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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There is a paper to be presented at the upcoming meeting of the American Aging Association (July 20-23) in which the researchers do one single dose of D+Q senolytics (D: 5 mg/kg + Q: 50 mg/kg) on aging nonhuman primates (species not specified, but I suspect they are chimps). They report that the senescent cell burden in the fat cells in their subjects showed a "24% reduction ... which rebounded at 1 month."
This is relevant to the question of how often one should do senolytic sessions.
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JGC
Here is the link to the paper you mentioned that was presented at the American Aging Association yesterday. (Titled: Senolytics reversibly improve metabolic health in nonhuman primates). Dramatic improvements were found after a single D&Q dose (5mg/kg dasatinib and 50mg/kg quercetin) as shown on a number of metabolic measures, including A1c and lipid profile as well as adipose tissue senescent cell accumulation.
https://whova.com/embedded/subsession/aaaa_202108/1784597/1796606/?view=
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After reading most of the comments I ordered Fisetin and Bioperine and will start some sessions. I think D is too expensive for me right now and I am not so sure about the quality of a similar product made in India . I plan to do 2 days per month of 2g Fisetin with Bioperine and black tea. So my questions are: Is it ok to start right away with 2g a day or should I start with lower dosage? Do I have to be careful what else I am supplementing that day ? Is there any advantage/disadvantage between the daily or monthly protocol? Is it better to take Fisetin on an emoty stomache ? I know there is no real study about the things I am asking but maybe you can just share your experience . Thanks in advance
Sebastian
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Sebastian I like to take it on an empty stomach, but I add 1 Tablespoon of oil and mix the fisetin into it. I don't have data to say taking it on an empty stomach is better, but I suspect it gets absorbed faster and more completely that it would mixed with a stomach full of food. Fisetin is oil soluble but not very water soluble so that is why I add the oil. I also add some bioperine or 1/2 tsp of ground black pepper. (Yeah, it tastes terrible...) It seems to have worked well for me. I would suggest not taking any other supplements those days so they don't interfere with the action of the fisetin. Maybe even stop supplements the day before and the day after.
You might want to take 1 capsule only at first to make sure you don't have any sensitivities to fisetin or bioperine.
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So, just asking... If bioperine made a substantial difference in fisetin absorption, why don't we see formulations for sale? Bioperine is cheap so it's doubtful a cost issue. Life Extension doesn't use it. Mayo didn't use it in their studies. ??
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Allen I'm glad they don't add it. If they added 10mg of Bioperine to each 100mg capsule of fisetin you would be getting way to much since you would use 10 or more capsules at a time. Better to add the amount you want separately.
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Allen
Papers in the literature indicate that BioPerine greatly enhances the bioavailability of the flavonoid Curcumin (which is contained in turmeric). Curcumin, like the other flavenoids, has a small solubility in water leading to its low bioavailability, and digestive enzymes break it down fairly fast. The BioPerine speeds its absorption and suppresses breakdown enzymes made in the liver, boosting the effectiveness of Curcumin. It's an extrapolation to assume that other flavonoids like Fisetin and Curcumin are boosted by BioPerine in the same way, but I think it's a reasonable assumption.
I note that Life Extension offers another way of boosting the bioavailability of Fisetin, Quercetin, and Curcumin, by coating the granules with fenugreek fiber to protect against digestive breakdown. This is claimed to boost the bioavailability by a large factor. The technique was invented by pharmacists in India to make Curcumin more bioavailable.
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JGC I am considering the possibility that using 1/2 tsp of freshly ground black pepper may be superior to using Bioperine. Previous discussion indicated that the effect bioperine may last for 15 minutes. Perhaps, like most refined products the bioperine is assimilated quickly and used up quickly. The ground black pepper I would expect to take more time to be absorbed and may therefore act over a longer period of time allowing more fisetin, etc, to be absorbed. I did notice a much stronger reaction when I took doses of F, Q, and C, when I took the 1/2 teaspoon of black pepper than when I took it with several pills of bioperine. Of course, this is just preliminary conjecture on my part, but I think the next time I will try the black pepper with my F + Q...
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Dan Nave I haven't been able to find any study that shows the amount of increased absorption of fisetin that is provided by piperine or Bioperine. I spoke to a scientist at Sabinsa and he guessed that based on fisetin's structure, the effect of Bioperine would be similar to to the effect on pterostilbene, about a 2.27 fold increase. But the effect is dose-dependent. So I scaled up from the mouse study that used piperine with resveratrol to get an enhancement of 229%. I calculated that for me at about 66 kg, I will expect an effective dose of 2000 mg fisetin if I coingest 1000 mg fisetin with 5mg Bioperine. Actually, I take 500mg each of F&Q on day 1. I do take the dasatinib separately, early in the day and the flavonoids about 5 hours later. On day 2 of my D&Q&F cocktail I take an additional effective dose of 1000mg of just fisetin. that seemed reasonable and I havent had any side effects.
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Hello everyone,
I'm new here but not new to anti-aging and longevity. I've read the 500+ replies above and it's all good stuff. Great community of like-minded people. Glad to be here.
I've been experimenting with NAD+ boosting compounds, not only the precursors mind you but also CD38 inhibitors, AMPK and NAMPT boosters etc... in the hopes of restoring the cells' ability to make its own NAD+ again...
This is all well and good but then something dawned on me during this experimentation, while I was reading about senescence, autophagy and related matters, that removing senescent cells (with compounds such as Fisetin for example) should be the primary objective here, especially when one is at an advanced age, rather than inhibiting and boosting certain enzymes to, in essence, block the toxic effects of zombie cells on the healthy cells.
It's like storing rotting food waste and garbage all over your house for years, never removing it and then buying a couple of HEPA filters to take care of the smell. I say clear out the garbage first.
Am I on the right track?
If I understand correctly, just the removal of a small portion of these toxic senescent cells, reduces CD38 expression and actually restores NAD+ production (even in older organisms), not to mention the reduction of chronic inflammation and many other problems associated with these zombie cells, hence your body behaves as if it were younger. If these are purged from the system via the senolytics of course..
I mean rather than use compounds such as Apigenin and Quercetin for the specific purpose of CD38 inhibition, wouldn't it be a lot better to actually go to the source of the problem and effectively purge those nasty zombie cells in the first place and keep them in control?
Having accomplished that, your NAD+ levels would presumably return to normal and there would be no more chronic inflammation and poisons affecting the healthy cells, once you take care of the toxic senescent cells.
I am still unsure if I should keep on the NAD+ boosting compounds, which can be expensive or move over to the "hit and run" Fisetin dosing to manage my senescent cells which, my intuition tells me, can possibly be more effective and less expensive too...
Actually, let me asking you a question.. If you had to pick one thing you'd do, the NAD+ boosting compounds, as I have laid out above, or senolytics? Which would you choose?
Sorry for the long post but I do have another question too: I am aware of the Mayo Clinic Fisetin protocol dosing but is there any data (even anecdotal) that a lower dose, for example 500 mg/day, for a longer period of time, for example for 5 days or a week, every month, would be effective and worth trying, to purge these zombie cells? I am of course planning to mix the Fisetin with some type of fat for better absorption.
Thanks for reading and I welcome any thoughts that you may have,
Dan
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Bioperine is to (flavonoids) Tumeric or Fisetin etc what white grapefruit juice is to Rapamycin or Dasatinib......about a 3x increase in bioavailability..... Grapefruit juice interacts with many other meds and the effect lasts upwards from 11 to 18 hours....so use caution when taking other meds with GF Juice. Cut back on the recommended Dasatinib when taking with GF Juice.
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GEdwards GEdwards ARE YOU saying that pink grapefruit juice does not work vs white.
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Van I use white grapefruit juice to enhance rapamycin bioavailability. Something I read, years ago, from a nutritional guru, is that the compound that inhibits the breakdown of relevant pharmaceuticals is much more concentrated in the skin of the grapefruit. When I've only had access to red gf (not juice) I include eating some of the skin, for possible enhanced benefit. Haven't looked into it lately, though.
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"Colored (pink and red) grapefruit pulp contains lower amounts of the furanocoumarin derivatives that cause pharmacokinetic interactions than white grapefruit pulp " ( https://pubmed.ncbi.nlm.nih.gov/18771009/ )
Both work.....but white version works better.
https://www.scientificamerican.com/article/grapefruit-juice-improves/#
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GEdwards The last line of the article reads, "Thus, colored grapefruit juice may produce drug interactions at the same rate as white grapefruit juice." May or may not is the operative word here.
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Hi All,
I’m looking for the link, recently posted, to a paper covering Fisetin and it’s excellent cancer fighting capabilities. It was on some .gov site as I recall.
Thanks !-
BobM
Fisetin and cancer fighting.
found it:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261287/
This is an excellent read.
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I just heard that quercetin with a bio-available zinc does the same as HCQ in that it escorts the zinc into the cell to kill viruses. Maybe off topic but thought you might like to know. It's to be taken as a preventative. Amazon is now selling them together in one supplement.
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Robert Olin
Robert Olin said:
I just heardEr, and where did you hear this?
Robert Olin said:
quercetin with a bio-available zinc does the same as HCQ in that it escorts the zinc into the cell to kill viruses.Since HCQ doesn't kill viruses except at crazy doses in test tubes, I don't think that's a very interesting claim.
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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.
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Jimmy2 Did you notice any changes? Why not do it monthly like the mayo protocol and other users here?
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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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Arizona Kid
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