Animal Data Shows Fisetin to be a Surprisingly Effective Senolytic

It is exciting to see animal data arrive for some of the potentially senolytic compounds that may turn out to destroy enough senescent cells in mammals to be worth using as first generation rejuvenation therapies. As a reminder, the accumulation of senescent cells is one of the causes of aging; countless cells become senescent every day in our bodies, but near all are destroyed. A tiny fraction linger to cause significant harm through the inflammatory signal molecules that they secrete. If these errant cells can be removed, then inflammatory diseases and numerous aspects of aging can be turned back to some degree. The results in mice stand head and shoulders above all of the other approaches to aging in terms of reliability and breadth of benefits.

Some senolytic compounds have been tested in animals, but a larger body of candidate senolytic drugs are presently only accompanied by cell study data. The ability to selectively destroy senescent cells in a petri dish does little more than indicate potential; there is a significant rate of failure in medical research and development for compounds with promising cell data, and any number of reasons as to why they may not work well enough in tissues or otherwise turn out to be infeasible for use in animals and humans. Fisetin was one such senolytic candidate with cell study data only, and I had not viewed it as a likely prospect. It is a flavonoid, and the one other well-known possibly senolytic flavonoid turned out not to be useful on its own - though it is helpful as a part of a combination treatment.

Given that, results from the recent animal study of fisetin noted here greatly exceed expectations, surprisingly so. Fisetin appears about as effective in mice as any of the current top senolytics, such as the chemotherapeutics dasatinib and navitoclax. Per the data in the open access paper below, dosing with fisetin destroys 25-50% of senescent cells depending on organ and method of measurement. The dose level is large in absolute terms, as one might expect for a flavonoid. For aged mice and a one-time treatment, the researchers used 100 mg/kg daily for five days. The usual approach to scale up estimated doses from mouse studies to initial human trials leads to 500 mg per day for five days for a 60kg human.

Given the wealth of new results emerging these days, it seems to me that people focused on self-experimentation, open human trials, and investigative mouse studies in this field should be moving to focus on combination therapies. 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 goal would be to see if it is possible to engineer a significantly higher level of clearance of senescent cells than any of these senolytics can achieve on their own. This seems like a plausible goal, and may turn out to present meaningful competition to efforts such as those of Oisin Biotechnologies and other groups developing more sophisticated senolytic therapies that should have high rates of clearance.

Researchers Have Discovered How to Slow Aging

As people age, they accumulate damaged cells. When the cells get to a certain level of damage they go through an aging process of their own, called cellular senescence. The cells also release inflammatory factors that tell the immune system to clear those damaged cells. A younger person's immune system is healthy and is able to clear the damaged cells. But as people age, they aren't cleared as effectively. Thus they begin to accumulate, cause low-level inflammation and release enzymes that can degrade the tissue.

Researchers found a natural product, called fisetin, reduces the level of these damaged cells in the body. They found this by treating mice towards the end of life with this compound and see improvement in health and lifespan. "These results suggest that we can extend the period of health, termed healthspan, even towards the end of life. But there are still many questions to address, including the right dosage, for example." One question they can now answer, however, is why haven't they done this before? There were always key limitations when it came to figuring out how a drug will act on different tissues, different cells in an aging body. Researchers didn't have a way to identify if a treatment was actually attacking the particular cells that are senescent, until now.

Fisetin is a senotherapeutic that extends health and lifespan

A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a-luciferase reporter and aged wild-type mice to determine the effects of fisetin on senescence markers, age-related histopathology, disease markers, health span and lifespan. Human adipose tissue explants were used to determine if results translated.

Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.

Comments

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.

Posted by: Corbin at October 3rd, 2018 6:07 PM

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.

Posted by: Proud Daddy at October 3rd, 2018 6:14 PM

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

Posted by: Stephan at October 3rd, 2018 6:31 PM

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.

Posted by: Reason at October 3rd, 2018 6:38 PM

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.

Posted by: Robert at October 3rd, 2018 8:35 PM

@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.

Posted by: cuberat at October 3rd, 2018 10:43 PM

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.

Posted by: CANanonymity at October 4th, 2018 12:03 AM

@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...

Posted by: Will at October 4th, 2018 1:21 AM

@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 :) :)

Posted by: John C. at October 4th, 2018 2:19 AM

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.

Posted by: Mark at October 4th, 2018 6:13 AM

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

Posted by: Lee at October 4th, 2018 6:18 AM

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.

Posted by: Proud Daddy at October 4th, 2018 7:01 AM

@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.

Posted by: Cuberat at October 4th, 2018 8:41 AM

@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.

Posted by: Proud Daddy at October 4th, 2018 8:45 AM

@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

Posted by: Cuberat at October 4th, 2018 8:48 AM

what is the right dosage for humans?

Posted by: scott emptage at October 4th, 2018 9:43 AM

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

Posted by: scott emptage at October 4th, 2018 10:08 AM

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.

Posted by: CD at October 4th, 2018 10:26 AM

@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.

Posted by: Proud Daddy at October 4th, 2018 10:35 AM

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

Posted by: DrugDev U.S. at October 4th, 2018 10:56 AM

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

Posted by: scott emptage at October 4th, 2018 11:03 AM

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

Posted by: Proud Daddy at October 4th, 2018 12:28 PM

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.

Posted by: Robert at October 4th, 2018 2:26 PM

@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...

Posted by: Proud Daddy at October 4th, 2018 3:00 PM

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.

Posted by: Benjamin Wade at October 4th, 2018 3:21 PM

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

Posted by: Norse at October 4th, 2018 3:38 PM

@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.

Posted by: Norse at October 4th, 2018 3:42 PM

@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

Posted by: scott emptage at October 4th, 2018 4:04 PM

@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....

Posted by: cuberat at October 4th, 2018 4:09 PM

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?

Posted by: Adam Hruby at October 4th, 2018 5:51 PM

@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

Posted by: The Transhumanist Runner at October 5th, 2018 12:45 AM

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.

Posted by: CD at October 5th, 2018 10:45 AM

@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"

Posted by: DrugDev U.S. at October 5th, 2018 2:25 PM

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.

Posted by: scottalias at October 6th, 2018 1:20 PM

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.

Posted by: Abelard Lindsey at October 6th, 2018 7:12 PM

@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...

Posted by: Cuberat at October 6th, 2018 9:36 PM

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.

Posted by: scottalias at October 7th, 2018 12:07 AM

@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.

Posted by: cacarr at October 7th, 2018 3:26 PM

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.

Posted by: Abelard Lindsey at October 9th, 2018 8:50 PM

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.

Posted by: Pete Koziar at October 10th, 2018 9:46 AM

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.

Posted by: Pete Koziar at October 11th, 2018 7:06 AM

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.

Posted by: scottalias at October 12th, 2018 1:36 PM

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.

Posted by: Pete Koziar at October 17th, 2018 11:25 AM

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)?

Posted by: august at October 22nd, 2018 2:30 PM

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.

Posted by: The Transhumanist Runner at October 22nd, 2018 3:44 PM

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?

Posted by: Wolfman at October 25th, 2018 7:08 PM

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

Posted by: fyego at October 25th, 2018 11:00 PM

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.

Posted by: Pete Koziar at October 26th, 2018 11:22 AM

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?

Posted by: Adam Hruby at October 30th, 2018 3:26 PM

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.

Posted by: scottalias at November 1st, 2018 9:33 AM

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?

Posted by: Michelle at November 4th, 2018 1:38 PM

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?

Posted by: Rice at November 4th, 2018 3:12 PM

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.

Posted by: Rice at November 5th, 2018 6:27 AM

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.

Posted by: scottalias at November 6th, 2018 4:11 PM

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.

Posted by: Corbin at November 6th, 2018 4:57 PM

Guys, any success stories?

Posted by: Cuberat at November 9th, 2018 5:53 PM

@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.

Posted by: Pete Koziar at November 9th, 2018 9:57 PM

Fisetin is good for health?

Posted by: peter at November 16th, 2018 9:38 AM

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.

Posted by: Corbin at November 19th, 2018 3:00 PM

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?

Posted by: Piotr at November 20th, 2018 10:06 PM

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?

Posted by: Rice at November 21st, 2018 3:17 PM

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

Posted by: Stephan at November 22nd, 2018 9:22 AM

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

Posted by: Stephan at November 24th, 2018 6:06 PM

@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...

Posted by: Rice at November 25th, 2018 4:34 AM

@Rice Cool, thanks again!

Posted by: Stephan at November 25th, 2018 6:59 PM

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.

Posted by: scottalias at November 29th, 2018 7:41 PM

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.

Posted by: BRIAN VALERIE at December 10th, 2018 9:46 AM

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.

Posted by: Lou T. at December 10th, 2018 1:09 PM

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)

Posted by: Papu at December 11th, 2018 7:35 AM

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.

Posted by: Piotr at December 11th, 2018 8:36 PM

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.

Posted by: deusexmachina at December 16th, 2018 1:21 PM

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.

Posted by: Pete Koziar at December 28th, 2018 12:08 PM

@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).

Posted by: Jim at December 29th, 2018 2:33 AM

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

Posted by: hans at December 30th, 2018 3:02 AM

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?

Posted by: hand at January 1st, 2019 9:01 PM

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!

Posted by: iwasaki at January 3rd, 2019 2:49 AM

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.

Posted by: iwasaki at January 5th, 2019 6:29 PM

↑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.

Posted by: iwasaki at January 5th, 2019 6:47 PM

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.

Posted by: Thomas at January 6th, 2019 8:41 AM

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.

Posted by: scottalias at January 11th, 2019 11:52 AM

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.

Posted by: August at January 12th, 2019 7:18 PM

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.

Posted by: J Bentham at January 13th, 2019 9:59 AM

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.

Posted by: barsell at January 14th, 2019 5:03 PM

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.

Posted by: Amadeus Note at January 15th, 2019 8:27 AM

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?

Posted by: RonP at January 22nd, 2019 1:37 PM

@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?

Posted by: Rick Davis at January 24th, 2019 11:29 AM

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.

Posted by: Chris at January 26th, 2019 2:52 AM

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?

Posted by: masashi at January 26th, 2019 10:33 AM

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.

Posted by: iwasaki at February 2nd, 2019 1:52 PM

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.

Posted by: Thomas at February 8th, 2019 8:01 AM

I take fisetin 500mg today.

I felt no sideeffect now.

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

Posted by: iwasaki at February 9th, 2019 3:58 AM

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.

Posted by: DJ at February 10th, 2019 3:08 PM

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.

Posted by: iwasaki at February 11th, 2019 4:52 AM

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.

Posted by: Ellie at February 14th, 2019 5:26 PM

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.

Posted by: iwasaki at February 15th, 2019 4:49 AM

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.

Posted by: Murray Duffin at February 16th, 2019 3:31 PM

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?

Posted by: Murray Duffin at February 16th, 2019 4:06 PM

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!

Posted by: Edward Greenberg at February 16th, 2019 7:15 PM

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.

Posted by: iwasaki at February 17th, 2019 7:38 AM

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

Posted by: danz at February 18th, 2019 3:27 PM

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?

Posted by: PW at February 19th, 2019 4:57 PM

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.

Posted by: August at February 20th, 2019 5:47 PM

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!

Posted by: iwasaki at February 22nd, 2019 12:11 AM

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.

Posted by: Rob at February 24th, 2019 12:20 PM

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!

Posted by: iwasaki at February 26th, 2019 5:07 PM

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.

Posted by: Murray at March 1st, 2019 4:44 PM

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.

Posted by: Cacogen at March 2nd, 2019 7:04 AM

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.

Posted by: Paul Rattner at March 5th, 2019 10:41 PM

@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

Posted by: Cuberat at March 5th, 2019 10:53 PM

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.

Posted by: Corbin at March 6th, 2019 11:06 AM

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.

Posted by: Gavril at March 7th, 2019 11:10 AM

@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).

Posted by: PW at March 8th, 2019 2:12 PM

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).

Posted by: PW at March 8th, 2019 2:40 PM

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?

Posted by: ellie at March 13th, 2019 7:01 AM

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.

Posted by: Corbin at March 14th, 2019 2:48 PM

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.

Posted by: Murray Duffin at March 15th, 2019 4:08 PM

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?

Posted by: san at March 16th, 2019 11:26 AM

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.)

Posted by: AGELESS at March 16th, 2019 4:31 PM

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.

Posted by: AGELESS at March 16th, 2019 4:47 PM

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?

Posted by: san at March 16th, 2019 11:07 PM

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?

Posted by: san at March 16th, 2019 11:16 PM

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

Posted by: Cuberat at March 16th, 2019 11:20 PM

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.

Posted by: AGELESS at March 17th, 2019 7:40 AM

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.

Posted by: AGELESS at March 17th, 2019 8:03 AM

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?

Posted by: san at March 17th, 2019 9:43 PM

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

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

Posted by: iwasaki at March 18th, 2019 6:52 AM

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.

Posted by: AGELESS at March 18th, 2019 1:01 PM

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.

Posted by: san at March 18th, 2019 2:52 PM

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.

Posted by: iwasaki at March 19th, 2019 2:14 PM

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.

Posted by: Deane at March 20th, 2019 12:41 PM

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.

Posted by: Ed at March 20th, 2019 12:52 PM

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

Posted by: Florin Clapa at March 20th, 2019 8:13 PM

■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

Posted by: iwasaki at March 20th, 2019 8:38 PM

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.

Posted by: Edward Greenberg at March 22nd, 2019 7:31 AM

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/

Posted by: Florin Clapa at March 22nd, 2019 1:06 PM

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.

Posted by: Allen at March 22nd, 2019 5:01 PM

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?

Posted by: san at March 23rd, 2019 10:18 PM

I have questions!

Fisetin has Senolytic effect!

But Quercetin do not have Senolytic effect!

Is it right or not?

Posted by: iwasaki at March 25th, 2019 12:37 PM

@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...

Posted by: Cuberat at March 25th, 2019 12:51 PM

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."

Posted by: Dan at March 26th, 2019 12:52 AM

@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!

Posted by: iwasaki at March 28th, 2019 1:01 AM

@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

Posted by: Cuberat at March 28th, 2019 2:59 AM

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.

Posted by: PW at March 28th, 2019 11:52 AM

@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/)

Posted by: Edward at March 29th, 2019 10:34 AM

@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.

Posted by: san at March 29th, 2019 3:37 PM

@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

Posted by: Cuberat at March 29th, 2019 5:54 PM

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.

Posted by: strollman at March 29th, 2019 8:29 PM

@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

Posted by: Cuberat at March 29th, 2019 9:07 PM

@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)

Posted by: Edward Greenberg at March 30th, 2019 11:47 AM

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...

Posted by: Deane at April 1st, 2019 5:35 PM

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?

Posted by: iwasaki at April 2nd, 2019 7:24 AM

@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 ;)

Posted by: Cuberat at April 2nd, 2019 3:32 PM

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

Posted by: rebis at April 2nd, 2019 10:34 PM

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.

Posted by: matson at April 3rd, 2019 3:20 PM

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.

Posted by: Blue Rice at April 3rd, 2019 7:48 PM

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.

Posted by: Pentacles at April 4th, 2019 7:50 PM

@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.

Posted by: Cuberat at April 4th, 2019 9:12 PM

Apologies for the bad typos in my posts

Posted by: Cuberat at April 4th, 2019 9:18 PM

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.

Posted by: Pete Koziar at April 8th, 2019 8:28 AM

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

Posted by: Pete Koziar at April 8th, 2019 9:02 AM

@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

Posted by: Cuberat at April 8th, 2019 9:13 AM

@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.

Posted by: Pete Koziar at April 8th, 2019 11:20 AM

@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.

Posted by: Nick Westgate at April 8th, 2019 10:25 PM

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...

Posted by: Dan at April 9th, 2019 11:47 PM

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

Posted by: Dan at April 9th, 2019 11:49 PM

@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

Posted by: Nick Westgate at April 10th, 2019 1:47 AM

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.

Posted by: Pete Koziar at April 13th, 2019 2:42 PM

@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?

Posted by: Cuberat at April 13th, 2019 4:11 PM

@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.

Posted by: Pete Koziar at April 15th, 2019 8:32 AM

@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.

Posted by: Cuberat at April 15th, 2019 12:06 PM

@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!

Posted by: Pete Koziar at April 15th, 2019 1:49 PM

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 :)

Posted by: Cuberat at April 16th, 2019 6:56 AM

Disagree=dosage

Posted by: Cuberat at April 16th, 2019 6:57 AM

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.

Posted by: Chris at April 17th, 2019 4:34 PM

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.

Posted by: Chris at April 17th, 2019 7:21 PM

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!

Posted by: Pete Koziar at April 22nd, 2019 9:48 AM

@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.

Posted by: Nick Westgate at April 22nd, 2019 5:09 PM

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.

Posted by: Chris at April 24th, 2019 1:02 PM

@Chris
You might consider fasting to offset those effects.

Posted by: Cuberat at April 24th, 2019 6:26 PM

@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]."

Posted by: Dan at April 24th, 2019 8:40 PM

@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

Posted by: Cuberat at April 24th, 2019 9:43 PM

@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.

Posted by: Dan at April 26th, 2019 11:36 AM

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...

Posted by: Dan at April 26th, 2019 11:44 AM

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.

Posted by: Stephan at May 1st, 2019 5:14 PM

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?

Posted by: Stephan at May 2nd, 2019 12:52 PM

@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

Posted by: Thanh Ly at May 2nd, 2019 2:40 PM

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?

Posted by: Stephan at May 2nd, 2019 11:34 PM

@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

Posted by: Cuberat at May 3rd, 2019 8:29 AM

@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?

Posted by: Stephan at May 3rd, 2019 2:51 PM

@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...

Posted by: Cuberat at May 3rd, 2019 5:44 PM

Inactive=invasive

Posted by: Cuberat at May 3rd, 2019 6:20 PM

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

Thanks, Stephan

Posted by: Stephan at May 3rd, 2019 10:20 PM

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.

Posted by: masahi at May 4th, 2019 6:28 AM

@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.

Posted by: Cuberat at May 4th, 2019 7:25 AM

@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 ..

Posted by: Cuberat at May 4th, 2019 2:03 PM

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.

Posted by: Ted at May 9th, 2019 2:34 PM

@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.

Posted by: Hung at May 13th, 2019 5:59 AM

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.

Posted by: AGELESS at May 17th, 2019 9:27 AM

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.

Posted by: Lou Thomas at May 18th, 2019 9:11 AM

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.

Posted by: Diego at May 20th, 2019 3:16 PM

@Diego

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

Posted by: Lou T at May 22nd, 2019 11:40 AM

@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.

Posted by: masahi at May 26th, 2019 1:16 AM

@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..

Posted by: masashi at May 26th, 2019 2:38 AM

"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?

Posted by: Harold Katcher at May 27th, 2019 1:01 AM

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.

Posted by: Pete Koziar at May 28th, 2019 6:15 PM

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.

Posted by: Elena Milova at May 30th, 2019 7:02 AM

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

Posted by: Christian Hunter at May 31st, 2019 12:25 AM

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.

Posted by: Elena Milova at June 3rd, 2019 4:09 AM

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.

Posted by: Daver555 at June 4th, 2019 6:43 PM

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.

Posted by: bunk0555 at June 6th, 2019 10:21 AM

@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.

Posted by: Reason at June 6th, 2019 1:52 PM

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.

Posted by: Allen at June 6th, 2019 8:05 PM

@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.

Posted by: bunk0555 at June 6th, 2019 8:23 PM

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.

Posted by: Allen at June 7th, 2019 11:40 AM

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

Posted by: TOMOTOMO at June 8th, 2019 5:59 PM

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

Posted by: Show man at June 15th, 2019 3:53 PM

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.

Posted by: Cuberat at June 15th, 2019 4:35 PM

Disprove==dissolve

Posted by: Cuberat at June 15th, 2019 4:37 PM

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.""

Posted by: harold at June 16th, 2019 11:43 AM

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.

Posted by: danzeb at June 25th, 2019 6:23 PM

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.

Posted by: Cuberat at June 25th, 2019 9:30 PM

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

Only this way↑

Another method is very dificult

Posted by: Show man at July 4th, 2019 4:35 PM

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

Posted by: Otto at July 7th, 2019 10:57 AM

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

Posted by: Cuberat at July 7th, 2019 11:24 AM

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).

Posted by: Otto at July 7th, 2019 12:46 PM

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?

Posted by: August at July 9th, 2019 4:36 PM

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.

Posted by: Chris at July 31st, 2019 1:40 PM

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

Posted by: Cuberat at July 31st, 2019 2:45 PM

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.

Posted by: Chris at August 1st, 2019 12:21 PM

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.

Posted by: Lynn at August 10th, 2019 8:06 PM

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.

Posted by: Haze at August 11th, 2019 10:14 AM

@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 .

Posted by: Cuberat at August 11th, 2019 11:23 AM

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

Posted by: Charles Grashow at August 12th, 2019 11:03 AM

One correction.

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

Posted by: Charles Grashow at August 12th, 2019 11:10 AM

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