1079 replies to this topic

[HBRU]

I think if that would be a patentable drug that would make someone rich....

[HBRU]

I think if that would be a patentable drug that would make someone rich....

[HBRU]

I think if that would be a patentable drug that would make someone rich....

[HBRU]

I think if that would be a patentable drug that would make someone rich....

[Dstein]

Is there any information on how long it took for these effects to happen after the taking fisetin?

 

 

 

I can tell you how long it takes to kick in for me.  I take 4gms/day (mixed with some stuff to make it more biavailable) for 5 days.  Initially, it makes me feel worse.  It takes about a week or two after I stop taking it to get back to my prior state that I was in before taking the fiseten.  After about two weeks, things start to improve.  This last for about 4 to 6 weeks, and then things start to level off.

 

I've done this about 3 or 4 times

[osris]

Thanks but I was asking specifically about how long the following things took to happen in the mice studied, and also how long they would take to happen in humans:

 

 

mice  12 weeks old,

   - in water, 60 mg/kg, daily on two intermittent weeks

   - reduction of SASP in fat, spleen, liver, and kidney

- mice 22-24 mo old

   - oral gavage, 100 mg/kg for 5 days

   - reduced senescent cells in T lymphocytes, NK cells, mesenchymal stem cells and endothelial cells

- mice 85 weeks (equivalent to 75 years!)

   - lower ALT

   - reduced pathology in several tissues

   - reduced SASP in several tissues

   - reduced oxidative stress in liver

   - Increased median and maximum lifespan

 

And also how long did it take the mouse on the right off the attached photo to look younger than the mouse on the left?

 

I've been asking these sorts of questions a lot in this forum but no one seems able to answer them. They are not really hard questions to answer for the scientifically minded. Very surprised at this inability to do so, given the number of knowledgeable people who post on this forum.

 

 

Attached Files

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Edited by osris, 12 December 2019 - 10:52 AM.

[osris]

Just saw this article about fisetin mouse studies:

 

https://livingbeyond...ural-senolytic/

 

It says that:

 

“A daily dose of the antioxidant FISETIN keeps mice—even those with genetic mutations linked to Alzheimer’s—from experiencing memory and learning deficits as they age.”

 

It doesn’t say what the strength of the daily dosage was. 

 

The following quote says that the mice were given a daily dose for 6 months:

 

“So Maher—who works with Dave Schubert, Ph.D., the head of the Cellular Neurobiology Lab—turned to a strain of mice that have mutations in two genes linked to Alzheimer’s disease. The researchers took a subset of these mice and, when they were only three months old, began adding fisetin to their food.

 

As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn’t received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of fisetin however, performed as well as normal mice, at both nine months and a year old.”

 

How are we to extrapolate this dosing frequency to human dosing regimens. My understanding is that fisetin is to be taken by humans at doses of up to and over 15000 mg on each of two days every 6 months or so. In light of the above quotes maybe that is not necessary but rather daily doses should be taken of strengths not mentioned in the article.

 

Edited by osris, 12 December 2019 - 11:19 AM.

[Rays]

In this 2013 study by the Salk people "a daily dose of approximately 25 mg/kg" mouse weight was used. See link below.

Human equivalent dose would be 25/12.3 = 2.0 mg/kg human weight.

 

https://onlinelibrar...1111/acel.12185

https://www.ncbi.nlm...les/PMC4804402/

 

[bhangchai]

Well on me taking 100 mg of Fisetin (a couple of years ago) after some hours caused tendon pain... (that went away the day after)...

I tried 3/4 different times after becouse I could not belive a single supplement in such tiny dosis coud cause me this.... and the same happened....

 

Taken also in another occasion a short Ciprofloxacin course and and that also caused me a quite similar tendon pain but delaied, after maybe 10 days ...

 

Well I'm ill with psoriasis so I'm quite prone to autoimmunity and I had the feeling Fisetin could be dangerous for me (I did not know the senolyitic capacities of the substance).... probably people on autoimmunity already have the mechanims of cell self lisis quite overactive....

 

same Ciprofloxacin... probably also a senolitic drug....

I think people should test their tollerance with the substance before taking big quantities....

 

I had fairly long standing (almost a year) tendonitis pain in my shoulder, verified by a chiropractor.  After taking Fisetin and Quercetin (1 gram each) in olive oil, with black pepper, for three consecutive days, the pain was reduced 80 to 90%.  I did a second course the next month, which I don't know if it was necessary, but as of now, there is no tendon pain.  However, I wouldn't recommend doing any strenuous exercising or stretching for about 2 weeks after taking this.

 

Incidentally, I also had some arthritic pain in that shoulder, and after taking Dasatinib and Quercetin it has mostly resolved as well.

[bhangchai]

 

Thanks but I was asking specifically about how long the following things took to happen in the mice studied, and also how long they would take to happen in humans:

 

 

mice  12 weeks old,

   - in water, 60 mg/kg, daily on two intermittent weeks

   - reduction of SASP in fat, spleen, liver, and kidney

- mice 22-24 mo old

   - oral gavage, 100 mg/kg for 5 days

   - reduced senescent cells in T lymphocytes, NK cells, mesenchymal stem cells and endothelial cells

- mice 85 weeks (equivalent to 75 years!)

   - lower ALT

   - reduced pathology in several tissues

   - reduced SASP in several tissues

   - reduced oxidative stress in liver

   - Increased median and maximum lifespan

 

And also how long did it take the mouse on the right off the attached photo to look younger than the mouse on the left?

 

I've been asking these sorts of questions a lot in this forum but no one seems able to answer them. They are not really hard questions to answer for the scientifically minded. Very surprised at this inability to do so, given the number of knowledgeable people who post on this forum.

 

 

Why don't you look into this and report back to us...

[osris]

I've tried, hence my asking about it here.

[osris]

 

In this 2013 study by the Salk people "a daily dose of approximately 25 mg/kg" mouse weight was used. See link below.

Human equivalent dose would be 25/12.3 = 2.0 mg/kg human weight.

 

https://onlinelibrar...1111/acel.12185

https://www.ncbi.nlm...les/PMC4804402/

 

 

Thanks. I'm hopeless at figures, so what would that be for someone of my weight 76 kg (168 lbs)?

[Rays]

76 kg x 2.0 mg/kg = 152 mg.

[HBRU]

I think there is an individual sensitivity to the substance... as I sayd I felt very well the (bad) effect of just 100 mg... For me it was "bad" because I did not knew what this substance was actually doing into my body.

[osris]

76 kg x 2.0 mg/kg = 152 mg.

 

Thanks.

 

I wonder if it would be worth taking it at such a low dose daily. What benefits would it have I wonder?

[bhangchai]

I think there is an individual sensitivity to the substance... as I sayd I felt very well the (bad) effect of just 100 mg... For me it was "bad" because I did not knew what this substance was actually doing into my body.

Are you perhaps allergic to strawberries?

[sedentary]

hi, i was going to post this 20 days ago before Mind banned me for making a joke about a wanna be scientist. he might as well banned me if i talked shit about trump at that period before his impeachment. something is wrong with the guy and ill talk with higher mods about his abuse.

 

anyway, i was gonna post this 20 days ago; https://medicalxpres...und-cancer.html

it seems to correlate with people's statements about slow wound healing while on fisetin. it might actually be beneficial against cancer after all

[osris]

 

anyway, i was gonna post this 20 days ago; https://medicalxpres...und-cancer.html

it seems to correlate with people's statements about slow wound healing while on fisetin. it might actually be beneficial against cancer after all

 

I can't really see the connection between this article saying that blocking HMGB1 reduces the risk of cancer formation in wound healing, and what you say are people's statements about slow wound healing while using fisetin. The article seems to say that fast wound healing by blocking HMGB1 reduces cancer risk. If so, then logically the slow wound healing said to occur with fisetin would pose a cancer risk. 

Edited by osris, 19 December 2019 - 02:50 PM.

[osris]

Just for clarification and rule-of-thumb purposes, how often should high dose fisetin be taken?

 

Some people say it should be taken every 3 months, some say every 6 months, some say once a year, so what's the consensus and the scientific reasoning behind it?

Edited by osris, 27 December 2019 - 06:52 PM.

[HBRU]

I see some people are fasting in senolitic periods... but is that -maybe- a wrong approach ?

I think this fasting can put senesent cells into a kind of sparing mode that doesnt lead them to apoptosis but instead lead them just to not usefull autophagy...

 

FOX04 serves to preserve tissue integrity under stress.

.

.

Copied  from a post of Fafner55

FOX04 is modulated by SIRT1. The activity of FOX04 is suppressed by SIRT1 inhibitors, such as nicotinamide, and enhanced by SIRT1  activators, such as resveratrol.

“SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress” (2005) https://www.ncbi.nlm.nih.gov/pubmed/16012755?dopt=Abstract

From this view, improvements to senolytic treatments could follow from

• Not fasting
• Not taking NR, resveratrol or pterostilbene
• Not engaging in vigorous exercise
• Inhibiting SIRT1 by large doses of nicotinamide, such as 2 to 3 gm.

 Nicotinamide is a potent inhibitor of SIRT1. I would expect it to decrease FOX04 but don't have support.

1. https://www.researchgate.net/post/How_long_does_it_take_for_Niacinamide_to_inhibit_SIRT1_and_how_long_until_it_stops
2. “Nicotinamide-mediated inhibition of SIRT1 deacetylase is associated with the viability of cancer cells exposed to antitumor agents and apoptosis” (2013) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789038/

Augmented SIRT1 expression was observed only at low concentrations (>80% cell viability) and the inhibition of SIRT1 deacetylase by Nicotinamide decreased the viability of the cancer cells exposed to low concentrations of antitumor agents. Nicotinamide induced typical apoptosis in the MCF-7 tumor cells, accompanied by the activation of the caspase cascade. SIRT1 promotes cellular survival at certain stress levels by its deacetylase function. The SIRT1 deacetylase inhibitor, Nicotinamide, triggers the activation of the caspase cascade and induces typical apoptosis in MCF-7 cells.

 

 

Edited by HBRU, 13 January 2020 - 12:45 PM.

[sedentary]

is senescence associated with severe bleeding? i dont really take any meds to thin the blood at all but i bleed a lot! i consume strawberries a lot, but is it really possible to such massive bleeding. i literally cannot stop bleeding. it might  be something else, i suppose. it cannot possibly be strawberries,seriously!  i told my doc but he didnt care as  i expected. he had more patients waiting, he had to see more to make more money so i cant blame him. if you are in this situation to make money why just waste your time discussing why you bleed so much? well, i guess ill turn to alternative for now. see how it goes. ill report back guys, peace!!!

[osris]

is senescence associated with severe bleeding? i dont really take any meds to thin the blood at all but i bleed a lot! i consume strawberries a lot, but is it really possible to such massive bleeding. i literally cannot stop bleeding. it might  be something else, i suppose. it cannot possibly be strawberries,seriously!  i told my doc but he didnt care as  i expected. he had more patients waiting, he had to see more to make more money so i cant blame him. if you are in this situation to make money why just waste your time discussing why you bleed so much? well, i guess ill turn to alternative for now. see how it goes. ill report back guys, peace!!!

 

 

There’s only been one case of protracted bleeding after use of fisetin, and that was with someone on this forum, who cut himself shaving and drip-bled for a few hours afterwards. And he himself is not sure if fisetin is the culprit as he was taking other supplements at the time.

 

Fisetin can affect wound healing, but that does not necessarily mean that in the absence of speedy wound healing protracted bleeding need also be present. Not all wounds under normal circumstances bleed that much anyway, unless a major artery is involved.

 

Another senolytic called Navitoclax is also thought to cause protracted bleeding, but Navitoclax is only one of many senolytics, so the protracted bleeding it causes does not necessarily apply to the other senolytics—including fisetin.

 

So I’ve come to the conclusion that the benefits of periodically (every 6 months) taking fisetin (at around 15000 mg) for 2 days outweigh any small risk of it causing protracted bleeding. 

 

And even if this risk were significant, the duration of time one is taking it (2 days) would likely not be enough time for it to affect blood clotting to any significant extent. And if, indeed, it did so, then one need only arrange not to have surgical treatment during that time—and for around 7 days after. And as for accidental injuries happening to us during this time, obviously, that is out of our control. 

 

It seems to me, that seeing as hundreds of supplements interfere with the blood clotting process—such as vitamin C and even green tea—that to jettison the tremendous benefits of fisetin due to being overly cautious would be an oversight.

[Psy]

 

 

So I’ve come to the conclusion that the benefits of periodically (every 6 months) taking fisetin (at around 15000 mg) for 2 days outweigh any small risk of it causing protracted bleeding.

15 g is a really high amount.

[osris]

It has to be that high to kill senescent cells. I thought it was a bit high myself, and was wary of taking it, but I did, and had no adverse affects at all.

[SearchingForAnswers]

My Fisetin Experience - amazing!

 

This is all my first hand anecdotal experience, unfortunately no funds for testing.

 

Protocol:

I am 58 1/2 yo.

I did one day at 20mg / kg. Took it at night a couple hours before bed. Head felt clearer, oddly.

Didn't realize how much 20mg / kg was, so I had to order another bottle with higher dosages.

So two days later, since I had no side effects, I decided to up it to 30mg / kg.

Took it before bed again.

Repeated the next day.

 

Nothing immediate, though I did easily bump my run time in the gym by .2 miles, likely just placebo.

 

However, after about 3 - 5 days, I have noticed the following:

Highly improved mental clarity, no "Fog".

Zero afternoon grogginess / sleepiness. This was a regular feature for me.

Improved gym performance (bodybuilding, muscles feel like they used to, get kind of "Pumped" way easier and feel tighter).

Far more energy, it seems to be improving every day (about 10 days out now).

I just really am feeling amazing. I don't know if this is placebo, but I'll take it. No supplement of any kind has ever made me feel this way.

I am convinced at this moment, I just can't believe how good I feel. No BS here; this is a game changer for me, if it sticks. I guess we'll see.

 

I will repeat it one month out per Mayo protocol.

 

My wife did the protocol with me, but strictly following 20mg/kg and just two days; She has not really noticed much. I was hoping it might help her allergies, but no difference so far. She is 49.

 

[ambivalent]

Caution should still be exercised. If you take a look at the post below and the one following, it is clear that I am not the only one to have experienced delayed healing. The only signal in my experience occurs during the healing itself, you may feel great but be vulnerable.

 

https://www.longecit...-37#entry884076

 

Referencing the earlier post by Osris, I was pretty confident it was Fisetin. 

[osris]

Ambivalent, those two posts your draw our attention to on that thread you linked to, don’t mention if the senolytic used was fisetin or not. And they don’t mention any impaired blood clotting ability, only that a wound took a while to heal. That’s different to the risk of bleeding to death that many people are more concerned with—though needn’t be, as senolytics haven’t yet posed such a risk.

[ambivalent]

Osris, risk doesn't materialise once its measured. The fact that no study has demonstrated fisetin to interfere with wound healing constitutes a lack of proof, not risk. There is good reason to suspect there is some danger - Fisetin has senolytic properties and some have reported healing related issues. Lost took large quantities of Fisetin, far higher cumulatively than I have, he stopped and he isn't shy. Thus far no one has had a setback not worth trading in for those senescent cells  - the sample space is small, though. If the experiences of Lost and I have resulted from high dosing Fisetin then doing so is likely running a gauntlet, at least for some window of exposure. 

 

I'm not here to only post anecdotes once there is some threshold of proof, so there isn't any need to respond with 'Yes, but....'. That's not the point of these forums, we are trying to build an understanding and do so rather crudely, but not ineffectively. I would say though, given your initial considerable and probably not unreasonable caution, it doesn't make sense then that you would choose to dose right off the bat outside the sample spectrum (unless I've missed users posting higher doses). It seems like the confirmation bias we are all prone to - you struggled to convince yourself it was safe, but once taking that position affirmed that belief by downing a megadose. That's how I used to gamble and in many ways still do. 

 

Fisetin may well be safe at these levels, but there is a possibility of danger. 

[osris]

Ambivalent, my main concern for hesitating before taking fisetin was due to your post about your prolonged shaving cut bleed. I then looked around online and found no other anecdotal or otherwise instances of any similar prolonged bleeding. Apart from one single reference to a theoretical possibility that Navitoclax (another senolytic) might cause prolonged bleeding in some instances. I could not however find any references saying that fisetin might also theoretically cause prolonged bleeding in some instances. 

 

It was the prolonged bleeding incident you experienced that was of concern to me, rather than any theoretical non-bleeding wound taking time to heal. I can survive a non-healing would—I cannot survive prolonged bleeding. So your frequent mentioning of non-bleeding wounds taking time to heal is, with respect, irrelevant to the more important issue of prolonged bleeding. Not that the latter is any longer important—at least in relation to fisetin, seeing as there is absolutely no proof that fisetin causes either prolonged bleeding or slow non-bleeding wound heal times.

 

It was unfortunate that you had prolonged bleeding when you cut yourself shaving, but that is not really a sufficient reason to warn other people not to take fisetin. I took it at high dosages for two days, and did not have any issues with it. That is not to say that had I taken it at high dosages continually for weeks on end issues would not arise. But as far as I understand only 2 or 3 days at high dosages are needed once in a while to do the job of killing senescent cells.

 

My reason in laboring the above points is simply to prevent people who read your posts in this thread from being afraid to take fisetin. I want to reassure them that it is safe and that they won’t bleed to death if they do happen to cut themselves. 

 

 

[ambivalent]

Osris, 

 

With respect you have no grounds to reassure anyone because there isn't evidence to do so. Delayed wound healing is not something of a mere inconvenience, it can be a matter of life and death if circumstances conspire. Antibiotic failure is non-trivial, that it took Lost 16 days to get rid of what appeared a minor skin infection prompted him to stop. 

 

The very point of my mentioning the bleeding (and the dry socket which appears not to have fully healed, given it is still very heat sensitive) is because it was so unusual, highly correlative to fisetin and relates to a clotting failure - a known characteristic of senolytics. If scientifically something as weird as this is witnessed (weird in the population, and weird for me) - you don't dismiss it, you investigate. Just because an O-ring fails on a cold day and nothing too serious came of it, it should be filed under 'nothing to report'. 

 

There are three possibilities of interest: risky, little benefit; beneficial, little risk; beneficial, risky.  People tend to resolve their beliefs to one of the first two, resist the third because tension persists - but its a dangerous bias. 

 

Feeling good after 15g is not a counter-argument. I felt good too and but for a couple of unusual instances, I'd have nothing to report. But that's how it goes with high-impact low likelihood events. 

 

If you have decades in front of you there is no need to go gangbusters on senescent cells at this early stage of research, at least stay with in sensible parameters - I don't have dependents hence my risk profile is somewhat different. 

 

Anyhow, hopefully the gain of your experiment is significant and the risk low. I'll look forward to hearing of any positive developments.