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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Hmmm...can you redo the link to the FB Israeli study...seems to be broken
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GEdwards Unfortunately you cant edit posts here.
But I assume everyone knows you could find the study yourself in about 10 seconds with google.
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Michael Mel
They claim that
"HBOT were able to elongate telomeres at rates far beyond any currently available interventions"
I dont think so. I have seen reports of people have been able to achieve the same or better telomere lengthening in the same amount of time with epitalon. I dont think these researchers do much homework.
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Michael I have always wondered about this supplement version, it may work, it may not. I was referring to injectable. Some people have had success with oral, but not sure it will work the same. Did you see the guy on reddit who used injectable?
https://www.reddit.com/r/Nootropics/comments/4vk596/my_experience_with_epitalon/
50 year old guy took so much it lengthened his telomeres back to the length of a 10 year old kid. You arent supposed to take that much.
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Fred Cloud Great! Thanks for the link
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Michael Don't put too much stock on the initial reports from inferior measuring services.
See his updated data from the much more reputable and accurate LifeLength: https://www.reddit.com/r/Nootropics/comments/65rd0q/followup_to_my_experience_with_epitalon/
Good but not exceptional.
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Anyone know what the cost of a typical two hour session might be?
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Here’s an interesting discussion on senolytics. Seems it could be harmful if taken without something to replace cells that are removed
also interesting that UBX0101 failed in part because of very high placebo effect
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Paul Beauchemin I think I see what they did wrong, these scientists killed off too many senescent cells. There is actually a therapeutic role of SASP, the normal function of the SASP is to restore tissue function by stimulating less-damaged neighboring cells to engage in tissue repair. So if they killed off all or too many senescent cells and your skin couldnt ever enter sasp mode you wouldnt be able to repair all the missing cells you just killed off and it would form skin ulcers. So there is a healthy range of senescent cells, if you have too many it accelerates aging, if you have too few you limit repair. Its a weird catch 22. Interestingly, if you put too much rapamycin on your skin, you get skin ulcers.
These senescent cells also seem to have other effects in the body, I see the mice not only had ulcers from the skin not repairing they also had liver fibrosis. Check out this quote from a study finding.
"acute myofibroblast senescence also has a role in repairing damaged organs such as the liver and thus is likely to represent a more common mechanism to limit fibrosis"
So sasp mode may even limit fibrosis in the liver
The role of senescent cells in ageing
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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.
My experience:
(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.
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Aaron Interesting symptoms. I felt like I had a sunburn the first time I took it and some random pains. I do get tired when I take it. I no longer get any pains while taking it, but some fatigue. I think it gets easier as you take it regularly. My husband, who had severe sepsis, feels like his muscles are sore like when he strength trains when he takes it, but he says that the soreness is getting less and less. I take that as a good sign that he is reducing his senescent cell load. It also does wonders for my arthritis, so the fatigue is worth it to me. I take it once a month for 3 days now. I was taking it twice a month for 2 days because I felt like there was too much regression month to month with just 2 days. Let us know how the full 5 days goes. Thanks for sharing!
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Aaron When I take large doses of Fisetin I feel a weakness in thighs and I easily get sore muscle after extercise. When I have large amounts of dried Parsley (rich in apigenin) it has a sedative effect on me. Spermidine and sulforaphane also makes me sleepy. So those supplements I take only at dinner or later in the evening, (sulforaphane, Apigenin, Spermidine).
When I take Quercetin, EGCG and curcumin (BCM-95) in the morning I get a boost of energy.
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Aaron . I have yet to start taking Fisetin.
I have some questions: is it recommended to not do vitamin IV drip while taking Fisetin or does that actually help to clear senescent cells?
Is there a combination of Fisetin with other compounds that are good for women and to maintain healthy and regular ovulation?
Are there any particular brands of Fisetin that are to stay away from?
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Aaron The 4th and 5th days taking Fisetin the effects were similar, but a bit more muted. No noticeable change after completing the five days vs prior to starting. Going forward I think I'll continue to do 20mg / kg on 2x consecutive days once a month. It definitely seemed to have a bit more 'kick' than other flavonoids I've taken that have senolytic buzz.
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Why such a 1600 mg and why combined with all those other things? That amount of fisetin far exceeds the Mayo protocol and as for the rest I'd worry about liver toxicity from too much of any one of them. Stacking and mega dosing them ... Is that based on any science done to date?
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Whoops! Reviewing the threads here I see now why the 1600 mg. Still not certain why you'd want to stack the stuff.
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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.
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Jack Black Yeah I would proceed with caution and work your way up to the 2,000mg per day dose. I have had reactions with 500mg also and so have others. I think people could really get into trouble with jumping into the deep end of the pool with 2,000mg without dipping their toe first at lower doses. I hope the mayo study results will share how some people reacted to the 2,000mg they used. Anyway, the old protocol of 500mg for 5 days should be the first stepping stone to everyone wanting to use fisetin. I was thinking one could do a hybrid protocol of using a dose escalation of say 500, 750, 1,000, 1,250, 1,500, 2,000mg once you clear the 500mg x 5 day round.
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Fred Cloud I wonder if you or others might want to try the same approach. Reason being I had just 100mg of Fisetin yesterday with the big pot of black tea, green tea, cinnamon stick and sliced lemon. Even then I felt a reaction though less than the 500mg.
The tea ingredients are intended to be synergistic but I'd be interested to know if anyone feels anything combining this with fisetin like I did. Small chance I know but maybe stumbled on a way to pep up the effect?
btw no fatty medium used this time I just took a capsule at the same time as drinking the tea.
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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!
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Brian Valerie hi Brian; try your formula , on an empty stomach, and take a 12 minute walk, also, ( maybe double the le feistin, and you will definitely, " feel" a difference. Enjoy; karl
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karl kuffner Thank you very much for sharing your experience with me, Karl. I reread your post in which you related positive effects, even including euphoria! Since I'm dosing weekly, I'm able to try different protocols. There are so many different individual experiences or perceptions, here and on the fisetin thread at longecity.org., with, for example, some folks reporting better effects by taking fisetin with oil. What do you think of the notion that perhaps we shouldn't expect to "feel" anything from what could well be simply a reduction in the rate of aging?
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Brian Valerie yes, I understand. I'm almost 71 yrs myself, however I strongly feel ," first thing in the morning, on an empty stomach w possibly some straight black tea , quercetin a (quarter teaspoon of olive oil?), and 12 minutes brisk walk, and you should definitely have some noticeable feelings/ sensations. On another note , my wife is much younger ," 40", and she took senolytics 3 days in a row, ( on my suggestion) and her results were STUNNING! karl
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