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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You might know about already, I did not: clinical trial to follow at Mayo. I might start with Fisetin after the first results appear, will see ...
https://clinicaltrials.gov/ct2/show/NCT03430037?cond=fisetin&cntry=US&rank=2
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albedo
Looking at the previous test #1 in the series (see the link there) the elegibilty requirements and exclusions are of interest. For example, they want you to be off statins and caffeine before and during dosing. And a long list of other things. I did not on my first dosing. Before jumping to the next round of very high dosing (1200 mg/day, 2 days), I want to get my blood tests back from the previous, and study this further. Any comments on the details of these studies as outlined?
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What are the by all of you on using a high dose of fisetin (600mg?), together with a 24-30 hour water fast. Taking only the fisetin/water throughout the fast?
Could this combo speed up the purge of senescent cells?
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BobM Pretty sure this hasn't been studied so nobody knows. A 5 day water fast is what really kicks in the autophagy - more powerful than fisetin by itself FWIW.
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BobM
For high doses, as far as I can tell, the largest Fisetin capsules available are 100 mg (which means that you have to take a lot of them). In contrast, one can get Quercetin in 1,200 mg capsules (which I use). I have also seen old ads for Fisetin in powder form promoting a bottle containing 50 g of powdered Fisetin and a 100 mg scoop. However, these don't seem to be available any longer.
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JGC Just FYI, caps are little (bottom one here). Taking 4 at each meal is not hard. And these are cheap. $16.26/bottle delivered. 😎.
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BobM
Yes, that capsule looks just like the 100 mg fisetin capsules that I have bought from Swanson and from Doctor's Best/Amazon. However, my point was that for senolytic doses one needs to take on the order of 2,000 mg or 20 capsules. It would be nice if someone would produce fisetin capsules that contained 500 mg or 1,000 mg, so that one would not have to take so any pills. This is done for quercetin, but for some reason, not for fisetin, although both are similar flavenoids.
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JGC RevGenetics offers 500 mg "senolytic" capsules which helps reduce the number of caps needed.
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RAW
I solved the too-many-pills problem with Fisetin by buying a 100 g bag of Fisetin powder, measuring the 2 g dose on a digital scale as it is spooned into warm olive oil, drinking the latter, and cleaning the glass with bread pieces that are then eaten.
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Hello team😉 can someone share where I can buy high dose fiestin?
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karl kuffner
i bought Regular dose (100 mg) from Lucky Vitamin. Took two 3x/ day. These are branded as Doctors Best. They were out of stock for quite a while.
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karl kuffner confirm my purchase last month from responsible vender on eBay (Philly based) sells bulk only: fisiten and apocynin. Well packaged, purity tested & extra info. Very helpful, communicative.
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karl kuffner Try "RevGenetics" or Amazon for 500 mg capsules. I haven't seen any analysis to verify their purity or actual content. Wish Consumer Labs would do a test.
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Thanks, how do you compare the fiestin w the synolytics prod. From life extention?
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karl kuffner I take both. Really can perceive a gain from either.
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BobM
this should have said “can’t”
sorry for any confusion!
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karl kuffner
Fisetin by itself has been shown in a publication in a refereed journal to cause senescent cells to go in to aptosis and disappear. Further Fisetin is relatively cheap ($12.99 for 30x100 mg caps from Swanson's).
LifeExtension's Senolytic Activator costs about $1 per cap for 74 mg of Quercetin + 275 mg of Theaflavins. Quercetin has been shown to have mild senolytic action, particularly on senscent cells in the linings of blood vessels, but it works much better when combined with the very expensive anti-cancer drug Dasatinib (D+Q). Dasatininb is prescription-only, so LifeExtension can't market a D+Q product. They have apparently therefore decided to generate a marketable senolytic product by substituting Theaflavins from black tea for the Dasatinib. There has been no research, to my knowledge, indicating that Theaflavins enhance the senolytic action of Quercetin or have any senolytic action alone. It's apparently a guess at best.
Further, the research shows that for known senolytics the action comes from taking LARGE doses of the senolytic drug separated by sizable time intervals (~1-6 months). On the other hand, one is supposed to take 2 caps of LifeExtension's Senolytic Activator every week, i.e., a relatively small dose at weekly intervals. That looks to me like a dosage schedule that is unlikely to produce much senolytic action.
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karl kuffner I am generally a fan of LEF supplements but since the Senolytic Activator is just quercitin plus some theaflavins, you're probably better off buying the quercitin by itself from a cheaper vendor.
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JGC stomach upset is likely just side effect of the pills, you need better biomarkers to test for senolytic effects. I'm putting a list up in a WIKI here in the near future. Clearing senescent cells involves a lot of recycling (e.g. the Golgi apparatus) which isn't something you generally feel, but there surely are parts that are discarded in your urine. I hypothesize that testing your urines specific gravity is a way to check - however during ad libitum feeding you need a baseline, and it might well be lost in that baseline level (lost in the noise).
For example during a fast, at day 5 is when it's clinically been measured that heavy senolytic activity occurs. Indeed during my last fast at day 4.5 my urine turned from clear to dark yellow and the specific gravity went from negligible to more than my test stick could measure (> 1.03) - in both cases the only other measured value was high ketone bodies (of course)*. I take this as significant senolytic activity, and is the only non invasive way of testing senolytic effects I can think of and I'm fairly confident of it, but this is just a hypothesis.
Note also this has to be calibrated to a given amount of hydration. I carefully measure my daily intake of steam-distilled water at 170 oz, and have that same level of hydration during a fast. Being dehydrated will also drive up your specific gravity.
* it also had a peculiar odor. Normally my urine smells 'green and spicy' from the vegan diet and supplements I take. During a fast in the early part it becomes clear as water with no odor, until day 4-5. Also to be clear my hypothesis is that the specific gravity is measuring the presence of discarded senolytic junk, which is why it's important (for measuring) to separate from the normal feeding activity.
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My Fisetin experiment:
First day 500 mg; no side effects. 2nd day 1000mg; no effects. 3rd day 1200mg; no effects. 4th day 1200mg with 20mg BioPerine; no side effects.
Following week noted increased energy, less lower back discomfort, and less/no arthritis in hand.
Will repeat Fisetin after 3~4 week interval. Certainly easier than 5 day water only fast.
This week will start Metagenics' SPM Active pills for 3 weeks. Pill is supposed to provide "resolvins" to help reduce my chronic inflammation.
And then back to 5 day water fast again.
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nealfg hello, how did you break up dosing your fisetin daily? Did you have a normal diet during that time? Do you also do a senolytics. LE program, during or before.? Thanks
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karl kuffner
jumping in here: my recent was 1200mg/day for 2 days. Divided daily into 200mg every 2-3 hours. Some with food, some not. No adverse signs. Extra energy and alertness throughout the day with no afternoon fade, which I usually get.
How soon are all of you thinking to repeat dosing? I’m thinking one month.... comments??
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karl kuffner ........full dose 1 time in the morning on an empty stomach. No change in diet. Only other "senolytic" is 5-day, water only fast, every ~6 weeks.
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Senolytic Bloodwork Results from 2 Fisetin and 3 D+Q+... Sessions
A while back I reported on the bloodwork results for my wife (PBC) and I (JGC) taken before and after two large-dose sessions of Fisetin. After that we had rwo sessions of 100 mg Dasatinib + 1000 mg Quercerin + 10 mg Bioperine a week apart, followed in a week with 100 mg Dasatinib + 1000 mg Quercerin + 1000 mg Fisetin + 10 mg Bioperine. In each of these sessions, the Bioperine, which is supposed to suppress the action of P-glycoprotein that normally gives drugs a short half-life in the bloodstream, an hour before the other items to give it a chance to do its work. After the last of these sessions we had more bloodwork to observe ant effects of the treatments. The spreadsheet image belowshows the results, and analyzed using three methods of estimating "blood age".
The bottom line seems to be that (a) there is a certain amount of "noise" in bloodwork (not surprising) and small difference are probably fluctuations, and (b) the D+Q sessions didn't do much that the Fisetin Sessions had not already accomplished. For the December bloodwork I had a big bruise on my leg that I speculated had increased my Levine age. That seems to have been borne out, in that it dropped by 3 years in the new bloodwork.
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I have Osteoarthritis around my knees. I started taking D+Q three months ago (70mg of D and 1,000mg of Q for three consecutive days / month). For the first two months, I felt fever around the knees a few days after the dosage. Actually, the knee temperature got 1.5 degrees celsius higher than that of thigh. It means that the inflammation around the knees got higher. I guess my immune system attacked the senescent cells.
However, my knees are much improved now. I feel no pain anymore when I go down the stairs. I am very impressed by the result.
I am wondering if your blood age would be younger if you had the blood work weeks after you took the senolytics.
Cheers,
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Have you considered doing a purity analysis of the Fisetin supplements that have been mentioned in the Forum like Doctor's Best, Swanson, Rejuvenation Therapeutics. Maybe we could fund a comparative analysis to the Fisetin used in the Fisetin article :
- https://www.ncbi.nlm.nih.gov/pubmed/30279143
- The article says the experiment used Fisetin from a company in Houston:
- https://www.selleckchem.com/products/Fisetin(Fustel).html
