
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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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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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.
$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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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?
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Just wanted to share this older study regarding the reduction of Fisetin methylation (into less effective geraldol) in the liver when combined with increasing amounts of red wine:
https://pubmed.ncbi.nlm.nih.gov/29454704/
In other study, both the ethanol and red wine polyphenols likely increased absorption of (Fisetin-similar) Quercetin:
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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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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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karl kuffner said:
al liStaffan Olsson said:
similInteresting. I've had my 77 year old mother on the LE Senolytic Activator once weekly and she always reports feelings of well being after taking it. She reported very similar effects when I had her on mega doses of straight fisetin, which makes me believe that LE Senolytic Activator works just as well.
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Looks like Metformin has senomorphic effects. Is that the reason for the anti-aging effects?
https://www.frontiersin.org/articles/10.3389/fbioe.2021.730813/full
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It seems Rapamycin is also considered a senomorphic by some researchers.
https://academic.oup.com/biomedgerontology/article/76/6/1144/6126488
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The well known ITP reports Fisetin does not extend healthspan or lifespan in mice. It also did not remove senescent cells. Video here: https://www.youtube.com/watch?v=42PzfNs9egA&t=3294s
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Yes, very disappointing news from ITP. I will discontinue the use of Fisetin until the Mayo Clinic releases their results on human subjects in June. If they show no senescent cell removal, I will stop Fistein completely.
In other news, the ITP did show an increase in mouse longevity for Glycine\NAC supplementation of 24% which is huge. Studies using Glycine and NAC in humans over the age of 70 also showed very impressive results!