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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  • @saxxnviolins Juan Daw My purpose in mentioning dramamine was not to correct anything. The "old" formula contains dimenhydrinate and the "new" contains meclazine. Both are listed as having high anticholinergic activity. From RXFiles.ca: Diseases associated with an essential cholinergic deficit include Alzheimer’s dementia, Lewy body dementia & to some extent other dementias (not frontal). Anticholinergic drugs worsen the deficit & are therefore highly problematic  (in older people- my add).

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  • I have recently stopped taking Fisetin and Quercetin daily (500 mg each) due to severe side effects.  My lips became painfully dry and cracked daily for about a month and this had never happened before in my life.  This also made them susceptible to bacterial infection and my lips puffed up like a clown.  It coincided with my taking Fisetin and Quercetin daily (as per Dr. Sinclair).  After taking antibiotics to control the infection, my lips were still very dry cracked and painful.  When I stopped taking fisetin and quercetin daily, my lips returned to normal.  Has anyone else had a similar physiological response?

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      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
      • Reported - view

      Chris M  Sinclair recommends high dose fisetin and Quercetin daily? Thats crazy. Senolytics arent meant to be taken daily long term. They are supposed to be pulsed, once a month at most. Not sure what Sinclair is thinking unless I am missing something, but no wonder you were having symptoms.

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    • Fred Cloud   "Recommend" is not the right word. Sinclair was asked in a recent interview about his daily regime and he confirmed he was taking F+Q in those quantities (he didn't elaborate on the reasons why). He certainly wasn't "recommending" that others follow suit. 

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      • Chris M
      • Chris_M
      • 6 mths ago
      • 1
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      Kaptain Asia I try to follow what the leaders in longevity are doing.  I figure that if they are the most knowledgeable people in the world regarding aging, I should do what they do.  However, I realize we all have different physiologies and genetic makeups so results may vary.  Also, daily F+Q giving me painful cracked lips every day.  Is that a sign that the senolytics are working? A bad interaction with one or more of the other 15 supplements that I am taking? or a sign that my genetics are different?  I haven't a clue, but the daily pain and inflammation was intolerable for me, so I am going back to pulsing F+Q until I run out and then wait for the Mayo report before I buy any more.  I am a little younger than Sinclair so it may be more beneficial when I am older.

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  • 50 year old guy here.

    Finally tried the fisetin hit and run regimen. Aimed for 30mg per kg dissolved in warm olive oil. Threw in 400mg of Q on top by taking a bio-available 250mg cap plus 2x the Life Extension Senolytic Activator. This for two days straight.

    In preparation I had dropped anything like rapa, aspirin or glynac for 10 days that some here have stated might block results.

    Honestly, I feel like I'm using my imagination to say that anything happened. My body temperature may have been half a degree C higher than normal. I might have felt slightly sweaty though it was hot weather anyway. I might have had a vague ache in my left hand finger joints. Now four days later I might have slightly better colour perception in my left eye.

    See where I'm going? Really difficult to judge.

    When I did a 500mg tolerance test last year, a cup of my black & green tea mix kicked off some sort of immune reaction for a while and the room swam. Much greater dose this time led to maybe something, but possibly nothing.

    I will say that since my tolerance test last year I have dosed 100mg fisetin a couple of times a week. I have done a rapamycin protocol for around 2 months. I have done the odd alpha lipoic acid cleanout. Basically I'm not a clean slate when it comes to self experimentation.

    However, all in all nothing really to report. I'm getting back on my rapa this afternoon.

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    • Jack Black Thank you for your report. which brand of fisetin did you use? I have observed different effects from Dr's best fisetin and the life extension brand Bio -fisetin. I got a strong reaction from the Dr’s best fisetin.

      And I have noticed a muscular weakness a few days after the fisetin session. And afte these few days of weakness I have experienced increased physical performance (at least when I have used Dr’s best fisetin. )

       

      In a few weeks I will do a new regimen with the Dr’s best Fisetin. It will be interesting to see what (if any) reaction I can observe.

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      • Jack Black
      • Jack_Black
      • 6 mths ago
      • Reported - view

      Staffan Olsson I was using the Dr's Best Fisetin with novusetin. Cut the capsules open to mix into the oil.

      Going to try again in a month and I might employ some D at the same time.

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      • Chris M
      • Chris_M
      • 6 mths ago
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      Jack Black I think the novusetin may be at too high of a concentration to dose.  I did my first Fisetin dosing using that brand and it made me nauseous.  I switched to HumanX Fisetin for massive dosing and I did not have nausea when O repeated the dosing the following month.  I did 1.5 g of Fisetin 3 days in a row for each mixed with 500 mg of Quercetin as well as black pepper and tumeric.

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      • Jack Black
      • Jack_Black
      • 6 mths ago
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      Chris M That's the strange thing, I had the opposite reaction of it being too strong. I was dosing 2600mg per day plus Q on top, and had had a 10mg BioPerine 20 minutes before the Fisetin. Frankly surprised by the lack of experience.

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  • My first reaction to Novusetin (Drs Best or Swanson) was wonderful.  I felt absolutely fantastic for a few days, almost like a drug, and I suddenly had the ability to stay up all night without experiencing discomfort the following day.  After not taking senolytics for months I have taken another set of doses.  I take all 30 capsules in the bottle once/day with lots of Q and did this 3x in one week.  No weakness or nausea.  I am noticing a strength increase in the gym.  I just added 10-20 lbs to almost everything I do.  Also, I do 209 stairs two at a time and for the first time have been able to get through that without pausing.  I have to say Novusetin is effective, theoretical absorbability notwithstanding.  I'm 70.

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  • Small update, I noticed today that I didn't have the minor ache in my injured hip joint that I've had since the Fisetin. Maybe that's a sign there has been some clear up this week.

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    • Jack Black 

      Yesterday I had 40 mg/kg Fisetin Dr’s best brand. And this morning (after approx 15 hours) I had another dose of 40 mg/kg Fisetin . 3 hours after the fisetin I had a large dose of Thornes Quercetin + life extensions Theaflavins.

       

      Now almost 12 hours after the Q I feel good. I report back in a few days.

       

      (My weight is about 71-72 kg)

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    • Staffan Olsson 

      This time I did not experience the same effects as I did when I had my first couple of senolytic treatments with fisetin. I still feel good and strong a few days after the session. But feeling good is not the same as I have gotten a beneficial effect. I keep fisetin on my list of intermittent treatments.

       

      There is also the possibility that my diminishing experience of fisetin is a result of “the law of diminishing returns”. In other words, I got the strongest effects from fisetin when my body never before had been exposed the senolytic  treatment with fisetin.  And at that time my body was in a state where it had plenty of senescent cells that  more easily were susceptible to treatments with Fisetin.

       

      With this logic my body need other senolytic agents.  This might be case since I the last year have experienced stronger effects from piperlongumine than from Fisetin.

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  • Sorry this is OT, I want to add spermidine to my 3-monthly protocol. Does anyone have a source for Canadians? (Powder is preferable). Thanks so much.

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  • I've been looking everywhere has anybody heard whether the mayo study has been done on fisetin and what the results were? Everybody was waiting for the results they were supposed to come out in June.

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  • This is the closest I can find.  Dr. Kirkland is speaking about senolytics.  Kirkland’s speech is mind blowing. Senescence spreads throughout your body? So senescent cells are like a disease. If you implant a mouse with senescent cells, it becomes frail and dies early. Wow. This changes my world view!

    Professor James Kirkland’s, on senolytics, starts at 42:20.

    https://www.youtube.com/watch?v=z0ddsQs9efk&t=3634s

    Metformin - talk by Dr. Nir Barzilai starting at 1:33:09.

    Like 1
      • Dan Nave
      • Dan_Nave
      • 9 days ago
      • Reported - view

      Chris M The Professor looks like he could use a senolytic course...

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      • Michael
      • Michael.1
      • 9 days ago
      • Reported - view

      Chris M What were the two he mentioned being used in trials based on safety data?

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      • Chris M
      • Chris_M
      • 9 days ago
      • Reported - view

      Michael They are testing Fisetin and Dasatanib I believe.  Not together though.

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      • Michael
      • Michael.1
      • 9 days ago
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      Chris M Thank you! I couldn't understand him. lol

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      • JGC
      • Retired Professor of Physics
      • JGC
      • 6 days ago
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      Dan Nave 

          In a Q&A session that I viewed, Kirkland said that he did not personally do courses of senolytics because they had not been sufficiently tested on humans.  Judy Campesi has said more or less the same thing.  IMHO, they should put their senolytics where their mouth is.

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