1079 replies to this topic

[osris]

Some questions about taking fisetin:

 

Is it ok to dissolve fisetin with any oil or just olive oil? All the people here who dissolve it in oil do so with olive oil, is there a good reason why olive oil is chosen?

 

Also, is it ok to mix in milk with the dissolved fisetin and oil mixture? Doing this would make the mixture more soluble so as to avoid any waste due to oily residue being left in the drinking container used. In other words, it would make the mixture more liquid and so less likely for particles of the mixture to not be drunk due to it sticking to the bottom and inside "walls" of the drinking container.

Edited by osris, 15 November 2019 - 11:54 AM.

[Empiricus]

How can you be sure that fisetin was the cause of your hair and face drying? And if it was, why did it cause this do you think?

 

 

My fisetin dosing was 0.5, 0.5, 0.5, 1, and 2.5 grams. The way I felt & looked on day 4 and day 6 were night and day.  
The 2.5 dose wiped me out for the following day. Got lot of diarrhea and felt really out of it.   That's when I noticed very dry hair and 

unwell look. These effects persisted but got worse after I started the curcumin.  

 

To the extent curcumin is probably also a senolytic, it makes sense that it would bring about more of the same.  

I suppose looking and feeling like crap after the fisetin what one might expect, if a lot of dead cells have been discarded.  

Though not everyone reports such.  However, not everyone responds even to small doses of fisetin as I do, so maybe 
I am highly sensitive to the stuff. Maybe also to curcumin.

 

[osris]

How long did this drying effect last afterwards? I hope it's not permanent!

[Oakman]

Taking even low doses of curcumin so soon after a high dose of fisetin has turned out to be not a good idea.

Just ending 2 days of quite low dose curcumin (2 capsules/day theremin brand with fish oil). 

 

My hair suddenly became shockingly dry (fisetin had dried it out already) and my face looks even more drained and sickly. 

 

Low dose curcumin following high dose fisetin seems to amplify fisetin's impact to an astonishing extent.  Won't do that again!  

 

Just a reminder that hair cells are dead, and therefore can't be affected by molecules in your blood. So I would seriously doubt there is any connection. Perhaps to much hair washing then?

[Empiricus]

Just a reminder that hair cells are dead, and therefore can't be affected by molecules in your blood. So I would seriously doubt there is any connection. Perhaps to much hair washing then?

 

Every time I take silica my hair becomes very shiny by the next day.  How does the silica I swallow in a capsule have an effect on my hair?  

 

Healthy hair is replenished with oil from the scalp.  I would imagine the silica is probably enriching this oil.

 

Likewise hair dryness after taking 5g of fisetin could have to do with changes to the production of this oil.

 

 

Edited by Empiricus, 16 November 2019 - 06:46 AM.

[Empiricus]

How long did this drying effect last afterwards? I hope it's not permanent!

 

It's been a week since I finished the 5g of fisetin. Just 2-3 days since I stopped taking curcumin.  

 

An effect of the fisetin I already mentioned is sleeping more deeply.  Also, I wake up at the same time every day. No matter how late I had gone to sleep, I bolt out of bed at the same time. Every day, by late evening I am unusually sleepy and crave sleep.  

 

I intend to start going to bed earlier, since I seem to need sleep more, and now find it impossible to sleep in beyond my usual wake up time.  

Edited by Empiricus, 17 November 2019 - 12:33 AM.

[sedentary]

so fisetin has an amazingly profound effect on sleep? so do you think it can cure my insomnia? i cannot afford it now, but if it really helps with sleep, ill try to safe on my usual meds. ill ask my doctor if its ok to lower the doses because of expense and maybe ask if fisetin might benefit me when i show the studies you guys provide. hopefully he can give me advice. i really already have a finance limit on meds and supplements i take on month bases, so its a bit difficult to incorporate it into my regime currently. but ill show this thread or the studies posted in here and probably convince my doctor maybe fisetin is good supplement therefore try to incorporate it into my regime and cut on the meds he already prescribes me.

edit: important to ask since i didnt see a study or maybe i missed on this, does it also help with blood pressure? im going to try to lower my blood pressure med cost as well and if this thing which is natural might help with this, then im really doing better with it instead.

Edited by sedentary, 20 November 2019 - 01:00 AM.

[Empiricus]

Another, indirect way fisetin could improve sleep (though think it's not the main reason it is helping):

from my experience, it's easy to cut back coffee while taking fisetin.  

 

[ambivalent]

A quick note: a couple of weeks after my last fisetin dose I noticed what appeared to be an infection on the arthritic knee which responds immediately after 3g+ fisetin doses (weakening then eventual strengthening). There is no obvious swelling and I don't notice it except when my knee is bent with pressure on it, it can be quite painful This is not something I can remember happening in recent times at all, I recall one large infection on the knee in my 20s, but other than that nothing. I also experienced dental infection blowing up recently, but this is common as it is something I keep under control, unless I weaken my immune system as I did a couple of weeks ago (the knee infection pre-dates this). It is a significant observation, I would say,quite likely fisetin-causative. I did have prolozone therapy (in both knees) a couple of months prior, which with injections runs some risk of bacterial infection, but it would be a long while incubated. It does seem bacterial infections appear to be a risk-factor with taking senolytics and since they are quite routine they may often not be reported. Do we have any non-anecdotal or theory supporting evidence of senescent cells increasing the risk of bacterial infections?

[JimWoodall]

Hi everyone,  I am planning my next senolytic cycle and am hoping for some help. I always prefer to come into things slowly and safely.   So my first senolytic cycle was a couple of months ago and looked like this:

 

    Day 1: 250mg  revgenics Fisetin, 1 revgenics curcumin, 1x10mg Swanson BioPerine .   Started fasting at noon. 

    Day 2: 500mg Fisetin, 1 revgenics curcumin , 1 BioPerine in olive oil,1 revgenics resveratrol

    Day 3: 750mg Fisetin, 2 curcumin, 1 BioPerine in olive oil

 

First my next cycle(January 1)  I am looking at:

 

Day 1: 500mg revgenics fisetin, 1 strong Curcumin, 1 pepper dose, 2xLEF senolytic activator 

Day 2: 1000 mg revgenics fisetin, 1 strong Curcumin, 1 pepper dose, 2xLEF senolytic activator 

Day 3: 1500 mg  revgenics fisetin, 1 strong Curcumin, 1 pepper dose, 2xLEF senolytic activator 

Day 4: 1500 mg  revgenics fisetin, 1 strong Curcumin, 1 pepper dose, 2xLEF senolytic activator 

 

Also I would like to go with a very low dose D to test it out, but the price is CRAZY and I don’t know which lab place online to trust.

 

Any comments are appreciated! THANK YOU

[ambivalent]

A couple of observations to report.

 

A week ago I endured a tooth extraction, I experienced one a few months earlier for an implant, which to my recollection no healing problems. However this time the pain from the extraction persisted and the gum appeared quite inflamed. Well, I returned to the dentist today to be diagnosed with a dry socket, which, I was informed, results from poor blood clotting at the site of the extraction. She mentioned it was likely to occur 10% of the time.

 

The second is what I believe to be a possible case of joint effusion. This appears to have surfaced only a couple of weeks after my previous dose and wasn't something which occurred before, but it appeared on the knee which I mentioned responded to Fisetin through an initial weakening, then subsequent strengthening. I noted one cause I've read can be gout which is due too elevated uric acid, a recurring problem in the last couple of years, though never taking this form on my knee (as far as I recall). It is correlatively strong certainly, but causative through senescent cell clearance? I can't say. I notice much in terms of volume of fluid but there has been significant pain when bent and pressured. If there are any other explanations I'd be interested. Several months prior I undertook prolozone therapy, requiring injections which might in theory cause a bacterial infection, though I'd have thought this unlikely.  

 

Thinking as I type I had also taken some very large doses of D3 to get rid of oral bacterial infection, might this cause problems with clotting due to depletion of K2? i.e. D3 - Calcium - k2 axis. I have significantly supplemented K2 but perhaps not proportionately to the D-dose. I certainly don't recall taking large doses of D3 at the time of the 5.5 hour blood-clotting-wart-nick episode, it was such an outlier of an event and so closely correlated with Fisetin that I'd say I was likely to be the trigger, but I suppose if D3 levels were high it might have compounded the problem.

 

  

 

 

 

 

 

 

[Empiricus]

If I went back to a daily dosing of fisetin, I would be tempted to experiment with 25mg/day to 50mg/day.  I think in that range there could be benefits if you're a responder, and maybe you could avoid the slower healing rate that I believe I was seeing at 200mg/day. And that seems to accompany the multi-gram senolytic dosing.  

[ambivalent]

Apologies for the considerable overlap between #849 and #851 - I'd not recollected posting. No problem in deleting and rewriting #851, with a reduced detail on the knee.

[osris]

At the risk of sounding incredibly stupid, how exactly do scientists know that senolytic drugs have successfully killed senolytic cells in mice? In other words, can the death of senolytic cells be “seen” or apprehended in some way by various scientific measuring devises, or is their death assumed from the positive effects fisetin had on the mice’s physiology etc?

 

Also, how long after the mice taking fisetin did these positive effects manifest—one week, one month, one year after they took it? And in humans how long would these positive effects take to manifest after taking fisetin.

 

Incidentally, I took a first dose of 1500 mg of fisetin at 10 pm last night mixed with a tablespoon of lukewarm olive oil for bioavailability, as has been suggested elsewhere in this and other threads. I was initially anxious about doing so in case it caused adverse palpable effects in me, such as headaches, aches and pains, nausea, etc. that some people have experienced taking it. So far (as I write this at 1 pm) I have had no reactions from it at all—neither good or bad ones. I will repeat the dosage at the same time tonight.

 

I’ve also started a new thread for these questions, in case answers in this one are unforthcoming.

 

 

 

[osris]

A couple of observations to report.

 

A week ago I endured a tooth extraction... the pain from the extraction persisted and the gum appeared quite inflamed. Well, I returned to the dentist today to be diagnosed with a dry socket, which, I was informed, results from poor blood clotting at the site of the extraction. She mentioned it was likely to occur 10% of the time.

 

 

 

Had you recently taken fisetin before your tooth extraction?

 

If so, and it affected blood clotting, how come you had a dry socket? I thought dry sockets were an indication that blood was not available to fill in the socket. That blood was not available, suggests that clotting wasn’t a problem but that its opposite was—over coagulation.

 

The clotting problem you associated with fisetin earlier in this thread, regarding your excessive bleeding over several hours from a shaving cut, sounded like a clotting problem, but the dry socket situation doesn’t sound like one to me.

Edited by osris, 05 December 2019 - 01:52 PM.

[ambivalent]

A lazy google search uncovered this article - dry sockets are quite rare down at 2%, causes appear unclear, but the article states the clot doesn't form in the vacated space. Naturally, I stopped bleeding so there was clotting, but I am simply intuiting that a fully formed clot would have required a greater resource of senescent cells, in which I am perhaps deficient.

 

I note, if it wasn't posted there has been some research out recently on blood clotting and senescent cells:

 

https://www.fightagi...blood-clotting/

 

Anyhow, according to the article the clot may have been dislodged, so alternative explanations are possible (and its not a wisdom tooth). No, no recent large doses of Fisetin just the odd 100 to 200mg. Probably 2-3 months since my last large dose. It'll probably be in the thread. 

[osris]

Thanks for the link to the article on blood clotting and senescent cells. It undoubtedly shows that senolytics prevent abnormal (age-related) blood clotting, but my major question about senolytics (especially fisetin) is whether the rumor that they prevent normal blood clotting is also true. I have a feeling that the rumor is wrong, as I have scoured the internet to see if there is any truth in it but can't find any. So I have to conclude that your unfortunate incident with the shaving cut was probably a one-off event, and not to be generalized.

 

By the way, what exactly your fisetin regimen? You seem to be taking it both at low doses regularly and also at high doses now and again. Why is that? 

Edited by osris, 06 December 2019 - 01:03 PM.

[ambivalent]

Hi Osris,

 

I'm not trying to persuade you, just reporting experiences. I would say though that since you're taking Fisetin because of its potential senolytic properties and given there is evidence that senescent cells impact blood-clotting, unless Fisetin doesn't target the senescent cell-type implicated why wouldn't there be some expectation of an effect? In addition, I'm not sure what's to be expected of cyber-space inquiries at this stage of research - unless there are studies specifically related to Fisetin and clotting or indeed a ton of high-dosing anecdotal evidence. People here have reported delayed wound healing and that is inline with expectation. And probably they like me are prepared for some trade-off with clearing senescent cells, cause retaining them sure is a trade-off. But it is a risk. I suspect there may well be confounding factors affecting my blood-clotting accounts, but there is an expectation of that on this site.

 

It seems you're trying to assess the risk of Fisetin by researching Fisetin which is dangerous when in the realms of experimentation and scarce data. The logic for me is quite straight forward: I'm trying to clear out senescent cells with Fisetin, what are the risks of clearing out senescent cells? We have far more evidence on the effects of reducing senescent cells than we have studies on Fisetin's blood-clotting properties.   

 

The occasional low doses are for nootrpic effects and regulating histamine.

Edited by ambivalent, 06 December 2019 - 03:32 PM.

[ambivalent]

Osris, 

 

I note in your post you mention looking generally too, rather than sepcifically just Fisetin-blood clotting. Apologies for overlooking that in my response. We do have evidence of a senolytic drug being withdrawn for inhibiting blood clotting, I believe in the 80s and we do have the age-related evidence cited above. Unless there are studies demonstrating no impact on clotting then it is the case, that as the quote goes, absence of evidence is.... There isn't a need to go hard at this if you have decades on the clock. 

[osris]

Ambivalent, have you a link for that drug being withdrawn for inhibiting blood clotting?

 

I agree that fisetin might have an impact on blood clotting but I have not seen any anecdotal reports apart from yours about your shaving cut bleed that show that fisetin or senolytics in general can cause protracted bleeding. And if I can remember correctly, you had no similar protracted bleeding problem when you had to have dental treatment while still taking fisetin after the shaving incident. I don’t mean the dental treatment where you mention your dry socket but another one in an earlier part of this thread.

 

It seems to me that any risk of protracted bleeding is very low.

 

[ambivalent]

The shaving incident was a few days after the first dose, which was 3 grams. Now there were not problems with bleeding since, which is suggestive of adaptability, but 5.5 hours to clot is crazy and there would need to be an explanation for this - it isn't just an outlier to be dismissed. This is a dangerous way to think. This outlier occurred shortly after taking a senolytic which there is known to be some mechanism to impact blood clotting. Sure other nicks occurred later with no problem (although not like it) and there has been no issue with any dental bleeding but there has been in the full formation of a clot after an extraction. Sure there was no excessive bleeding but the clot didn't develop sufficiently to cover the socket, the clotting process appears to have been aborted before completion. 

 

The article was from SENS but the article appears to be gone. 

 

https://www.longecit...e-9#entry862959

 

I certainly don't understand the mechanism in play here; however, I've had two unusual incidents since taking Fisetin  - one from my own sampling of dozens of shaving nicks over 30 years and the second from the general population - dry socket after tooth extraction. Given the evidence of senescent cells and wound signalling it would be expected that these kind of effects would occur with some threshold of clearance. It is optimistic to expect that the number of s-cells cleared required to elicit the desired health benefits will not coincide with any healing risk increase. 

 

If my experience is real and attributable to Fisetin then it is either intermittent or quite specific to certain characteristics of injury or timing etc. So if it is real, its not always showing itself - I've not become a haemophiliac - and so wouldn't necessarily display in others. And clearly, we don't currently have a large pool of subjects taking and reporting on grams of doses. 

 

Anyhow, as I said I'm not here to persuade you - that's not the purpose of this thread or my accounts - I'm just reporting and relaying my experiences. However, there is real danger in ignoring outliers with nascent experimentation particularly when there is a credible explanation behind it, especially when time is on your side. In addition there has been an article published indicating senescent cells might suppress tumours  - we're not going to know about that risk for a while. 

 

 

 

[Florin]

The article was from SENS but the article appears to be gone. 

 

https://www.longecit...e-9#entry862959

 

 

https://web.archive....senescent-cells

[osris]

The shaving incident was a few days after the first dose, which was 3 grams. Now there were not problems with bleeding since, which is suggestive of adaptability, but 5.5 hours to clot is crazy and there would need to be an explanation for this - it isn't just an outlier to be dismissed. This is a dangerous way to think. This outlier occurred shortly after taking a senolytic which there is known to be some mechanism to impact blood clotting. Sure other nicks occurred later with no problem (although not like it) and there has been no issue with any dental bleeding but there has been in the full formation of a clot after an extraction. Sure there was no excessive bleeding but the clot didn't develop sufficiently to cover the socket, the clotting process appears to have been aborted before completion. 

 

The article was from SENS but the article appears to be gone. 

 

https://www.longecit...e-9#entry862959

 

I certainly don't understand the mechanism in play here; however, I've had two unusual incidents since taking Fisetin  - one from my own sampling of dozens of shaving nicks over 30 years and the second from the general population - dry socket after tooth extraction. Given the evidence of senescent cells and wound signalling it would be expected that these kind of effects would occur with some threshold of clearance. It is optimistic to expect that the number of s-cells cleared required to elicit the desired health benefits will not coincide with any healing risk increase. 

 

If my experience is real and attributable to Fisetin then it is either intermittent or quite specific to certain characteristics of injury or timing etc. So if it is real, its not always showing itself - I've not become a haemophiliac - and so wouldn't necessarily display in others. And clearly, we don't currently have a large pool of subjects taking and reporting on grams of doses. 

 

Anyhow, as I said I'm not here to persuade you - that's not the purpose of this thread or my accounts - I'm just reporting and relaying my experiences. However, there is real danger in ignoring outliers with nascent experimentation particularly when there is a credible explanation behind it, especially when time is on your side. In addition there has been an article published indicating senescent cells might suppress tumours  - we're not going to know about that risk for a while. 

 

Ambivalent, I appreciate that you are not trying to persuade me, and I accept that protracted bleeding occurred in your case regarding the shaving cut.

 

My questioning of you is merely to establish if what happened to you was a one-off or just bad luck. This is more to reassure people reading this thread, and who are thinking of taking fisetin, not to be needlessly put off should they interpret your protracted bleeding experience as being the norm regarding use of fisetin. I’m not suggesting that you are needlessly alarming people, but some people could misunderstand you.

 

As I said, your case is the only one I am aware of regarding protracted bleeding after use of fisetin. I would really need to hear of a few more cases to come to see your experience as being the norm.

 

I accept that 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.

 

The article you posted the link too only mentions Navitoclax in relation to protracted bleeding, but Navitoclax is only one of many senolytics, so the protracted bleeding it causes does not necessarily apply to the other senolytics.

Edited by osris, 08 December 2019 - 03:03 PM.

[ambivalent]

This needs to be wrapped up. Irrespective of my experience nobody should be complacent about taking senolytics, senescent cells serve an important function. Bear in my mind my two experiences were quite unusual - a nick to a wart (which might typically take say 1.5hrs max to clot) and a tooth extraction - if it weren't for these two incidents I would have nothing to report - I would be part of your evidence against risk rather than for it. As for bad luck, the dry socket might well have been, but not the shaving clot - because it just doesn't happen and it occurred a week after the initial large dose. It is highly likely to be Fisetin-related. The two instances which occurred are not big deals but there might be a context for me or someone else where indeed it will be. Additionally, I may have made the dose more bioavailable through adding black pepper, olive oil and in the last dose a drop of DMSO. As for navitoclax, we have a senolytic that was withdrawn for causes symptoms which I have had demonstrated to some extent.

 

Osris, you have transitioned from wanting to be excessively reassured there is no risk in taking Fisetin, to excessively needing to be reassured there is one. It is obvious there are benefits in eliminating senescent cells, clearly there are risks in eliminating those cells too - we don't have the human data to know these trade-offs. 

 

Be reassured at least there are probably more people up-threat than you. Good luck, but I'm not going to add anything more on this until /if more unfolds.

 

 

[Oakman]

I liked this thread, but it has devolved into one about shaving cuts and bleedings. Could you folks consider taking the discussion to a new thread? The input of experience is useful, don't misunderstand, but can't we please move on, the issue has been assimilated.

[osris]

Ambivalent an Oakman, I will respect your wishes and not discuss the matter of protracted bleeding any more.

 

I am still a supporter of fisetin use, and feel that it needs defending when necessary. Such as in the case of an interview I found yesterday with a man who thinks senolytics are very dangerous. I posted a link to it in a new thread but so far it has been ignored, so here it is again::

 

 

"Here is an interview with senolytics skeptic Michael Fossel who says that senolytictherapy is dangerous:

 

https://www.leafscie...-for-longevity/

 

The interviewer seems to get the better of him though, and questions his many assumptions.

 

Here is a rebuttal of the interview and a critical discussion of it:

 

https://www.fightagi...nst-senolytics/

 

Your thoughts."

[HBRU]

Ciprofloxacin is an antibiotic that works through topoisomerase inhibition and it can cause tendon ruptures.

I'm just speculating here, but maybe the senolytic mechanism of action of fisetin is through topoixomerase inhibition, which I believe generates DNA breaks. Perhaps senescent cells can't repair them (hence apoptosis) whereas normal cells can?

 

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....

Edited by HBRU, 10 December 2019 - 12:28 PM.

[HBRU]

Well it seems Fisetin to downregulate MMP-2/MMP-9 (and in this regard is different from ciprofloxacin)

 

https://link.springe...1010-009-0217-z

Edited by HBRU, 10 December 2019 - 12:35 PM.

[osris]

I hope not Daniel.  If this is in any way translatable, it's a game changer.  This is a fantastic study, and after a quick read, here are some of the other main points.  I am not including any progeroid stuff even though it is also interesting:

 

- 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!!!  (though I can't find the %, just a graph)

 

https://imgur.com/qPetBZn

 

This study is a goldmine, there is much more than this synopsis

 

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

 

And from that, is there a way to extrapolate to humans how long after taking fisetin these effects would show up in humans?

[HBRU]

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