Fisetin to Clear Senescent Cells

Following studies with mice that showed significant senolytic clearance of senescent cells following large doses of the readily available flavenoid supplement Fisetin,  my wife and I (ages 79 and 84) decided to try it.  We have just completed two sets of massive Fisetin doses.

We had Life Extension blood-work done in October before the start, and we will have more again next week to observe any changes.  The first set of Fisetin doses was on October 22-25 with 800 mg/day for three days followed by 600 mg on the fourth day, for a total of 4 g.  I didn't notice much in the way of effects.  Perhaps some reduction of small aches and pains and some increase in energy and mental acuity.

For the second set of doses done November 22-26, since we experienced no negative side effects in the first set we decided to increase the dosage a bit and to add 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids.  For five days starting on Thanksgiving we took 500 mg of Fisetin and 10 mg of BioPerine twice per day, for a total of 5 g of Fisetin.

This time. I did experience one negative side effect.  A few months ago, about 2 AM in the morning I awoke from a deep sleep and experienced a severe episode of vertigo.   I turned over in bed, and the the whole room seemed to tilt.  Suddenly, I didn't know which way was up.  I staggered to the bathroom and vomited.  The symptoms tapered off and disappeared in a few days, but it was a very distributing experience.

On the 2nd day of our 2nd Fisetin series, I experience a recurrence of that vertigo in the middle of the night, not as bad as my initial experience but still rather disturbing.  I tolerated this mild vertigo and continued the treatment.  My wife had no similar symptoms, and after my last dose I experienced no further vertigo symptoms.

On the positive side, following the second set of dosages I did feel very well, and very sharp and alert.  This past weekend I ran my Shetland Sheepdog Taliesin in an AKC Canine Agility Trial in Mt. Vernon, WA, and we did very well, qualifying in 7 runs out of 15 and getting various colored placement ribbons.  I was feeling quite sharp, and I even invented a new dog-handling technique that fixed an ongoing problem we were having.

Next week we will do the blood-work again, and I'll report any changes.

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  • I am 42 years old.  I just finished 1500mg of fisetin for 5 days.  No issues.  Urine was a little foamy the first couple of days.  I plan to do this once every 2-6 months.

    Like 2
      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
      • Reported - view

      Jimmy2 Did you notice any changes? Why not do it monthly like the mayo protocol and other users here?

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      • Jimmy2
      • Jimmy2
      • 2 mths ago
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      Fred Cloud I figured I am still young so I don't have senescent cells.  But, now that you mention it maybe I will do it again next month.

      I didn't feel any major effects with fisetin this time around with the 1500mg/day dosage.  However, the first time I did it six months ago I took 600mg/day for five days.  On day two or so I felt slightly weak, just barely.  I attributed this weakness to cells being destroyed.  I did not feel weakness this time, even with the larger dose.  I am going to get some Dasatinib and try it out.

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  • Here is an excerpt from the article on the grapefruit juice effect on sirolimus. I didnt realize that the effect begins within a few hours of ingesting the juice. I thought it was faster than that.

    "Consuming 8 ounces of grapefruit juice increases sirolimus levels by 350%, allowing persons with cancer to take less toxic doses of the drug.        

    This information was obtained from three simultaneous phase 1 studies involving 138 persons with advanced cancer. The trials employed an adaptive escalation design to find the doses of oral, weekly sirolimus alone or in combination with either the antifungal agent ketoconazole or grapefruit juice that would achieve similar blood concentrations as temsirolimus, the intravenously administered and approved prodrug of sirolimus.

    An mTOR inhibitor, sirolimus is approved to help prevent organ rejection in transplant recipients, but may have anticancer effects as well. Grapefruit juice inhibits intestinal P450 enzymes that break down sirolimus as well as several other drugs.

    According to a statement from the University of Chicago Medical Center in Chicago, Illinois, where study director and cancer specialist Ezra Cohen, MD, practices, the effect of grapefruit juice begins within a few hours of ingestion and wears off gradually after a few days. Although this effect has long been considered an overdose hazard, “We wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus,” explained Cohen in the statement."

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  • I tried the protocol of 3days of 3000mg and did not notice any effects. Granted, I have other bigger issues going on. 
     

    nonetheless, I came across a review on Amazon by an 81 year old women in a retirement home who noticed her memory was failing. She takes 2000mg a day, every day and has noticed great memory Improvement.  Her review showed excellent abilities as well. 
     

    Her dosing is the highest I have heard to date, and just like rapamycin, this begs the question of: what makes 2grams a day a mega dose? Perhaps if trials of 3 days are done the dosage should be 10 grams. 
     

    This women, at her age would be most sensitive to negative side effects, yet she has reported none. I will see if I can screenshot the review. 
     

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    • Arizona Kid 

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      • GEdwards
      • GEdwards
      • 2 mths ago
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      Arizona Kid 

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      • GEdwards
      • GEdwards
      • 2 mths ago
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      GEdwards As far as rapamycin, mTOR1 is said to be exquisitely sensitive to Rapamycin while mTOR2 (associated primarily with the innate immune system) is far less so affected. Rapamycin taken daily at only 2mgs build up over a week enough to suppress mTOR2, not desirable unless you want to suppress a kidney transplant.  Taken only weekly, 5-12mgs of rapamycin largely reduces mTOR1 without impacting mTOR2.... Suppressing inflammation, encouraging autophagy, clearing many senescent cells.

      I am not aware of dose toxicity for Fisetin. But it is not thought to affect mTOR2

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      • Aka Loo
      • Aka_Loo
      • 2 mths ago
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      GEdwards Have you ever heard of increased blood sugar from taking Rapamycin or Fisetin? 

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    • GEdwards GEdwards thank you for the info! I just wonder the maximum dose of Rapa, I tend to believe everyone is conservative with dosing, we may be missing out on the optimal dose.  

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      • GEdwards
      • GEdwards
      • 2 mths ago
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      Arizona Kid I've read that a single 20mg dose is enough to stop mTOR1 for almost a full week but I don't believe that's thought to be ideal..... As mild to moderate suppression is sufficient to provide benefits.  Certainly mTOR1 should not be suppressed after surgery of any kind requiring wound healing!  

      Remember that male dosing of the same amount as a female results on~30% less bioavailable Rapamycin. Also taking with high fat food results in higher absorbtion. And taking with GF juice also leads to a ~3x increase in absorbtion.  I take 3-4mgs weekly with GF juice.

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      • GEdwards
      • GEdwards
      • 2 mths ago
      • Reported - view

      Aka Loo yes and it can spike lipids a bit....https://www.nature.com/articles/s41419-019-1822-8#:~:text=Rapamycin%20(Sirolimus)%20slows%20aging%2C,glucose%20intolerance%20without%20insulin%20resistance.

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      • GEdwards
      • GEdwards
      • 2 mths ago
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      Arizona Kid It may depend on if you have issues.....I heard from Dr. Attia that the son of the discoverer of Rapamycin that got it to novartis was beset with cancer and took 1mg a day.....but we know that daily comes with issues.... I can tell you that my doc, Dr. Allen Green (RapamycinTherapy.com) is the best way to find out.....I went to NYC through La Guardia and had a regular appt with him in his home.....he will want blood work....he can show you how to get the tests. Dr. Green is an older gent, not chatty or terribly social but sharp sharp! He advises my close friend with an aggressive cancer.....and notes that if you already have a chronic disease, rapamycin is more a preventative than a treatment at weekly doses.
      Anecdotally, I am taking the equivalent of 10-12mg once a week....eg 3-4mgs with GF Juice and I am shortly going to be 68 and have a somewhat less aggressive prostate cancer......Dr. Green asked that I up from 9mgs to 12mgs.....or 3mg to 4mg w/ GF Juice.  If your C Reactive Protein blood test is high or high normal.....tend to take more....suppressing systemic inflammation if a major major benefit.  I had mild gout, and virtually none, I have painful hand arthritis, and now that's 70-80% gone......Do not buy from Biocon of India.....go through Dr. Green who has a compounding pharmacy that sells 3mg pills for about $10.  I also take 500mg ER metformin on days I do not work out....two pills.  That is also helpful....remember, there is no single magic bullet but Rapamycin is pretty close.

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    • GEdwards thank you for the reply! I am sorry that your going through cancer. With your attitude and measures I am sure it will be gone soon!

       

      I have a good source of Rapa hear. I am, actually 31… but I am obsessed with anti aging because I have a nuerodegenrative like disorder. Best way to describe it is, like Parkinson’s and dementia combined. I have lost all of my twenties to this and want them back. Out of the 30 people who have this condition, I am only one of two that has never had a suicide attempt. I have to thank my faith in Jesus Christ for that… knowing I would always get better, but also being able to accept if I don’t I don’t. 
       

      So my goal is to stay and look as young as possible!  Especially because my dating life has taken a back seat, will need to date younger if I want a family ;)

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      • J Man
      • J_Man
      • 1 mth ago
      • Reported - view

      Arizona Kid I'm sure the lady is giving her honest opinion, but I looked at her profile on Amazon.  She currently has 13 reviews and rates every product she reviewed with 5 stars.  I rate products on Amazon sometimes, but my ratings are across the board from 1 to 5 stars.  I suppose I'm just more critical.

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    • Jay Orman That’s valid, but she could also only be leaving reviews in products she really believes in!  At the least, it’s worth trying for a month if someone has the funds, no?

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  • Age 69 and no known health problems other than chronic migraine for which I take a triptan more days than not. This is an inherited trait as my mother had them and my daughter also suffers daily.  So I took my first dose of fisetin and Q two days in a row. 1200 mg F and 600 mg Q. Mixed them in EVOO. So far, absolutely no reactions. I was a little negligent in that I also had antioxidant supplements (C,D, NAC and astaxanthin). So will repeat in a month sans those and maybe take some black pepper beforehand. I used 500mg caps of F from Austin Nootropics.

    On another note, does anyone know of a Dr. Green type in Canada? 

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  • With all the interest and experimenting with ways to increase the absorption of Fisetin I'm wondering if anyone has tried the lipisomal sublingual gel offered by "Alive by Science"?   Assuming the liposimal coating does in fact increase the absorption as much as claimed,  I'm wondering how to estimate an equivalent dose of this product to compare to a typical dose of Fisetin powder or capsules.    Any thoughts or ideas would be appreciated.

    Liquid Liposomes

    $64.95

    • 75 mg liposomal fisetin per serving
    • 1 serving = 2 pumps = 2 mL
    • 60 servings per bottle

    Liposomal Sublingual Gel™ (LSG) is designed for sublingual (under the tongue) use for superior bioavailability. Our proprietary liposomal manufacturing process uses no heat, no pressure and only high-performance, pharmaceutical-grade ingredients.

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    • RAW Good question.  With no way to estimate the dose and no real way to tell if it did anything, it seems like all you could do is take a wild guess. 

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      • RAW
      • Ancient Sage
      • Robert_Weinhardt
      • 1 mth ago
      • Reported - view

      Paul D Wolf   Since lipid "encapsulation" has been shown to significantly increase absorption I'm surprised that more experimenters apparently haven't tried or haven't commented on the recently  released "micro encapsulated" gel formula.   Any significant improvement over the estimated 2% absorption of Fisetin seems like a potential game changer in getting effective doses into the blood stream.   In the absence of other comments, I guess I'll have to try a wild guess at an effective dose and adjust according to results. 

          I keep hoping some researchers will come up with a practical method of monitoring Fisetin levels in blood or urine in real time.    Urine test strips could provide easy, periodic tests.    Perhaps some transdermal sensor reacting to a chemical change related to Fisetin?

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  • My 41 yr young wife just took her first 2 capsules of " updated w fisetin "life extension " senolytics " caps with grapefruit juice on a relatively empty stomach followed by raking/ weeding in the  yard....   she is now experiencing energetic,  euphoric feelings.   She will take this 3 days in a row...   last time she tried this approach, " without fisetin" she looked 18 yrs old!!   Anyone else had similar experiences?

    Like 1
    • karl kuffner What do you mean last time she tried this approach with out fisetin? In what ways did she look 18 years younger?

      Like 1
    • Arizona Kid Arizona Kid the original life extension formula of "senolytics activator" was made without fisetin.  She took on a much healthier,  much younger ," look" that was kind of shocking for me...  then she reverted to normal appearance within a few days.   Shes planning  to take ," 2 LE senolytics caps ,( again), tomorrow and Thursday morning... ask me Friday morning what results we experience, if you'd like.     *note*  the correct dose is "3 caps"      my wife only takes 2.

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    • karl kuffner sure. But my memory is worse than yours. I do think there is an opportunity to megadose these. Or at least 3 days a week. 

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    • karl kuffner I have had similar feelings of high spirit and a very good mood after taken the original senolytic activator + increased capacity for endurance exercise the next day. 

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    • karl kuffner Thats an impressive reaction. Fairy8i8 had a similar response, she is female similar age. But the effect lasted 3-4 weeks and so she repeats every 3-4 weeks. She was taking just straight fisetin like the mayo protocol. You can do a search and find her experience.

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    • hi fred;  my wife, Marilou, would benefit from ," chatting " w the young woman who reported similar experiences,  to my wife's.  I'm not sure how they might ," touch base" with each other.. Any suggestions would be helpful.   Thankyou.

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  • I tried it again...1,300 mg same brand fisetin with added black pepper, and the quercetin. Again, nothing to report. I will use Swanson next time. 

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    • Moonlitnight 

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    • Dale Piggott To Moonlitnight and all others who have mentioned (or take) quercetin. www.Mountsinai.org states in part that: " Anticoagulants (blood thinners). Quercetin may enhance the effect of these drugs, increasing your risk for bleeding. Anticoagulants include:."  So, consider it as well..

      Like 1
      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 2 wk ago
      • Reported - view

      Dale Piggott  Thank you so much. I personally don't take anticoagulants (except for the occasional aspirin) but this is good to know.

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  • Also, how often is this repeated (on average) by the experimenters here?   I can't seem to find any references other than Fairy's, which I am presently planning to follow. However, Fairy is not in her very late '60s like I am. Thank you. 

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