Fisetin experimentation one year (reposted as topic for info purposes)
Hello everyone I wanted to make my first post here as I have been doing a fisetin routine for a year now just about and I have results that are not placebo and very profound. I honestly do not know if this is the senylotic effect or some kind of interaction with fisetin in other ways.
To get it out of the way, I will give the fast and short version. I am taking Swanson’s Fisetin. I take around 2g a day for 3 days( now 2.5g). I repeat this for 3 or 4 times with varying intervals (I was trying to find optimal intervals).
My my first regimen was 3 days treatment with a 2 week delay, then a 3 week delay, then a 4 week delay, then a 2 month delay. I am now convinced a 3 week delay is the minimal amount of time you want taking this the way I am, though I will continue with 4 week delay for safety sake and because of my own observations.
So results. Well I feel like this must play on hormone levels in the short term. Immediately after starting a 3 day regimen, usually on day 2 or 3 I feel strong as hell. In particular my legs are tight and super strong. My muscles in general are firmer and overall strength is amazing. My mind is clear, thinking concise anddynamic. I feel more dominant, self confident, and aggressive. Libido is enhanced as well. This all led me to believe that this acts as a testosterone mimic or elevates testosterone in the blood which is why I cycle monthly and then take a few months off every so often.
i can tell you that at the age of 43 this makes me legitimately remember what early 20s feels like. The effects of one 3 day regimen last strongly for 2 weeks and even on for 4 weeks. In particular during week one and two I was amazed at the amount of pure emotion and clarity of the world around me. I could hear and appreciate sounds and colors seemed more vibrant. Mentally I am on overdrive with super memory and crystal clear logical thinking. I remember the first time I took this I was shocked. I was in a cafe just looking at a coke I had bought in a glass amazed at how more real and present it looked. A small thing but it was profound just how the world seemed more alive. It literally felt like going back in time 20 years.
So for long term effects. A stronger posture, better muscle tone, improved gum health, vastly more energy, in fact this has become all the norm after around 8 months of this. Many of the effects I described in the first two weeks following a 3 day regimen do taper off to an extent, but never completely.
As far as side effects there has not been anything thus far. When you are taking the 3 day dose you might get amped up a little jittery but that gives way quickly after the last dosage and it normalizes into a even effect that is positive in nature. I was very concerned about hair loss as I could not believe how impactful this was. But I have noticed no hair loss at all. I cycle it with a 3 or 4 week break to ensure that there is no negative effect on hair or otherwise. With a two week interval I had some scalp itchiness. That was enough to back me off to to four week intervals.
I honestly think that most of what I experienced is not the senylotic effect. It’s way too fast and profound. But I have no ill effects and feel incredible. And overall I have a youthful vigor and look and feel younger. I think a senylotic evaluation, as far as a laymen just observing himself goes ,can only really be done after 2 years or so. However the initial results ( especially gum health) and from what else I can observe are overwhelmingly positive.
I can tell you that this does have an affect and it is profound and noticeable. How much of this is hormone I do not know. But I have other improved health as well, however it’s always tricky to quantify this objectively yourself sometimes.
Good luck on your experiments. Let me know if this has the same effect for you. I just bought Swanson’s with nouvestein. Nothing fancy. Cheap and on amazon.
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so, if someone claims testosterone is increased via fisetin, take a blood test and show results. Guessing is for the artists, not the scientists
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Fred Cloud I would like to see his entire regimen before reaching any conclusions. All the improvements mentioned are impossible by fisetin alone. So yeah, I don't buy his version of events.
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aribadabar Like I said, he isnt the only one saying they are getting improvements on senolytics in their 40's. Are you going to reject all the others too?
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Fred Cloud If they ALSO do TRT, HGH and all other exotic interventions that they fail to mention, yeah, I will reject that fisetin is responsible for these improvements. It is good but not THAT good.
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aribadabar Aribadabar, I have been doing HRT ( Testosterone) DHEA-S, pregnenolone for the past 20+ years. Do not do HGH as my IGF-1 is marginally OK.
The use of these steroids are not responsible for the almost instantaneous increase in the benefits I realized in June, 2020 after my first use of fisetin following the Mayo protocol. I think your initial consideration that the benefits were due to some kind of mitochondria enhancement is the best "guess". I also think it was unlikely the initial benefits were due to elimination of senescent cells as these benefits occurred within a day after completing my first dose (comment for Fred). This is not to say that fisetin does not remove senescent cells. It certainly does based on the literature which indicates that it can remove 4 of the 6 main types of senescent cells.
It is also a mTOR1 inhibitor which causes me some concern at my age. If I remove a large number of senescent cells in the interest of alleviating senior frailty, there is limited data to suggest that this may not be advisable in that I may need mTOR1. There is beginning to be a limited number of publications which suggest this may be the case and I may need mTOR.
As a great mind once said: everything changes and nothing changes.
Have a nice holiday.
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Peter H. Howe Hey Peter, the opposite is true about the mTOR signal - it increases with age and thus needs to be suppressed more which is why senior people have been taking higher Rapamycin doses than the younger ones. You do need SOME mTOR but without inhibition is much more than you really need for healthy aging and you definitely don't need an mTOR boost.
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@aribadabaYour post is accurate up to a point.
There is literature to suggest that inhibition is not good in old age. See attached. Note authors recommend stimulating mTOR, in part with omega 3 fatty acid to correct sarcopenia. There are more examples if you search.
@https://link.springer.com/article/10.1007/s40520-019-01146-1r
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Peter H. Howe They hypothesize that Omega-e FFAs increase mTOR and that's how they try to explain the anabolic effect. Looking at the papers they base that HYPOTHESIS on, none of them cite mTOR as the reason. I.e. it's a guess, not a scientific fact. You do need some mTOR for muscle building/maintenance and to avoid sarcopenia no doubt but saying that it is done via mTOR activation due to Omega-3 supplementation is a stretch at this point. Protein consumption does boost mTOR, O3 one - not really.
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Peter H. Howe For overall health , it is best to have short mTOR bursts during muscle building exercises as opposed to constant strong mTOR signalling which is unquestionably deleterious.
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aribadabar It is a point and it is really.. As I said, there are multiple papers on this issue. Attached is another one dealing with exercise, stimulation of mTOR and eliminating frailty. It has multiple references on this topic. There are many more, some of which deal with protein as indicated in the first paper along with O3.
https://journals.physiology.org/doi/full/10.1152/japplphysiol.01266.2009.
Point is stimulation of mTOR for treatment of frailty in seniors is beneficial.
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Peter H. Howe And I don't reject that point, I just go further into its nuanced understanding i.e. the mTOR activation needs to be pulsatile, not continuous, to get the benefit without the detriment.
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aribadabar Now we are going to discuss strong vs weak? What about protein in seniors. Again increase consumption from ~.5 gm in middle age to 1-2gm/kg to stimulate mTOR and muscle growth. Give you some papers on this also.
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Peter H. Howe It's a tradeoff. Frailty vs. inflammation/oncogenesis/oncoproliferation. One has to decide what's more important for them. For myself, frailty is of lower priority to the other issues.
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David C Not only is fisetin a senolytic but it also acts as an MTor inhibitor.
So this may explain the profound effects you are getting beyond what may be explained from strictly senolytic activity.
Not sure how it compares to rapamycin in its ability to inhibit mtor but it would be an interesting study to compare them.
Have you tried rapamycin to compare the effects?
Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin
https://pubmed.ncbi.nlm.nih.gov/23293889/
Fisetin regulates obesity by targeting mTORC1 signaling
https://pubmed.ncbi.nlm.nih.gov/23517912/
studies have suggested that fisetin inhibits mTOR activity through direct binding
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Fred Cloud Wow amazing stuff... might explain my placebo results.... LOL
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So, my 2 day of 1.5g of bulk fisetin extract, 98% from cotinus, Chinese origin. Yellow-brown powder.
Tried the buttermilk, yes, it dissolves quite well, after waiting 1.5hr and some occasional stirring.
I am 33 years old, with hypertension and on valsartan.
During the first day, no side fx noted. Blood pressure systolic around 7-9 units lower than usual hour after taking it, dia 5-6 lower, so no significant interaction.
A bit up and hard to fall asleep, but can be placebo.
On the next day, notably more stamina and energy, very energetic and active physically. Like on caffeine. A bit elevated pulse. Definitely not a placebo, as I've experimented with some other substances which claim energy boost, no such result there.
Did not notice any dry mouth or anything of a sort.
Will continue for two more days.
As I am relatively young, senolytic effect was not a main priority, but mainly - chemopreventive (I am a smoker), improving heart condition and overall health, have some bowel issues. Also, a bit of rejuvenation expected as well, as after 30, you anyway start notice some aging effects.
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Andrew Whitfield Did I
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JGC
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Andrew Whitfield
I am doubtful if the Fisetin powder actually dissolved in buttermilk, as opposed to going into suspension. The distinction makes a big difference in whether it was present in good concentration later in your bloodstream.
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JGC
Well, maybe the suspension case. I am no expert. What I was able to observe is that no powder or chunks remained in my cup and buttermilk became yellowish.
About the bloodstream concentrations - can you be more specific, like what is what in each case, and suggest your own alternative or better approach, if any?
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JGC
If you have any good advice and relevant experience to share, it is appreciated
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Andrew Whitfield
The problem is that flavenoids like Fisetin, Quercetin, and Curcumin are fairly insoluble in water, and only slightly more soluble in oils. (They are more soluble in ethyl alcohol, but you would have to imbibe a dangerously large amount of alcohol to get a suitably high level dose of the flavenoid.) There are some work-arounds for this problem, but none are easily achieved. I tried taking 10 caps of LifeExtension's Bio-Fisetin (which is supposed to be 25 times more bioavailable). However, based on my body's lack of response, I am not convinced that it delivered the dose level needed to clear senescent cells.
The alternative is to just take a big enough dose of Fisetin to get a senolytic-level concentration in the blood stream. My wife and I have done that several times by stirring 2 grams of Fisetin powder into a jigger glass of olive oil which has previously been warmed by 1 minute in the microwave. This produces a mustard-colored suspension. We drink it and scoop the residue out of the glass with bread fragments. I guess there are some oils in buttermilk, but the main liquid is water and I would not expect it to dissolve as large a fraction of the Fisetin as warm olive oil would.
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JGC Thanks for the tip! I will try your approach with oil on my next round, after a month.
For now, I've completed 4 days of 1.5g. On the last one I've tried putting it into 35% dairy cream. Visually it dissolved pretty well.
Not much effects to report this time.
Ordered some more 99% from AliExpress. Risking a bit regarding the quality, but 50g is just 22 dollars. And they put screens of CoA there, kind of.
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So I will add one more thing. My sugar cravings have completely vanished. I was eating a lot of sweets routinely. And it was noticeable early on but I never gave it much thought. However I don't crave sweets anymore. And my health overall has improved. I think I had the beginnings of diabetes. And this stuff got rid of a lot of the senescent cells that are postulated to cause diabetes.
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Guys, anyway knows a way to easily distinguish what is fisetin and what is not?
I've ordered some with a Chinese supplier. One was obviously a scam, with some curcuma taste.
Now I've got the other. It is fine yellow powder with a bit greenish hue, from cotinus. With CoA of 99%. Well, this one IS the most bitter tasting thing I've ever tested on my tongue! It is quite stainy, and smells musty.
But what puzzles me, is that Doctor's Best is not bitter at all.
Do you have any experience/ideas of how to figure this out?
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Andrew Whitfield
The bitterness is suspicious. To be really sure, you need to have a sample tested by a lab that does HPLC-mass-spectroscopy. Fisetin has a molecular mass of 286.2363 g/mol, and the mass spectrum should show a big peak there and nowhere else.
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