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.
A clinical trial run by the Mayo Clinic and aimed at improving skeletal health in elderly women is upping the fisetin dosing schedule from two days to three and from one or two consecutive months to five months.
Now scientists at Tel Aviv University have shown that giving pure oxygen to older people while in a hyperbaric chamber increased the length of their telomeres by 20 per cent, a feat that has never been achieved before.
Scientists said the growth may mean that the telomeres of trial participants were now as long as they had been 25 years earlier.
The therapy also reduced senescent cells by up to 37 per cent, making way for new healthy cells to regrow. Animal studies have shown that removing senescent cells extends remaining life by more than one third.
For the last 3 days I've added 1600mg Fisetin (20mg/kg) to my normal mid-morning routine which includes 1g Quercetin, 1g Curcumin and 200mg Ubiquinol (kaneka) taken with a smoothie. The smoothie is loaded with fats and whole food sources of sulforaphane, pterostilbene, apigenin, luteolin, curcuminoids etc. which may be boosting the effects.
(1) First day - odd jaw tightness, trouble focusing, extremely hard to resist urge to nap
(2) Second day - more intense jaw tightness, trouble focusing, unable to resist extended napping
(3) Third day - continued jaw tightness, trouble focusing, continued desire to nap
The effect takes 30-45 minutes to kick in and lasts for 8-10 hours. I am going to continue for 1-2 more days (4-5 total).
So far I seriously can't imagine taking Fisetin more than 2 days a month. Never expected it to have such a noticeable impact on how I feel since none of the other flavonoids with senolytic potential that I've taken have had similar effects. It feels a bit like my body is going into some kind of battery saver mode where full functionality isn't available. Like the onset of napping doesn't feel like an inability to resist a desire for sleep as much as it does like a bit is being flipped and my body starts much more aggressively shutting down unecessary processes.
The Fisetin I'm using is 400mg / pill from Do Not Age.
Decided to do a tolerance test before going ahead with fisetin.
According to the info in this thread I might go for a dose north of 2000mg based on my weight for a hit and run treatment (92kg and age 50, good health).
I've had 100-200mg fisetin a day via capsules in the past and noticed nothing.
3 days ago I cut 5 of the Doctors Best capsules into a bowl (500mg) and mixed with fresh cream and some ground black pepper. Consumed with some fresh blueberries and rasperries.
After around 90 minutes I started to feel like I was coming down with something. Then I started getting an ache in the finger joints on my left hand. Starting wondering how severe the feelings would get, and ended up lying down for 20 minutes. Then it all started to recede to the extent I went on my normal 3 mile lunchtime hike as I usually would.
Comments in the thread above have me thinking. It seems like a quarter dose had a reaction, but why so easy? Maybe the lecithin in the dairy cream was beneficial? Also perhaps it was my beverage; an hour after taking the fisetin I had my usual late morning brew a pint of hot green & black tea with lemon. (Two teabags with half a lemon sliced in). The lemon is to increase the bioavailability of some compounds in the green tea. Then was it warm water, the black tea, or just a coincidence I started to feel results after drinking this?
So, I'm going to take it steady. Some folks experienced nothing at higher doses than mine and that was not my experience. Next week I might try 700mg etc, and work towards an eventual 2000mg weekend shot.
I've also ordered some of the Senylitic Activator pills by Life Extension (they kind of fake the D+Q action). Once again I'll take that careful with an initial half dose, and certainly not weekly as they suggest. Also, won't be combining fisetin and other senylitics at the same time. There's that nagging concern of kicking off something unpleasant like an auto-immune reaction.
I'm not put off, in fact it might have taught me I have things going on in my left hand that I didn't know about. I have a slight arthritic ache in 1 finger joint as I type this, but now I'm thinking maybe I did before?
My energy levels are certainly improved but were already perhaps due to AKG, NMN or the vitamins I've been deficient in for years. Will report back when I do my proper senolytic dose with any observations.
The journey continues.
I don't have high regard for anecdotal evidence, even my own, due to its great susceptibility to variations, confounding variables, placebo effect, etc. Nonetheless, I figure that it can't hurt to offer my own experience for those who might be interested. For the past three months I've been taking once weekly doses (as suggested on the package) of Life Extension's Senolytic Activator (theaflavins 275mg, bioavailable quercetin phytosome 74 mg, and apigenin 50 mg) along with a weekly dosing of 64 to 72 mg of their bioavailable fisetin, which they claim is the equivalent of up to 1600 to 1800 mg of regular fisetin. My age is 70 and my weight is 82 kg (about 180 pounds). I have felt no differences whatsoever on dosing compared to non-dosing days, but don't feel confident enough to offer any interpretation (or misinterpretation) of that fact. I'll leave that to you, friends!
Brian Valerie I have been doing the same thing for almost 6 months now. I just add the Fisetin dose to the Senolytic Activator. I have done it weekly and haven't seen any benefits or reactions. The 2 times I took D&Q, I had a general malaise for ~12 hours but also no noticeable benefit. I will probably continue the once a week protocol but I think it's time I moved on to Rapamycin. I am 69 yro and feeling like I was born a little too early and not quite rich enough to experience age reversal with the coming CRISPR technologies.
Yes, I will definitely be starting the Rapamycin soon as well as continuing the senolytic therapy. I have been tweaking my diet since my early 20s and exercise as I can. I have chronic Lyme Disease so all this is a challenge. My motto, "Live long and suffer!" I figure if I can live long enough, maybe there will be some answers to the Lyme conundrum.
D+F+P Side Effects with BioFisetin
Yesterday my wife and I did a senolytic session for the first time since September-2020. We took 10 mg of BioPerine, followed in an hour by 200 mg of Dasatinib (4 x 50 mg) and 80 mg (10 x 8 mg) of LifeExtension's BioFisetin. The nanoparticles of BioFisetin are coated with a LE-proprietary concoction involving Fenugreek extract that is supposed to boost the bioavailabity of the Fisetin by about x25, so our dose should have been the equivalent of taking 2 g of uncoated Fisetin powder (as we have done before).
This is the first time we have combined Dasatinib with BioFisetin. In all of our previous senolytic session experiences, the side effects were relatively mild. We had done D+Q+P and D+Q+F+P with Fisetin powder, and we had done a triple session with BioFisetin alone. This time, I would say that the side effects have increased to moderate. I had belly cramps all night and didn't sleep well, had multiple soft bowel movements this morning, and experienced a general feeling of unwellness all day. (My dog Taliesin and I did one run at a dog agility competition this afternoon, but we failed to qualify, partly due to my lack of energy and quick response near the end of the run.) My wife, who has never reported any senolytic-session side effects before, had a headache, a general feeling of unwellness, and decided to stay in bed until mid-afternoon today.
I'm not complaining. I take this experience as an indication that our session of D+F+P using LE's BioFisetin had a stronger senolytic effect than we had previously experienced. Possibly this is because LE's claim of a x25 boost is an underestimate of the LE BioFisetin's actual increased bioavailability, or possibly because taking the BioPerine one hour before D+F increases the boost factor. In any case, I'm impressed.
We will compete in dog agility again tomorrow, and based on previous experience I expect to be fully recovered and more energetic. We plan to do two more senolytic sessions soon, the next on Monday (4/19) and the last on Thursday (4/22), spacing the sessions with two off-days. I expect less side effects from these subsequent sessions. I'll report it if I'm wrong.
In the interest of full disclosure, I should mention that my wife and I have just completed a 15-day session of taking a 3 mg sublingual tab of Super-Nutrition's Epitalon (AEDG) every morning from April 1-15. We will repeat this on the 1-15 of May and June. We experienced zero side effects from this Epitalon session, and I doubt if it contributed to the side effects I am reporting above.
Elsewhere on the forum someone states "some senolytic substances works through ROS activated apoptosis....stay away from antioxidant supplements before a senolytic treatment"
This led me to thinking is there any use in temporarily boosting oxidative stress before or during a senolytic session? Vigorous exercise, junk foods, even smoking?!
Hi there , I am quite new to the subject but managed to read all 543 posts….. With the result of being totally confused. Since I am quite young (42y) and D is a) to expensive for me in germany and b) to experimental fir my taste I will go ahead and do Q F and P . Among all the combinations you guys tried : Is there one that is specifically recommended? I am completely unsure about dosage/ repetition intervall/ Daytime / ect …. What would you recommend to start with?
Thx for this great forum
For anyone concerned about BPH or prostate cancer here is an interesting artlcle related to possible benefits of fisetin as a treatment. There is a lot of medical detail, but the essence of it is that fisetin seems to help increase high molecular weight HA and lower low molecular weight HA. The human dose noted near the bottom of the article looks like (1.5–2g/day) as dietary supplement. https://academic.oup.com/carcin/article/37/9/918/2450013
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.
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
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,
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.
"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.