1079 replies to this topic

[ambivalent]

If you are unwilling to spend the time to do the research, I'd suggest to save yourself those 10 mins spent here and use them elsewhere.

Nobody should be expected to spoonfeed you, ok?

 

Whilst I agree in a sense with this, people whouldn't be too discouraged from querying on points which could or have been answered somewhere in the thread, or indeed repeating questions. Repetition reinforces knowledge and of course we are all interested in experiences, new data points and should seek to aid informed decision-making in order to achieve that goal - that is broadly what happens.   

[aribadabar]

Whilst I agree in a sense with this, people whouldn't be too discouraged from querying on points which could or have been answered somewhere in the thread, or indeed repeating questions. Repetition reinforces knowledge and of course we are all interested in experiences, new data points and should seek to aid informed decision-making in order to achieve that goal - that is broadly what happens.   

 

That's not the case with the user quoted - if you read his comment history and overall tone he almost demands replies but he can't be bothered, by his own admission, to do much, if it at all, himself.

That's a far cry from querying on certain points and I don't think such behaviour should be encouraged/tolerated and that was my point.

 

Everybody here asks questions but most do it in a cooperative and respectful manner - something that it is not evident in the case discussed.

[ambivalent]

An update:

 

Two days ago I entered in to my third dose of Fisetin, a couple of months or so since the last dose. Previous doses were of 3 and 4 grams, mixed in with olive oil. I upped the dose once more to 5 grams again in oil mixed with a sprinkling of black pepper. A minute prior I took a couple of lecithin gel capsules, I can't confirm the dose at this moment, but they were probably around a gram each, with 8 turmeric + black pepper capsules which were either 500mg or 600mg each. I undertook this a few hours before bed, which happened to be late am. (I don't have evidence anecdotal or otherwise that these extras improve the bioavailability of fisetin, though I appear to have experienced more than others have reported at these doses.)

 

Within an hour or so I experienced a mild headache and subsequently a restless night. I awoke to a sore throat, with my glands hinting at their presence, I also experienced an intermittent cough during the day. I would describe the experience as feeling a little run down as we do a the beginning or tail end of a sickness, but nothing that would cause the cancelling of plans - you'd just prefer to rest. Today I felt a little off when I awoke, but nothing significant.

 

This was certainly different to the previous experiences, with brief mild hints of flu-like symptoms: this was far more significant. Naturally, one can only speculate that the effect would have been more severe if this had been my first dose, without any prior senescent cell clearance. One observation I noted yesterday, as I had on the previous occurrences, was increased pain in my arthritic knee, which initially weakened and then strengthened on the previous two occasions. Also, I'm just reminded of something of an intermittent eye-socket pain which started yesterday, which I've experienced before but can't recall the context, possibly fasting.

 

Also, one of the notable first dose experience of fisetin was an overnight 90% cessation of an allergic/asthmatic cough I'd been struggling with towards the end of last year. I have passed through the pollen season with no problems thus far, I'm hesitant to attribute the long lasting effect on fisetin as I believe the problem was due to zinc deficiency which I subsequently addressed, a couple of weeks after the dose. Also red wine always seemed to trigger a cough, but has not done so that first dose.

 

So the question is what next? The dose related flu-like symptoms of fisetin I've experienced and the known effect of Dasatinib on senescent cell clearance (in people) with coupled with severe flu-like symptoms, leads one to ponder whether the fisetin dose needs to be ramped up significantly to attain similar effects. It is crude conjecture a Dasatinib is a drug and fisetin a flavonoid, but if the flu-like effects are purely down to senescent cell clearance then it seems a reasonable hypotheses.   

 

 

edit I should add this was the first time I used lecithin, black pepper and only may have taken a capsule or two of turmeric on the previous occasion. The primary difference between my experience and others, apart from dose, was the use of olive oil.

    

Also, I should add for those who don't recall the update, I experienced delayed blood clotting a few days after the first dose when I nicked a small mole while shaving - which is a known risk /effect of eliminating senescent cells (linked earlier in the thread) 

 

 

Edited by ambivalent, 25 April 2019 - 02:38 PM.

[GABAergic]

personally, ill wait for a guinea pig like you ambivalent to continue this and maybe if you are ok after few years, ill probably finally give fisetin a try.

so far this thing is too much speculation not enough substance. of course, its costing money. huge hole in your pocket over time. while there is some senescent clearing thats free like fasting. i guess doing natural things like that is absolute no by the supplement junkie community.  not to say the least that nobody tests those batches for quality and percent of labeled ingredient. FDA continuously reports adulteration and fake ingredients in supplement industry. that is only IF fisetin were to actually work, most of you using it, wont even know if its even in your bottle.

ill also wait for aridibabar to continue and report his experimentation. 

Edited by Mind, 29 April 2019 - 05:16 PM.
Edited to remove mildly offensive terminology

[LarryG]

A note on using fisetin/water/PEG400/d-limonene to try to increase absorption of fisetin by decreasing particle size, as noted in studies.  Because d-limonene is too strong to use in a concentrated manner, I've experimented with different levels as follows....now I am using 3/4C of water, lemon juice, and stevia to make the d-limonene more palatable.  I put the fisetin into this mixture, then add 1/4t of both d-limonene and PEG400 (food grade) and you'll notice that the fisetin will go from floating a the top to dispersing into the liquid.  If you still have clumps of fisetin, you don't have enough d-limonene and PEG400.  I find this very easy to drink.  How much it increases absorption, if at all, I have no idea, but it is far more soluble and certainly decreases particle size form 1 giant clump to no clumps at all. 

[GABAergic]

"How much it increases absorption, if at all, I have no idea"

 

you know this sums it up

[LarryG]

One of the main problems with absorption is particle size.  It's a huge problem that limits many, many beneficial supplements....resveratrol, for instance.  There are other problems...for instance, bioperine (piperine) increases absorption because modifies the rate of glucuronidation by lowering the endogenous UDP-glucuronic acid content and also by inhibiting the transferase activity.  Berberine is great for blood sugar but is poorly absorbed because of P-glycoprotein, which is inhibited by milk thistle extract.  Fisetin degrades and one product of that process is fisetin glucuronides.  So, there is a lot that is not known yet.  There is good evidence for nano particles with the above recipe and that article was posted earlier in this thread my me.  My thought is this...although we don't yet have a study on improving absorption of fisetin by this means, it makes sense to me and costs little to dramatically decrease particle size, and add piperine at the same time to avoid glucuronidation.  Rosemary and fisetin are synergistic in the treatment of lung cancer, so I take rosemary at the same time, which is also cheap.  If it isn't affordable, it won't help a lot of people, which is why I mention the low cost of doing it this way.

[GABAergic]

what is the study you are referring to where rosemary and fisetin were used to threat lung cancer?  is this a reason why you combine this?

when i checked wikipedia it mentions the problems with bioavailibity when it comes to resveratrol, curcumin and various other bioactive plant chemicals and that scientists have tried to create their own versions that are bioavaible but those have caused too many side effects to be useful in medicine so they have all been abandoned. except of course the natural starting material thats still being sold as dietary supplements that make millions of dollars. but even if you have the money to throw away, with their low bioavailability and low toxic side effects at least they wont kill you.

now, if you and the other supplement junkies are now trying to enhance their bioavailibity through some methods you are basically trying to turn them into drugs that can have some potent activity in the body but that would cause toxicity and too many side effects just as scientists have found out already. dont think you are innovative in this department, its already been tried. why do you really want to do this? you must have a very good reason i hope. if you are healthy and young, i think you are just being stupid

Edited by GABAergic, 27 April 2019 - 02:25 AM.

[ambivalent]

An update:

 

Two days ago I entered in to my third dose of Fisetin, a couple of months or so since the last dose...………………………………………..

 

Further update: I have a definite cold now, not too heavy but quite obvious. Whether it is just a cold that has tacked on to the end of the fisetin symptoms or is an expression still of the effects of the senescent cell clearance, naturally I don't know.

 

My knee is pretty strong but there are confounding factors such as stearic acid + allicin, NMN, NR. But the strengthening of the knee after initial weakening is consistent with other fisetin experiences. The recovery seems quicker this time, and the pain was not as significant as certainly it was the first time.  

 

Additionally, my 72 year old mum took 400mg with olive oil a few days ago before bed and awoke to a modest cold lasting a day or two. This happened previously at lower doses too. The post-fisetin runny nose has happened too with my father and friend. Also said friend has reported on occasion a noticeable sharpness post-fisetin. 

 

It will be interesting to see if anyone wishes to repeat what I've done, this definitely produced different effects from previous the previous two doses. Naturally at some point I will do this again with a not excessive dose increase.

[GABAergic]

ambivalent, if you want i can see how it affects me too if you have some to spare. ill keep a tight report and remove all other things that might interfere. that is of course if you are interested in others and how they react to it. i really do not have enough interest for myself to go and buy this. but if someone like you wants to know how others feel on this and is interested in reports, you might as well help me out and i will help you out

[ambivalent]

Gaba, I have a imited supply currently. I have to say you spend an awful ot of time on this thread for someone who's not that interested in Fisetin. It's not that expensive to repeat my endeavour (though perhaps too risky first out):

 

https://www.swansonv...-mg-30-veg-caps

 

Then at least you can contribute from an experiential perspective.

Edited by ambivalent, 28 April 2019 - 08:18 PM.

[LarryG]

Here's an article that proves that very small particle size improves absorption.  In this case, by using b-cyclodextrin and other materials.  PLGA, PLG, or poly(lactic-co-glycolic acid) is biodegradable and FDA approved for safety.    But, "Herein, we have prepared FST-hydroxyl propyl beta cyclodextrin (HPβCD) inclusion complex (FHIC) to increase the aqueous solubility of FST followed by incorporation in polymeric-based nanoparticles. Cyclodextrin derivatives are well known for their ability to enhance the solubility of poorly water soluble compounds. Additionally, cyclodextrins inhibit the p-gp, responsible for drug efflux and cytochrome P450, responsible for drug metabolism that assists in enhanced oral bioavailability. Among cyclodextrin derivatives, HPβCD has the highest drug solubilizing capability along with least toxicity."  If anyone finds a ready source of PGLA, please post.  If not, then making a b-cyclodextrin/PEG400/water/ethanol (as wine) solution would be easy and cheap.  https://www.tandfonl...44.2016.1245366

 

[GABAergic]

im not buying anything from swanson. there is a reason its so cheap you know? there were several independent lab tests done and swanson is always at the bottom of quality. i posted a reddit on this forum recently on a lab test on one of their supplements and it scored low, same with NowFoods. i cant remember which thread it was, its like a week ago now. anyway, if you do your own research you will see for yourself. the other choice it seems to be dr's best which i dont really like much either. and the only fisetin on the market is that novusetin isolated from japanese wax tree. same with resveratrol, isolated from an obnoxious weed. both are things you do not want to deal with and put in your system.

Gaba, I have a imited supply currently. I have to say you spend an awful ot of time on this thread for someone who's not that interested in Fisetin. It's not that expensive to repeat my endeavour (though perhaps too risky first out):

 

https://www.swansonv...-mg-30-veg-caps

 

Then at least you can contribute from an experiential perspective.

 

 

[ambivalent]

Then its not clear why you requested fisetin from me if you believe no product meets your safety standards. I've had positive effects using Swanson, one risky downside consistent with senolytics; however, if you're not interested in fisetin then just move on to another supplement. 

[LarryG]

Along the line of improving absorption of fisetin inexpensively, it turns out that quercetin, a cousin with the same solubility/absorption problems...absorption/solubility is improved by dissolving it in water and stevia.  Keep in mind that a lot of commercial stevia is  Rebaudiosides, but it's not the only one that works, but it does work.  I assume that the reason for this is that forming glycosides of flavonoids improves their absorption, and stevia does exactly that when mixed with quercetin and water.  "CONCLUSIONS: The present study demonstrated that quercetin can be solubilized in water with rebaudioside or rubusoside treatment. As Ru concentration increases, the solubility of quercetin in water increases. Interestingly, the solubilization of quercetin in Ru solution did not reduce its biological functions such as the DPPH radical-scavenging and mushroom tyrosinase activity.  Additionally, Q-Ru increased the inhibition activity against the 3CL pro of SARS and human intestinal maltase, when compared with the activity of quercetin in DMSO. Therefore, Ru and rebaudioside are promising compounds which enhance the solubility of poorly water soluble compounds (including quercetin, rutin and astragallin)."  The same could be said for fisetin.  I ordered and have on hand stevia extract from Pure Bulk and paid $10 for 100 grams.  The PDF of the study is here: https://www.google.c...VhCcGAxbdDeGhbu

[LarryG]

On forming glucoside to improve absorption: "Thus, the sugar moiety of quercetin glycosides seemed to be an important determinant of their bioavailability, which was confirmed when pure quercetin-b-glucoside or pure quercetin-b-rutinoside was administered to healthy human volunteers (Hollmanet al., 1999). The peak concentration of quercetin (Cmax)in plasma was 20-times higher and reached (Tmax) more than 10-times faster after intake of the glucoside than after the rutinoside."  This is very likely true of fisetin, so tomorrow I'll do the fisetin 2g/water/stevia extract trial.

[LarryG]

Maybe not.....this study concluded "Urinary excretion of <1% confirms that flavone C-glycosides are poorly absorbed (136), and 10–88%recovery from feces indicates that they may be resistant to degradation by gut bacteria in rats (136, 138). As with flavoneO-glycosides, the C-glycosides are less bioavailable inhumans than in rats (Table 7)."  That doesn't sound good for stevia/fisetin/water to improve absorption.  This needs for investigation.

[cjacek]

Sorry if this was discussed before or is off topic but what do you guys think of the supplement called Senex by a company called Life Code? The product has a number of ingredients in it including Fisetin AND Piperlongumine! 

[GABAergic]

Then its not clear why you requested fisetin from me if you believe no product meets your safety standards. I've had positive effects using Swanson, one risky downside consistent with senolytics; however, if you're not interested in fisetin then just move on to another supplement.

i thought you brought it 99% pure from a lab like sigma aldrich and the likes which do not directly sell to consumers. i hope someone does order from such well established and regulated place, and distribute it among its peers. its not that most products on the market do not meet MY standards, its that they have been tested by independent labs to not meet general standards for amount and quality. since you can take "senolyitics" for the rest of your life and wont know if it works or not, its the easiest place to be scammed. but if you really believe swanson works for you and you have the money to waste, then you made up your mind.

Edited by GABAergic, 30 April 2019 - 12:25 AM.

[maxwatt]

i thought you brought it 99% pure from a lab like sigma aldrich and the likes which do not directly sell to consumers. i hope someone does order from such well established and regulated place, and distribute it among its peers. its not that most products on the market do not meet MY standards, its that they have been tested by independent labs to not meet general standards for amount and quality. since you can take "senolyitics" for the rest of your life and wont know if it works or not, its the easiest place to be scammed. but if you really believe swanson works for you and you have the money to waste, then you made up your mind.

 

If it truly kills the majority of senescent cells, I would expect some benefits would be immediately obvious.

[ambivalent]

I am unlikely to be wasting my money when I and others have demonstrated very clear effects consistent with senoytic activity. It is true that I can't prove cells have cleared; however, as I reported very stubborn allergic cough cleared overnight, when little would alleviate it  (this was quite amazing_.* Also, I no longer reacted and still don't to red wine. I nicked a small wart while shaving and bled for 5 hours (delayed wound healing), my arthritic knee weakened considerable after the dose and then strengthened (likely cell clearance). Of the three people I have given it to all have experienced runny noses at small doses, I have experienced greater but not severe flu like symptoms at much higher doses. Combined with DMSO it had strong ex-foliating properties. I appear to no longer experience what I would describe as a waking apnea. There may be another modest benefit which I am not sure enough to report, which might become clearer over time. 

 

If there were no metrics beyond measuring senescent cell levels, then I would agree with you, it is too important to trust to blind faith - go with a reliable source. In fact I may well do in the future, however, at the moment I am experiencing clear effects at a cheap price and I like many have spent a ton on experimentation. Its a cheap entry point, its unlikely to be the complete senolytic solution. I've experimented with 3, 4 and 5 grams of Swansons Fisetin with some very clear effects, there is little more for me to add.

 

 

 

*there is a link earlier in the thread demonstrating fisetin has this effect

Edited by ambivalent, 30 April 2019 - 02:13 AM.

[LarryG]

As to Senex, the reason I passed on it is the "formula", really the ingredients, are stated as a blend so that you have no idea how much of each is included.  I see no fisetin.  I see Piper Longum extract but not how much actual piperlongamine it contains.  It's pointless and smacks of a con since any piper longum contains some piperlongamine.  It's the third ingredient as it is.  The rest of the ingredients....are there any studies showing that they have a senolytic effect?  It's a lot of money for garden variety ingredients.  I really question this company...they sell a product called Stem Cell 100+, which subliminally gives the message that you'll live over 100 years if you take it, costs $74.99 for 60 pills.  The ingredients are common and not expensive, but in this form, it is unlikely that you could get effective doses of them, and it's expensive AND likely not effective in humans (as opposed to fruit flies)  As to fisetin and senolytics generally, we are in the infancy of the science, and much is yet to be discovered, but I'm 74 and I don't think I'll wait passively for 10 years until someone brings a product to market that has studies to prove it works in humans.  The cutting edge is studies on living patients now who have nothing to lose by trying senolytics and we know their health dramatically improved.  So, I will do what seems best, given what we know now, and I'll change as the information changes.  I can do no more.

[cjacek]

@ LarryG Thanks for answering my question about Senex. Much appreciated. I do understand what you're saying especially about not knowing exactly what's in there and in what amounts. They do mention "Fisetin" as an "extract from the branches of Cotinus coggygria" above the supplement facts label but on label it says "extract from the branches of Cotinus coggygria". But, again, it does prove the point that you've made that there's really no way to know precisely what's in there.   

[GABAergic]

i was also wondering for those who do take the questionably efficient fisetin, are you planning to take it for the rest of your lives? BECAUSE you know, since there is not a single supplement or drug now or any time in the near future that will cause permanent positive change without side effects and without the need to redose and eventually being dependent, as in addicted. but is it really worth taking any supplement, in this case fisetin, for the rest of your life??

i mean, you will say well i just want to clear some senescent cells now and ill stop any time. im not sure thats how it works tho

Edited by GABAergic, 01 May 2019 - 02:04 AM.

[GABAergic]

whoever put needs references, you give me references of a drug or any supplement that will cause perm change in a positive way for the rest of your life please. that is, without the need to redose or continue regime

Edited by GABAergic, 01 May 2019 - 02:05 AM.

[Woody42]

About a month ago I took 500mg of fisetin ( I thought it was 1000 mg but it was only 50% pure )  

500mg turmeric and 500mg quercetin mixed in a few ml of DMSO , lecethin, olive oil and water for 5 days. 

I was also doing a very low calorie almost protein free diet at he time.  Oh have also taken ppq, berberine 

leutin and nicotinamide riboside.  So I don't know if it was the fisetin   or all that other stuff that has reversed

a lot of my age and noise associated high frequency hearing loss.  

[ambivalent]

About a month ago I took 500mg of fisetin ( I thought it was 1000 mg but it was only 50% pure )  

500mg turmeric and 500mg quercetin mixed in a few ml of DMSO , lecethin, olive oil and water for 5 days. 

I was also doing a very low calorie almost protein free diet at he time.  Oh have also taken ppq, berberine 

leutin and nicotinamide riboside.  So I don't know if it was the fisetin   or all that other stuff that has reversed

a lot of my age and noise associated high frequency hearing loss.  

 

 

Thats interesting, I assume its a subjective observation?  I tested crudely using an online frequency generator just the other day and coudn't say I noticed an improvement, my tinitus has been more noticeabe the last couple of days. I may add querceitin and DMSO next time , though probaby all in one shot. Did you experince anything else, such as mild flu symptoms, changes in skin?

[Woody42]

I have my own audio oscillator,  I started taking 25mg of zinc a day a few years ago

and my tinnitus very slowly cleared up.

[ambivalent]

I have my own audio oscillator,  I started taking 25mg of zinc a day a few years ago

and my tinnitus very slowly cleared up.

 

Thanks for that, I started taking zinc towards the end of last year and hadn't paid attention to the improvement - I've dropped off it a bit lately so that might account for it. 

 

Could you define the range improvement experienced?

Edited by ambivalent, 03 May 2019 - 05:57 PM.

[Ducky-001]

i was also wondering for those who do take the questionably efficient fisetin, are you planning to take it for the rest of your lives?

 

At any given time I will take whatever I think it's the best thing currently on market for a reasonable price. I do not expect that to be Fisetin for the rest of my life since things are moving very fast in this branch of science at the moment. I just got a huge load of Fisetin from Revgenetics, maybe that was the last load I ever needed because something better is on the market when I'm finished with it.?