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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    • Koo
    • Koo
    • 4 yrs ago
    • Reported - view

    Thanks for the feedback, I really like the idea of trying fisetin in cream, I'll give that a try next week :-)  I might also try the coconut oil on its own at some point, to see if I react to that like you do, that's good info. I don't want to even look at it at the moment!

    Like 1
  • FWIW, I get a sore throat from plain virgin coconut oil with nothing added.

    Like 1
    • Carl D
    • Carl_D
    • 4 yrs ago
    • Reported - view

    Hello everyone I wanted to give you a breakdown of my fisetin experience over the last year.

     

    I went in fairly hardcore trying to emulate the experiments done with mice only in humans. And I also repeated the treatment routinely. 

     

    I think the math worked out 100mg for every 15 pounds of weight. I did the math back then. Suffice to say I was around 220 lbs and I took 18 tablets (100mg each).

     

    Me: 43 years old, male, 220lbs

     

    The specific amounts I took were:

     

    DAY 1: 18 x 100mg tablets (Swansons Brand) 

    DAY 2: repeat

    DAY 3: repeat

     

    Initial observations where that by day 2 I was a little jittery, not a lot, but I had amazing strength in my legs and a firmness throughout all muscles. By day 3 I was feeling fantastic and this feeling became more intense for a week after and even was noticeable 3 weeks out.

     

    I suspect that fisetin raises hormone levels as well. Because I felt 20 years younger and full of strength, Mentally I twice as sharp. I remember distinctly that when walking around during week one I could hear every thing brilliantly, the world was crisp and alive. So there is definitely some kind of hormonal effect or other stimulation than just senescent cell clearance. These effects were much too fast to be a result of that. 

     

    I repeated the treatment at 2 weeks, then at 4 weeks, then at 6 weeks, and 8 weeks again and then gave it 5 months or so and now I am doing a repeat but at a slighty higher dosage.

     

    In each iteration I noticed a powerful effect for the first week, and a great 2nd and 3rd week. And then I still maintained much of the muscle density and firmness and increased energy thereafter. I decreased the frequency I was taking fisetin due to my concerns that it was spiking testosterone somehow. After all the goal was to clear senescent cells not mess with hormones. 

     

    I can say that in the year since I started, I have maintained a stronger physique, my posture is better, my abs and chest are firmer, I don't look my age, but I kinda was that way before to an extent. If I shave close people will honestly think I am in my late twenties. 

     

    My view on this is the following: Any senescent cell clearance benefits will show up slowly, just like the negatives of having them in your body to begin with.  I would use hormone therapy for gender reassignment as an example. If you see how long  HRT takes to have real results its about 6 months to a year with the most dramatic results at the 2 year mark. So quickly making assessments about fisetin is likely foolish as the body needs time to regenerate lost cells, and cells which were antagonized by senescent cell signalling need time to adjust back into equilibrium.

     

    Additionally fisetin is shown to be more effective in certain tissues. I think more so in muscle tissue, and some organs.

     

    Overall I am seeing and experiencing good results. My energy levels have remained high ever since dose one. I still remember myself a year before starting and even 4 years back. I was dead tired after work, hard to stay focused on anything mentally and lethargic. That is no longer the case and my new norm is lots of energy and focus, and I can stay up till 2 am if I want.

     

    My current regime is 25x 100mg tablets. I will do this for 3 days. The main thing is I noticed no side effects. A little jitterness in the first few days when doing a treatment and then that goes away. I was worried about my hairline but it does not seem to have a lasting effect though I suspect if you dosed constantly it could so something there. All in all I suspect this is effective in humans just as in mice, but we have to look 2 years out to see results and then compare ourselves to our no longer existing former selves who did not take the treatment. 

    If there are any questions for me I can answer. I will say this, fisetin works, it's safe, and likely it does exactly what it does in mice, only in humans. Fairly exciting stuff.  

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    • Mel
    • Mel
    • 4 yrs ago
    • Reported - view

    Carl D

     Thanks for sharing.   So you did not use piperine nor mix the fisetine with oil or cream?

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    • John W
    • John_Whitling
    • 4 yrs ago
    • Reported - view

    Some really good info in this study on Fisetin for improved cognition and neuro diseases. Lots of great detail.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527824/

    Like 1
      • Ajax
      • Ajax
      • 4 yrs ago
      • Reported - view

      John W Thanks for posting that. Lots of good info indeed!

      I was especially glad to read the toxicology section, though given the widespread lower-dose supplemental use of fisetin, I'm not too surprised.

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      • John W
      • John_Whitling
      • 4 yrs ago
      • Reported - view

      Ajax I was particularly floored by the work on Alzheimer's and the idea that it raises cognitive abilities even among normal people. Fisetin could really be a game changer, way beyond just senescent cells. I haven't digested it all yet but I am on board, having just purchased a lot of it to see how it goes. My wife is APOE4/4 so this is welcome news to me.

      Like 2
    • John W 

       

      When I translate the doses used on mice it quals a daily dose for humans of 2 mg/kg. 

      Like 1
      • John W
      • John_Whitling
      • 4 yrs ago
      • Reported - view

      Staffan Olsson I was reading 25 mg per kg. I really take a deep dive into this study. I have read  a few of them on fisetin but this has the most useful info. Here's what I found in the Alzheimer's section ..

      Two groups each of wild type and AD mice were used for these studies. Fisetin was fed to one set of wild type and one set of AD mice between the ages of 3 and 12 months in their food at 0.05%, resulting in a daily dose of approximately 25 mg/kg body weight (bw). This dose of fisetin was chosen based on earlier studies on fisetin and cognitive function in mice (21).

      By my way of thinking that would be the same for humans but is that correct?

      Also there's a comment on 40 mg per kg being equivalent to donepizel in response for AD.

      Like 1
    • John W 

       When it comes to translate the animal doses that is used in experiments it is a science of itself. Difference in size as well as differences in metabolism. I post a link to a guide to basic calculations.

       

      In table one they show that a basic approach to translate a dose given to mice is to divide the animal dose by 12,3. They you get to HED = human equivalent dose.

       

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

       

      So 25 mg/kg to a mouse equals 25/12,3=2,03 to a human.

      Like 1
      • John W
      • John_Whitling
      • 4 yrs ago
      • Reported - view

      Staffan Olsson I would have never guessed! Thanks much for explaining and posting that link.

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    • John W 

       

      When using fisetin as a geroneuroprotector, most humans would need to take at least 150 - 200 mg fisetin daily. this based on to the above posted link and according to a basic dose translation. That is a very reasonable amount to take every day. But we will not reach strong (if any) senolytic effect when dosing is in this range. 

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      • John W
      • John_Whitling
      • 4 yrs ago
      • Reported - view

      Staffan Olsson Thanks to that dosing study you posted that is the plan but I do have enough to do some spiking sessions maybe in concert with quercitin. I am excited to begin.

      Mixing with olive oil would be a daily pain though, but we'll see how it goes. I used to make a poor man's lipo vitamin C for my dad who had T4a cancer. I was a lot of effort.

      Like
  • The place where Ive been getting my 98% pure Fisetin also sells pure Apocynin powder.  They suggest that the combo dovetails benefits. Has anyone else had any experience with Apocynin?

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      • DIANE B
      • DIANE_B
      • 4 yrs ago
      • Reported - view

       I got it from same place most presumably.  The only uses I really found for apocynin were topical claims to skin rejuvenation.  Anyone else?

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  • For the past week I've been taking 125mg of Apocynin every morning, dissolved in a shot glass of hot water.  Seems to give me energy without the jitters. I also made up a batch in a light saline solution and am trying it out on my face.  

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

      Zack Lonetree   Hi Jack, what is the amount of apo you are using in the saline?

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    • Antonia Gauer 

      For the topical Apocynin solution I started out by dissolving 50mg in 10 ounces of a light saline solution.

      Like 1
    • Mel
    • Mel
    • 4 yrs ago
    • Reported - view

    I finished my second 3 day protocol of fisetin today.  I'd to get some thoughts on how long I should wait to do the follow up blood testing.  Current plan is 2 weeks.

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      • Koo
      • Koo
      • 4 yrs ago
      • Reported - view

      Mel Hi Mel,

      I'm new to this, but my feeling is that you should wait longer, at least a month before you have a blood test. This will give the fisetin time to have noticeable effects. As others have said, it will most likely take some time, and you most likely want to keep the number of blood tests you have to a minimum.

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      • Mel
      • Mel
      • 4 yrs ago
      • Reported - view

      Koo thanks for your thoughts.   Why would one want keep the number of blood tests to a minimum?   Thanks again. 

      Like
    • Mel
    • Mel
    • 4 yrs ago
    • Reported - view

    I received an email recently from age reversal and it had a link to a video in which Bill Falloon gave an updated presentation.  In one of the slides shown in the video it showed the senolytic as dasatinib quercetin and fisetin.  That's the first I've seen him include fisetin with dasatinib.  I believe they are using combo for there study.  Does anyone know what dosage they are recommending?

    Like 2
    • Mel
    • Mel
    • 4 yrs ago
    • Reported - view

    Karl Thanks.  I am aware of that study.  I looking for the dosage that Life Extension is using in its study wherein they use Fisetin and dasatinib and quercitin.  I've attached a slide from the video where Bill Falloon mentions it.  The slide is at 29:30 of the video which is at :

    https://www.youtube.com/watch?v=fPH0sBfUK5U&feature=youtu.be

      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Mel I would think that life extension doesn’t have any more info than we do. You could use the dose from the study.

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