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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John, I believe I remember that you are 74 or 75. Please correct me if I'm wrong!
Reading your description of your max achievable heart rates before and very shortly after ingesting fisetin, and knowing a bit about the pharmacology of fisetin, AND using my background of 40 yrs coaching endurance runners, and a decade as a USA triathlon coach and having run an endurance athlete coaching business for 15 yrs ... I have a few questions & comments.
A. In males in their mid 70s who exercise regularly, max heart rate is quite variable from person to person, ranging from about 155 to 170 or so, BUT it is also VERY consistent over many weeks in any one person unless affected by known issues like heat, dehydration, drugs, etc... So Why does your max vary by almost 20 % after taking your fisetin? I've witnessed that in coaching clients, but only with stimulants (which are both possibly dangerous, & also illegal in competition)
B. I'm concerned about whether or not the OTC fisetin you are taking might contain another substance responsible for your almost immediate change in performance. I've previously expressed my concern about taking fisetin from an industry that basically almost never provides verification thru assay of the content or quality of what they sell, AND what we almost all take regularly. Several university pharmacology studies of OTC supplements have shown wide variation in the actual content. In one study, the majority of the Walmart house brand supplements contained little or none of the compound listed on the label.
C. as I am sure you must know, one issue we all have to sort out in the quest for this component of the fountain of youth, is both the nocibo and the placibo effects. I've previously expressed in this blog site, that I'm dubious of folks reporting immediate effects of drugs like fisetin on aerobic performance, strength, etc... when the physiology of what's happening inside of us when we ingest fisetin should take at least some days, weeks or even months to become evident.
D. I'll site one well known example for our collective education of the fact that supplements we are all taking are not necessarily what they seem or are marketed to be. In the past Hammer Nutrition was producing an electrolyte supplement called Endurolytes that was extremely popular, especially in long distance triathlon were I raced and coached. I trained, recommended them to clients, and raced with them for about 15 yrs. At least 17 or18 yrs ago, as I recollect, two pro triathletes failed post race urine drug tests for illegal steroids. This resulted in two yr suspensions for them, thus ruining their careers as athletes. Extensive investigation revealed a number of production runs of Endurolytes (including some of ours) were in fact contaminated with an illegal androgenic steroid widely sold on the dark web to weightlifters.... The cause was Hammer nutrition outsourcing to a company that basically puts your drug or supplement into capsules fro a price. That company was not cleaning their capsule making machine between runs for different customers. Hammer Nutrition's runs were after a run for the steroid discovered in the investigation, thus the contamination. We, and our clients at the time all went rather faster, and were all just lucky that urine post race drug testing is (even today) almost never seen in amateur triathlon worldwide
This and other similar issues are why I posed the general question to this blog in the past.... Does anyone know a company selling fisetin w quality ensured by assay.... The answer so far has been "crickets"
Allen DeLaney
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Fred Cloud thank you for the helpful information. That encourages me continue taking it as I do enjoy the boost in athletic performance as I like my pulse to be at least in the 150s when working on the bicycle.
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Fred Cloud s
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Allen DeLaney
Fred, So, if I umderstand you correctly, The Mayo Climic studies got it all wrong w their senolytic dosing intervals because the senolytic effects dissapate or resolve after 2 weeks, & the senolytic celks really weren't killed...
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Fred Cloud
Fred, could you please supply a reference or article for 'the known effect of boost in performance' from ingesting a senolytic' I haven't come across any science supporting this purported immediate effect.. I must be looking in the wrong place...
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Allen DeLaney It looks like you are dealing with some personal struggles Allen, I wish you the best.
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Fred Cloud Thanks for sharing your anecdotal evidence, Fred. I should share mine as well, so here goes.
My own anecdote is different in that I haven't yet been able to clearly correlate (without highly suspecting intervening variables) any boosts in performance with my ingestion of senolytics, which is typically at least a monthly double strength dose of Life Extension's Senolytic Activator along with relatively high doses of a few other possibly senolytic (by preliminary evidence) supplements such as grape seed extract, gingko biloba, etc.
An example of something that I have more clearly correlated, not surprisingly, is the lowering of my resting heart rate with my increased number of daily minutes of vigorous exercise (at roughly 90% [?] of my maximum heart rate). I controlled as much as reasonably possible for confounding variables.
We're all different, of course, which could be one explanation. I'm a quite healthy semi-retired 72 year old, but no doubt have (or had?) a fair number of senescent cells. Perhaps I'll eventually see a senolytic ingestion/performance boost correlation in myself. Or maybe not!
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Allen DeLaney Brian Valerie We may be assuming the wrong action of Fisetin. People have written since 2011 about Fisetin "killing" senescent cells by making them targets of the cell cleanup machinery. But what if fisetin simply shuts down the production of the harmful SASP that those cells secrete?
I just read this at FightAging.org about fisetin: "Fisetin has the potential to reduce senescence markers in multiple tissues in murine and human subjects." The bold type is mine. So maybe these researchers found that the Markers of senecence were reduced but did not go looking for individual senecent cells (which is probably very difficult).
This would go a long way to explain why several people here seem to get almost immediate results from Fisetin and seem to need to repeat the treatments every 2 to 3 weeks.
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Dean W.
As I recall, the Mayo Clinic work identified Fisetin and D+Q as senolytics, i.e., senescent cell killers, in part by observing cultures of human cells that had been made senescent by X-rays and then killed by applying a test senolytic to the cell culture. (There are other things that suppress SASP, but Fisetin and D+Q do not.) That cell culture test on many possible molecules is how they identified Fisetin as a senolytic in the first pace.
Further, there is the subjective evidence that those of us who do periodic senolytic sessions experience symptoms for a day or so that resemble coming down with the flu. Shutting off SASP would not be expected to produce those, while dumping the residue of killed cells into the bloodstream should.
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JGC All good info. Personally, I have not read about anyone getting flu-like symptoms and I have experienced zero change after completing 3 days of fisetin at 30 mg/kg a day. For the past 3 years, twice a year. I am old enough to have senecent cells too.
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Dean W. You might need to do it once a month to really get results. Many people when they first start out do get flu-like symptoms or it just feel weirded out. I'm not sure if flu like symptoms is actually what you would call it. But definitely something where you feel a little off center. Now I just feel better with less pain in my joints and I can do a better yoga with more bending etc lots of little things that show a difference
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Dean W.
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Dean W. Also you might try the dasatinib combined with a question which was the original Mayo study. I mix that into the mix. I do that first and then a couple 3 hours later I do the fisetin large doses like you...
You can start off with 50 mg of dasatinib but always get approval from your doctor first,.... Hopefully they'll come out with a special with something that is not a cancer drug although this is a relatively mild one and well researched as people use this one for many years when they have leukemia so it's one of the more benign ones but you never know everybody's reaction can be different
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garland woops u mix the dasatinib with the quercetin to start off with.... You might try the ones from Life extension as they stay in the system a lot longer
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garland Yes, as part of my senolytic protocol I use the Life Extension Senolytic Activator, which they say contains "ultra-absorbable" forms of quercetin and fisetin, along with apigenin, and substitutes relatively benign tea leaf extract theaflavins for the dasatinib, but only provides references to what seems to me rather less than particularly meaningful preliminary evidence that these theaflavins, while evidently senolytic, are as effective to use with quercetin as is dasatinib.
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garland Thanks for the suggestions. I will try it once every 2 months for awhile. I am a bit leary because a recent study found a slight increase in epigenetic age after taking fisetin with or without D+Q. (see https://www.fightaging.org/archives/2024/03/human-data-on-epigenetic-age-following-senolytic-treatment/ )
My doctor will not prescribe dasatinib for me. She is very worried about any off-label prescription writing. I need a new doctor and so I am looking for a doc who keeps up with the latest science.
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Dean W. In defense of your doctor, very, very few doctors will prescribe off-label dasatinib (or rapamycin). It's not because they're necessarily unaware of the research either, which most of them (and I) see as still in a rather preliminary stage, but many no doubt fear that a future malpractice lawsuit may actually have legal merit. I'm okay with waiting what may well be only another year or two for further evidence from the significant amount of currently ongoing research. In the case of rapamycin, some of its analogs ("rapalogs") that are being researched have given hope of potentially being more effective and/or safe for long-term use than rapamycin itself.
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Brian Valerie I forgot to mention that I use 24 mgs of fisetin about 3 hours after I do the dasatinib quercetin combo. i use the one from Life Extension which stays in your system for many more hours.....I like the Fisetin more than the other combo.... seems to add a sparkle to my life...
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IMPORTANT DASATINIB SUBSTITUTES UPDATE! Just published: Meiners, et al., "Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data", Scientific Reports, 14, 6286 (2024). I quote from lifespan.io: "Unfortunately, dasatinib activity frequently leads to adverse side effects, such as skin irritation, fluid retention, reduction in blood cell production, and diarrhea....the authors used computational approaches to identify natural senotherapeutic candidates that have similar properties to dasatinib....these included piperlongumine, parthenolide, curcumin, and phloretin, with piperlongumine [found in long pepper] being the most promising candidate." I find it interesting that Life Extension's Senolytic Activator's (which I use and which garland suggested to Dean W. ) substitute for dasatinib, black tea theaflavins, was not identified.
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Brian Valerie Thanks, Brian. Good to know someone has looked into this. I always wondered why Life Extension thought black tea theaflavins would be a substitute for dasatinib. There is nothing in the literature that I could find which supports it. I tried one bottle a while ago with no noticable effects.
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Brian Valerie I see that Amazon sells one pound jars of Long Pepper seeds for about $25. I found that an extract of the seeds with methanol yields 99.3% piperlongumine:
"Together with their analytical characteristics, the P. longum fruit extract analytically characterized to contain 1.75% piperine (PLE) and almost pure piperlongumine (99.33%) isolated from P. longum roots used in this study were generously supplied by Sami Labs Limited, Bengaluru, India. The extract PLE is a methanolic extract of dried and powdered fruits of P. longum fruits and purity of piperlongumine and piperine contents of the PLE sample were established by HPLC using acetonitrile and water as mobile phase."
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Dean W. That quote is from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067934/
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Dean W. Thanks for sharing that, Dean. Another alternative on Amazon is CellFend brand fermented (to increase bioavailability) long pepper extract capsules, with 10 mg of piperlongumine per two capsule serving. I have a subscription from Amazon for this product for which I pay $22.91 for a bottle of 60 capsules.
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Brian Valerie Piperlongumine is fascinating.
"PL is a natural product that is reported to have many pharmacological effects, including anti-tumor activity. We show here that PL preferentially killed senescent human WI-38 fibroblasts when senescence was induced by ionizing radiation, replicative exhaustion, or ectopic expression of the oncogene Ras. PL killed SCs by inducing apoptosis, and this process did not require the induction of reactive oxygen species. In addition, we found that PL synergistically killed SCs in combination with ABT-263"
"Androgen receptor (AR) signaling is regarded as the driving force in prostate carcinogenesis"
"RESULTS
The results of our experiments demonstrate that PL rapidly reduces AR protein levels in PC cells via proteasome-mediated ROS-dependent mechanism. Moreover, PL effectively depletes a modified AR lacking the ligand-binding domain, shedding light on a new paradigm in the treatment approach to prostatic carcinoma that expresses mutated constitutively active AR. Importantly, PL effectively depletes AR in prostate cancer cells at low micromolar concentrations, while concurrently exerting a significant inhibitory effect on AR transcriptional activity and proliferation of prostate cancer cells.CONCLUSIONS
Our investigation demonstrates for the first time that PL induces rapid depletion of the AR in prostate cancer cells. As such, PL may afford novel opportunities for both prevention and treatment of prostatic malignancy." -
Staffan Olsson Thanks for sharing this truly fascinating info, Staffan. My best guess is that PL will also prove to have fewer side effects than dasatinib.
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Allen DeLaney said:
Walmart house brand supplements contained little or none of the compound listedAllen, can you please provide a link for this study? I agree that there is far too little verification of supplements. I also question the few here that claim immediate benefits of fisetin. I'd think that killing senecent cells and replacing them with new ones would take weeks or more. Personally I have yet to feel any diffierent after taking 3 day doses of 2+ grams of fisetin, 6 months apart.
