1079 replies to this topic

[pamojja]

(and I can’t find any information or research on fisetin that even mentions potential lack of blood clotting issues)

 

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079
 

Edited by pamojja, 23 October 2019 - 11:27 AM.

[OP2040]

Yes, vitamin K2 probably countered any lack of blood clotting in you. I'd take it too if I were on fisetin.

 

Can you list here, for convenience, and to have it all in one place, the reasons you think fisetin is a waste of time regarding longevity? You have made some good points on this, but this thread is so long, that it would be handy to have it all in one place.

 

Presumably, you are going to take dasatinib and quercetin to simply remove senescent cells rather than for any longevity benefits. If so, why are dasatinib and quercetin, in your view, more appropriate than fisetin -- I thought the research suggested fisetin was better for senescent cell removal?

 

 

I never said Fisetin was a waste of time.  I just think it's effects are far less powerful than D+Q, possibly due to bioavailability.  It may be that it does eliminate senescent cells at a sub-clinical level, and therefore several interventions over the course of years may have the same effect as one or two D+Q interventions.  Aside from that, Fisetin seems to have many other positive affects that are not related to senescent cells.  I encourage it's use as an anti-aging intervention, the only downside being that it is fairly expensive.

 

The research does not say that Fisetin is better than D+Q for senescent cell removal.  The research says that for mice, Fisetin is the most effective senolytic among an array of natural compounds, including things like Quercetin and Curcumin.  It's senolytic effects were never compared directly to D+Q.

 

The appeal of D+Q is that it has many, many studies backing up it's very effective senolytic action, and now it has the first one showing that it works in humans as well.  Almost all the information we have on the healthspan benefits (in mice) of eliminating senescent cells, comes from studies that used the D+Q combination.  

 

I wanted Fisetin to be a simple and safe answer to the problem of senescent cells.  But I have now taken three courses of it and with no obvious effect.  Others have taken both Fisetin and D+Q and said the latter has an obvious beneficial effect and the former does not.  I strongly believe that an intervention that is actually eliminating senescent cells should show an immediate and obvious benefit to anyone over ~40.   Fisetin may still be a good choice for those looking for something more subtle and beneficial over the course of years.  Perhaps it removes 10% of senescent cells and you need 10-20 high dose sessions to achieve the same as 1 or 2 sessions of D+Q.  That is absolutely a possibility and well worth pursuing for the more patient and risk averse among us.

 

I'm not on board with worrying about blood clotting, and not convinced that K2 is what prevented it from happening to me.  This was one users unique experience, and what he described is far, far, far from a threatening situation.  Even if it was an accurate depiction and attributed to Fisetin completely, then logic dictates that it would be a temporary effect.

[osris]

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079
 

 

That’s a very long list. But do they all really cause serious bleeding issues. I’ve been on some of these, and not found any lack of blood clogging problems.

 

Maybe fisetin is the worst of them—at least in Ambivalent's case.

[ambivalent]

The persistent debate over whether or not fisetin is bioavailable or not is a suprise to me. As I reported back in post208 I experienced three very distinct effects which were attributable to either known properties of fisetin or senolytics (after my first dose osris). First of all my breathing improved dramatically the following day after struggling badly for months.(Fisetin inhibiting mast cells and another users experience.) I had no prior knowledge of this property.  My problematic, likely arthritic knee weakened considerably (another contributor reported the same, and it has been a consistent personal fisetin effect), then eventually strengthened above prior baseline - we know senolytic, UBX0101, can treat arthritis and trigger cartilage regrowth in mice. Several people I've known who've taken small doses of Fisetin have experienced minor detox symptoms. Then of course there was the bleeding. Once again a known property senolytics is delayed wound healing. 

 

These three effects were quite dramatic and a clear indication that fisetin was bioavailable when taken on that occasion. What is also clear is that the expression of this bioavailability would not be experienced by everyone, unless they had arthritic knees, raised levels of histamine and an untimely wart cut. As for the risk of bleeding, which is the one symptom I have some measure of doubt over as there might possibly be some other explanation* and it was not repeated, it does appear to be a transient risk, at least with me. I certainly cannot confirm whether the window of risk is repeatable, but, if it is there, it is only a window, at least personally.  My breathing has remained excellent, although this has been confounded subsequently with zinc supplementation and the knee weakness a consistent response to the fisetin dose.

 

I believe there may have been other benefits but I am far too unsure to confidently assert them such as better skin and flexibility but they definitely subjective and there is quite simply far too much noise with other protocols and most definitely not night and day effects: these were. Lost would indicate that he has had those experiences, but he has been comparatively off the scale in net-dosing. His most pronounced observation was probably the need for anti-biotics over 16 days after a skin infection - it is a chance anecdote and not necessarily attributable to fisetin, but it is an outlier of an effect.

 

As for comparing with D+Q unless they are targeting the same senescent cells, why would we expect comparable effects?

 

 

*as well as proximity to dose, a week later or so.

Edited by ambivalent, 23 October 2019 - 03:26 PM.

[osris]

I wanted Fisetin to be a simple and safe answer to the problem of senescent cells.  But I have now taken three courses of it and with no obvious effect.  Others have taken both Fisetin and D+Q and said the latter has an obvious beneficial effect and the former does not.  I strongly believe that an intervention that is actually eliminating senescent cells should show an immediate and obvious benefit to anyone over ~40.   

 

....

 

I'm not on board with worrying about blood clotting, and not convinced that K2 is what prevented it from happening to me.  This was one users unique experience, and what he described is far, far, far from a threatening situation.  Even if it was an accurate depiction and attributed to Fisetin completely, then logic dictates that it would be a temporary effect.

 

Not trying to call you out, but earlier in the thread, you were critical of people who expected anti-aging supplements to have observable affects on them. What has made you change your mind? Serious question, meant respectfully.

 

Regarding Ambivalent’s bleeding incident. In itself, it wasn’t serious—being only a small shaving cut. But the fact that his blood clogging ability was not working properly during this period, doesn’t rule out the possibility that he could have bled to death if the injury had been more serious, such as hitting his head on something, or merely having a tooth extracted—some tooth extraction bleedings aren’t that easy to stop under normal conditions, let alone when one is taking things like fisetin.

 

I agree that any lack of blood clotting problems would likely be only temporary, but this is no comfort if one happens to become injured to the point of significant bleeding during this temporary period. This temporary period would be enough time to bleed to death.

 

Can anyone reassure me that fisetin does not cause blood clotting problems, and that Ambivalent's experience was just down to bad luck?

[osris]

Ambivalent, I posted my last post before I saw your recent post.

 

Did you have the shaving cut after the first time you tried fisetin? If not, then fisetin can't be the cause of your excessive bleeding. 

 

[ambivalent]

Osris, no one can reassure of this: my experience was as reported, it is a known property of at least some senolytics. However, this was my first dose and it was something unexpected to my body. Also most haven't taken it with olive oil and black pepper and people have been around taking this stuff for a while at lower doses, which is obviously where you could start, without being wiped out. The tails of the distribution are undoubtedly where the risks lie, but sometimes the reward too. It is an experimental place, few of us have not been on the wrong side of our experimentation at some point. No one can tell you want you wish to hear which is that taking large doses of senolytics won't interfere with wound healing, because it seems likely that it does, nor of course that such a condition does not pose a significant risk under certain condtions. There is too of course the risk of cancer posed by senescent cell clearance, which has been discussed. 

 

 

[pamojja]

 

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079

That’s a very long list. But do they all really cause serious bleeding issues. I’ve been on some of these, and not found any lack of blood clogging problems.

 

Maybe fisetin is the worst of them—at least in Ambivalent's case.

 

In this long list I even marked 80! substances I regularly take - but never experienced increased bleeding (except with an additional baby-aspirin). As already pointed out, this list was compiled from case-reports. Even if only 1, there would be 1000s others never experience bleeding with the same substances. Or the 1 case-report was simply confounded by other things.
 

[ambivalent]

Osris, its there in the post. Besides it would only have been a dubious timing if it occurred after a subsequent dose and I had nicked myself after prior administering of fisetin to no reduced clotting effect. Reading my initial report, I may not have added black pepper, just olive oil.

[OP2040]

Not trying to call you out, but earlier in the thread, you were critical of people who expected anti-aging supplements to have observable affects on them. What has made you change your mind? Serious question, meant respectfully.

 

Regarding Ambivalent’s bleeding incident. In itself, it wasn’t serious—being only a small shaving cut. But the fact that his blood clogging ability was not working properly during this period, doesn’t rule out the possibility that he could have bled to death if the injury had been more serious, such as hitting his head on something, or merely having a tooth extracted—some tooth extraction bleedings aren’t that easy to stop under normal conditions, let alone when one is taking things like fisetin.

 

I agree that any lack of blood clotting problems would likely be only temporary, but this is no comfort if one happens to become injured to the point of significant bleeding during this temporary period. This temporary period would be enough time to bleed to death.

 

Can anyone reassure me that fisetin does not cause blood clotting problems, and that Ambivalent's experience was just down to bad luck?

 

No worries, you are absolutely right.  The short version is I changed my mind which I tend to do quite often because the evidence is all highly speculative at this point.

 

The long version is for a number of reasons, the least rational of which is just frustration and impatience.  I still want incontrovertible evidence in the form of lab tests.  But on a personal level, we are here to help eliminate suffering, not get better grades on lab tests.  So I've come to believe I was insensitive not just  to others but even myself, by dismissing the "aches and pains" testimonies.  

 

In line with that, I had never seen someone phrase their "aches and pains" argument in black and white, nor have I ever had a black and white difference in subjective experience until recently.  So i was convinced that these descriptions were utterly worthless.  Well, I recently experienced one in the form of being alleviated from what was IMHO memory impairment.  I cannot say for sure which intervention did this though I have my suspicions.  And I have no hardcore before/after proof.  But after 4/5 months of improvement, no one can tell me the effect was not a back/white improvement.  And then I started investigating D+Q again and saw some of the posts from people here describing very clear improvements.  I reviewed all the mouse studies for D+Q, of which there are hundreds, all showing very clear lab improvements as well. 

 

And so my thinking now is that a senolytic that is working should offer that at the least.  Fisetin is not producing those results for me or others.  We get some of the more ambiguous descriptions but nothing clear as a bell.  

 

My stance on Fisetin is that it also has hundreds of studies backing it's efficacy in general and a couple now in mice as a senolytic.  But something is keeping it from producing very clear results in humans, and the current speculation is bioavailability.  Fisetin is still worth taking because it could have a sub-clinical or synergistic senolytic effect, and it has many other positive potential effects.  And I will continue to take it once a year.  But my overriding motivation is results, and when the results aren't there, I move one.  Senolytic results should be immediate, unlike perhaps inflammation results.

[osris]

Ambivalent, your case is, indeed, a puzzling one for me. Until others come forward who have used fisetin at high dosages over the course of, say, 18 months, and who have had no experience of profuse bleeding, I have to assume that fisetin has the potential to cause profuse bleeding -- at least at high dosages.

 

Low dose fisetin does have health benefits in general, but not to the extent that the high price of a 30 capsule bottle justifies the expense. If I weren't taking other supplements, then the cost of 30 fisetin capsules a month would be acceptable, but costs mount the more supplements one feels the need to take.

 

Besides, the health benefits of low dose fisetin are probably replicated in cheaper supplements.

 

I might try, instead, Gamma Aminobutyric Acid, as I was reading that it can reduce neural activity, which some researchers say is a cause of aging. See:

 

https://www.newscien...to-live-longer/

 

Edited by osris, 23 October 2019 - 05:13 PM.

[osris]

No worries, you are absolutely right.  The short version is I changed my mind which I tend to do quite often because the evidence is all highly speculative at this point.

 

The long version is for a number of reasons, the least rational of which is just frustration and impatience.  I still want incontrovertible evidence in the form of lab tests.  But on a personal level, we are here to help eliminate suffering, not get better grades on lab tests.  So I've come to believe I was insensitive not just  to others but even myself, by dismissing the "aches and pains" testimonies.  

 

In line with that, I had never seen someone phrase their "aches and pains" argument in black and white, nor have I ever had a black and white difference in subjective experience until recently.  So i was convinced that these descriptions were utterly worthless.  Well, I recently experienced one in the form of being alleviated from what was IMHO memory impairment.  I cannot say for sure which intervention did this though I have my suspicions.  And I have no hardcore before/after proof.  But after 4/5 months of improvement, no one can tell me the effect was not a back/white improvement.  And then I started investigating D+Q again and saw some of the posts from people here describing very clear improvements.  I reviewed all the mouse studies for D+Q, of which there are hundreds, all showing very clear lab improvements as well. 

 

And so my thinking now is that a senolytic that is working should offer that at the least.  Fisetin is not producing those results for me or others.  We get some of the more ambiguous descriptions but nothing clear as a bell.  

 

My stance on Fisetin is that it also has hundreds of studies backing it's efficacy in general and a couple now in mice as a senolytic.  But something is keeping it from producing very clear results in humans, and the current speculation is bioavailability.  Fisetin is still worth taking because it could have a sub-clinical or synergistic senolytic effect, and it has many other positive potential effects.  And I will continue to take it once a year.  But my overriding motivation is results, and when the results aren't there, I move one.  Senolytic results should be immediate, unlike perhaps inflammation results.

 

I see what you mean.

 

I had thought of trying D+Q, but don't like idea of taking dasatinib, with it being a synthetic cancer drug. Maybe, I'm being over cautious. 

[OP2040]

I see what you mean.

 

I had thought of trying D+Q, but don't like idea of taking dasatinib, with it being a synthetic cancer drug. Maybe, I'm being over cautious. 

 

 

Right there with you.  Although I will likely take it, Dasatinib is indeed for people with a higher risk tolerance.   Others have been saying that most of the side effects relate to chronic use in leukemia patients and short term use in non-cancer patients will not have the same risks.  Logically, I accept these arguments as likely true.  Emotionally, I'm not sure if I'll be able to down that first pill.  The deciding factor in even pursuing it for me is the fact that it seems like quite a few people here have taken it with no side effects at all.  This provides some reassurance, but we will see. 

 

In the larger perspective, it's always an issue of age and timing.  I want to be the type of old person that would rather go out experimenting than bed-ridden.  Enough chronic pain and senescence should make anyone prefer to take risks.  In that sense it is only a matter of time for when I decide to take Dasatinib.  Ceteris Paribus, I might take it now, 10 years or 30 years.  But by 30 years, when I will be in my 80's, assuming the exact same conditions as today, there would be a 100% chance I would take it.

[wbtmwbwm]

Why no piperine? That would likely help the most. Fats only do so much. 

 

My curcumin and resveratrol sources both contain piperine.
 

[sedentary]

so whats the source of dasatinib? lets stop beating around the bush here keep going back and fourth how fisetin doesnt seem to work as intended and just move on to getting this dasatinib and starting some real progress here. at least im ready to move on, anyone else?

[osris]

Right there with you.  Although I will likely take it, Dasatinib is indeed for people with a higher risk tolerance.   Others have been saying that most of the side effects relate to chronic use in leukemia patients and short term use in non-cancer patients will not have the same risks.  Logically, I accept these arguments as likely true.  Emotionally, I'm not sure if I'll be able to down that first pill.  The deciding factor in even pursuing it for me is the fact that it seems like quite a few people here have taken it with no side effects at all.  This provides some reassurance, but we will see. 

 

In the larger perspective, it's always an issue of age and timing.  I want to be the type of old person that would rather go out experimenting than bed-ridden.  Enough chronic pain and senescence should make anyone prefer to take risks.  In that sense it is only a matter of time for when I decide to take Dasatinib.  Ceteris Paribus, I might take it now, 10 years or 30 years.  But by 30 years, when I will be in my 80's, assuming the exact same conditions as today, there would be a 100% chance I would take it.

 

The fear I have with Dasatinib, is that it might be carcinogenic. As far as I know, carcinogenicity studies have yet to be done on it. If such studies are done, and show no carcinogenic risk, that might make me less cautious about experimenting with it.

 

I know this is off topic, but are there any truly safe anti-aging supplements out there—apart from antioxidants and vitamins? 

 

Maybe risk aversion is what needs to be developed in us to fight aging. Some people on this forum are fearless. I am not one of them.

 

If I were very old—in my 80s—I’d be braver, as by then I’d have nothing to lose. I’m in my 50s (56 to be exact, but I can pass for 55) but still regard that as not being old—as well as being risk averse, I suffer from delusions also.

[aribadabar]

 

The fear I have with Dasatinib, is that it might be carcinogenic. As far as I know, carcinogenicity studies have yet to be done on it. If such studies are done, and show no carcinogenic risk, that might make me less cautious about experimenting with it.

 

I know this is off topic, but are there any truly safe anti-aging supplements out there—apart from antioxidants and vitamins? 

 

Maybe risk aversion is what needs to be developed in us to fight aging. Some people on this forum are fearless. I am not one of them.

 

If I were very old—in my 80s—I’d be braver, as by then I’d have nothing to lose. I’m in my 50s (56 to be exact, but I can pass for 55) but still regard that as not being old—as well as being risk averse, I suffer from delusions also.

 

 

You have to decide for yourself. This forum is testing bleeding-edge interventions that probably would not suit risk-averse individuals.

D is not carcinogenic, especially for the duration taken for senolytic purposes.

 

As to fisetin - I'd be more worried whether it will do anything (positive) due to poor bioavailability than doing too much when taken straight (if not improved by oil, bioperine, liposomal encapsulation).

Chances are if it doesn't help you profoundly it won't harm you.

 

I have tried both - I am still alive and kicking 

Edited by aribadabar, 24 October 2019 - 12:14 AM.

[Oakman]

 

I know this is off topic, but are there any truly safe anti-aging supplements out there—apart from antioxidants and vitamins? 

 

 

Being concerned with safety, you might reconsider your idea that supplemental antioxidants and vitamins are without issues. Antioxidants can, foe example, reduce response to cancer, while excess of some vitamins can do likewise (ex. Vit. D and lung cancer). There isn't much out there than cab't hurt you, given certain situations. Danger lurks everywhere, if you are super cautious stay on the sidelines and see what happens to others.

 

https://www.abc.net....xidants/8457336

 

"More is not always more in nutrition. And too much can be a bad thing, especially in the mega high doses coming in the supplements," Dr Beckett said. In fact, research has shown that, in some instances, taking antioxidant supplements can cause harm, and even increase the risk of cancer."

 

https://www.vitamind...ns/lung-cancer/

 

"A number of studies have connected lung cancer survival rates with vitamin D blood levels, seasons, and vitamin D plus calcium intake. These studies strongly suggest that vitamin D can play an important role in improving prognosis of those diagnosed with lung cancer."

Edited by Oakman, 24 October 2019 - 12:30 AM.

[sedentary]

how about melibiose to enhance the weak bioavaibility of quercetin; https://pubs.acs.org...cs.jafc.6b03714

[Florin]

According to the results of an as-yet unpublished study by Dmitry Bulavin (and referred to by Michael), some senolytics (including fisetin perhaps but to a somewhat lesser extent) causes severe liver damage in mice.

 

Search for "researchgrounded, on 02 Apr 2019 - 4:08 PM, said:"
https://www.longecit...red-supplement/

Edited by Florin, 25 October 2019 - 03:35 AM.

[William Sterog]

I hurt myself while taking Fisetin and my bleeding wasn't excesive at all. It clogged fast.

Cordyceps, for example, crazily increased my INR and made me feel weird in my head.

Fisetin should be bioavailable because I feel very clear anti-inflammatory effects from it and my mind works much better when I take it. I think that I have a problem with neuroinflammation, or alergy, because I breath much better with it.

Edited by William Sterog, 26 October 2019 - 08:34 AM.

[osris]

What dosage of fisetin were you taking when you bled? Was it a daily 100 mg dose or the high (3000 mg plus) dose every few months?

[osris]

I’ve come to the conclusion that the benefits of periodically (every 6 months) taking fisetin (at around 3000 mg) for 2 days outweigh the risks of it interfering with the blood clotting process. (I have yet to find any evidence that it does interfere with the blood clotting process—and I have been searching online now for such evidence for several days.)

 

The duration of time one is taking it (2 days) would likely not be enough time for it to affect blood clotting to a significant extent. And if, indeed, it did so, then one need only arrange not to have medical 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.

 

Fortune favors the brave, as they say.

[osris]

Can any one suggest how much fisetin I should take in relation to my weight, which is 76 kg (168 lbs)?

[aribadabar]

Can any one suggest how much fisetin I should take in relation to my weight, which is 76 kg (168 lbs)?

 

I would say start with 1800 mg/d and if no major adverse reactions occur up the dose to 3000 mg/d. Do it for 2-3 days.

[osris]

Thanks. I'll try that.

[osris]

Another question...

 

In the mouse and human study of fisetin, was fisetin taken with another substance to enhance its bioavailability?

 

If not, then how come the mouse study showed good results for fisetin in mice? In other words, if bioavailability is a problem, and the mice were not given another substance to compensate for it, how come fisetin worked well on the mice?

 

Obviously, we'll have to wait for the results of the human study to come in. 

 

[sedentary]

im planning on getting this senolytic powerhouse of a supplement; https://www.amazon.c...ref_=ast_bbp_dp it was recommended to me by a doctor in europe who seems to know more about senolytics than most doctors ive seen here

[aribadabar]

im planning on getting this senolytic powerhouse of a supplement; https://www.amazon.c...ref_=ast_bbp_dp it was recommended to me by a doctor in europe who seems to know more about senolytics than most doctors ive seen here

 

IMHO the ingredients and composition look fine but the dosages are woefully underpowered at the recommended daily serving size. Taking 400mg quercetin, 300mg theaflavins and 100mg Fisetin per day won't make any dent to senescent cells population - the purpose of senolytic protocols are to stress all cells and the dysfunctional ones like the senescent ones to fail the stress test and thus be destroyed. To achieve this, one needs to reach decent serum levels of these compounds - given their low bioavailability, these dosages won't do much, if anything.

[Nate-2004]

Any truly effective senolytic substance should only need to be taken once every few years. There is little data on how effective fisetin is in humans. If it is very effective, then it should NOT need to be taken once a month, maybe once every other year. Taking it more often at this point is an experiment. Your body NEEDS to produce senescent cells in some instances, so constantly taking senolytics is likely to produce unwanted side effects.

 

Our brains are wired to think "more is better". This forum is littered with failed attempts of "more more more....". There is a dose-response curve to almost every therapeutic. Don't be surprised if you have negative side effects when going outside the "curve".

 

I took a course LEFs senolytic activator twice this year. Even for me, it was hard to beat back the natural inclination toward "more is better". I intend to try fisetin or the D+Q product next year, because these are currently theorized to be more effective senolytics.

 

I completely agree, and yeah the only reason I'd do it more often than that would be to experiment with a new combination just to see if there is a difference or improvement in effectiveness. Like adding piperine and fish oil to the mix with a small dose of vitamin c (to prevent its oxidation) to deal with all the bioavailability issues. Outside that, the current widely available options are likely limited in scope of target areas and effectiveness in general. Either the future will bring us a combination drug that targets several areas at once using a variety of molecules, or there will be a drug that targets all areas somehow (harnessing NK cells)... or maybe even something that isn't a drug at all, a device.

Edited by Nate-2004, 02 November 2019 - 05:27 PM.