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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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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GEdwards As far as rapamycin, mTOR1 is said to be exquisitely sensitive to Rapamycin while mTOR2 (associated primarily with the innate immune system) is far less so affected. Rapamycin taken daily at only 2mgs build up over a week enough to suppress mTOR2, not desirable unless you want to suppress a kidney transplant. Taken only weekly, 5-12mgs of rapamycin largely reduces mTOR1 without impacting mTOR2.... Suppressing inflammation, encouraging autophagy, clearing many senescent cells.
I am not aware of dose toxicity for Fisetin. But it is not thought to affect mTOR2
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GEdwards Have you ever heard of increased blood sugar from taking Rapamycin or Fisetin?
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GEdwards GEdwards thank you for the info! I just wonder the maximum dose of Rapa, I tend to believe everyone is conservative with dosing, we may be missing out on the optimal dose.
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Arizona Kid I've read that a single 20mg dose is enough to stop mTOR1 for almost a full week but I don't believe that's thought to be ideal..... As mild to moderate suppression is sufficient to provide benefits. Certainly mTOR1 should not be suppressed after surgery of any kind requiring wound healing!
Remember that male dosing of the same amount as a female results on~30% less bioavailable Rapamycin. Also taking with high fat food results in higher absorbtion. And taking with GF juice also leads to a ~3x increase in absorbtion. I take 3-4mgs weekly with GF juice.
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Aka Loo yes and it can spike lipids a bit....https://www.nature.com/articles/s41419-019-1822-8#:~:text=Rapamycin%20(Sirolimus)%20slows%20aging%2C,glucose%20intolerance%20without%20insulin%20resistance.
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Arizona Kid It may depend on if you have issues.....I heard from Dr. Attia that the son of the discoverer of Rapamycin that got it to novartis was beset with cancer and took 1mg a day.....but we know that daily comes with issues.... I can tell you that my doc, Dr. Allen Green (RapamycinTherapy.com) is the best way to find out.....I went to NYC through La Guardia and had a regular appt with him in his home.....he will want blood work....he can show you how to get the tests. Dr. Green is an older gent, not chatty or terribly social but sharp sharp! He advises my close friend with an aggressive cancer.....and notes that if you already have a chronic disease, rapamycin is more a preventative than a treatment at weekly doses.
Anecdotally, I am taking the equivalent of 10-12mg once a week....eg 3-4mgs with GF Juice and I am shortly going to be 68 and have a somewhat less aggressive prostate cancer......Dr. Green asked that I up from 9mgs to 12mgs.....or 3mg to 4mg w/ GF Juice. If your C Reactive Protein blood test is high or high normal.....tend to take more....suppressing systemic inflammation if a major major benefit. I had mild gout, and virtually none, I have painful hand arthritis, and now that's 70-80% gone......Do not buy from Biocon of India.....go through Dr. Green who has a compounding pharmacy that sells 3mg pills for about $10. I also take 500mg ER metformin on days I do not work out....two pills. That is also helpful....remember, there is no single magic bullet but Rapamycin is pretty close. -
GEdwards thank you for the reply! I am sorry that your going through cancer. With your attitude and measures I am sure it will be gone soon!
I have a good source of Rapa hear. I am, actually 31… but I am obsessed with anti aging because I have a nuerodegenrative like disorder. Best way to describe it is, like Parkinson’s and dementia combined. I have lost all of my twenties to this and want them back. Out of the 30 people who have this condition, I am only one of two that has never had a suicide attempt. I have to thank my faith in Jesus Christ for that… knowing I would always get better, but also being able to accept if I don’t I don’t.
So my goal is to stay and look as young as possible! Especially because my dating life has taken a back seat, will need to date younger if I want a family ;)
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Arizona Kid I'm sure the lady is giving her honest opinion, but I looked at her profile on Amazon. She currently has 13 reviews and rates every product she reviewed with 5 stars. I rate products on Amazon sometimes, but my ratings are across the board from 1 to 5 stars. I suppose I'm just more critical.
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Jay Orman That’s valid, but she could also only be leaving reviews in products she really believes in! At the least, it’s worth trying for a month if someone has the funds, no?
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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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Logged in under wrong address. Please ignore above post from Antoniag. I can't seem to delete it.
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. -
Moonlitnight I get a different experience (placebo?) if I take fisetin with black pepper or if I take fisetin with piper longum (long pepper). Piper longum contains both piperlongumines and piperine. Black pepper contains only piperine. I get a stronger respons with piper longum.
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Staffan Olsson Thank you Staffan. I will use the Piper longum and keep it all crossed. I am wondering if I should try again in a week rather than a month.
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Moonlitnight Doctor's Best Fisetin featuring Novusetin is the brand that I have used. Others have used Swanson's fisetin and gotten positive results.
The fact is that we don't know which brands that are high quaity and which brands that are poorly produced.
Besides Doctor's Best Fisetin have also bought bulk Fisetin, but that was a terrible experince. That fisetin had a taste of an undefined chemical solvent.
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Staffan Olsson Austin Nootropics has third party certification on their NMN supplement and has this to say on the fisetin: Every batch of FISETIN is independently verified to have a purity of at least 99%, with no dangerous levels of heavy metals or micro-organisms. Of course, anyone can say anything, but there is nothing in the taste to indicate the presence of an unnatural substance. I will try it once more, then switch to Swanson to see if there is a difference. Thanks for your input! @robert_weinhardt I would like to know this too. I use their face serum with NAD, NMN and apocynin, and their NAD+
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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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RAW Good question. With no way to estimate the dose and no real way to tell if it did anything, it seems like all you could do is take a wild guess.
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Paul D Wolf Since lipid "encapsulation" has been shown to significantly increase absorption I'm surprised that more experimenters apparently haven't tried or haven't commented on the recently released "micro encapsulated" gel formula. Any significant improvement over the estimated 2% absorption of Fisetin seems like a potential game changer in getting effective doses into the blood stream. In the absence of other comments, I guess I'll have to try a wild guess at an effective dose and adjust according to results.
I keep hoping some researchers will come up with a practical method of monitoring Fisetin levels in blood or urine in real time. Urine test strips could provide easy, periodic tests. Perhaps some transdermal sensor reacting to a chemical change related to Fisetin?
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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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karl kuffner What do you mean last time she tried this approach with out fisetin? In what ways did she look 18 years younger?
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Arizona Kid Arizona Kid the original life extension formula of "senolytics activator" was made without fisetin. She took on a much healthier, much younger ," look" that was kind of shocking for me... then she reverted to normal appearance within a few days. Shes planning to take ," 2 LE senolytics caps ,( again), tomorrow and Thursday morning... ask me Friday morning what results we experience, if you'd like. *note* the correct dose is "3 caps" my wife only takes 2.
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karl kuffner sure. But my memory is worse than yours. I do think there is an opportunity to megadose these. Or at least 3 days a week.
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karl kuffner I have had similar feelings of high spirit and a very good mood after taken the original senolytic activator + increased capacity for endurance exercise the next day.
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karl kuffner Thats an impressive reaction. Fairy8i8 had a similar response, she is female similar age. But the effect lasted 3-4 weeks and so she repeats every 3-4 weeks. She was taking just straight fisetin like the mayo protocol. You can do a search and find her experience.
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hi fred; my wife, Marilou, would benefit from ," chatting " w the young woman who reported similar experiences, to my wife's. I'm not sure how they might ," touch base" with each other.. Any suggestions would be helpful. Thankyou.
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