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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  • Hi Everyone!  I just stumbled across this thread and find it very informative. I would like to ask the group their opinion of what I should do next.  I am 65 and have had chronic pain for 10 years: knee pain, L4-5 issues, nerve pain in butt (probably die to L4/5), neck pain (severe OA there) and more recently should/arm pain. It just keeps expanding to new areas. I work with an Anti-Aging institute and they can find little to work with as my blood work is, in their words, impressive: lipid panel 30 yr olds would love to have (their words), C reactive protein WNL, nutrients all good, liver enzymes low, etc...I feel like I have tried everything with no symptom relief.  Here is what I've done over the last couple years:  a variety of Peptides ( one combination worked on my knees but we couldn't replicate it), PPS, EGCG, high doses of Melatonin, bioidentical hormone replacement, intermittent fasting, Spermidine, and a stint of D+Q about a year ago; all of this they recommended to me to reduce inflammation (which hasn't worked). I thought maybe I was focusing on the wrong thing so I took a blood test that measures cytokines and I'm waiting for the results.  After reading much of this thread, I decided that my D+Q protocol was under-dosed, so just yesterday I started a more aggressive protocol of 200 mg D+ 1250mg of Quercetin which I will do for 4 days. Does anyone have any other ideas of what else I can try? I would really appreciate your suggestions. Thank you in advance.

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      • Van
      • Van
      • 2 yrs ago
      • Reported - view

      Peter H. Howe I know it is disappointing in that we need an honest supplement reviewer.  Best thing we can do is buy supplements from well know and trusted retailers like Costco, and be sure to be educated enough to read the labels. 

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    • Van If I do not get from Costco, I get from LEF. Note that Consumers Lab found Costco's green tea inferior as it had little or no EGGC but found Costco's   Kirkland fish oil one of the better brands. Consumers Lab also get into arguments with some manufactorers about some of the products it evaluates. I will still check Consumer Labs but with skepticism.

      Like 1
      • Dan Nave
      • Dan_Nave
      • 2 yrs ago
      • Reported - view

      Denise Shugerman This may be a bit of a different approach from what you have tried, but you mention OA which I assume is osteoarthritis, and joint pain.  The first thing I would do is supplement with Borax.  (Yes, 20 Mule Team Borax...)  Borax is a clean and excellent source of Boron.  Boron has been shown to be a necessary trace element and low levels in the water and diet has been shown to correlate with higher levels of arthritis in both people and animals.  I have used this myself with excellent results and have recommended it to about 15 or so people and every one of them has experienced some level of improvement in their joint pain. 

      You need to take at least 100mg of Borax (which contains about 10mg of Boron) a day, and if you take more initially it is not a problem.  The daily maintenance dose of 3mg a day is definitely not enough to get ahead of the curve on this.  You can think of it like table salt and take a fair pinch of it, as much as you would use for a good salting of ones eggs at breakfast.  I would recommend taking it like this for about 3 weeks.  I usually get results in a week and then forget to continue as I don't continue to have pain...  After this, you can supplement at 3mg if you like.

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    • Dan Nave that is quite unconventional!  But I will try anything.  Thank you!

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    • Denise Shugerman I'm hearing that fasting is an excellent way to cause autophagy.  It starts at 17 hours and if long enough you get stem cells released.   Google or duckduckgo fasting+autophagy.   

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    • Robert Olin Yes, I know about fasting for autophagy...just waiting to get inspired to do it!

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    • Denise Shugerman    I just had a big chocolate milkshake before starting my 1st 48 hour fast.   Autophagy is supposed to start at 17 hours.     Wish me luck.  

      https://www.youtube.com/watch?v=5RT4qIO27uw

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    • Robert Olin I find a nice approach to fasting is to eat my last meal on the afternoon of a Friday (2-3pm as work allows). Go through Saturday on green tea or black coffee -> add a little salt for electrolyte balance. Gently refeed on Sunday morning starting with a small amount of bone broth or protein. Should get you into the autophagy space. Frequency once a month for me. As long as your insulin levels are already tamed by having avoided snacking and the like for a while this degree of fasting is almost effortless, in fact it's pleasurable.

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    • Jack Black Thanks for the advice.  I would prefer to snack all the time, but realize that I probably have insulin resistance and am also a hyper responder to carbs.   My wife is serious about feeding everything around her and can eat all the potatoes and rice she wants and never gains a pound and her HDL is 88.  

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    • Robert Olin wow, if I had a chocolate milkshake before fasting, I'd be starving due to the sugar. Actually I am on the Peptide Semaglutide which controls sugar levels really well and makes you not hungry so i do not have an excuse to avoid fasting. I am just not disciplined, I want my coffee and I want it with milk every morning. The longevity institute I work with says 16 hours of fasting is good so I've done that here and there but yeah, 48 hours I'm sure is better.

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    • Denise Shugerman Dr. Mindy say autophagy starts at 17 hour and slowly ramps up.   I'm like an alcoholic with food.   I'm either on the wagon or I'm not.   It's a lot easier once the decision is made.  No food today period.   Of course, I still have 1.5 days to go.   Talk is cheap.   Stem cell production is another interesting effect of fasting.   We'll see if my back stops aching so much.

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      • Brian Valerie
      • Semi-Retired Health Education Teacher
      • Brian_Valerie
      • 2 yrs ago
      • Reported - view

      Robert Olin I'd just like to clarify that autophagy does NOT "start" at the 17 hour mark, which is by no means a definitive dividing line in any case.  Actually, autophagy is happening ALL the time, but does increase with fasting. On different pages of her website (which also seems geared towards product sales), Dr. Mindy Pelz also cites Dr. Ohsumi's 13-15 hours and Naomi Whittel's 16 hours, but peer reviewed academic research has demonstrated that depending on the size and composition of the last full meal, the liver may use the last of its glucose reserves in as few as 8 to 12 hours, hence the popularity not only of the 18/6, but also the 16/8 and even 14/10 time restricted eating protocols.  My best wishes for your aching back!   

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    • Brian Valerie Thanks for the information.  At 71 I can use all the autophagy I can get.   I understand some people also take fisetin and Quertcetin while fasting.   Others say go easy as your body starts detoxing when you are new to fasting and there might be a lot of toxins to deal with.   I'm at 18 hours.  Last night while in bed I fantasied eating a large BabyRuth candy bar.   Last thing I remembered as I fell asleep.  Better than counting sheep...grin.

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    • Robert Olin At 40 hours into my fast I took my blood sugar and it was 99.   I've had lower when not fasting.   I assume my liver is dumping stored sugar?   I never got really hungry.   What I missed is the pleasure I get from eating.    This is the 1st time I've said no to my stomach, in my entire 71 years.    Hope to do it at least once a months.

      Perhaps I'll take some fisetin  next time.

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      • Michael_123
      • A is A
      • Michael_123
      • 1 yr ago
      • Reported - view

      Denise Shugerman I was searching another topic, but saw your post.  20 years ago I also had L4-L5 issues with herniated disc.  Pain can radiate to all different areas.  I investigated various approaches, & decided on protocol which was 100% effective:  spinal decompression.

      Likely you could find MRIs online, showing how the disc is actually inflated by the decompression.

      In those days there was 1-2 high-end units, available only at MDs.  These days there are several computer controlled machines, with cost to MD / chiro for equipment from $13,000 = $150,000.

      Individual treatments are generally about $70 - $120 per 40 minute session.  I think protocol is for 21 consecutive days.  When I started it was covered by insurance, but not sure these days.  I was unable to walk without a walker (about age 50 then,) but after session 10, about 50% improved; by session 17-18, fully recovered.

      Every 3-4 years I get about 5 sessions to prevent possible back problems.  Very successful.

      Related, but vits/supplements with decompression is helpful.  One I did not know then is CMO (Cetyl Myristoleate,) available both in capsules & topically.  It helps to shuttle various nutrients into the discs.  I assume F+Q etc. to remove senescent cells would be helpful too.

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  • Thanks Peter!  Yes, my PA at the longevity institute has recommended this and I did it for as long as I could stand it (I think it was until the bottle was gone). Since I take so many supplements, those horse pills were hard to get down every day and I had little faith because nothing else worked. Have you had a good experience with fish oil? I will do it again if you think it'll work.

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    • Denise Shugerman Yes, I have had a good experience. Been using high dose ( 5.5 grams of EPA/DHA from 6, 1.4 gram Natures Bounty capsules. )  for more than 25 years with low dose statin as part of a  preventative cardiac problem  after a bypass.  At 81 I have no joint  issues or arthritis.  My inflammatory cytokines  ( IL-6) are below detection limit. It also inhibits the brain shrinkage and cognitive  decline that are part of the aging process. 

      The Barry Sears books will describe the chemistry and multiple benefits, and he recommends at least 5 grams if you have a chronic inflammatory condition.

      Again, wish you luck in correcting the problems you have. 

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    • Peter H. Howe What do you mean by: " 5.5 grams of EPA/DHA from 6, 1.4 gram Natures Bounty capsules"? 

      Thanks

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    • Denise Shugerman I purchase my Nature's Bounty fish oil from Costco. Each capsule weighs 1.4 grams ( 1400 mg) and contains 0.88 grams of EPA/DHA total. I rounded it off to 0.9 grams of EPA/DHA /capsule. I take 6 capsules/day ( 3 in am and 3 in pm ).  6 capsules x 0.9 grams/capsule = 5.4 grams of EPA/DHA.

      There are 130 capsules/bottle and each bottle costs~ $16.00 when they go on sale every other month. Not on sale cost is ~$21.00 at my Costco. 

      I suggest you may want to read one of Barry Sears books as he goes into detail about the numerous benefits of fish oil for multiple systems which include cardiac, inflammation (arthritis),  neurological and vision.   He recommends ~2.5 grams /day for maintenance, ~5.0 gams/day for chronic conditions and higher levels for acute conditions.  There are over 7,000 peer reviewed publications on fish oil. 

      As I indicated, I started on fish oil almost 30 years ago after an emergency bypass. It came to my attention from articles in LEF 's magazine and the author  ( Dr. William Davis) was a cardiac physician who also  published a book entitled "Track Your Plaque" . I visited him in Wisconsin and over a period of about 1.5 years he balanced my cholesterol with  high dose  fish oil and low dose statin to lower several critical factors to a non threatening condition. Basically fish oil lowers triglycerides which in turn lowers LDL-P and particle size to an acceptable level.

      At the time, I was using LEF's oil but switched as Natures Bounty was it somewhat less expensive and more convenient. I also made the switch at the time based on Consumer Labs findings. Since that time, Consumer Lab no longer tests Natures Bounty and the historical record has been removed. Consumer Labs most recent analyses indicate the Kirkland Brand ( Costco) and LEF's straight fish oil are OK as well several other brands.  As regards Consumers Lab, please note Vans' ealier comment in that Consumer Lab's only test if they are paid. This is a conflict but I do not know what else to tell you as pharmaceutical grade fish oil will cost you orders of magnitude more  than the 3 over the counter brands I mentioned above.

      Wish you the best on your efforts

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  • Did you have joint pain and then the fish oil helped?  Or are you correlating taking it for other reasons and no joint pain?

    Thanks,

    Denise

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    • Denise Shugerman In my case, it is a correlation issue in that I started high dose fish oil due to cardiac issues almost 30 years ago and have never developed any arthritic type issues. The literature documents extensively the benefits of high dose fish oil in preventing joint pain and some of my brothers and sisters have joint pain as did my mother. 

      Note  I just doubled my dogs  (12 year old Aussie) fish oil and his stiffness has disappeared. My previous dog was a lab who made it to 15 without any noticeable joint pain and she got at least 2 grams/day.

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  • I'll try anything, really.  My cod said to take 3 grams but maybe I should try 6 grams like you.

    Thank you!

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    • Denise Shugerman Please make sure you do the calculation based on the EPA/DHA content of the capsule. My capsules ( Nature Bounty) are 1.4 grams but the EPA/DHA fraction is 0.9 grams which gives me 5.5 grams of EPA/DHA if I take 6 capsules. Note that Consumer Labs identified Costco's Kirkland brand and Life Extensions straight fish oil as  two of the better brands in terms of quality based on testing.  I selected Nature Bounty based on Consumer Labs testing several years ago but they have not tested Nature Bounty lately.

      Good Luck 

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    • Michael
    • Michael.1
    • 2 yrs ago
    • Reported - view

    Question: If one lives a bodybuilder lifestyle, where eating multiple times a day is optimal for muscle growth, how can one best mimic the life extension benefits of fasting?

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    • Michael Fast sometimes anyway. Everything I find about our metabolism seems to scream that we're highly adapted to survive famines. Fast and feast seems very agreeable to the human body. Feast all the time poisons us.

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