. Not that krill is a sustainable resource, either....

Since the dog is different yet again from mice and humans, I do not know how to assess success. Doing many other things for him as well and he is going strong more than a year from diagnosis, but the tumors are not gone, either. Just began him on rapamycin and starting Low dose naltrexone and tagamet shortly. I'm healthy and trying to get him there again and of course anti=aging is high on my list of interests. Will report as I know anything.

I am 48 year old.(I am humanbeing.)
February 9th, I took 500mg fisetin
February 10th, I took 500mg fisetin
February 11th, I took 1000mg fisetin
February 12th, I took 500mg fisetin
February 13th, I took 1000mg fisetin
February 14th, I took 1000mg fisetin
I felt no sideeffect now. I have no next plan. If there is some way to measure the effect of fisetin, it is good thing. But I don't know about that. So, if someone know the method about that and write the comment, it is good thing.

Having read all of the posts here and all of the research papers I could find I decided to give Fisetin a try. Mouse trials imply a dose of 8.1 kg/mg for humans. Mayo clinic trial starting is 20mg/kg for 2 days one time per month for 2 months. Two contributors have combined with oil to increase bioavailability - EVOO or MCT oil. Effectiveness not known, but seems like good idea.Then I found this item - "http://www.rexresearch.com/fisetin/fisetin.html "These data demonstrate that a treatment combining DHA and fisetin or fish oil and fisetin is a synergistic treatment for cognitive deficits. Since beta amyloid and tau/tangle pathology occur in normal aging and many years prior to Alzheimer diagnosis, DHA and fisetin can be effective in slowing cognitive decline with aging or Alzheimer's, or an effective treatment for these or other conditions with beta amyloid and or tauopathy related cognitive deficits including frontal temporal dementia." The combination of the two agents was found to have a strong synergistic effect on inflammation. Effective ratios include without limitation those where fisetin is provided at a concentration of at least 5 μM, and where the ratio of DHA to fisetin may be at least about 1:2, 1:5, 1:10 or more". My add - is it synergy or fish oil increasing bioavailability?
Finally decided to go with 10mg/kg for 4 days - lower daily dose but same total dose as Mayo Clinic. But I added DHA as fish oil ratio 1:2 DHA:fisetin, and 1 tsp MCT oil. Also decided to start slowly 60% day one, 80% day 2, 100% days 3 and 4 and then add 100% Fisetin (in capsule) day 5 w/o oil.
Days one and two - prepared mixture 2 hours before dosing and then took with dinner - added to sweet potato mash. Days 3 and 4 took immediately after mixing, about 2 hours after dinner - just drank it and then used hot water to get the residue in the shot glass. Much more residue without sitting for time for oil and powder to mix. I recommend mixing early and letting sit for a while. Effects -
Day 3 early AM- very sharp tingling (almost stinging) under skin of left thumb in space between knuckle and root of nail that lasted for 5-6 minutes, 1/2 hour later tingling at tip of tongue on left side lasted about 6-7 minutes, 1/2 hour later tingling under skin of left elbow lasted about 6-7 minutes. Never had such symptoms before - was it the fisetin? Night after 4th dosage - slept very soundly 2 hours longer than usual - woke up feeling refreshed. Day 5 - usually arthritic big toe was pain free during usual morning walk. Only point of pain I have where anti-inflammatory effect might be noticeable.
In another paper it was noted that elderly mice showed muscular endurance improvement after 4 days of Fisetin treatment. Mice heartrate is about 10x human and rapamycin half life in mice is about 1/10th human. Does that mean we should expect to see benefits in about 6 weeks? I will do my next 5 day treatment in 2 months. NB- I am 84, in good health and exercise regularly. My wife is also on this trial - she is 79, physically healthy but diagnosed with MCI. Should be interesting.

Just found this one https://www.sciencedirect.com/science/article/abs/pii/S0006295211006149 "After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice, the maximum fisetin concentration reached 2.5 μg/ml at 15 min and the plasma concentration declined biphasically with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h." Suggests a 1/2 life of approx 0.9 hours in humans and clearance in a little over 24 hours. Is there a biology major out there that can critique this assumption?

The paper @Reason cites (Yousefzadeh et al. EBioMedicine 2018, https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext) also uses a 60 mg/kg/day chronic dosing strategy (500 ppm with food), which would be a HED of 4.9 mg/kg/D.

For a 70 kg human, this would be 341 mg/day - much less than the megadoses some people are using!

If mouse takes drug 60mg /kg , humanbeing takes drug about 5mg/kg !
This is same relationship about almost drug.

and Spermidine prolongs lifespan in mice, we determined that life extension of up to 25%. Spermidine is rich in nattou. Taking nattou is good thing.

Over 70 yrs old. Took Fisetin 3 days: 1000mg, 1200mg, 800mg. No detected side effects. Went to gym 2 of the days feeling normal.

I am going to be 58 in about a month, and have been interested in extending my lifespan (and healthspan) for as long as possible, for quite some time. I belong to Life Extension, which has come out recently with a Senolytic Activator which combines black tea theaflavins with an ultra-absorbable form of quercetin. You are supposed to take 2 capsules one time/week. I just took my 4th dose yesterday. So far, no noticeable effects, but I think that it isn't intended to be instantaneous (nor, do I expect, is fisetin in any doseage). Not being a biologist or a doctor (or even sleeping at a Holiday Inn Express), I suspect that biology just doesn't work that way. Harm takes a while to accumulate through natural biological processes, and it makes sense that repair by any mechanism would work the same way, just in reverse.

Here is the site for the Senolytic Activator:
https://www.lifeextension.com/Vitamins-Supplements/item02301/Senolytic-Activator

I am thinking about also taking fisetin, probably in 1,000mg doses for 4 days (20 mg/kg would be 1800 mg, and that just seems a bit high) to get approximately the same dosage over a slightly longer timeframe. My reasoning for this is to utilize a different senolytic with (almost certainly) a different mechanism, to try to clear out more senescent cells. I'll be ordering the fisetin shortly, though I won't take it at the same time as the Senolytic Activator - I'll continue dosing with the SA on Sundays, and probably go Tuesday - Friday on the fisetin. I'll try that for a month or 2, and let everyone know what (if any) differences there are in how I look or feel.

Any thoughts from the crowd?

It has now been one month since finishing my second monthly round of 3 days of fasting combined with 1200 mg of fisetin mixed in mct oil for each of two days and Life Extensions senolytic activater on the 3rd day. I feel or see nothing different. Either it doesn't work in humans, it's not absorbing enough, or perhaps - it killed off a bunch senescent cells, but that didn't correspond with any subjective experience. I am 61 years old.

I am 48 year old.
February 9th, I took 500mg fisetin
February 10th, I took 500mg fisetin
February 11th, I took 1000mg fisetin
February 12th, I took 500mg fisetin
February 13th, I took 1000mg fisetin
February 14th, I took 500mg fisetin
February 16th, I took 500mg fisetin
February 17th, I took 500mg fisetin
February 18th, I took 300mg fisetin
February 20th, I took 300mg fisetin
February 21th, I took 200mg fisetin
February 22th, I took 300mg fisetin
I felt no sideeffect now. Perhaps, 300mg per day is right! 300mg for 2 week and check the result!
And to take spermicide, I am takes nattou everyday!

Male
No health issues
58

Took 500mg, noticed nothing
Next day took 1000 mg, had some brief light headedness, felt that I was getting more oxygen per breath, nice feeling.
Felt hotter all night.
feels like a vasodialator.
I'll do 1500 tonight.

I am 48 year old
I takes 100mg fisetin/day.
l takes 100mg Metoformin/day.
I takes Spermidine from nattou.
I have questions about fisetin that takes fisetin about 300mg/day(←for humanbeing dosage) is called "fisetin-diet" about paper and this site, But is it safety for humanbeing to taking fisetin 300mg/day everyday for long time?
Best regards!

did my first 5 day Fisetin treatment Feb 12-16. Feb 27, during my Super Slow Zone resistance training workout I had a noticeable increase in performance for all of my exercises (lower body). At 84 years of age, just not losing strength has been quite satisfying. I hope the increase is not a one off.
Today (March 1), my TRX workout also went better and I had less sense of fatigue at the end. I was not expecting to see any effect so soon.

I intend to take, once my supply arrives, 5 grams fisetin a day for 5 days, and repeat monthly.

I am curious if fisetin at such doses might plausibly target myofibroblasts, in addition to senescent cells. Apoptosis resistance in both fibrogenic myofibroblasts and senescent cells may derive from the same anti-apoptotic proteins, the expression of which might be inhibited by fisetin -- that's the idea, anyhow. Navitoclax has been shown to actually reverse fibrosis in mouse models of scleroderma. It would be neat if fisetin were to turn out to be useful for Dupuytren's, Peyronie's, etc ... or maybe even IPF, which is a horrible disease.

I am 51 and in good health. On March 1, 2019 I took 1000 mg Fisetin and 500 mg quercetin, then repeated the dose 24 hours later. I noticed mild tiredness and hunger on both days, but it wasn't a powerful effect and could have been subjective. Today is March 6th, and I started noticing yesterday an improvement in energy and focus, today especially. It could all be in my head, but I'm beginning to think there was an actual benefit here. I've noticed no other symptoms or benefits.

@Paul Rattner

If you are in a rather good health then it will be hard to measure the improvements.

And 51 is not that much, after all...

I too lower dudes of quercetin plus fissetin and whole not noticing any ill effects, I would say that at least as placebo it works well.

I am 43, so even less chances to notice minor improvements

At around 8:00 pm last night I took 1,600 mg of Swanson brand fisetin with 1 tablespoon of olive oil. I am age 45, 174 pounds and in good health. This morning I woke up at 6:30 am with nasal congestion that feels like a mild cold that is still persisting. No other symptoms except for slight light headedness about half hour after administration that may have just been imaginary. Tonight I'll take a second dose around the same time and post an update later.

I've now done two months of Fisetin * 2 days * 1800mg per day. I'm 65, 6'2", wt. 197 lbs.

I've noticed (or believe I've noticed) that problems I'd been having with word retrieval seem to have disappeared. Placibo? I don't know. But for some reason, I seem to be a lot more articulate these days.

I'm planning to do an additional couple of days of Fisetin at the end of March. I also plan 2 days * 1 gm of Azithromycin in about a week. May repeat that in a month, as well.

I've also seemingly developed a head cold, which is rather unwelcome.

I've been taking 2 grams of Metformin a day as a prophylactic against cancer (mom had BC, dad died from PC) and a tendency to have prediabetic levels of FG in the mornings (115).

I walk a couple of kilometers each day, and do weight training three times a week.

I'm also planning to add Rapamycin to my stack, interval dosing. 5mg every two weeks, maybe try it for a few months.

God, what else? Oh yeah, Telmisartan, Nebivolol, and Isradipine for Hypertension, and because the first two are seen as excellent for LE. IS is currently under study to prevent PD, which my father had (as well as diabetes). I also take 5mg of Selegiline each day for the same reasons. I take a 20mg dose of Tadalafil everyday because of my prostate being about 50% larger than it should be, and because TD is ALSO recognized as being a great LE drug. Besides, the missus is about 20 years younger than I and still pretty frisky at 46. So far, so great. As the Boy Scouts say, "Be Prepared!"

Baby Aspirin, 2 grams of Niacin B3 (the kind that makes you flush), and 10mg Lipitor. My LDL is about 80, HDL 65, and TG almost non-existent.

Last Bloodwork in September was all normal except: RDW-SD 46.8% (46 is the highest normal, I believe). Serum Protein was 60 (which is kind of low, and previous was 64, but Albumin was normal, though the AGR was 2.8, so, I've added protein shakes to my daily regimen), and my Monocytes percentage was 12.5%, (and have risen from 10% over the past couple of years) though the absolute M/C was .7, and all other WBC were in normal ranges. My doctor wasn't concerned by any of that, but then again, it's not his blood, so why would he care? German doctors tend to be pretty fatalistic in my experience. They're good at resuscitating you after a heart attack, not so proactive at preventing them.

All this seems to be working for me. I'm the eldest of 4 kids, my brother's already had 3 stents, dad had stents just about everywhere, then a quadruple bypass, mom and sis had strokes, sis also diabetic. So far, none of that for me. Maybe I'm doing something right.

So, the only thing really different since the last check is that I got more serious about low-carbing, and started the Fisetin, and will try the Azithromycin.

I only mention all the above to say that I will be getting BW done again in May, and I will be very interested to see if there are any measurable differences there.

Anyone have any other suggestions for things I ought to check that might indicate that Fisetin is having an effect?

After that, I start the Rapamycin.

Sorry for boring you all with all these details, but maybe it'll add to the general knowledge about Fisetin.

@Gavril: Where are you getting the Rapamycin?

I ask, because in this paper: https://age-reversal.net/wp-content/uploads/2018/11/Age-Reversal-Protocol-RAADfest-2018-1.pdf

the recommendation is to do age-reversal in 4 stages:

1) MTOR reduction with Rapamycin;
2) NAD+ restoration (orally or, for those who are older, with patches or IV);
3) Use of senolytics; and
4) Use of young plasma or stem cells.

Of course, the paper also recommends getting a series of blood tests BEFORE starting, to get an idea of how (or if) the treatment is successful - that'll help the actual patient and also be more data for future patients.

The first 3 one can do on one's own, and at relatively low cost (if you have a reasonably low-cost on the Rapamycin, and also on the Dasatinib, both of which require prescriptions).

WRT the paper referenced in my prior post, Step 1 (reducing MTOR via use of Rapamycin) can also be accomplished by boosting AMPK. There are several ways to do this:

1) Take Metformin;
2) Take AMPK activators (Life Extension sells a formula for this https://www.lifeextension.com/Vitamins-Supplements/item02207/AMPK-Metabolic-Activator); or
3) Taking BCAAs https://www.lifeextension.com/Magazine/2011/5/Can-a-Power-Booster-Also-Be-a-Longevity_Booster/Page-01

Please note that I don't own or work for Life Extension, I've been just a regular member since about 1995.

So, other than the young plasma/stem cell treatments, one can apparently do ALL of the steps outlined in the paper that I linked to by buying nutritional supplements (and, of course, one of the senolytics would be Fisetin).

Update from Feb 14th post. Re the dog with cancer. He tolerated the 800 mg fisetin well, three days running. His grasp of English is poor so I can't ask how it feels, but since that time what I see is more physical activity, more responsiveness--he just seems to feel better. Mind you, since then he also has started other anti-cancer therapies (cimetidine and LDN) so it is hard to tease out the individual effects. For myself, I took 1200 mg fisetin for three days. The only thing I noticed was a few days of increased exhaustion. Since it's spring and I am readying the garden and cleaning barns etc, it's also hard to sort what's the cause of what. Otherwise I see no changes but I have no health issues to speak of other than aging itself.

Does anyone know or even suppose what is a reasonable interval to repeat fisetin? Is once a month too often?

Update from my 3/6/19 post: The mild cold symptoms started gradually dissipating in the afternoon. I did experience mild increased fatigue and appetite but it was difficult to tell if it was the fisetin or anything else. The next day I took my second dose the same as before, this time I didn't feel anything different and haven't noticed any changes since then. I think it's safe enough to take periodically and plan to do this every three months.

Now 27 days since my first fisetin treatment. As a fairly elderly senior I have experienced gradually increasing stiffness/creakiness, most apparent when I bend down in the morning to step into my undershorts. About 2 weeks after the treatment the creakiness seemed to diminish, and over the next few days I became increasingly supple. The effect has now lasted about 8 days. I wonder if the fisetin has diminished low level chronic inflammation of the lower back muscles that doesn't show up in my labs. Hope it lasts. Next treatment in 4 weeks.

So I've been taking the Fisetin too, and experiencing significant benefits. I want to know what the rationale is on why a certain kind of dosage is better than others - ie. the reasoning/conjecture behind it, rather than just pure observations.

Some say taking mega-doses occasionally (every few months) is better, but why? How selective is Fisetin in what it kills - is there an actual number? Does Fisetin, and do senolytic treatments in general, have any downside on telomere length? (In which case, shouldn't even exercise have a similar downside impact?)

Some say taking Quercetin with the Fisetin is better, but why? Is the Quercetin somehow distracting the liver from breaking down the Fisetin? What other supplements can slow down the liver, so that it breaks down Fisetin less quickly?

Etc, etc. Where's the best forum to discuss Fisetin? Is it here?

Here's some info that may be useful to persons interested in taking so-called "Mega-Dose" FISETIN in the form of the capsule products that are currently available from SWANSON, and DOCTOR's BEST.

I sent DOCTOR's BEST an email requesting their MSDS and/or Certificate of Analysis. Their email response said: "Our products are independently tested for safety and label claim. We supply all necessary information about the product on the label, and cannot release any manufacturing documents." They stone-walled me ! The label lists the ingredients as being: Fisetin (as Novusetin) 100mg ; Cellulose (no wt. given); and Modified Cellulose (vegetarian capsule).

WEIGHT ANALYSIS : Using a digital scale accurate to 0.001g (1mg), I weighed 10 capsules. Total Wt = 3.499g. (=350mg per capsule avg.)
I then emptied the capsules and found their total Content Wt. was 2.752g. (= 275mg contents per capsule, on average).
So, the 10 empty capsules themselves weighed 0.747g ( = 75mg per empty veggie capsule ).
Veggie caps are typically composed of "HPMC" (HydroxyPropylMethylCellulose), which would be the "modified cellulose" on the label.
Since the Doctor;s Best label says each capsule contains 100mg of FISETIN (by Novusetin), this means that each capsule must also contain 275mg - 100 mg = 175mg of something else, as a filler. This must be the "Cellulose" ingredient. A substance called "microcrystalline cellulose" is commonly used for that purpose, so perhaps this is the Cellulose indicated on the label.
In summary, these are the results:
Average Wt. of 10 filled capsules = 0.350g (= 350mg)
Average Wt. of 10 empty capsules = 0.075g (= 75mg)
Average Wt. of capsule contents = 0.275g (= 275mg)
Average Wt. of Fisetin content = 0.100g (= 100mg) = 36% of the capsule contents
Average Wt. of "Cellulose" filler = 0.175g (= 175mg) = 64% of the capsule contents

Keep in mind that we are left to assume the actual Fisetin weight is accurate, and we are not provided with the % purity of the Fisetin that is being used.
Someone taking 10 capsules, is presumably consuming 1g (=1000mg) FISETIN, along with 1.75g (=1750mg) of Cellulose filler, and 0.75g (= 75mg) of Modified Cellulose (in the empty capsules).

SWANSON also refused my request to provide any MSDS or Cert. of Analysis. The SWANSON label lists: 100mg FISETIN (by Novusetin); Microcrystalline Cellulose ; Hypromellose; Magnesium Stearate; and Silica.
Hypromellose is just another name for the "HPMC" I mentioned above. Magnesium stearate and/or Silica are used to make the capsule-making go better: these things can help the powder flow better into the capsule, and let the capsule close more easily once filled. (Some people have concerns about the magnesium stearate, which is technically considered to be in the 'soap' family.)
I did the same weight analysis for 10 capsules of SWANSON's "Ultra Fisetin" product. Using the same procedure described above, this is what I found:
Average Wt. of 10 filled capsules = 0.347g (= 347mg)
Average Wt. of 10 empty capsules = 0.075g (= 75mg)
Average Wt. of capsule contents = 0.272g (= 272mg)
Average Wt. of Fisetin content = 0.100g (= 100mg) = 37% of the capsule contents
Average Wt. of "other ingredients" = 0.172g (= 172mg) = 63% of the capsule contents

[ NOTE: VitaCost is another current vendor, but I haven't purchased their product yet, and I haven't yet tried to contact them. Based on the close similarity of the results I got with Swanson and Doctor's Best, it's probably safe to assume that a weight analysis of their capsules would likewise be similar. Viewing the label on their website, I can see they use "Rice Flour" as their filler. Magnesium stearate is also listed. ]

I only recently discovered this Forum, and I'm not able to view it every day (I'm pretty busy these days), so please understand if I'm slow with responses. Let's all live to be a healthy 100 years old (like my Aunt Jennie,,, still driving and going strong at age 100. True.)

OOPS. I noticed a recurring typo in the Comment I just posted.

At 0.075g (75mg) apiece, TEN of the empty veggie caps weigh 0.75g (=750mg),,,,, not only 75mg. That's a lot of needless crap being ingested. Toss the empty caps and only swallow the contents.
It's bad enough they are 66-67% FILLER. No sense in adding to it.

So can anyone comment on whether a time-release version of Fisetin might be more desirable? Since we all know that Fisetin is broken down in the body quite quickly, then wouldn't time-release be a way to prolong its presence in the bloodstream more? In which case, then what time period for release would be best? Shouldn't it correspond to the amount of time it takes cells to regenerate/replenish following senolytic death? How much time would that typically be?

AGELESS, since you've spoken to vendors like Doctor's Best and Swanson, would you mind asking if they'll consider coming out with a time-release version of Fisetin, which could maintain its presence in the bloodstream for longer?

Given the pathetic solubility of fisetin, everything taken orally ( not injected) should be effectively slow release.

SANS: I merely sent each of them an email, to the address posted on their websites. They responded by essentially saying 'we don't give up that type of info', and I gave up. I never spoke with them. Here are the nearly-identical emails I sent each of them :

To: info@Drbvitamins.com 2-18-2019
I've purchased and received 5 bottles of your "FISETIN with Novusetin" (100mg / 30 veggie caps), via Amazon.
LOT NUMBER: 11251 FEB 2019..
Please send me your MSDS and/or latest Certificate of Analysis for this item.
Thank You.
---------------
To: customercare@swansonhealth.com 2-18-2019
I've purchased and received 5 bottles of your "Ultra FISETIN" (30 X 100mg veggie caps), via Amazon.
LOT NUMBER: B 232207 Best by 06/20.
Please send me your MSDS and/or latest Certificate of Analysis for this item.
Thank You.
---------------
If you wish to inquire about timed release formulations, you can try initially contacting them via the email addresses shown above, and hope this opens the door to further communication with them.

SANS: Here's another quick thought,,, you could take the Fisetin in doses spread apart by 2-3 hours. If you take (for example) 3 capsules at once, you'll get a bloodstream 'spike' of Fisetin that unfortunately won't last very long (as you mention) due to the short half-life of the circulating Fisetin. If instead you take the three capsules a few hours apart, your maximum blood concentration will be lower, but it will be present in your bloodstream longer (at a lower concentration). It's hard to say which is better, at this point.

AGELESS, some people are suggesting to take it with Tween80 (aka. polysorbate80) or Limonene, or some combination of the two. Apparently studies show these things can nano-emulsify the Fisetin to keep it around for much longer in the bloodstream. What I've found is that if I just keep the capsules in my mouth and suck on them, then that lasts long enough for me to take it during a cardio workout, which is good enough for me, as I prefer to take Fisetin in combination with the additional stress of exercise.

Since I also like to take Creatine before a workout, and Creatine is known to have neuro-protective effects, I'd like to know if the Creatine might interfere with the senolytic effect of the Fisetin. What do you all think?

March 18, I took fisetin 1000mg.
March 19, I took fisetin 1000mg.

Taking fisetin for 2days is the same way of clinical trial!

SAN : You and many others have been at this Fisetin thing a lot longer than I have, and have given it more thought than I have. In all honesty, I'm not qualified to answer the questions you pose about the possible effects of using Fisetin in combination with emulsifiers and/or Creatine.
I can say that there are many variables involved, such as: your unique genotypical body chemistry; your internal bioflora; your medical history; the source and true purity of the Fisetin you are taking; your diet; the interactions of the substances themselves, and numerous other things that are unique to anyone's individual situation.
Person A may find that an emulsifier acts like a Fisetin 'booster' in their situation, but Person B may report that it only gave him/her a headache, or something equally vague. Most of the comments I see on this excellent Forum are of the "anecdotal" variety, reporting how it made them "feel". Of course, this is unavoidable because we are left with little alternative. But when our feelings and perceptions come into the picture, we've left the world of true empirical science (numbers & hard data), and entered the much blurrier world of our personal perceptions
In a perfect world, each of us would be able to go on this Forum to report the results of our own controlled "in vivo" studies on ourselves. We would have each had extensive bloodwork done on ourselves BEFORE ever taking Fisetin, and we would have each taken precisely measured amounts of high-purity Fisetin (of known analysis), at the exact time(s) which we duly recorded. We would have also had a series of blood samples withdrawn at precise intervals. And we would have been able to report and compare our BEFORE & AFTER blood analysis results.
But the reality is far different. We don't do the before & after bloodwork, we're taking Fisetin capsules manufactured by outfits who won't provide any information at all about the purity of the Fisetin they contain. And, virtually everybody who is on a Forum like this is very likely taking various other supplements at the same time, which can affect and blur the entire picture. Then we go on this Forum to post our comments about how we "feel". It's not very scientific, but I do like the communal spirit of this Forum, and I am participating in it at this very moment, so I'm not judging anybody or anything here.
There are finally a few HUMAN clinical trials currently under way but, as of the present time, all we have are some "in vitro" (petri glass) studies, and some "in vivo" studies with rodents,,, and those "rodent model" results may not translate accurately into the "human model". What works in mice may not work the same way in humans.
I very much like the idea and purpose of this excellent FIGHT AGING forum, and I like reading your comments along with everyone else's, and I am currently taking the Fisetin myself (2 or 3 x 100mg along with my other "vitamins" on most days), so I am keenly interested.
But I am not able to definitively answer any specific questions such as, 'What are the effects of combining Fisetin with this other stuff'? I simply lack the knowledge to answer a question like that, SAN. I don't think anybody really can.
OK! Having said that, let me say this,,, Emulsifiers generally work by sort of grabbing onto an individual 'particle' (molecules, molecular groupings, etc) and then keeping that particle from getting too close to a similar particle nearby.
Nano-coating is an incorrect way to be visualizing an emulsifier. The emulsifying agents you mention will not provide any micro-encapsulation or nano-encapsulation of the Fisetin. No coating. It's better to think of emulsifiers as being tiny pins being stuck into a pin-cushion particle, with Fisetin being the pin cushion. On the outer tip of each tiny pin is a sign that says "Keep Off. Stay Away". The Fisetin particles no longer want to touch and clump together: instead, they want to keep their distance from each other. But, by keeping the particles spread out from each other, the effective combined Surface Area of all those Fisetin particles becomes increased. Greater absorptive surface area of Fisetin = quicker absorption. But those tiny 'emulsion pins' on the Fisetin particles may possibly slow the absorption rate. So now you have an "absorption contest" going on. And on top of that, emulsions typically respond to changes in pH, and they can lose their emulsion properties in the low pH (acidic) conditions of your stomach.
My answer to your Question is therefore, "Who the hell knows?", SAN. I sure don't. Whatever you decide upon, I hope it goes well for you, my friend.
Please understand if I disappear from this Forum occasionally. Life has a way of making its own demands.
I currently lack the time to participate in this Forum as much as I would like, so please understand if I 'disappear' from time to time.

Thank you for your kind response, AGELESS. When I said 'nano-emulsion' (just repeating what was told to me), what was meant to refer to the size of the droplets of the emulsion. So apparently the Tween80 or Limonene can form very fine droplets inside the bloodstream.

March 18, I took fisetin 1000mg.
March 19, I took fisetin 1000mg.

Taking fisetin for 2days is the perhaps same way of clinical trial.

Ｉf someone know about the result of clinical trial about fisetin, I am very thanks to get information by this internet forum.

Since everyone here seems to be taking fisetin from the Nouvastin company and it contains other pill modifiers I thought I would see what else is available. I found this link:
https://www.alibaba.com/showroom/pure-fisetin-powder.html All of these are from China and take a look at the huge differences in color, price and source of the fisetin. Does anyone know which plant source is the best? They all advertise "pure" but that is really questionable.

March 19th 100mg every 2 hours for a total of 800mg
March 20th 100mg every hour for 5 hours then 200mg every hour for a total of 2000mg.

I have 3 more doses to take today to complete the 2000mg. I felt great this morning but I feel a little weird today. Nothing bad just different. Two weeks ago I took Quercetin with Bromelain 800mg/165mg twice a day for a week. I felt fantastic by the end of the week. I'm hoping Fisetin will have the same effect.

Without extensive lab testing, no one can know if what's claimed to be supplemental fistin is the real thing or guarantee that it doesn't contain dangerous contaminants. Bioriginal, the company that provides Novusetin to supplement manufacturers such as Swanson and Doctor's Best, claims to have a policy of extensive lab testing, but AFAIK, no independently-verifiable info is publically available. And besides weighing the content of pills by AGELESS, I haven't heard of anyone else trying to do any serious lab testing on fisetin. AGELESS has also claimed that both S and DB refused to provide testing data. Perhaps Bioriginal should be asked about this data as well.

https://www.bioriginal.com/why-bioriginal/full-service/
https://www.fightaging.org/archives/2018/10/animal-data-shows-fisetin-to-be-a-surprisingly-effective-senolytic#comment-35804

■Pattern1■ Taking fisetin about 1000mg for 2 days only , and check the effect of fisetin by going to hospital by blood check

↑This is the almost same method of clinical trial.

■Pattern2 ■ Taking fisetin about 300mg everyday , and check the effect of fisetin by going to hospital by blood check

↑This is the same method of this paper↓,
https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

The reason why every source of legitimate Fisetin contains "Novusetin" is because the Salk Institute holds a patent for using Fisetin for cognitive enhancement (Maher US Patents 2007 exp 2027) and they have exclusively licensed it to Cyvex, the producers of Novusetin (formerly called Cognisetin):
- https://www.nutraingredients-usa.com/Article/2013/04/17/Cyvex-uses-forced-rebranding-of-Novusetin-as-chance-to-rethink-messaging-for-ingredient

I get my source of Fisetin from Swanson Vitamins, because they follow GMP and are a member of the NSF international (a third-party source that certifies manufacturers meet quality standards for purity, identity, and potency): http://info.nsf.org/Certified/GMP/Listings.asp?Company=C0054895&Program=DIETSUPP

Swanson labs reports that they test for purity, ID, potency, microbial contamination, and heavy metals for:
- All contract manufacturer vitamins, minerals, standardized botanicals
- All in-house capsule products raw materials and finished products.

According to Consumer Lab, four of S's products flunked CL's testing out of a total of 35 S products that CL tested. Two S products contained elevated lead content. I didn't look at DB. Unfortunately, CL hasn't tested any fisetin supplements.

https://www.consumerlab.com/search/swanson-review/

Early Parkinson's and Fisetin: I'm 74, in good health, and was recently diagnosed with Parkinson's Disease, mostly mild tremor. I'm currently not taking any Parkinson's medication. My son, who is a physician, suggested Fisetin, with no specific symptomatic relief expectations. Daily usage of 100 mg of Fisetin A.M. and P.M. was started on February 28. The initial results have been unexpected. There has been an immediate positive mood shift after each 100 mg ingestion, and about a 90% reduction of tremor. The effect last 3 - 5 hours. I haven't experienced any significant side effects, other than some occasional transient light headedness. I'm experimenting with taking 100 mg of Fisetin after each meal. It would be valuable to compare notes with other Parkinson's patients taking Fisetin.

When I've taken Fisetin, I later get hyperactivity/energy combined with hunger pangs (I've nearly always taken it during exercise)

The other day, I tried using Piperlongumine - on its own, because I didn't want to stack things the first time out. I also later got hyperactivity/energy combined with hunger pangs.

Today, I tried both the Fisetin & Piperlongumine together during my workout, and felt a totally different reaction afterwards. I felt extremely and uncharacteristically fatigued and lacking in energy, for a period of a few hours following the end of my workout. Then after that passed, I had some extra energy, felt myself tapping my feet, even while feeling hunger pangs (I'd already had a big lunch after my workout).

Has anyone else tried both Fisetin & Piperlongumine together, and experienced this latter kind of reaction? Is the kind of reaction I experienced a sign of something good or bad?

I have questions!

Fisetin has Senolytic effect!

But Quercetin do not have Senolytic effect!

Is it right or not?

@iwasaki
Qercetin alone had very little senolytic effect. However, when combined with Dasatinib it does increase the senolitic action. At least in mice. We do hope, albeit without a scientific proof, that quercetin will enhance the effects of fisetin. I am not aware of peer reviewed studies on mixing fisetin and qercetin. Also, if planning on doing self experimentation keep in mind that both quercetin and fisetin have a terrible solubility in water. So if taken orally, most of it will go with the stool.

For me, personally, I felt somewhat positive effects. So at least as placebo, F+Q combination performs well. Not as well, mind , as fasting 8 days, though...

Several people have noticed having trouble getting to sleep and so on while taking Fisetin. I wonder if that isn't a result of caffeine not being eliminated as efficiently as usual. I noticed that the Mao Clinic has the following disclaimer at the end of their study description:

"Participants will be educated about the risk of excessive caffeine usage. Participants will be encouraged to reduce use by 50% prior to and during the 2-day drug dosing periods. Due to drug-drug interaction, subjects may not clear the caffeine from their system properly/as usual."

@Cuberat ,thanks very much for your advise!!

I think ■quercetin is not soluble in water.

But ■quercetin glycoside is soluble in watar,

so.

■Fisetin is not soluble in water.

But perhaps ■fisetin glycoside is soluble in water , I think !

And perhaps ■Fisetin is soluble in oil !

so, I want advise how to take fisetin into body!

@iwasaki

Here is the most recent information I have found: https://www.caymanchem.com › pdfs

>Fisetin is supplied as a crystalline solid. A stock solution may be made by dissolving the fisetin in the
solvent of choice. Fisetin is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide
(DMF), which should be purged with an inert gas. The solubility of fisetin in ethanol is approximately
5 mg/ml and approximately 30 mg/ml in DMSO and DMF.
Fisetin is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, fisetin should
first be dissolved in DMSO and then diluted with the aqueous buffer of choice. Fisetin has a solubility of
approximately 0.5 mg/ml in a 1:1 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend
storing the aqueous solution for more than one day.
Description
Fisetin is a natural flavonol that is structurally and functionally related to kaempferol (Item No. 11852),
myricetin (Item No. 10012600), and quercetin (Item No. 10005169). All are potent antioxidants and have
anti-inflammatory actions with possible relevance to cancer.1-3 Fisetin and other flavonols act as activators
of sirtuin 1, inhibitors of the spleen tyrosine kinase SYK, and suppressors of CD36 gene expression.4-6

So alcohol solubility is about 10 times better than water but still very poor.

Here I find something that suggest it has better solidity in oil, though here they take about qercetin https://www.nutraingredients.com/Article/2017/02/14/Oil-could-boost-quercetin-absorption-but-researchers-caution-against-it

With a socially crafted nano-emultion the bioavailability can increase 20 times. But I doubt you can make it home. Read the following PDF. It has charts on blood plasma levels: https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.hal.inserm.fr/inserm-00709735/document&ved=2ahUKEwj2g7P6qaThAhVhm-AKHTkJBHwQFjADegQIAxAB&usg=AOvVaw39nf_HIUWm0VVn1NnClOQH&cshid=1553759032359

Life Extension Foundation has a formulation of Quercetin that is much more bioavailable than pure Q. It is encased in a plant-based phytosome delivery system, and is about 50 times as bioavailable. https://www.lifeextension.com/Vitamins-Supplements/item02302/Bio-Quercetin

I imagine that something similar could be devised for fisetin.

@Florin Clapa: I am actually reassured by the 4/37 "flunked tests" on the Consumer Labs Swanson Reviews (https://www.consumerlab.com/search/swanson-review/). For better or worse, this seems to actually be significantly better than the industry average:
- 6/10 St. John's Worts supplements had significantly less hypericin and hyperforin than advertised (https://www.newsmax.com/health/headline/stjohns-wort-supplements-fail-tests/2016/10/18/id/754044/)
- Almost 80% of Ginseng, Echinacea, Gingko Biloba, and St. John's Wort in NY Walmart, Walgreens, GNC, and Target contained ingredients not reflected in the label (https://abcnews.go.com/Health/bogus-herbal-supplements-fail-ingredient-test-investigation/story?id=28684472, https://www.cbsnews.com/news/herbal-supplements-targeted-by-new-york-attorney-general/)

In addition, Swanson Labs has actually won numerous ConsumerLabs awards (https://www.swansonvitamins.com/quality/consumer-labs.html), including the 2015 top/rated catalog/internet brand (https://www.consumerlab.com/news/top-rated_vitamins_supplements_2016/02-25-2016/)

@Cuberat,

Isn't DMSO harmful for mitochondria? That's what I've read. Maybe booze/ethanol is better, since it's more readily available and cheaper. Also, Fisetin has been shown to protect the liver from toxic effects of alcohol.

@san

I don't know how harmful is DMSO. it is considered safe for temporary use, from what I see. But even fissetin can lead to cancer in rats if taken in excess

I read, mice were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400: 10% ethanol or vehicle only by gavage. This is the way to take fisetin, but for human being, 100mg/kg → about 10mg/kg. I want more easy method.

@strollman
10mg/kg . For a 80kg person. Would require 800mg. If the solubility in alcohol is 4/1 in the best case you need 200ml of ethanol. At 40% concentration as in vodka you probably can dissolve it in half a liter... Thats a tad too unhealthy... Most people without lover problems could survive it but many will have a bad hangover. If the solubility in alcoholic was 10 or 20 times more, than it would be a viable approach. Alas the only non pathetic solvent is
DMSO. I guess there is a lot of room for patenting bio available variants

@strollman: Mice were also dosed with 60 mg/kg of Fisetin added directly to their food. This would be about 4.9 mg/kg for humans (per the 12.3-fold conversion from mice to humans cited in Nair et al. Basic Clin Pharm 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402)

Just to add another data point to the list of experiments:
On March 25 and 26 I took 1400 mg of Nouvusetin (Swansons brand Fisetin)mixed with about 2 tablespoons of EV Olive Oil.I am 69 and in good health and weigh ~70kg. I did not have any noticeable effects on either day and have not noticed any difference at all in the 7 days since!
Maybe I had a very low amount of senescent cells? I will repeat this in one month and report again. Thanks to everyone for submitting their reports and comments. We learn...

Thanks very much for writing people. I tried fisetin solved by ethanol and add water. It looks wholly yellow water. Next I tried fisetin solved by only water, but fisetin doesn't solve by only water. What is the more good way to takes fisetin?

@iwasaki

You might try a mix of oil and alcohol. But note that even alcohol solubility is quite poor 1-4 mg per ml which is in in the other of one to thousandths. To solve 2000 mg you would need to get wasted... And if you cold easily tolerate such quantity it means you be don't need senolitic that much yet ;)

Mayor clinic use fisetin for patients for human being.
I want to know how they use fisetin to take into blood.

The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antitumour activity but its administration is complicated by its low water solubility.

For oral administration of fisetin, mice were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol

or,

Solubility and emulsification tests allowed to develop an optimal nanoemulsion composed of
Miglyol®
812 N / Labrasol®
/ Tween®
80 / Lipoid E80®
/ water
30 (10%/10%/2.5%/1.2%/76.3%)

I want good idea to solve above problem.

Again, take this with a grain of salt. Just sharing my experience.

I do NOT believe in magic bullets, wonder drugs, or anything else. I'm very conscious about my health and just listen to my body.

I started taking 100mg of Fisetin maybe 6 months ago. I added it to my routine of resveratrol, NAD and a few others. Thought nothing of it. Expected nothing out of it. I mean 100mg orally is clinically insignificant.

I have genital herpes and nothing has ever really cut down the outbreaks. I get them regularly - along with pretty bad nerve pain all down my legs, feet, butt etc. That's life.

After taking Fisetin I had zero outbreaks. For 6 months. This had never happened for the last 12+ years, in addition I had some occasions when it SHOULD have happened (stress, damage to skin etc).. I wrote earlier about this as a one-off.. Isn't that odd kind of thing.

This last month I ran out of Fisetin and didn't re-order in a hurry. I was off it for 11 days. All I can say is I experienced a total immune system collapse. I got a herpes outbreak on my lip (something almost never happens - twice in 12 years) had a constant outbreak on genitals that lasted for 9 of those 11 days, my shoulder injury started hurting again (it stopped after fisetin) and just 4 days ago I got an earache.. rare.

Again, could all be non-related.. But it's weird.

Fisetin came in mail. I took 500mg two days in row, and back to 100mg - after two days the shoulder stopped hurting, the herpes outbreak just flat out stopped - as in just stopped out of nowhere, and earache stopped as well. Normally I would be on antibiotics.

Nothing changed that I'm aware of during this time, same diet, no stress. Only variable was the tiny amount of Fisetin.

Again, I can't see how this drug could make these specific changes - but for me - it appears to have.

I find it valuable, and interesting, when people share their health history,age, as well as their supplements/meds/activity regimen. Something that concerns me is whether or not certain supplements should be taken with or without food, since I rarely find this in the research studies. It would be great if participants on this forum would also include this detail.I am 58 y/o, soon to be 59, and the only issue I have that I have been diagnosed with is arthritis in my neck (although I have it in my hands, and probably in my back). However, I had a basal cell carcinoma removed and I notice other signs of aging such as Arcus Senilis, a large number of cherry angiomas, vertical ridges in my nails, sebaceous hyperplasia, etc. My father had bladder cancer (he was 85 at the time), which was cured.He currently struggles with osteoarthritis.My mom has been on chemo for about 6 years for stage 4 breast cancer. I take a long list of supplements, and I practice the 16 hours of Intermittent Fasting every day. I am currently completing 3 cycles of 4 day consecutive fasting, and today (the second day of my 4 day fast) I have taken Fisetin for the first time. I took 1,000mg of Doctor's Best Nouvesetin with 1/4 tsp of Brain Octane MCT oil. I will repeat this tomorrow, and again on my next 4 day fast. So far the fasting has done more to improve my health than any supplement. For example, I had chronic pain in my back, and sometimes in other areas. Alot of stiffness when getting up out of a chair, etc. Also, I had a large lump in my neck, probably a Thyroglossal Cyst. After just 4 days of fasting, all of these were gone.My doctor was so shocked that she ordered another test because she could not understand why or how the cyst had disappeared. I have been taking anti-inflammatories for a few years- Theracurmin, Curamed, Omega3, Krill, aspirin, Bosmed- none of these got rid of the pain/stiffness completely the way the fasting did. I also cut carbs dramatically (no starchy foods or sugar), but I may modify this. I will update on my Fisetin experiment asap. Thanks to everyone on this forum- I have learned so much, now this is my way of giving back.

@Pentacles
I also personally find that fasting so far beats supplements. For example even a 24 hours fast improves my blood pressure, back pain, and improves vision. The effects of the day hold about one to two. Then the effect fade. 4 to 8 days can give more laying results about 2-3 months. More than 8 days can even heal, or rather bring remission to back pain, skin rush, and minor chronic pain. I also take periodically fisetin, combined with ellagic acid and quercetin. So far, only the combination of those supplements seems to have barely noticeable effects. They pale in comparison to fasting. I try combining those with farting too. I did one 24 h last week, and do 4 days about every 6 months. Sometimes it is easy, sometimes I feel off the wagon. 10 years ago I did 22 days and the effects were profound. I was much younger, though. One of the things I noticed that the skin of my hands became smoother, probably reversed some of the collagen cross links. A year ago I did 8 days and the effects weren't as impressive but for a few months I looked and felt younger. And then I referred to the base trend line. I couldn't muster the willpower to do another 8-10 fast.

I am 43 and in the last couple of years I started noticing that I do age. Lots of small things with temporary improvements and deteriorations.

Usual disclaimer that my results are not representative, YMMV, fasting for more than 3 days requires special techniques and preparation and if done improperly can be harmful. Breaking the fast requires special attention and regimen.

Apologies for the bad typos in my posts

I made plan to take fisetin. I tried mix fisetin with water and oil.

https://www.amazon.com/Liquid-Lecithin-Fearn-Natural-Foods/dp/B00016QZTS

This site is lecithin selling site.

Fisetin mix with water and oil and lecithin is good I think.

I want comments about this.

Looks like the solubility of fisetin is so poor in water that I wasn't getting much of a dose. That explains why the cocktail tasted "gritty" - it was the undissolved crystals I was tasting.

I don't think the solubility in stomach acid was much better than water. I haven't read anything in that regard.

I have DMSO on order to try for my next go-round. Solubility in DMSO is 30 ml/mg, so for 1500 mg, 50 ml (or about 3 ounces imperial) should do the trick.

DMSO apparently doesn't taste all that great, so I might try flavoring it with some powdered drink concentrate like Crystal Light.

I'm picturing dissolving the fisetin in DMSO, then adding water and flavoring to make 8 ounces.

Should be happening in the next week or two.

Sorry, I was off by a factor of 2 - 50 ml is about 1.7 ounces, not 3.

@Pete Koziar
Be very careful. Fisetin is safe because of its low solubility. In hung does it could cause cancer in rats, if taken for a long time. DSMO is considered safe but again, for sporadic use and low doses

@Cuberat, methodology is to do what I've done before (see my postings above from late 2018) - a two day course of treatment, 1400-1500 mg/day, now dissolved in 50 ml of DMSO, repeated every 2-3 months.

No, I wouldn't take this every day, nor advise anyone to follow in my crazed footsteps.

I'll post what the results are this time, as usual.

@Pete Koziar
Since you're playing with DMSO, I wonder if you plan to try some fisetin in DMSO topically - on a small patch of skin somewhere out of the way, or a small patch of grey hair.

I've been playing with pterostilbene in DMSO topically, but don't have anything positive to report.

As for fisetin, so far I've just done one cycle at the tail end of a Fasting Mimicking Diet fast: 1000mg 3 days in a row. I didn't feel anything specific, though I've felt fine since; no flare ups of my usual things that might have.

thanks for a lot of comments!

https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

in this experiment, mouse eat fisetin everyday and mouse live long life!

but eating fisetin everyday is dangerous, from above comments!

eating fisetin everyday is dangerous or not?

Both fisetin and quercetin seem to dissolve readily in oil. I used 1,000 mg of fisetin and 1,000 mg of quercetin dissolved in 1 Tablespoon of oil. I let it sit for about 1 hour which may not be necessary. I also added 1/4 teaspoon of freshly ground black pepper which, of course, didn't dissolve in the oil. The reason I used the pepper was that I reasoned that it would increase the amount of F and Q that got into the bloodstream.

An article on tumeric and black pepper states:
"Just like approximately 5% of the spice turmeric is composed of an active compound called curcumin, about 5% of black pepper by weight is comprised of this compound called piperine. Curcumin is responsible for the yellow color of turmeric and piperine for the pungent flavor of pepper. Piperine is a potent inhibitor of drug metabolism. One of the ways our liver gets rid of foreign substances is making them water soluble so they can be more easily excreted. But this black pepper molecule inhibits that process.

And it doesn't take much. If people are given a bunch of turmeric curcumin, within an hour there's a little bump in the level in their blood stream. We don't see a large increase because our liver is actively trying to get rid of it. But what if the process is suppressed by taking just a quarter teaspoon's worth of black pepper? Then you see curcumin levels skyrocket (See Boosting the Bioavailability of Curcumin). The same amount of curcumin consumed, but the bioavailability shoots up 2000%. Even just a little pinch of pepper-1/20th of a teaspoon-can significantly boost levels."

I took this for three consecutive evenings at least 3 hours after eating. I didn't feel any effect to speak of initially. After the last dose, for about the next 3 days I had a certain amount of pain, enough to feel uncomfortable, in and around the bones of my knees, femurs, backbone, shoulders and elbows. I also felt vaguely out-of-sorts and didn't want to do much of anything. After that it pretty much dissipated and I felt pretty normal. I take this to be a sort of Herxheimer-like reaction indicating good absorption of the substances and that they produced an effect, hopefully the senolytic effect that we are looking for. I also noticed somewhat unpleasant sensations in my face and scalp when drinking strong tea, which reminds me of the caution given by the Mao Clinic about reducing caffeine intake during their fisetin trial.

I have a tendency to arthritic or rheumatic pain in those areas mentioned. I have also had tendonitis or bursitis like pain in my shoulders for some months and it seems to have reduced greatly. I am 67 yrs old...

I plan to do another course of this in 1 month.

@Dan
Yes, I used olive oil and bioperine.

@Pete Koziar
Rethinking DMSO after reading this!
"Unexpected low-dose toxicity of the universal solvent DMSO."
https://www.ncbi.nlm.nih.gov/pubmed/30874586

Well, just took 700 mg of Fisetin in 25 ml of DMSO.

As soon as the DMSO hit the Fisetin, it immediately dissolved into a brown liquid. No more grit.

The taste of the DMSO, however, is not for the faint of heart. I tried mixing it with a raspberry lemonade mix and water, to make a total cocktail of about 10 oz. Didn't quite do it, still a struggle chugging it down.

Not dead yet.

@Nick, that toxicity was, I believe, with respect to embryo storage. I don't think it relates to adult humans, but ya never know. As a friend of mine used to say, "you pay your dues and you take your chances."

Plan to do another 700 mg tomorrow. I'll let y'all know how it goes.

@Pete Koziar
DMSO is non toxic per se but can enhance and modify bioavailability of other substances to the point they become toxic. Be extremely careful not to keep it in contact with anything but water and don't take any medication and supplements at the same time as experimenting with DMSO.

BTW, what does it taste like? Do you notice any effects so far?

@Cuberat, I never went back to do the second dose. Although DMSO is non-toxic, one side effect is nausea, and my stomach definitely felt queasy even up to this morning (36 hours later), although it is getting better with time. I also have a slight headache today, which is another one of its potential side-effects.

Initial unpleasant effects of the dosage also including pounding heart (although the rate was still very good, down around 70 bpm), and some light-headedness. There were also mysterious muscle twinges that came and went, and my skin, particularly on my back, was quite itchy.

I woke up the next morning feeling VERY hot with flushed skin, particularly on my forearms - once again, the "feverish" effect, but much stronger than the last time. It passed quickly.

Interestingly enough, a few months earlier when I had taken fisetin dissolved in water, it cleared my head, but when dissolved in DMSO this time, it had the opposite effect - head was very congested.

DMSO tastes like an alien culture's attempt to make garlic oil using industrial chemicals. It's nasty tasting stuff, hard to get down. Some people use tomato or grape juice as a mixer. I would NOT recommend raspberry lemonade. Just saying.

As far as positive effects, other than seeming a little more cognitively focused than usual, I'm not seeing anything in particular. I did, however, have a kidney stone a few years ago followed by lithotripsy, and since then, the area around that kidney has usually been a little sore, but since the dose it feels unusually good. Something to keep an eye on.

By the way, I have read that fisetin also dissolves reasonably well in HOT water. Might be something else to try.

@Pete Koziar
Thanks for sharing your experience.
What was the fisetin dose and hope much DMSO did you use?

I would say that for a clear v experiment one had to first ingest DSMO without fisetin and now the side effects as they are quite some. And probably after a few days take it with fisetin or other active ingredient...

Fisetin has notoriously poor water solubility but you can afford flushing it with a couple of liters of water. You cannot do the same with DMSO or even alcohol.

@Cuberat, 700 mg Fisetin in 25 ml of DMSO.

As thoroughly and quickly as the Fisetin dissolved, I might have been able to get by with 20 ml.

Continuing to feel better. Headache is almost gone, along with the nausea.

Someone else can try the DMSO with and without Fisetin test!

It seems the solubility is 30 mg/ml , so you were pretty close.

In the other hand in ethanol it is 3-5 mg/ml. In water it is as low as 0.151 mg/mL. So your disagree would require a gallon of water. Still more palatable than DSMO :)

Disagree=dosage

Just had to end my 2nd regime of Fisetin, 3 months after my first. First attempt just resulted in lots of muscle pain. Was taking 500mg of Fisetin, 4 times daily (I'm 210 lbs). 2nd regime was the same Fisetin dosage as 1st run, however this time I introduced 400mg of Quercetin w/ 82.5mg of Bromelain (again 4 times daily). After just 8 doses (2 days), I'm either having a heart attack as I type this, or it's triggered another bout of pericarditis. Original plan was to go the full 3 days--but no way. Be careful all.

regime=regimen. BTW, haven't died yet. Took some back pills (ibuprofen). Looking more like severe muscle pain in a real scary place. No shortness of breath or any of the other accompanying symptoms one would expect with a heart attack.

So, it's been a little over a week, so here's a status update.

It really took 5 days for my digestive system to calm down again, so this was something more than just irritation at an unpleasant substance. Not sure what.

It took a full week for the congestion in my nose to go back down again.

Late last week (didn't note the exact day), I was still smelling a faint trace of DMSO in my body odor. Now it's gone. That stuff is persistent!

As far as positive effects, soreness over my kidney is still much improved. Cognition is hard to judge, but it certainly hasn't gotten any worse!

@Pete Koziar
I posted the wrong link before. I didn't mean to post the in vitro one, though it has potentially more interesting (frightening) information about the epigenetic effects.

I meant to post this one showing toxicity in vivo:
https://www.ncbi.nlm.nih.gov/pubmed/24327606

This tallies with warnings I've seen elsewhere (e.g. comments on Josh Mitteldorf's blog) about people more recently being careful to use very weak solutions of DMSO.

Anyway, interesting to read your results. Good luck.

Still alive and still in pain one week after posting about heart issues following the Fisetin/Quercetin/Bromelain regimen. I've been diagnosed with pericarditis once before suspected from a flu infection. This feels now exactly like it did then. Would love to know what triggered an excess of fluids building up around my heart. Did not experience this the last time I took Fisetin alone. The chest pain is decreasing, but still have trouble finding a comfortable position to sleep with a perpetually throbbing back and chest. Took some OTC diuretic, but I'm not sure it's helped drain the fluid from around my heart.

@Chris
You might consider fasting to offset those effects.

@Chris
You were taking a relatively high dose of quercetin. Is it possible that it adversely affected some types of cells. I came across a caution in one paper for quercetin at the level you were using (as far as I can determine), but don't know if it is entirely relevant to your case. You may also have an issue with allergy to quercetin or bromelain, or it may be unrelated to your experiments...

"However, quercetin has been reported to induce cell type-specific cytotoxicity in vitro, where quercetin was relatively harmless to murine thymocytes and human lung embryonic fibroblasts at 100 μM, but significantly increased cell death was observed in human umbilical vein endothelial cells (HUVECs) at the same concentration [7, 8]. Despite this, following the finding that clinically relevant concentrations of glutathione completely suppressed quercetin's mutagenicity, and that no significant harm was observed in animals fed quercetin, it was determined to be safe for human consumption [9]."

@Chris,@Dan
Given that both fisetin and quercetin have very low bioavailability the side doesn't look extremely high. The suggested fisetin dose on the packaging is 100mg . So 5 times more is hardly extreme. Could be a confidence

@Chris, @Cuberat
Yes, could be a coincidence.
Just for clarification, Chris' dosage was 400 mg 4 times a day. That is 1600 mg per day, which makes it 16 times the package recommended dose of 100 mg.

Actually, I have mistakenly used the fisetin dosage while talking about quercetin. Please disregard the previous comment since I can't find a way to delete it. Sorry...

First ever Fisetin treatment:

I'm 64, 183 cm tall and weight 80 kg. I'm very active and still quite athletic. Also, I'm living on a Paleo diet for about 20 years and have no known health issues except slightly higher blood pressure.

Yesterday I took 1500mg Fisetin dissolved in EV Olive oil with added freshly grounded Black Pepper and let it sit for an hour. So far I haven't experienced any difference, no issues. Went to the gym this morning as usual everything seems to be just average.

Tonight I will take another 1500mg, during the two days treatment I don't take any of my other supplements to make sure there is no issue possibly caused by them. I will report here how it goes.

Yesterday at 4 PM I took a second dose of 1500mg Fisetin, after that I went for my daily 5 km evening walk and to the sauna. Nothing unusual happened. I had a good sleep, but today I'm feeling somehow dazed.

Is it known for how long Fisetin stays in the body?

@Stephan

You should feel like having a fever , after all it's internal work of the cell system I guess.

I skipped the 2 days trial dosage and went straight for 5 days of 1.2g Fisetin last month. Have improving vision at night and feeling hungry more often.

Plan to start second round next week

The strange feeling went away after a few hours. Everything feels like usual. I can't report any exiting improvements yet, at least I haven't experienced any harmful side effects either.

I plan the next round in 3 months this time after five days fasting and I might add 1000mg of Quercetin per day as well.

Any thoughts about that approach?

@Stephan
I think fastung before the senolytics reduceds their effectiveness, because fasting suppresses, albeit temporary, some senescence pathways. I would rather do first fisetin, and after that fasting

@Cuberat
Thanks, I will try it the way you recommended.

Some people here have reported fever like symptoms which didn't happen
to me. Since I'm very active and have a healthy diet as well as practicing intermittent fasting, I'm wondering whether I might have a low amount of senescence cells?

Is there any method available to measure the number of senescence cells in the body?

@Stephan
There are some tests measuring
β-galactosidase but they are quite inactive and require lab equipment and skills. But again, taking tissue samples could be harmful on its own. You could probably measure some inflammatory markers. So for now the only feedback you have is how do you feel...

Inactive=invasive

@Cuberat
I noticed that you contribute a fair amount of quality comments to Fight Aging!, may I ask you about your background?

Thanks, Stephan

The problem with Fisetin is not only its low bioavailability but also its rapid removal from the body.

Therefore, when we personally overdose Fisetin, not only simple daily doses, but also the number of doses might be important.

So I plan to take a Fisetin capsule every hour on a continuous vacation.

@Stephan
I am just a concerned individual without professional background in biology night medicine. My knowledge is amateurish but when we are on the bleeding edge carefully following the research probably is the best you can get, unless you do research yourself.

@masahi
Another big problem with fisetin self experimentation is that we don't have an objective evidence based protocol. Everything is based on how one feels. If the effects are profile enough, like reversing grey hair it would be ok ..

I am 65 and weigh 170 lbs. Last fall I took 15 100mg capsules of Doctors Best Fisetin divided into 3 equal doses for each meal of the day for two days/month. I repeated this for 4 months. During these days I did not drink any alcohol or take any other supplements. Four months after my last dose I have had a few noticeable changes. The most significant to me just became apparent, I've suffered from severe seasonal allergies for 56 years, this spring I have not needed and haven't taken any antihistamines at all. I also had a small patch of eczema on one knee that has disappeared/normalized over the winter, typically a time when it gets a bit worse. I am also sleeping much better through the night. All of these changes and a few other less important ones happened very gradually and were a surprise to me when I finally noticed them. if you repeat one of these self experiments on your self I think you should not expect to see anything happen right away, rather you'll have to wait for your body to do work slowly in the background.

@ellie

Can I please ask how you worked out the Fisetin and cimetidine dosage for your dog? I have a Jack Russel who has been diagnosed with leukemia and I want to try and give him these, but don't know how to work out the dosage.

Thanks in advance for any advise you can give.

@Hung

Please take a look here

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/fisetin

Dosage

Typical oral doses for animals ranged from 5-25 mg/kg, and intraperitoneal doses were 0.3-3 mg/kg, in the presence of a chemical carrier (DMSO). Commercial doses for humans are at the lower end of this range and typically are 100-200 mg daily for the oral compound.
Precautions

As you may know (from my comments submitted here a couple months ago), I don't like fillers and I prefer knowing exactly what I am putting into my body. I tracked down a great source for pure Fisetin powder for my own use. I was surprised by how difficult it is to obtain it here in the USA. I also found a source for another interesting herb-based medicinal (APOCYNIN) that is worth learning about.
As of Monday (May 13th) I have small quantities of the FISETIN powder (currently 98.13% purity) for sale on EBAY. Also small quantities of the other one, the APOCYNIN.
Go to the main EBAY site, and then do a search for "Fisetin powder". You'll see a PIC of a yellow pile of the Fisetin. That's the stuff I have. (I little lower, you'll see a PIC of a pile of white powder. That's the Apocynin).
If you read my listing(s) you will learn that, in addition to its benefits when taken orally, FISETIN has some very interesting TOPICAL skin properties. I'm taking the FISETIN internally (at 200mg per day as a yellow "shot" stirred into some warm water and gulped down before it settles), but I've also been checking out its TOPICAL uses. I've successfully used it to clear up some minor (but growing) basal-cell 'breakouts' on my own skin. I'd had them for years, but they were starting to get worse.
For the topical 'basal-cell' use, I made a mixture by stirring some of the pure Fisetin into some natural Vit. E oil. This forms a yellow suspension that, if allowed to settle a few days, produces a clearer, orange-ish top layer above the solid yellow excess of Fisetin powder that didn't get dissolved into the VIT E. The top layer is the part that gets applied.
But be warned that it makes the basal area look worse before it looks better. You could even say it becomes GROSS looking.
Before trying it anywhere else, I advise first trying it on a relatively unseen area, so you can gauge your own personal response to it. You do NOT want to first try it on your face or any other highly-visible body location!!
With me, it was a persistent basal-cell eruption on my upper left arm and I did the applications in late-winter, when I was always covered in clothing anyway. I dabbed the Fisetin + E mixture onto the basal spot, then covered it with some surgical tape/cloth to seal it and keep the Fisetin mixture in place. The Fisetin seemed to seek out hidden basal cells I wasn't aware of, within a 2 inch radius of the original visible basal 'spot', so it got pretty messy looking. However, I'd been on YouTube and had watched vid-clips of people applying an prescription cream called IMIQUIMOD to their basal-cell spots, so I wasn't entirely surprised by this 2-inch radius thing.
After about 3-4 weeks of the daily FISETIN treatments, I stopped and let the treated area dry-out and heal over, only keeping it moisturized with a little Aquaphore (an improved Vaseline). It gradually became less "weepy" looking and is now a healed little reddish spot that is vanishing, -just in time for summer.
For the science end of all this, you should read the links I provide in my EBAY listing.
EBAY generally discourages the posting of LINKS in product descriptions,,, most get rejected. To get around that, I sometimes had to resort to posting round-about directions on how to get the info, since I couldn't just post the easy, direct LINK. Sorry about that.
I agree with what "Ted" just said about the Fisetin producing g-r-a-d-u-a-l effects that are not immediately obvious. To me personally, it acts like an energizer. I take it in the morning. I used to drink 3 cups of coffee,,, now drink just one. My handwriting was getting 'shaky" before, but now it is smooth again. I can remember numbers better now, but still suck at names. Less morning stiffness. Sleep a solid 7 hours. Of course, these are all merely subjective, anecdotal things: the beneficial effects are hard to quantify. I can't say I feel 20 years younger, but I trust the Science. Maybe in 5 years, I'll be able to say I feel just as good (or even better) than I do today?
- - - - - -
The APOCYNIN is a brand new one,,, it just hit my own radar 6 weeks ago, when a Japanese research group published their findings (April 3rd) that Apocynin can revitalize the stem cells needed to keep replacing epithelial cells that are always wearing out. It is totally unrelated (chemically) to Fisetin, and it operates along separate cellular-metabolic pathways than Fisetin does, but they both exhibit anti-inflammatory, anti-oxidant, anti-aging properties. Naturally, I am curious about the possibility of them acting synergistically with each other.
Anyway, I tracked down a source for 99.5% pure, white Apocynin, and I am taking 60mg of it orally, along with the 200mg of pure Fisetin I am taking daily. I just put some warm water into a shot glass, stir in the powders, and quickly swallow it before the Fisetin can settle out of the suspension. It basically has no taste, except for some bland 'chalkiness'.
The APOCYCNIN is reportedly able to rejuvenate skin stem cells, so I also apply an extremely dilute solution of it to my face. As I mention in my EBAY description, the Japanese scientists applied it to the skin of MICE as a 100 micro-molar solution of Apocynin, in a phosphate-stabilized saline solution containing 0.5% of pure DMSO (w/w ratio).
This actually works out to being about only 2 mg Apocynin dissolved into 4 fluid ounces of warm 'water', with a single drop of pure DMSO added. For myself, I'm dissolving 12 mg of Apocynin into 4 fluid ounces of warm distilled water, and am skipping the DMSO (because my fair skin happens to have a bad reaction to DMSO). This works out to being a 638 micro-molar solution,,, about 6 x's higher concentration than the Japanese researchers applied to the MICE. I've only been using it for about 15 days now. I'm guessing it could take a month or two for the re-energized stem cells to produce any discernable results in the visible top layer of my skin. We'll see ...
If you're interested in any of this, read the descriptions I provide with my EBAY listings, and also try reading the LINKS. The April 3rd research publication (26-27 pages) is very remarkable, but is also very difficult for most people to follow. Those darned geniuses can really drive you nuts, at times.
I'm not in this for the money. I merely want to make available to 'YOU' the same things that I decided to go out and obtain for 'ME'. If you're interested in this sort of thing, then you now have a source for it, in small quantities.
Keep in mind that the APOCYNIN is pretty powerful and is thus used in smaller quantities. Ten grams of it is the same as 10,000 milligrams, so a little can go a long way.

I'm planning to try the two-day, 20mg/kg regimen soon.

But for now, just some general comments:

Senescent cells send out signals to the immune system to come and kill them off. But after reaching a certain age, the immune system finds it difficult to succeed in doing that. Nonetheless, it gets called into action by these signals, resulting in a constant low-level inflammatory signal, due to the persistence of these senescent cells.

Taking anti-inflammatories (e.g., curcumin, baicalin, EGCg, etc.) may offset this signal by desensitizing the immune system - e.g., by blocking receptors for Pathogen and Damage Associated Molecular Patterns (PAMPs and DAMPs) on macrophages. This is an acute effect that lasts as long as the anti-inflammatories are in your system, but not much longer.

Compare that to a senolytic agent like fisetin, which apparently helps the immune system to succeed in removing senescent cells, thus removing that signal until such cells accumulate again, rather than merely offsetting it as anti-inflammatories do.

So we can see that a senolytic may have effects that are similar to, but longer lasting then, anti-inflammatories.

What complicates this picture further is that fisetin is itself not just a senolytic, but also has anti-inflammatory acute effects.

So, it seems possible that there *could* be some confusion regarding whether certain effects being observed are due to the anti-inflammatory effects of fisetin, or due to its senolytic effects.

Also, if people are already taking anti-inflammatories on a regular basis (as I am myself), it could be that even if senescent cells do get culled by the application of fisetin, the effect might not be apparent, if the inflammatory signaling of such cells might have already been masked by the anti-inflammatories *prior* to taking the fisetin.

Just a few thoughts for your consideration.

Thanks to everyone for sharing their experiences; it has helped me in arriving at my decision to try this substance myself. I'll be contributing my own experience once I've gone through the process.

I used Dr's best 1.5g/meal for 2 days, wait a month then repeat. My meal was breakfast (leftovers) hamburger meat, avocado and some coconut oil. Not standard but there it is. It was intentionally fatty.
The men in our family line have prostate problems and I'm 60 and have BPH at least. I set up an experiment. Living in the country with a long drive home from work, my teeth are/were floating when I'd get home. So I set up a range to see if fisetin relieved prostate issues. Firing line and range markers.
For 5 days over 1 week in advance I measured how far I could pee for a baseline, at a consistent 23" max sustained over a short period. After the first 2 days of fisetin I had an increase to 27" and 28" then dropped back down to 23" for the rest of the month. After the second round of fisetin I increased over a 3 day period to 30" and dropped back down to 26" where I remain now 10 days later.
Quantitatively after the first round I no longer had to take a leak when I got home despite the same baseline of always doing so just before I left work. Perhaps with fisetin I was better able to empty my bladder prior to leaving work.
YMMV, but I thought I'd post some quantitative data. I plan to repeat for 1 - 2 more months and see if things continue to improve.

@Diego

Video documentation would help us to ascertain the accuracy of your claims.

@Cuberat

Thanks for your comment. And sorry for the late reply.

Certainly, as you say, it is difficult for individuals to report the effects of overdose of fisetin in an objective and reproducible manner. So, it can never be science..

However, at least some of us can not wait for the results of the trial, and what we ultimately want to improve is subjective symptoms. So I look forward to this community report. Even if it is not a case study.

Please let us know if you know a better way to report the effects of fisetin overdose.

On the other hand, I think it is also important to bring our personal experiences as close as possible to science.

So, I would like to report a physical examination (mainly blood chemistry tests) before and after overdose of fisetin. Aging is also related to blood chemistry, so increasing these reports has some statistical significance, although the background factors are not controlled.

@Hung

Note that the values reported in the paper are mostly for mice (30 g of body weight).
And because the rate of metabolism is different, we can not simply apply the mouse values to your dog's weight.

There is a law known as allometry between weight and dose. HED (Human equivalent dose), which links human doses and values of animal experiments dose, is also calculated by this law.

In particular, it is calculated by the 2/3 power of the weight ratio. Alternatively, it can be obtained by dividing the dose calculated from a simple weight ratio by 1/3 power of the weight ratio.

例：
mouse（30g）
Human（60kg）
weight ratio = 60,000/30 = 2,000

So, HID = 2000^(1/3) = 12.3

With this HID, 10-25 mg/kg of a typical animal experiment (oral doses at mice) will be 50-125 mg/60kg for humans.

In that sense, the doses administered by the Mayo Clinic are more aggressive. It is close to the 3/4 power of weight ratio. This seems to emphasize that of metabolic rate.

The story has been derailed, but the same is true for your dog.
Assuming your dog's weight is x [kg], the doses you want to obtain are (at your own risk):

Low (10 mg/kg): 10x/(x/0.030)^(1/3) = 3.1x^(2/3) [mg/kg]
High (25 mg/kg): 7.8x^(2/3) [mg/kg]

P.S.
Although I did not follow allometry, when I administrated the same dose (20mg/kg) as Mayo Clinic to my Border Collie (8 years old, 15 kg) suffering from myoarthritis, the symptom was significantly improved.

P.S.2
In your case, you might consider fenbendazole rather than fisetin..

"In my mind, the cell 'age memory' is what determines longevity, this signature is (so far) irreversible/permanent once written (the cell Never forgets its age and thus 'act' appropriately to its age despite being reverted to immature state ('Age 0'))." Where do you get that idea from? It is wrong. Cell induced to pluripotence can form entire organisms with normal lifespans. Nuclei from aged somatic cells can become entire organisms with normal lifespans. In vivo transient and sequential application of Yamanaka factors reverses the age phenotype of entire organims, as does heterochronic parabiosis. So in what way is a pluripotent stem cell 'acting' it's age when it forms a young tissue?

Well, I did another round of 700 mg of Fisetin tonight, but I tried a different method of application. Instead of dissolving it in DMSO and drinking it, I still dissolved 700 mg of Fisetin in 25 ml of DMSO, but then, basically, took a sponge bath in it. I'm trying to avoid the week long nausea I had when I drank the stuff.

It turned some of my skin slightly yellow, mostly under my arms, but not as yellow as I would have expected.

25 ml covers a surprisingly large area, and took about 15-20 minutes to apply so that it soaked in and didn't run off. In addition, my skin was still "greasy" with the DMSO for about another half hour after that. I put on a plain tee shirt, and it does have some small yellow patches where there was enough DMSO left on my skin to stain it.

Effects so far are a mild burning sensation on sensitive areas like the back of my neck. The tops of my legs above the knee were good places to apply it, seemingly, with little reaction.

I figure the DMSO will carry the Fisetin through the skin barrier into my blood stream. I'll let you know if anything notable happens.

Hi guys! I started my course of fisetin. I am a 40 y/o woman, mostly healthy, low BMI (but within the normal range), low lipid profile and no other permanent peculiarities, good HOMA-IR, normal thyroid hormones. I have got a full check-up one week before starting fisetin, including blood work, ECG and measuring the intima-media thickness. I have a mostly healthy diet with reduced fast carbs and red meat, no processed meat, no fried or smoked or salted food, no fast food, lots of vegetables and fruits, salads, chicken, fish, nuts, vegetable oils, whole grains etc. My diet didn't change in the last half of a year.

I took 1 g of fisetin obtained through a friend from the producer HuiChem and tested for purity in a local lab. Purity was found acceptable.

I decided to begin with 1 g to test tolerance before taking a higher dose. If tomorrow I see no side effects from today's 1 g, I plan to be taking 3 g daily over the course of 3 days. Then I wait 1-2 weeks and repeat the blood work and other tests. I'll share my impressions with you if I survive, lol.

I've been following this story and comments for a while now, and appreciate all the thoughtful input.

This story prompted me to read the fisetin studies in full, and ultimately to test it for myself. I shared my thoughts on fisetin as a senolytic in this posting:

https://www.christianhunter.com/2019/05/best-new-senolytic.html

Best,

Christian Hunter

Hi guys!

I was taking fisetin powder for 4 days as follows:
- the first day, 1 g (to assess tolerance)
- the next 3 days, 3 g per day

Side effects that I have noticed: very weak tingling or itching on my face and hands for 3-5 hours after taking fisetin, and apparently a slight stimulation of kidney function for ~6 hours after taking fisetin.

No other noticeable sensations were observed.

Next week I will be making my blood work again (a big check-up identical to what was done before the test of fisetin) and will let you know if there is something intriguing.

BTW for those of you who are interested, there will be a report of Dr. Pamela Maher on fisetin at our conference Ending Age-Related Diseases: Investment Prospects and Advances in Research that we are hosting at the Cooper Union, NYC, on July 11-12 2019.

This is a really active thread. Thanks to everyone for all their input. If Elena Milova could update us on fisetin at the Ending Age-Related Diseases conference that would be really cool.

Hello all. I'm a nutritionist working with people with parkinson's disease among others. I saw an article by a nutritionist with PD in the Journal of Medicinal Food (2012) who had vast improvements using strawberries for fisetin (@2 cups/day) and wheat germ (good source of hexacosanol, @2tbsp/day). She did not take either in supplemental form, only from food sources. She also ate a mostly mediterranean type diet from mostly plants with 30% non-saturated fats. I could not find any replication in further studies, however the study advocated clinical trials. Given that PD is a highly variable condition, I'm sure this will not work for everyone, but I would like to give it a try with my patients. I am aware that many people would have a hard time eating two cups of strawberries per day, and even finding or affording the organic ones since these are #1 on EWGs list of most highly pesticided fruits and I would not advocate eating them conventional. So, my question is, has anyone had any success with using fisetin for PD, and if so, which supplemental form has been tried? I found one source that comes from strawberries (37 strawberries) but it is not organic, and the others seem to be mostly from a member of the poison ivy family (rhus). Also, for a chronic degenerative condition, would taking a lower dose several times daily seem to be a better idea than for several days a month only? Any comments are appreciated.

@bunk0555: Human trials are using 1200mg/day for a 60kg human on two consecutive days. The human equivalent dose from the mouse study in this post is 500mg/day for 60kg human for five days.

Per https://doi.org/10.1089/ars.2012.4901 strawberries contain 160 μg/g of fisetin, or 160mg/kg. So unless you are up for eating 7.5kg of strawberries on each of two consecutive days, I'd give up that line of thinking.

This business of noting that fruit X contains compound Y so everyone should go have a small helping of fruit X is a frustrating, irrational behavior.

There is no particularly compelling evidence for fisetin to be interesting at low doses. Go exercise or eat fewer calories instead. There is compelling evidence for both of those approaches to reliably improve general health and symptoms of age-related disease.

Otherwise, Parkinson's is absolutely a condition in which cellular senescence appears to play a role, based on recent research into animal models. Human trials will no doubt emerge, but I expect people to take matters into their own hands (with senolytic drugs and supplements, not fruit) and report anecdotally on successes long before that happens.

I was diagnosed with Parkinson's disease last December. I don't currently take any prescription Parkinson's medications. I started taking 300 mg of Swanson's Fisetin daily in February. Dosage is generally 100 mg A.M., 100 mg 5:30 P.M., and 100 mg 8:30 p.m. No negative effects have been observed. Insofar as I can tell, there has been no advancement of Parkinson's symptoms. The major benefit I receive is a general calming effect, and 95% elimination of stress or anxiety tremors. In general, I feel normal again, except for a periodic mild thumb tremor. I've reached out to Parkinson's researchers and institutions, and have received zero interest in my experience. I intend to continue taking Fisetin daily, as it has substantially promoted my daily well being.

@Reason, thank you for the comments.
The case study I was referring to was continuous long-term low dosage of fisetin and hexacosanol via food sources, which worked very well for this individual with PD. I don't find eating foods in their natural forms for certain benefits frustrating as that is what we all did before pharmaceuticals co-opted nature and isolated and concentrated individual compounds. If someone is comfortable with getting his medicine from food, that's just the old-fashioned way. Nevertheless, this is what this person tried with success--continuous low dosage through her food. Hence my question as to chronic degenerative conditions--perhaps continual low dosage is advisable?
The link to the study in your post was a membership and I could not access it. Is this a PD study?
My PD patients are quite thin (putting on weight is difficult with a lack of smell, difficulty swallowing and continuous movements) and exercise is not so easy if one can't move well or with confidence due to balance issues.
@Allen, this is very interesting to me. How did you come to determine your choice of supplement and dosage? I am generally working with more advanced patients, and wonder if the dosage would be different due to that progression. I appreciate your comments and would like to know if your positive outcome continues and/or if you need to increase dosage or frequency. Best to you.
Any other experiences with taking lower doses continually, or have any supplement suggestions? Thanks.

My son is a physician/scientist with a research interest in diseases of aging. The choice of Fisetin, and the dosage amounts were his based on published animal results. The dosage frequency is empirical, based on what I find to be most effective. You can't get the same amount of Fisetin from food sources as I'm currently taking. My experience may not be relevant to your patients, who are much further advanced in their disease progression. I've also been continuously involved in endurance athletics since my teen years, and largely eat whole grain products, fresh fruits and vegetables, along with some chicken and fish. All of these elements probably contribute to mild, late disease onset. Parkinson's is a plague in my family, most probably because of an LRRK2 gene variant. In other family members, it has first surfaced at about age 60, and the initial symptoms were much more significant. I was 74 at first diagnosis, and my clinical symptoms are mild, and don't interfere with my life.

Iam TOMOTOMO.

I solved Fisetin by Extra Vergin Olive Oil. But It looks not perfect. And some people who take Fisetin with Extra Vergin Olive Oil says they do not feel effection.

I solver Fisetin by DMSO. It looks solved perfect. But it is difficult to drink DMSO.

So, I want advise, how to take Fisetin.

Best regards!

by TOMOTOMO

If you search fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol,

You will find a lot of people trying various method of taking fisetin,

Showman

I would advise against drinking DSMO. While not outright toxic on its own it can help anything harmful in your stomach, or even you come on contact with readily disprove and get absorbed. It might have cancerogenic effects.

Disprove==dissolve

https://www.nutrientinsider.com/News/762/Medicine-Has-Known-About-This-AntiAging-AntiAlzheimers-Nutrient-for-Over-100-Years--But-Youve-Probably-Never-Heard-of-It.htm

"In other words, fisetin is a nutrient that you can take in relatively large doses to slow the aging process, including the mental decline that comes with an aging brain. And you can use it to protect your body against diabetes, cancer, Alzheimer's, and many other neurodegenerative diseases, such as Parkinson's.

This is big news! But there is bad news. There aren't a lot of studies on humans. Dr. Schubert says we may not see those human studies for some time. He says clinical trials are daunting because it's difficult to protect patents on natural products. "We will never know if a compound like fisetin works in humans until someone is willing to support a clinical trial.""

Regarding using DMSO with fisetin: Chemicals interact. Are there any molecular changes to fisetin when dissolved in DMSO? If the purpose of dissolving fisetin in DMSO is to increase bio-availability what studies show that to be true? Considering how inexpensive fisetin is, increase the amount taken if the goal is to increase the amount absorbed into the body.

For DMSO it is often, if not routinely , used to dissolve chemicals and inject into mice. While not toxic to humans it still considered dangerous and is suspected cancerogene. So I would advise to avoid consuming it without a good reason.

If you search fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol,

↓You will find a lot of people trying various method of taking fisetin,

https://forum.age-reversal.net/t/80dgas/how-to-increase-the-bioavailability-of-fisetin

If there is good way, I want to know!

Show man

fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol

Only this way↑

Another method is very dificult

I have been taking 1.5 grams of Fisetin and Quercetin once a week (on Sunday) since this thread began. I have recently added 1 gram of rutin. I always take it with food and extra oil (MCT or coconut). I have no negative effects that I know of as of yet.

I decided on a weekly schedule of supplementation because the idea of once each quarter (every 3 months) never completely undid the accumulation of sencesent cells in rats. https://marlin-prod.literatumonline.com/cms/attachment/36de5cc1-57e1-447e-9495-b21ccda809d1/gr2.jpg

FYI - Here is link to "A Diet Low in Animal Fat and Rich in N-Hexacosanol and Fisetin Is Effective in Reducing Symptoms of Parkinson's Disease" https://www.researchgate.net/publication/230587812_A_Diet_Low_in_Animal_Fat_and_Rich_in_N-Hexacosanol_and_Fisetin_Is_Effective_in_Reducing_Symptoms_of_Parkinson's_Disease

@Otto
You have no negative effects. Can you witness positive ones?

I do other things for my health so it is difficult/impossible to ascribe any positive changes to fisetin.

With regard to negative changes, I was expecting that I would need to dial-back the frequency but I have not found any ill-effects. Perhaps, I am still too young (only 65).

Ageless, I really appreciate your sourcing the Apocynin! Do you have an update on the topical use since May? How many mg does the tiny spoon hold?

Today I started another attempt at a 3-day regimen of Fisetin: 2 grams spread across four hours, per day.

Back in April I commented that I thought I was having heart failure. That turned out to be a flare up of an old esophageal ulcer.

After an ER visit, and the usual blood tests, they eliminated heart failure including pericarditis, from a chest x-ray.

After a few days home, still in pain, I took some TUMS and felt immediate relief.

Remembering the treatment for the ulcer years prior, I took 40mg of omeprazole (Prilosec) for 4 weeks, and then 20mg of omeprazole for another 4 weeks, to repair the ulcer.

Until I resumed the Fisetin this morning, I hadn't felt that ulcer pain in about 5 weeks. It's back now however.

At least now I know it wasn't the Quercetin or Bromelain included in the previous attempt.

So I'm either allergic to Fisetin, or I have a mass of senescent cells in my stomach that cause my ulcer to reopen after only a 1000mg dose.

I don't think I'll be able to continue without doing significant stomach damage.

And I'm worried my old ulcer may have progressed into something much worse, which will require another endoscopy to confirm.

Interesting. It might be that fisetin in high doses is toxic to the stomach lining. You might consider telling fisetin while fasting.

I'm done self-experimenting with Fisetin. Any benefits of the three attempts were imperceptible.

The previous heart attack scare from the presumed destruction of my stomach lining, the muscle pain, and general malaise for weeks, is just not worth the risk of creating some other serious health problem.

I'll keep my eye on this study - https://clinicaltrials.gov/ct2/show/results/NCT03675724.

If there are proven benefits at a much lower dosage that my stomach can tolerate, I'd consider trying it again.

Chris, my guess is that Tums and Prilosec are the issues with your stomach. A good nutritionist, along with some apple cider vinegar, can help you with this.

A big thank you to all the folks who posted here. I'm going to order and try Fisetin.

High dose of Fisetin has also higher doses of Magnesium Sterate and Silicone dioxide or Silica in capsule form. I wouldn't be takeng those. Finding a good source of Fisetin powder only, would be a good way to go, Ps other supporting supplements and life style changes ( exercise food and fasting, detox) that can go well with Fisetin. But i agree this is only a band aid to healthy life extension. If nobody comes up with a more effective life extension or age reversal technology. Late Bill Thompson a former secret government agent talked about a pill taken 3 times, reversed ages of agents who worked for government their whole life, where given a chance to age reverse and retire. Bill Thomson claims that this pill taken 3 times revered the age of men to 28 an women 26 or so, if its true. He lined up for the pill but it was too late for him. he was 90 something. This is what we need and should not settle for anything less, in my opinion.

@Haze
I am not surprised that there are such rumors among the agents but I highly doubt they are true.

First there should be an agency that produces and supplies those magic pills. And that organization would have priorities. Field agents are coffee if not at the bottom of the pyramid. You have head of the state, head of the intelligence organization. And there is no need to change ones identity of over 60. Just a bit of plastic surgery to make the face look older and you can roll on till mid nighties without about some questions. Then you will have powerful and connected rich people, then there are valuable specialists and scientists, and other useful people you might want to keep around. However 70 something is the age the politicians start to crumble and step aside .

I'm 65. I've taken 1 course of Fisetin, Dasatinib and Quercetin.

Took first dosages in March 2019 and will repeat in October.

180 mgs of Dasatinib, 1250 mgs of Quercetin and 1500 mgs of Fisetin for 2 consecutive days.

The immediate effect was an increase in my cardio workout.

Only side effect was a very noticeable fever approximately 1 week later which I attribute to the body purging the zombie cells..

I use a brand of Fisetin which is 3rd party lab tested and is >99% pure.

BTW, I also take 3 mgs of Rapamycin once a week and 500 mgs of MetforminER 2x/day.

I had my biomarkers of inflammation tested in May and they were all low. For example, hsCRP was 0.4

One correction.

Dose of Quercetin was 2250 mgs per day for 2 consecutive days NOT 1250 mgs

I've been recently (last two days) taking larger doses of fisetin as well as curcumin orally and applying small amounts of fisetin solubilized in DMSO to my knee to treat what is probably arthritis. I have read many of the scientific articles mentioned here about the antisenolytic properties of fisetin and other substances and especially the animal model ones.

What I'd like to know is, does anyone know of pharmacokinetic studies of any of these compounds, where they specifically look at where the purported antisenolytic partitions in the body, i.e. not just its circulating lifetime in the blood but what other organs/bones/joints/tissues fisetin e.g. might specifically have affinity for? This kind of study seems especially important for predicting the efficacy of, for example, orally ingested fisetin for treating any kind of ailment, and is much more important than finding a better formulation for absorption of a compound through the gastrointestinal tract.

thanks, Timouthy

Hi Mr Charles Grashow
Would you let us know where you are able to purchase the fisetin powder you mention is third party tested at >99% purity?
Many thanks,
Melissa, Australia

An interesting Fisitin risk-benefit analysis:

https://brain.forever-healthy.org/plugins/servlet/mobile?contentId=63602860#content/view/88867062

Fisetin of course, sorry for the typo.

@Stephan

A nice summary of what is known. For example, u don't know it could lead to fibrosis during wound healing

My wife has chronic hives and issues with insomnia. Isn't clear if insomnia is related to hives or not because is present even during the non-hives days. I will suggest her to try fisetin as long term low-dose. Did anyone had any experience with fisetin and hives?

Also I was wondering if it was worth to try instead with 2 cups/day of organic strawberries. However, one thing that puzzles me is that strawberries contain a chemical that can cause body cells to release histamin, so usually it's been avoided by people with allergies or eczema. Could be that strawberries work in a different way when administered in high doses

I did my second round of Fisetin treatment, this time with added Quercetin:

1500mg Fisetin
1500mg Quercetin

mixed and added three teaspoons of virgin olive oil and let it sit for one hour, taken two consecutive days.

However, like the first round of treatment, I have no symptoms, no side effects everything as usual.

I don't exactly know how senolytics remove senescent cells. If they got flushed out of the body with our stool and / or urine, is there any method to analyze the success of a treatment?

"I don't exactly know how senolytics remove senescent cells. If they got flushed out of the body with our stool and / or urine, is there any method to analyze the success of a treatment?"

I assume these cells are treated as other dead cells, which are absorbed by the tissue and somewhat reused. It's difficult to test the success of the treatment, I read a comment on that further up in this tread, you might want to look again.

I continue to do a round of fisetin each Sunday and I have not noticed any ill effects. It seems that there may be support for idea that fisetin has positive long term effects on the brain. see https://patentimages.storage.googleapis.com/27/10/4a/3818fac9ec04a7/US7897637.pdf

Well, another try, another method of administration.

Someone here said that "it would take a gallon of water to dissolve my daily dose." Well, shoot! I take in to work with me a gallon of water every day since I don't like the taste of the city water where I work, so I dissolved the fisetin in that and will be drinking it throughout the day.

So far today, four glasses, about 40 ounces. After the first glass, got a sudden headache and some itchiness on my face and the bottom of my foot, but it passed. Didn't notice anything with the other glasses.

Like the first time I tried it dissolved in water, my sinuses did suddenly clear out.

I'm now doing my third self experiment with high doses of Fisetin. The first was in October 2018 (see above). In April of 2019 I took five bottles of 37 Strawberries brand fisetin in five days. The supplement claimed to contain 70mg of fisetin in addition to other ingredients. I felt better soon after.

My lower back pain all but disappeared last summer and I no longer need medication for my BPH, which may be caused by senescent epithelial cells. I definitely feel better and look forward to exercise, which I forced myself to do last year.

I cannot find the 37 Strawberries brand or I would have bought it again. Yesterday I started with fifteen 100mg capsules Wellness Resources Fisetin and took the same dose again today. I plan to take fifteen capsules for six days, thirty capsules for three days, then fifteen capsules for six days, or something like that. I have 270 capsules and I plan to take them over the course of about two weeks.

If my previous experience is any guide I will feel better in a couple of months. I have lost 49.8 pounds since the initial experiment in October 2018, most of which I attribute to Intermittent Fasting, and my Fasting Blood Glucose is quite healthy, now 86-90, I am no longer considered pre-diabetic. I have gone from walking frequently in 2018 to Interval Training five days a week, weight training three days a week, long walks on the weekend and short, 1.5 mile walks almost every day, often seven days a week. I have taken NR for years and other supplements, but something seems to have changed with the fisetin, I plan to take a high dose every six months from now on. My biomarkers all seem good and though most were not bad, several have improved.

One thing I have noticed that is a concern, the minor cuts and scrapes I have suffered over the last year heal slowly. Recent literature connects fisetin with slow healing time. I've been fortunate that I have only received very minor injuries, a serious injury could be a problem.

I've been taking the Wellness Resources brand for four days and I haven't felt the same noticeable buzz, a feeling like excitement that I felt with both the Doctor's Best and 37 Stawberries brands. I have an extra bottle of Doctor's Best so I compared the capsules. The contents look and taste identical, a very bland powder, although the Wellness Resources brand capsule was slightly larger. I took 15 capsules of the Doctor's Best brand and then, after reading some of the comments above, decided to dissolve 15 capsules of the Wellness Resources brand into a about a tablespoon of olive oil (California Olive Ranch brand olive oil). I added 500mg of Quercetin and 1200mg of Resveratrol, as I have been meaning to dissolve Resveratrol in olive oil for a while, then added a little more olive oil, less than two tablespoons, total. The resulting mix wasn't terribly gritty, very slightly bitter but it wasn't hard to swallow. It is 9am, I am thirteen hours into my daily eighteen hour Intermittent Fast, nothing to eat since 6pm, nothing to drink but black coffee and my Fisetin, Quercetin, Resveratrol and olive oil concoction. I'm sure it's psychosomatic but I do feel like something is happening. I will update this forum whatever happens, good, ill or indifferent. Be forewarned that self experimentation is ill advised and possibly dangerous, no one has tested Fisetin at these doses in humans until recently, there very well could be unwanted long-term side effects.

That should read fifteen hours without food, not thirteen.

Rick Davis, yes, I have all that data, I am not going to type it all in here because I don't have five hours to spare. If you want to provide an email address I can send you screen captures and scans of my biomarkers, my doctor does blood work every 3-6 months. My LDL is down a little, HDL is up but not much, PSA is always excellent, testosterone got too high, 1500, I had to switch from a gel to a cream, and we're still working on the dosage. Triglycerides are slightly improved but were not bad. Nothing was very bad before, but there are some improvements. My Fasting Blood Glucose was occasionally of some concern, up to 114, then back to 90. My hemoglobin A1c was always fine at about 5.2 to 5.4. I have lost weight mostly due to Intermittent Fasting, which is likely what brought my blood sugar under control, ranging from 86-90.

My non diabetic Benign Prostatic Hyperplasia (BPH) has all but disappeared and I can think of no other explanation other than fisetin. I sleep through the night, sometimes I wake up once, rarely twice. I am 52 years old.

Fisetin may have played a large part in my improved health. Since this is just an anecdote, I say without hesitation, I feel younger, healthier and more energetic, and I am sure that is due to Fisetin, NR, melatonin, IF, HIIT, green tea and a few other health fads.

Chris, that is fascinating. Are you still in remission? I will mention this to my friend with herpes.

Two days ago I took 30 pills of 45 mg each of Fisetin, and the day after 27 pills of 45 mg (there were 3 pills missing). On average that is 16 mg/kg pr day. The Fisetin was bought from 5greensuk.
I didn't experience any side effects.

@Martin Andersen
With no measurable effects you cold have more expensive pee. I got the impression that the human equivalent dose should be about 2 grams per day for a human. But I guess the most important part is the solulabilty

@Cuberat
Yes it could be just expensive pee. I can't test the effect. It's unclear if there should be side effects. Some have written about sensation in an arm and headache. Even so, who can tell if it's working as hoped? I was aiming for 20 mg/kg pr day as in the Mayo trials, but I bought the package with 60 pills (although I only got 57).

As I have mentioned earlier I have done a couple of Fisetin + Quercetin rounds with no noticeable difference/effects.

At the age of 64 I still pump iron five times a week and walk/hike/ski 30-50 km weekly. I do most days time-restricted feeding 16/8 and also intermittent fasting on weekends. Needless to say that I live on a very balanced diet as well.

These routines may induce autophagy daily for some hours.

Now I'm wondering maybe there is nothing left for Fisetin to clean up?

Any thoughts?

I am on my third round, 2 months apart, using the Mayo protocol for taking fisetin to clear senecent cells. While I have not noticed any "results", I am experiencing mild fever. This happened last time as welI, showing up a few hours after 20mg/kg dose. Fever indicates that a Reved up immune system is going after something. Let's hope it's going after those senecent cells. Of interest, I Quote:

"Exactly how fever works its magic is ill-understood. But research just published in Immunity by Chen Jianfeng of the Institute of Biochemistry and Cell Biology, in Shanghai, sheds light on the matter. Dr Chen's work shows how febrile temperatures encourage a particular protein to shepherd immune-system cells to sites of infection."..........could it also Shepherd the immune cells to sites of senecent cells? It is after all, a top notch immune system that keeps senescent cells at bay when we are young.

Has, anyone got any more information about the wound healing problem with high-dose fisetin that scottalias mentioned could be a problem. I heard that it also causes blood clotting to become less effective. If so, how long after a 2-day course of fisetin does this wound healing and blood clotting problem last-one week, two weeks etc?

And should dental treatments be avoided during a fisetin-taking period? Tooth extraction could be dangerous while fisetin is still in your body.

If it was working wouldn't we know by now?

Quick report and some info I kind of wish I had read before calculating my dosage, but never mind, Im still here.

Found this advice on converting animal dosage - human dosage:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

Excerpt:

"Key Points in Scaling of Dose
Larger animals have lower metabolic rates

Physiological process of larger animals is slower

Larger animals required smaller drug dose on weight basis

Allometry accounts the difference in physiological time among species

Do not apply allometric scaling to convert adult doses to kids.

Dose Calculations and Examples
The dose by factor method applies an exponent for body surface area (0.67), which account for difference in metabolic rate, to convert doses between animals and humans. Thus, HED is determined by the equation:

HED (mg / kg = Animal NOAEL mg/kg) × (Weightanimal [kg]/Weighthuman [kg])(1-0.67)      Eq. (1)

For example, for a newly developed drug molecule, the NOAEL value in rat weighing approximately 150 g is 18 mg/kg. To calculate the starting dose for human studies, use Equation 1.

HED (mg / kg = 18 × (0.15 / 60)(0.33) = 2.5 mg / kg

Thus, for a 60 kg human, the dose is 150 mg. This HED value is further divided by a factor value of 10; thus, the initial dose in entry into man studies is 15 mg."

So based on the Mayo clinic mouse study, the human dosage should be less than 15mg / day (including a safety factor of 10X) ? Even discounting the safety factor, it seems the dosage should be less than 200mg ?

Seems very low to me, Im slightly concerned that the dosages I have been taking are a little high compared to that, but anyway, (I'm 56, not bad health, a bit of arthritis, around 15kg overweight, and low on energy. Have also had some fairly problematic mind fog for approx 2 years. I;m not taking any other pharmaceutical longevity medication but I do take a multi vitamin(solgar omnium) and some powdered spices/herbs daily(turmeric/clove/ginger/st johns wort/ashwaghanda/cinnamon) which I mix myself into a paste with some hemp oil and raw honey. Also take black seed oil).

3 days ago I took approx 20g of Fisetin powder standardized at 10% Fisetin (approx 2000mg Fisetin).

Within 4 hours I had mild flu symptoms, blocked sinuses, stuffy head, and a strange feeling of "not being 100% ok" Felt like I had a fast onset of cold or flu. Went to bed and next morning, felt amazing. All arthritis pain seemed to have gone,lots of energy, thinking was very clear, tasks seemed easy, confidence was high due to a feeling of enhanced cognitive processes. I work online doing SEO/SEM for cannabis/cbd companies which can involve multitasking between process based work, and creative work, which can cause a problem switching between mindsets.

Well, the morning after Fisetin I felt like I was on top of everything and could have trebled my tasks and enjoyed it (some kind of cognitive ability confidence). I tested my lack of arthritis symptoms by clicking my fingers a couple of dozen times (something i cant usually do without some difficulty and pain). Seemed easier climbing the stairs, and it was like I had been "uplifted"I have retained the perceived benefits since, but decided to do another 40 capsules this evening (i bought 120 caps). So had another 20g this evening (2000mg Fisetin) and within 3 hours, have the same mild flu like symptoms (inc some sneezing and a stuffy head/tickly throat), the clear head feeling i had for last 2 days has gone, and I feel very lethargic and cant think very clearly. Another strange thing is the muscles/tendons in my right wrist have been visibly spasming making my middle finger on my right hand jerk up an down rapidly approx 1", its very strange, like nerves firing. Also experiencing some internal muscle spasms, not painful, but its some kind of reaction to the Fisetin I assume. Overall I feel OK, but feel like something is "going through me" working its way round and triggering a few things on the way. I actually quite enjoy it as I feel like its an active compound.

Im not overly concerned about taking high doses of "strawberry powder", I think its prob very safe, but you also possibly expect some mild side effects which may vary depending on your own body chemistry/other supplements/medication etc

Ref the method of ingestion, I simply emptied 40 X 500mg capsules onto a piece of tin foil, then made the foil into a semi funnel and emptied the lot into my mouth, WARNING...do not breathe through your mouth while you are doing this , Fisetin is a very fine dust and loves travelling up through the back of your mouth into your lungs and sinuses, it is then extremely difficult to stop yourself coughing the whole lot out over your laptop/coffee table etc). I then kept the Fisetin in my mouth, mixing slowly with saliva, and kept it moving around for approx 20 min to help absorption through the mucous membranes/under tongue/cheeks, before swallowing. I dont even know if Fisetin can be absorbed through the membranes in the mouth, cant find any info on that, but its a no lose gamble as it gets swallowed anyway!

Im hoping that I will feel great again in the morning, I plan on doing the final 2000mg in 3 days. Will update here....

UPDATE: quite run down today (prob due to lack of sleep)

Didnt feel great this morning after only 4 hours sleep, Fisetin seems to cause insomnia for me after a high dose. Felt wide awake after the first dose, but even wider awake after 2nd dose. Feeling quite run down today (prob due to lack of sleep), but no other noticeable negative symptoms at all. So, after 2 fairly high doses, it would appear that Fisetin(2000mg), for me, is perfectly safe in the short term. Will update in a couple of days after dose number 3.

Update: 3rd Fisetin dose.

Waited a while before taking my 3rd dose as I have been enjoying the feeling of actually feeling good in myself and didnt want to somehow possibly jeapordise the positive results I have experienced. Obviously an illogical assumption, but also didnt feel that I needed to improve anything.

But decided to take my 3rd 2000mg Fisetin dose this evening, approx 2 hours ago.

Within 30 min I noticed some slight muscle spasms in my legs, very similar to previous occasions, and a sensation that something is happening inside my body.

That is the only thing I have noticed so far, so will update soon after the Fisetin has had a chance to take effect, or not.

Also found this amazing summary of Fisetin research/effects/dosage: https://brain.forever-healthy.org/display/EN/Fisetin+Senolytic+Therapy

UPDATE 3rd Fisetin dose (24 hours later)

The 3 rd Fisetin 2000mg dose has had virtually zero noticeable effects.

I noticed a major feeling of wellbeing improvement following first 2 doses, but this dose hardly anything.

My guess is that the first 2 doses did some senolytic clearing, so there wasnt much action going on for the 3rd dose. Thats just a guess, but would explain the absence of effects. Also, I have been feeling really good since first 2 doses, so no useful baseline to relate to.

This would make sense considering recent research that concluded Fisetin is useful as an intermittent supplement, 3 or 4 times a year to clear some accumulated senescent cells.

Overall, I rate Fisetin as safe and effective, (2000mg dose safe for me), but because of lack of human research, everyone needs to be their own guinea pig and find how it works for themselves.

I am also beginning with NMN, and trans-resveratrol. Thats my stack.

Good luck everyone! :-)

@Allen and @bunk055 some very valuable information about Parkinson's at minute 10:59 at this YouTube video of Ivor Cummins interviewing Dr. Paul Mason :
https://www.youtube.com/watch?v=WsO-t1nBFtY&t=2s

Also I checked this numerous times in the PubMed database and each time discover new things about the harm of certain lectins. Some of these lectins travel up the vagus nerve to the brain and so cause Parkinson's type symptoms. This is well validated by placing tags on the lectins and then actually watching, and photographing them while traveling up the vagus nerve. One study I found examined 7 different lectins and they found 4 had this ability to travel up the vagus nerve. One study showed paraquat could also bind to the lectins and so gain entry to the brain.

At minute 12:44 he mentions the pea lectins in the brain of the dog. At minute 13:59 he mentions certain specific very harmful lectins, of the 109 so far discovered.

This was June 6, 2019, Ivor Cummins and Dr. Paul Mason, part 4 of 5, if you wish to google it and not click on a link.

It seems like my presbyopia has become better after taking Fisetin. Probably most likely it has nothing to do with Fisetin, but it seems odd. Has anyone noticed something similar?

Fisetin as a Senolytic: Fights cancer, extends life, is affordable and the protocol is stupidly easy.
The Mayo Clinic Protocol consists of taking 20 mg/kg of oral fisetin on two consecutive days and repeating the same dose, one month later.
As a rounding number, the Mayo Clinic Protocol is to take 2.0 grams of fisetin, for only two days at the beginning of each month. That would be 8 capsules of Fisetin500 (250mg per capsule) or 20 capsules of the 100mg Doctor's Best, for two consecutive days, at the beginning of each month.
It is best taken with DMSO and grapefruit juice for solubility and bioenhancement. You can also take Fisetin with alcohol and grapefruit juice but the alcohol needed is excessive.
Fisetin is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF). The solubility of Fisetin in ethanol is approximately 5 mg/ml and approximately 30 mg/ml in DMSO and DMF. Fisetin is sparingly soluble in aqueous buffers.
My protocol is to do DMSO, grapefruit juice and ground pepper with the Fisetin. It's slightly bitter but it works and by now, I don't even mind the taste as I take all my supplements with DMSO and grapefruit juice. The math for the Fisetin protocol is again based on my weight of 80 kg. I need to take 1.6 g of Fisetin per day, for two days. I split the dose each day meaning that I need to take two separated 750 mg dosages of Fisetin (3 capsules of 250 mg). 750/30 means that I need to dissolve the 750 mg into 25 ml of DMSO. Add 200 ml of grapefruit juice to that and you can easily swallow the mixture. Then chase it again with grapefruit juice. The colder the grapefruit juice, the better it hides the taste of the DMSO.
In the US, a shot of an alcoholic 1.5 ounce beverage is 44 ml. Thus, for 80 proof spirits (40% ABV) you are ingesting 17.6 ml of pure ethanol, or 13.89 grams of alcohol. As a result, one 1.5 ounce shot will only be able to make approximately 100mg of Fisetin soluble. Obviously, the alcohol is not a great solution but it's better than using water (depending on how much alcohol you are willing to swallow).My suggestion is to stick with the DMSO.

?Fisetin is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of fisetin in ethanol is approximately 5 mg/ml and approximately 30 mg/ml in DMSO and DMF. Fisetin is sparingly soluble in aqueous buffers."

While fisetin looks promising just in a few months av whole bunch of dasatinib parents expire. That means the prices will drop soon after. At least outside of US. Was there any research of combining D+Q and fisetin?

@Cuberat: I believe James Clement at Betterhumans is now using dasatinib + fisetin in his human trials of senolytics.

Hi Murray
You keep taking 5g a day for 5 days and repeting monthly?
Some improvement? I'm curious!

Unlike most posters to this blog, for the past year I have been taking 400 mg of Fisetin daily to deal with early symptoms of Parkinson's disease. 100 mg doses are taken with a large amount of water at approximately 3 hour intervals, which appears to be the most effective use. On a daily basis, tremor has been been reduced by 90%, anxiety has been largely relieved, sleep quality has improved, and focus is substantially better. No side effects have been observed. Over a one year time period, the disease has been stable, with only minor increases in tremor. I don't have any impairment to activities, including those as a professional musician. I don't take other medications of any type. Diet is largely plant based, with some chicken and fish. I'm currently 75, and also exercise daily for at least an hour-- weight work, bike riding, walking, and swimming.

Again, I'll chime in. I take the lowest dose (100mg) daily. I've been doing it for well over a year. I have genital herpes that used to come regularly. When I take my 100mg I NEVER get an outbreak - even if I damage the skin or get sick. When i forget to take my Fiseten for 3 to 4 days (mostly when traveling) I get an outbreak right away. I have tested this (involuntarily) many times. The one time it failed to work I was confused - then realized I was taking Basis pill instead for last 5 days... (they look very similar).. except under the light of my cellphone - the Fiseten turns yellow.

So, for what it's worth - it does something, even at low regular doses. I wish someone would study it. I would be open to taking more - but not sure what benefits I'd get - I don't want to megadose periodically like a lot of you because the daily low dose seems to keep my immune system up - or at least keeps the herpes virus dormant.

@bobbby fisetin, wogonin, quercetin, apigenin (derivatives of rutin), isorhamnetin, kaempferol (derivatives of quercetin) and some other flavonoids derived from rutin and its derivatives are strong antiviral agents. Of those 6 I find from personal experience of taking them that isorhamnetin the strongest, even stronger than fisetin.

I Gave it to my 12y dog (9kg) with idiopathic Pulmonary fibrosis 100mg F + 100Q (in oliver oil) for 5 days! After just 15days no more coughing attacks and no more codeine,as prescribed by the vet! I intend to repeat the same dose in 30 dias but for the 3 days this time!

Hello,

I've started taking 500mg TID with food. I weigh 63kg and I'm 61 years old. I noticed my temp went up .05 degrees and my sleep was restless. I started taking timed release melatonin before bed and that has resolved somewhat. I wear an OURA ring for sleep tracking. I'll be taking this for 5 days and repeat next month. My 93 year old dad is also trying it. I'll let you know how it goes.

Having seen most of the post on Age Reversal Forum about Fisetin. I think that many of you are not taking enough and long enough. Many of those folks are taking it for 3 days and using up to 2 to 3 thousand Mg. This is done once every month or so. Of course only do this after experimenting to make sure that you are not allergic and if you are under the care of a doctor please get permission. Very common experiences include feeling more athletic and alert and more energy. I have done 4 of these now and my muscles feel much younger and vibrant. I am walking further and with a greater intensity. All o this is very similar to others. I do take with Quersitin and with Olive Oil. Try to use the life extension version of quercetin which is supposed to be highly absorbable. Also I do intermittent fasting on these days... and try to get a good walk in. The first couple of times you do this high dose it may include some down days as your body gets rid of old cells.... Hope this helps....

One more thing... I only use 2000 mgs of Fisetin and started much lower dose than that. I did the lower dose of 500, than 800, and 1000 for 3 days and then waited 3 weeks. The people that do 3000 are usually over 200 pounds etc....I did on empty stomach and had the runs the first two times I did this protocol. I do not have the runs now.

4 doses per day, 1 hour before breakfast, 1 hour before lunch, 1 mid-day and 1 hour before dinner. All apart from foods. 
- - -
Fisetin 100mg (Dr.s Best)
Quercetin w/Bromelain (NOW Brand)
Lemon Bioflavinoids: 1000mg, w/Hesperidin Complex: 100mg, and Rutin: 100mg. (Nature's Life Brand)
Milk Thistle: 150mg. (Jarrow Brand)
Turmeric: 500mg. w/Piperine: 5mg. (youtheory Brand)
Resveratrol: 500mg (We Like Vitamins Brand)
--------------------------

2 times per day, 1 hour before breakfast and 1 hour before dinner.
- - -
Ginko Biloba: 120mg, w/Vinpocetine: 5mg. (trunature Brand)
D-Limonene 500mg (Jarrow Brand)
--------------------------

Thank you to everyone for posting your experiences and findings. The above is what I am trying based on everything I have read on this thread along with the research inspired by the reading. I've been on the above listed protocol for about 10 days. I will keep you updated as I progress.

Though I have started slowly I have had some of the same sensational experiences as those of you that are doing the larger more acute dosing. Always in the same places throughout my body, which leads me to believe that there is something about fisetin that paints a target on the back of senescent cells allowing for all of the accompanying proteolytic and systemic enzymes to do their work.

Here is some additional information about myself to better understand what it is I am trying to accomplish.

I am 47 years old and previously diagnosed with Cutaneous T-Cell Lymphoma. Supposedly there is no cure for this type of lymphoma but I am hopeful to prove that wrong. Wish me luck...8)

I am working with the assumption that disease is simply a result of aging and that there is a sweet spot between incline(youth) and decline(middle age?). Kind of like that period of time after you make your last monthly car payment and that cars first major repair bill.

What I originally thought was an allergy to gluten back in 2012 ended up being a form of lymphoma. Accurate diagnosis however didn't happen till November 2018. My stubborn self and dislike of anything hospital was partially at play but also cutaneous t-cell lymphoma is one that goes misdiagnosed for some time with most. Having spent 7 years of my childhood in and out of the hospital having had two surgeries, countless catheterizations and a handful of intravenous pyelograms in an attempt to correct VUR(vesicoureteral reflux) left me a little twitchy when even driving by hospitals. I was one of the experimental kids that helped them determine that their new experimental procedure(1970's) didn't work for most.

Strangely it wasn't my doctor that identified it, but someone I was giving a ride to(UBER) who had been diagnosed with the same thing and in treatment for many years before we met.

Fortunately for me I have a friend of the family that is an oncologist who's specialty is lymphoma and leukemia and he was able to confirm the diagnosis. There's just something different in the care and advice that comes from a doctor who is also a friend. Highly recommended...8)

Now here is the interesting twist. Through diet, supplementation and Dr. Google, I had been addressing what I thought was something systemic but by no means did I really think that I had cancer. I had my primary Dr. do all of my blood tests to make sure that everything internal that I couldn't see was functioning properly and continued on my path to recovery in ignorance.

Have I made all of the right decisions for treatment along the way? I don't know. We will see. I still am not sure I agree with the official diagnosis but I have accepted it and respect it, however I reserve my right to remain a skeptic.

Back to the diagnosis and my oncologist friend. Though he recommended that I have further tests done, by the time I had seen him many of the neoplasia(tumors) had already resolved or reduced in size significantly. In other words my skin was fixing itself and expressing all of the diseased tissues gradually over time. By no means a pleasant process but it's not like I had anything else to do. On the other hand, no nasty scarring. Just a prolonged recovery and a lot of self care.

Cutaneous T-Cell Lymphoma which was originally called Mycosis fungoides was first described in 1806 by French dermatologist Jean-Louis-Marc Alibert. The name mycosis fungoides is very misleading-it loosely means "mushroom-like fungal disease". The disease, however, is not a fungal infection but rather a type of non-Hodgkin's lymphoma. It was so named because Alibert described the skin tumors of a severe case as having a mushroom-like appearance.

Which is exactly why I had no clue that it was cancer. I frankly thought I was just a dirty bird that drank way too much and ended up with a really bad fungal infection that was paying the piper.

When all this started back in September of 2017 I made some drastic lifestyle changes and dedicated myself to learning how to optimize health and existence. Along the way I have explored many different diet trends and tried many a different thing eventually arriving where I am at today almost fully recovered.

I still have a little ways to go, but I expect that the full recovery process will have taken about 42 months or 3.5 years to complete. And the best part is my body looks and feels significantly younger and I don't think it is anything magic that I have done. Just followed some basic ideas and rules.

What if cancer, dementia, diabetes and cardio vascular issues were all simply the process of aging taking its course? I imagine that would mean that all we have to do is figure out what it means to be simply younger and go there.

That is my starting point...Simply Younger

In conclusion, we found that melatonin enhanced the anti-tumor activity mediated by FISETIN in melanoma cells. Furthermore, we elucidated the underlying molecular mechanisms of such enhanced action. The combined effects of FISETIN and MELATONIN on melanoma cells might be achieved through activating cytochrome-c/caspase-dependent apoptotic signaling and inhibiting p300/NF-κB-mediated COX-2 and iNOS expression. These results not only indicate the great potential of natural products, such as FISETIN and MELATONIN, in cancer chemoprevention and therapy, but also might serve as a basis and direction for the application of the combinational treatment of natural compounds in improving therapeutic efficiency for cancers.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085069/

I thought this might be a possible way to reduce the amount of fisetin needed to accomplish the same end.

One thought that I had regarding melatonins ability to positively affect fisetin may have more to do with getting our bodies into a better circadian rhythm facilitating better healing and recovery through a better sleep cycle that can better use fisetin.

Cheers, Michael

Michael, i've been reading everything I can find about melatonin since the late 90's. I've taken it every single day since.
The early researchers considered melatonin to be "The general on the field of the immune system". That is because melatonin is the master regulator of the immune system.
Anyone curious can type "melatonin ncbi" into a search engine to see a bounty of research that has been done on it.
I recently saw research which showed that melatonin was able to quiet the cytokine storm created by the coronavirus. And it is the cytokine storm which causes pneumonia and kills us. No cytokine storm, you live to see another day. My own personal experience confirms this for me, as I have fought off every single last flu for the 20 years that I have taken melatonin.
This is a very long read, but it will go a long way towards filling in the average reader on the potency of melatonin vs, coronavirus.
https://www.evolutamente.it/covid-19-pneumonia-inflammasomes-the-melatonin-connection/

So yes, it makes perfect sense to me that melatonin combined with fisetin could have such vast benefits for us.

Dogs and cancer. I know this is off topic, but i decided to post this anyway. I would recommend looking into Salvestrols. One of my dogs showed a mass on her trigone area (ultrasound) in her bladder. Two vets diagnosed her with bladder cancer. We did not do biopsy. She is 10 pounds. We placed her on 2 Salvestrol capsules on an empty stomach first thing in the morning and another one about 2 hours later. Three months later a follow up ultrasound showed that the mass was gone. Could the mass have been something else? Maybe. Prior to this, I had recommended Salvestrols to 7 other people with dogs that had various types of cancer. I lost contact with two of them, but the other dogs were cancer free after a number of months. I hope this helps.

To Thomas who posted above regarding testosterone increase after fisetin.

FOXO4-DRI(senolytics) alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.
https://www.ncbi.nlm.nih.gov/pubmed/31959736

This is fascinating. All of the male testosterone andropause age related decline may be due to senescent cells in the testes and can be treated rather than taking lifelong testosterone replacement.

Took a single dose of 500mg. and it wiped me out, I was in bed all day. Next day tired and groggy. But now I feel great. I wonder if I have a huge amount of senescent cells. I am 52. It definitely killled off something as I felt bad when I took it and now I feel great, so I made progress. But I dont understand how others are saying they took 2 or 3 grams and felt nothing. That might have killed me. I will continue to try 500mg at a time until I can handle it and have no reaction then I will move up to 750mg and 1,000mg depending on if I can tolerate it. I feel like I have a long road ahead of me but I look forward to making progress and addressing this issue.

Today I took a teaspoon of 50% extract + double quercetin. I felt whiskey nothing. My batch might be detective. I will take two more doses today. I am 44 and in the last couple of years I started to see small degradation in my body. However, I feel no subjective effects of fisetin, whatsoever. No I'll effects, no big improvement in the days after.

Hey Cuberat, I'll be 48 next month. What I notice when I take fisetin in addition to all of my other stuff is that there are specific spots on my body where I feel something like a sore muscle. I am using fisetin specifically for my lymphoma.

Our skin, our largest organ of elimination mind you is filled with microbial life and I imagine we all have various volumes of excess microbial overgrowths throughout this organ. I imagine they are often in the form of biofilms throughout the interstitial layers of our skin. Probably like the fascia we see between the skin and muscle on our roasted chicken.

I imagine that fisetin is painting a target on pathogenic dysbioses allowing the systemic enzymes we take in conjunction to better target the pathogens. I also like to rotate Quercetin and Hesperidin when taking fisetin.

I've also started taking 2-3000mg of NAC. N-Acetyl L-Cysteine replenishes the most powerful antioxidant in our body, glutathione.

@fred 50% fisetin can be bad tolerated (even form coggygria which is not poisonus but other substances can cause diarrhea). From rhus suddancea or accacia greggi '50% fisetin' is poisonus DO NOT TAKE IT orally. What form (purity, plant, manufacturer) do you take? If you are male, prostate pulls out any it can get so sperm gets yellow/yellow-green (depending on source of light) starting from around 0,2-0,5 gram dose, so male can easily verify if it is fisetin at all and if it gets absorbed. Only kaempferol have similar effect, but in sunlight daylight fisetin is lemon-yellow and kaempferol is light yellow-green (similar to fisetin in fluorescent light).

Hello, is anyone using fisetin on BP and heart medication? I using perindopril 5mg (acei) and bisoprolol 2.5mg (beta-blocker) and a bit concerned wouldnt there be any bad interactions? Flavonoids are known to interact with some liver enzymes.

@SilverSeeker and others, why did you mention rhus suddancea extract is poisounous? A lot of such is sold on ebay, browneish capsules, for example 10% 450mg. Sounds alarming.

@Andrew sources on herbs list rhus suddancea as not edible and poisonous. Have this ebay source has any credible certificate that what they sell is safe for consumption? Cotinus coggyria is a known herbal bush that can be consumed raw for short periods of time, and you can grow it in your garden, although currently it's differently colored varieties are cultivated only for ornamental purposes. Fisetin from cotinus used to be a vital source of yellow leather dye just a century ago (cause a raw 5-10% has high content of tan, hence colouring lether during tanning).

@SilverSeeker I bet they do not, but this plant is used in many commercial brands. Like the ones using Novusetin (Doctor's Best, for example). So yeah, I am a bit afraid with the ebay stuff which is quite cheap also.

Doctor'sBest/Swanson/RevGenetics use it >98% pure. If this was safe to get less purity then they would go for it, 'cause it costs uncomparably lot more to get >98% purity than to 10%...

https://en.wikipedia.org/wiki/Toxicodendron_succedaneum "[...] The fruits are edible though their consumption is not recommended because of the general toxicity of the plant. [...]".

Even 50% fisetin from coggygria caused me light diarrhea starting at dose of 1500 mg, after I get accustomed to it I can take up to 2500 mg at once with the same or smaller mild symptoms.

https://pfaf.org/user/Plant.aspx?LatinName=Rhus+succedanea

Known Hazards: This plant contains toxic substances which can cause severe irritation to some people. The fresh sap causes skin blisters[145]. The leaves contain the ubiquitous carcinogen shikimic acid[218].

https://pfaf.org/user/Plant.aspx?LatinName=Rhus+sylvestris

Known Hazards: This plant contains toxic substances which can cause severe irritation to some people. The fresh sap causes skin blisters[145].

Yes, I know this one is toxic. I have ordered capsules 450mg 2:1, so I was told it is 225 fisetin. It is written in the item desc that it is with novusetin, but I have doubts as manufacturer seems unclear and price is low (around 30$ for 365 capsules). They also sell quercetin and other supps.
On the other hand, the customer feedback is 97% positive..

Is there a cheap/easy way to see if it is really fisetin?

I am also thinking two experiments like put some on the wet skin. And some powder in the mouth to make sure no allergy or irritation occurs. And only then try to swallow some of it.

I still have another question, does anyone try fisetin with ace inhibitors and/or beta blockers? If yes, any issues?

Now that liposomal Fisetin is available, what would the dose be? One company claims that their sublingual nano-liposomal fisetin is 48 times more bioavailable than fisetin powder. One pump provides 75mg. So if it's more bio available do I use less than the normal 1,200 mg a day for my 2 day senescent cell clearing, or do I go for the full 1200 mg ( about 18 pumps) with the highly bio available version?

@august33
The safety of fisetin might be due to its low bio availabilitie. If you have a pro drug that is much more available or might change its safety profile.

And even with regular fisetin we don't know what is the correct protocol. For example, my latest self experimentation was 8 grams daily of 50% fisetin. Sort of the bad taste I didn't feel any defects good or bad after 3 days. It might be that senecent cross burden is low. And the aging directs I see are due to other causes. It cold mean that my prevalent scenesent cells are immune or not to susceptible to fisetin. It could mean also that I it went absorbed and I just stained my poo. Or simply that my supplies are not good.

@august33 I found only https://nadlab.uk/product/fisetin-liposomal-sublingual-gel-60-servings/ . Do you mean this one? They claim it be only 1.6 to 2.7x more bioavailable.

I only used homemade emulsion from fisetin dispersed in buttermilk, and it's difference between zero (water) and some (buttermilk) getting into blood. Sperm gets yellow coloured with fisetin dispersed in buttermilk starting from 200-400 mg of fisetin. What minimal dose would it be for this crude biological bioindicator measurment for this liposomal formulation?

I also got the rhu extract, its from a stem it says. Also, think that those amazon/ebay 450mg caps are way of correct dose. It seems to be a company that have 3-5 different prints on the jar, but same raw. You can acully see it, just look at the sellers dosage and how many different supps he sells.

The seller for 450 fisetin is from UK, and he got 100s of supps, really crazy, its everything.
And print almost a identical brand but change the name.

Either way. are these not recommended to use at all? i have even been up to 10g
2g x 3-5 times per day. Did glutathione im before bed to clear the liver from the damage.

Almost looked 10 years younger due to waht i tought was MTOR activation. and the gluta cleared and gave a really good effect tougheter.

In highsight or what its called, i shouldent used a anti oxidant the same day, even if the halflife was out for the fisetin. Think days should go.

Never got any permanent effect, the face effect and body went away 2 days efter.

Also, everyone here who aalways aaalways talk about how it helps with pain, and so on. YOU ARE AWARE FISETIN WORK ON SEROTONIN RIGHT? all the pain reduction is from the serotonin. Just go and get some 5htp. you will love it

Now to my question. I just started Rapamycin, will also ad a senolytic protocol 2-6 days after every time i do rapa. Will do HIGH dose rapa once per month, and do seno 2-6 days after

Will use Fisetin and vitamin B17, and resveratrol, for those days

(B17, i think people have missed out probably the strongest senolytic we have, think it would ruin fisetin, b17 even kill cancer cells, so it must be senolytic)

So i will ad 1 cap 2 times per day with my fisetin and resveratrol.

Now to my question .. i cant use resveratrol due to side effects, but my tought are that i just want the MTOR effect, on those days rapa is as most active just to act synergistic. Would that work? it feels like it

Fisetin, Resveratrol (1 gram or 500mg x2-3) and b17

Sounds amazing right .. all 3 work on MTOR, and highdose rapamycin to that... damn.

Dont understand why not more ad rapamycin to there senolytic protocol, dont must use it allways. Could be used even once per month, and have there other stack hours after and days after as the rapa is the most active, it will help ALOT.

EDIT: forgotten, that seller seem to have like maby half the product in, it cant be possbible to sell 350 x 450mg for 25 dollars ... saw another who tought his resveratrol was half dosed. So maby all products are half dosed. All his products are REALLY good dosed, and extreamly cheap. Looks like scam, but with active product just alot less

There might be someone interested in knowing that there is a Fisetin + Quercetin + Q10 liposomal product which claims to have superior bioavailability due to the phospholipid encapsulation. The product is called Vibrance, made in Germany under the Actinovo brand and tmk not directly available in the U.S.
Couldn't find anything close to this, but would be happy to get updated news here.
Cheers,
Thomas

I see many people in the comments are concerned about the very poor water solubility of Fisetin.

Being one of the many polyphenols, just like e.g. Quercetin, Kaempferol, Myricetin, Hesperetin, Naringenin, etc, etc, Fisetin should also be highly soluble in a cheap & widely available solvent.... Propylene Glycol (PG).

Most vapers among you will already be aware that PG is used in the 'base mix' for vaping liquids (the other one is Vegetable Glycerine (VG)). PG is also widely used as a food additive, thus having a reassuring safety profile (except arguably in very high amounts). It's virtually odourless and tasteless, which helps! Conveniently, it's readily miscible (mixes) with water too.

I've used PG as a solvent for several polyphenol flavonoids I've used (e.g. quercetin and taxifolin). It works. Thus far I haven't tried Fisetin, though I may be doing so very soon, once I've researched it more. I see no reason why it wouldn't also dissolve in PG.

Be aware however that some of the many fillers/additives used in tablets and capsules may not dissolve in PG so readily, if at all. Nonetheless, the polyphenol substance you want to dissolve will still do so, even if the fillers won't. Such fillers might not look or taste too good in your final mix, but hey.

Preferably you can find whichever polyphenol product you want that has no fillers/additives, like pure powders. If you're buying capsules, just crack them open and mix the contents with a little PG (I use say 1/4 teaspoon for a 500mg capsule), then mix that with however much water you want. Add any flavours you might want to that mix of course.

PG is easily available from many vape suppliers, and should be pharmaceutical or food grade. Also very cheap. In my own experience the poorly water soluble polyphenol substances all work better once first dissolved this way, so you may want to reduce the advised dosages in order to achieve the same effect, to be on the safe side (and hopefully save some money!).

Increased solubility usually provides better absorption, though doesn't always necessarily translate to high bioavailability. But at least it helps to overcome that first common hurdle.

Paulus.

Just to add a safety disclaimer to my last post above:

It strikes me that some of you might take large (or even ludicrous!) amounts of Fisetin, or other polyphenols. Therefore, you should consider how much PG you would be taking if you were to dissolve each 500mg in 1/4 teaspoon of PG (as I suggested above).

The W.H.O. recommends a maximum daily intake of 11.4 mg of propylene glycol (PG) per pound of body weight (25 mg/kg). This equates to 1250 mg for a 50KG person (which just happens to be roughly 1/4 teaspoon by volume).

As ever, please do your own research and draw your own conclusions, especially regarding safety. I accept no responsibility whatsoever for any ill effects caused by consuming PG in excessive amounts, or being due to any allergies, interactions etc.

Paulus.

@Paulus I have taken safety into account, and tried natural products found in my refrigerator. The best emulgator for fisetin found is buttermilch. The sperm gets yellow (the natural test of how much of it gets into bloodstream...) within few hours at doses as low as 500 mg. Do you have any tables how much of it enters bloodstrem when it is dissolved in propylene glycol, DMSO or other solvents?

@SilverSeeker
It is the cynical me talking, but if you can extract sperm often enough to follow the color, you are probably not that old nor frail...

@Cuberat almost 50 but after 5 years on scuttelaria (baicalin+wogonin) and more than a year on fisetin, in this respect more like less than 25 :D

@SilverSeeker: I don't currently have any hard data for solubility & absorption with PG I can point you to. I only recall it was something I'd looked into a fair while ago, and at that time I found some strong indications that polyphenols generally are very highly soluble in PG (a quick Google again just now didn't turn up the links I was hoping to find). Therefore I tried it, since I conveniently had some PG to hand.

My experience with e.g. curcumin, quercetin and some other polyphenols is that when I first dissolve them in PG, there's a definite difference in the effect I feel, as compared with just taking them straight with water.

I wouldn't know about buttermilk in particular, though I can see it would make some sense, given that polyphenols are known to be fat soluble at least. However, I don't seem to notice a major difference whenever I've taken them with fats, oils etc in the past.

I guess one attraction of the PG route might be that PG is also in turn miscible with water, which oils/fats are not of course.

A water-based mixture is convenient to take, though whether that actually contributes to the absorption I'm not too sure - it's hard to tell but I'd think it may be more absorbable through the GI tract than fats (?). Adding the water after PG doesn't seem to decrease the absorption at least anyway. It would be interesting to find some clear study & data about that question.

I'll pass on the sperm aspect for now! If I can re-find some links about solubility in PG I'll update here later. Unless someone else could kindly add in the meantime.

@Paulus buttermilk also contain lecithin, another known flavonoid solvent. I've made simple test - three glasses of kefir, yogurt and buttermilk, and opened I poured one capsule into each. The fisetin (swanson brand) dissolved the fastest in buttermilk and the only one without mixing content. I've tried also olive oil and butter, but they do not work as good as buttermilk. I'm prudent a bit too, but it's a science, and looking what eBay and other such places sell, even more importantly safety, ie. distinguishing real from fake. Prostate usually do not assimilate such intrinsically folded proteins, but it definitely makes exception for fisetin, kaempferol and wogonin, and it makes it very efficiently. And no matter what I dissolve fisetin with, the first visible effects start form 25 mg/kg of body weight (with the best solvent I've found). A little less and no effect at all. A little more and much stronger effect. Mayo dose of 20 mg / 1kg may be enough for a woman but probably too low for man. Definitely doses for males (as opposed to females) must account for this effect, and be bigger by considerable margin. :<

@SilverSeeker: Interesting that buttermilk contains lecithin, since that is also the base emulgator for some Quercetin Phytosome (Quercefit) I have here.

Clearly, there are several candidates for solubility (to varying degrees) with the polyphenols family, including DMSO of course (which I prefer to avoid).

Since my last post, I did manage to find one of the study links about the PG, for solubility with paepalantine (another polyphenol) :-

https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2015000400395&lng=en&nrm=iso

A quick 2 excerpts from that study:-

"... Thus, propylene glycol may be the solvent of choice for paepalantine, a compound that has significant biological potential".

... and, a mention of DMSO interference there...

"... The results of the current study demonstrate that propylene glycol can be an alternative to the use of DMSO which shows interference in biological assays as antioxidant assays"

I believe that for PG the same will be true for Fisetin and other polyphenols, though I've still not tried it yet.

I will bare in mind your comments on dosage if & when I do begin to explore fisetin, and maybe even try some of the other emulgators you've mentioned, for subjective comparisons at least.

Do you have any thoughts about the PG being miscible with water? i.e. do you think that could help further to aid the absorption, as compared to fat based emulgators? I really don't know, but I'd imagine water is more easily digested and absorbed than fats, in which case it should help I believe.

I could always just take the PG and its payload neat without water of course, though I'd prefer to dilute it further with water first I think, especially since some of the payload substances (and/or any additives) don't taste very pleasant to begin with, so better if diluted.

... and just to add a further thought, regarding a Phytosome carrier (since I mentioned it above), It woud be good if Indena were also to include the same liposomal Phytosome option for fisetin in their product line, as they do for Quercetin (i.e. their Quercefit).

I see Alive do a liposomal sublingual fisetin, but it's VERY expensive. Though I'd expect Indena also could be just as tempted to cash in on the fisetin bandwagon, if they do decide to go that way (I bet they will!). It sure is an effective way to overcome any solubility concerns, albeit at a price.

... and some government sourced further info about PG:-

https://www.atsdr.cdc.gov/phs/phs.asp?id=1120&tid=240

Excerpts:-
Re Safety: "The Food and Drug Administration (FDA) has classified propylene glycol as 'generally recognized as safe,' which means that it is acceptable for use in flavorings, drugs, and cosmetics, and as a direct food additive... It is used to absorb extra water and maintain moisture in certain medicines..."

Re characteristics: "... Propylene glycol is clear, colorless, slightly syrupy liquid at room temperature." (Also tasteless and odourless btw).

@Paulus after it is dissolved in the medium, I haven't observed any further weakening difference on taken dosage, when taken before/after main meal and/or fruit juice.

In 2017 Salk Institute was starting a trial on J147 (modified curcumin) but did not have the needed $20million and neither did I. So they sent me to UCLA where I learned my friend could use their patented Longvida Curcumin (more bioavailable for the brain) and a Mediterranean diet (get out of pre-diabetes) to stop and reverse Alzheimer's Disease. It worked for her with about 4000 mg per day. I have COPD and went back to them to see if J147 would stop all the phlegm I got and generally reduce inflammation. They said they were trying to start a trial on CMS121 which is based on Fisetin. They suggested I start with 200 to 300 mg per day of the standard Fisetin (they preferred Doctors Best brand because they new the source of the materials used). I now have 8 months of success. I take 100 mg before each meal and it usually almost stops the phlegm. I was getting a lot of phlegm about 30 minutes after I ate. Now, maybe once a day, I get some phlegm, but it is clear and about 10% of the old volume of sputum. I feel better, I breathe better. Oxygen level is up about 2%. A study run in Korea listed about 3 things that were being changed by Fisetin in the epithelia of the lung that reduces, but does not totally stop, mucus production. We do need mucus to keep the lungs flexible. I hope there are trials someday, but you can get Fisetin via internet, so try it. I have no side effects at this dosage. If it helps the brain that would be great, too. I expect CMS121 is designed to be more bioavailable.

Guys, what is the taste of the fisetin? I've bought some bulk from China, which claims to be 99% from cotinus. It is a fine yellow powder,with practically no smell, but the taste is a bit sweet and herbal. Remind me of curcuma a bit, but slightly different.

Is there any easy and reliable way to check this is fisetin and not some curcuma with glucose? :D

@Andrew
The one I had was bitterly disgusting. Also very staining and not very water soluble. It is time to restock...

Hi All, I gotta say I've been following these posts for a while and I find you guys contributions fantastic. Great to swap notes. I kinda fell down a rabbit hole of research the past few months. Nothing crazy, I actually have a science background, sift evidence and value large scale data over opinion. Anyhow, the more I look the more fisetin is validated as a promising approach.
You'll see huge excitement in the healthspan community these days around NAD+ and I think that is justified (I leave you to do your own research). But why is NAD+ depleted? CD38. Where does CD38 mainly come from? -> macrophage interactions with senescent lipid cells.
Does Fisetin induce aptosis in such cells? You bet. So I'm very excited. I bought a warchest of high quality fisetin a few months back, but have been trying the various other regenerative procedures first, e.g. [not medical advice, consult your doctor] ;
1. Significant weight loss of 12kg basically from avoiding high GI foods and not eating between 7pm to 8am (in just 2 months!)
2. I have done two Fasting Mimicking Diets as esposed by Valter Longo (once you've stopped eating sugar r.e. step one fasting is almost natural. I used to nearly fall over when I missed a meal)
3. Bumped up on some nutrients I figured I was missing e.g. Choline, magnesium, K2, spermidine, B Complex, glycene, alpha lipoic acid. (The choline had me kicking the ass of cognitive tests like I was 20 again, could not believe it!)
4. Semi strenuous walk for 45 minutes 5 days a week
5. Occasional strength exercises (google why this is important, calorie burning potential is amazing)
6. Maintain gut health with soluble and insoluble fibre. The feeling of wellbeing this gives after a while is amazing.
7. Some things like daily blueberry consumption; I never have those senior moments when I can't recall the memory anymore
8. NAD+ precursor supplements like NMN and Niacinimide with some of the CD38 inhibitors like fresh parsley, apigenin, and quercitin.
9. AKG supplements. Common exercise supplement but has me racing up the local hills after just 3 days. Also has my hair growing back which happened in the mouse studies.

Fisetin is next. CD38 suppression with apigenin is great, but a lot of CD38 expression is coming from zombie fat cells that studies indicate that fisetin is going to cause to die. Cutting CD38 alone can raise your NAD+ by 60% !!

Ageing is a result of a highly complex system, but my research and your inputs have me convinced that the sharpest effects can be turned if not wholly avoided. I'm going to try a combination of fats and alcohols to dissolve the fisetin.

Is there a forum where such researches are best shared?

Decided to do a tolerance test before going ahead. Interesting results.
According to the info in this thread I might go for a dose north of 2000mg based on my weight for a hit and run treatment.

I've had 100-200mg fisetin a day via capsules in the past and noticed nothing.
Today I cut 5 of the Doctors Best capsules into a bowl (500mg) and mixed with fresh cream and some ground black pepper. Consumed with some fresh blueberries and rasperries.

After around 90 minutes I started to feel like I was coming down with something. Then I started getting an ache in the finger joints on my left hand. Starting wondering how severe the feelings would get, and ended up lying down for 20 minutes. Then it all started to recede to the extent I went on my normal 3 mile lunchtime hike as I usually would.

So, I'm going to take it steady. Some folks experienced nothing at higher doses than mine and that was not my experience. Next week I might try 700mg etc, and work towards an eventual 2000mg weekend shot.

I've also ordered some of the Senylitic Activator pills by Life Extension (they kind of fake the D+Q action). Once again I'll take that careful with an initial half dose, and certainly not weekly as they suggest. Also, won't be combining fisetin and other senylitics at the same time.

I'm not put off, in fact it might have taught me I have things going on in my left hand that I didn't know about. The journey continues.

@Cuberat

Isn't AKG an mTOR activator? I want to use it along with pycnogenol for better NO, but I am wondering if it doesn't mess too much with senolytic action etc. Any tips? Thanks

@Cuberat

I've got a supply from another Chinese seller. Well, this one is bitter a.f.! I've put a tiny bit on my finger and in my mouth and it was so bitter I've nearly got panic attack :D Also, very stainy just as you've told. Most likely the first one was fake.

Anyone knows how should fisetin look light in UV light? Someone has mentioned this in the previous posts.

@Andrew
There bitter taste is a good for placebo. It is supposed to stai in yellow but don't dissolve much in water..

I have got a new batch around easter and this time I have had for a weird reaction but. I was taking other stuff. I am not sure if the new batch is not contaminated. Anyway this time I have got burning skin sensation and hot and cold flashes and skin pain like after sunburn. It was quite bad. I tend to attribute it to some poisoning. I will wait a few weeks and try much smaller dose in isolation

@Cuberat

What do you mean being good for placebo? In some previous post you wrote to me it should be distustingly bitter..

Yes, it doesnt dissolve ane falls to the bottom in the water.

Do you know how it should be in UV light? Doctor's best is almost black in UV, and this one glows yellow-greenish there.

@Cuberat

Pure (98-99%) should be light yellow as a powder. Clinical dosing is 20mg per kilo of body weight and then give it a rest. I'm not sure of the rest period but I think it's about 4 months.

Why the UV test? Where did you get that from?

John

Does anyone have info on dissolving Fisetin in DMSO or the use of Bioperine as an enhancer?

NEW formula of Life Extension Senolytic Activator (SA) includes Bio-fisetin (their own) that is equivalent to 7 doses of daily Bio-fisetin. According to LE, taking high dose of fisetin intermittently (weekly) is an optimal senolytic approach. Since I still have old SA formula, I am taking it with 7 caps of Bio-fisetin once a week, instead of 1 fisetin daily.
My experience w Senolytic Activator (weekly) and fisetin (daily) taking separately were obvious. SA got rid of keratosis pilaris (chicken skin) on my upper arms and white tongue, while fisetin helped my insomnia. My arms are smooth and no more (40+ years) bad breath. The night that I take my weekly SA + 7 caps of fisetin, I am able to sleep 8-9 hrs straight.
Note: I buy either LE fisetin or Dr Best fisetin depending on price

Hi John, How long did it take for the Keratosis Pilaris to go away?

there are quite a few substances in anti-cancer domain that may have senolytic effect too, on some classes of tissue at least. This study is just the scratching of the surface. I would test for starters wogonin, lunasin, tyrosinase, AHCC and few others too. And more, combination of these studied substances, even when single substance have no meaningful antisenolytic effect on studied tissue, when combined with others may come suprisingly effective on the same tissue, like fisetin + wogonin on some pulmonary cancers. Was this trail followed since? Both on widening the list on the study and testing combinations of the substances in the study? Any info on continuing this study, just wider and deeper?

very interesting reading all of you(r) all comments !!! Im not very computer literate---actually hate having to get emails each day. BUT, am delighted to find that there are other persons that use themselves as human guinea pigs and are willing to share their findings ! Have been taking one bio-fisetin from lef (they say that theirs is the best of course) for about 6 weeks. . . .and have been wondering what has mase me to do so much better in several areas.-----as all of you all will agree, that there are so many "moving targets" in life, it is difficult to do a "double blinded" study on oneself--- even with such a perfectly captive audience--- like in a prison setting. (sounds confusing !) BUT after reading you(r) alls comment, I would like to confirm my own observations. I was not expecting ANY immediate reactions at all and had assumed that fisertin would be another supplement to be taken (on faith) for long range effects---that -sadly- may never come . In ten days, I will be 69 y.o.. I go to work,lite construction every day, 4-6 hours, since beginiing with fisetin, my nightime urination has gone from 6 to 3 times a night , I have had several 8-9 hour days at work, I FEEL more mentally alert, leave the house earlier each day, have less back and joint pain. and ,and ,and I was able to "mount" my wife two days in a row ! ! ! ----which is REALLY unusual (and really pissed her off.) So there! is this real , or (is it memorex---for those of you who are old enough to remember the old commercials with Ella Fitzgerald). I honestly dont know , but will begin enlisting some of my friends into another guinea pig study! ALSO, To "ivo" 21 sept 2019 4:35 am " allergies,histamine etc" if you can contact me, ( but I am uncertain how to safely do that) I will be happy to tell you what I have learned about allergies and how they work. ------ ( there also seems to be a connection between allergies and depression)--it seems so simple, but I have had trouble finding people to listen to me . I think all of you people who are willing to share your experiences are TERRIFIC !!!!

I'm going to try the Mayo Clinic protocol, and see if that helps w/ arthritis. I've been searching for a reliable source of fisetin w/o fillers, and came across Austinootropics. They claim to have certified 99% pure fisetin, "made in the USA, at a FDA registerd facility," at a reasonable price, and say they can supply lab test results. Looking at their website, they claim that the products are manufactured in the US, they lab test every lot of all of their products, and can supply reports on request. I did a search of their address, and apparently, it's in a building that rents out shared office spaces. They also sell their products on eBay. Does anyone here know if they're legit? A google search of them doesn't turn up much info.

Regarding Fisetin, I bought from a bulk supplier, was the right color, light yellow, supposed to be 98%, sang all the right bells. So, I did 3g/day for 3days with a month off. I felt nothing. Some say the have positive reactions to doing this protocol.

Here is the interesting thing, I have a supplier in China that I have been buying from since 2015, always the right paperwork and excellent pricing. But, I have to buy 1kg at a time, some of these supplements are ether expensive or so much quantity that that you won't use it in a year or 2.

Here is their pricing, notice 50%, how many of the suppliers say it's 98%, we may be buying 50% in some cases. Shipping is $35 single kilo.

For Fisetin 98%,the price is $ 890/kg FOB Shanghai.
For Fisetin 50%,the price is $359/kg FOB Shanghai.

I have some from Vitacost(60 caps) which I know to be real, some from Wellness Resources(90 caps) and some coming from Swanson's(60 caps). So far I took the bulk from another supplier, AgeLessExtracts that I didn't have a reaction from but they have 5 star feedback. Doesn't mean it's not good but no reaction in my case.

What brand are you taking that you're getting a reaction from and what kind of reaction did you get?

Thanks, John

@DrugDev - "This story is eerily reminiscent of the Phenoxodiol saga, from the Australian company Novogen, back in the late 1990s-early 2000s"

Fisetin is a naturally occurring compound. Phenoxodiol is not.

I'm in my early 80s and suffer from moderate mitral valve regurgitation. As a result, I have left
atrial enlargement and atrial stretch. For the past few years, I have experienced steady atrial
palpitations or PACs, but no AFIB. I have tried numerous supplements like resveratrol, quercetin, and berberine, but with only modest improvement.

Two months ago, I started on Liposomal Fisetin 500 mg, once daily. Within two weeks, my
PACs have virtually disappeared. I have never seen such results from my other phytonutrients.

I would be interested if anyone else has seen improvement with arrhythmias after taking fisetin.

Hayes

One year until the Mayo study concludes.

I purchased DoNotAge (DNA) pure fisetin.
The clinical trials I read initially proposed an intermittent dosing regimen of a few days with a relatively high dose as most effective.
Last year, 2022, I started DNA's fisetin, taking 3200mg/daily with 500mg quercetin (solar ray brand.) To make the flavonoid more bio available I added 2 tsp olive oil mixed with 1/2 tsp of cracked black pepper and quickly drank that from a shot glass.
An hour or so later I began to feel very tired and had mild stomach discomfort. I slept hard and woke up well rested. The morning side effects were straight up liquid bowel movements (temporarily,) and I felt more energetic that day.
Fast forward to today, yesterday I took another round of flavonoids: 4g of Fisetin with 2g Apigenin, and 1g of hesperidin/rutin. This time I took it all in the middle of a fatty meal: 4 cheese tortellini.
Same thing happened, onset of lethargy marked by the need for sleep, mild stomach discomfort, my vision would get blurry for a split second then instantly clear again. I slept deeply and woke up rested.
So, I'm 38, healthy on the skinny side. Used to have bad habits like smoking cigs.
Hopefully, supplementing flavonoids will stave off age-related illness.
I use this flavonoid regimen in cycles, usually every 4 months for 2 days.
My daily stack includes hesperidin with Rutin and vitamin C (solar ray,) CoQ10, krill oil, Panethine, niacinamide, and Astaxanthin on the weekends (bc asta inhibits muscle protein synthesis, although it's an amazing anti oxidant/anti inflammatory.)
Hope this anecdotal experience helps, for informational purposes only, always do your research.