Fisetin ( + quercitin)
Among flavonoids, fisetin appears to be an effective senolytic:
Because it is cheaper, easier to acquire, and probably safer than dasatinib, self-experimenters should consider examining fisetin in combination with quercitin.
May clinic is performing a study on elderly subject, and using two grams of fisetin on two separate days. https://clinicaltrials.gov/ct2/show/NCT03430037?cond=fisetin&cntry=US&draw=1&rank=2
I utilized this protocol over three days, one longer than the study. My observations other that slight malaise I did not notice any definable improvements. Of course I did not take Quercertin with it. I have just finished the first round of C+D, and describe the process under the C+D section of this site. I obtained Fisetin from Trillium Health Solutions, 50 gram powder with 50 servings. They supply a small one gram spoon. I mix two spoonfuls in a warm glass of water and take on an empty stomach. No too bad tasting.Reply
Since BioPerine (black pepper extract piperine) supposedly increases bioavailability of curcumin (a flavonoid) by 2000% and resveratrol by 220%, it would seem to be a good idea to use with the flavonoid fisetin. I am taking 500 mg fisetin with 10 mg BioPerine twice daily for a few days. Warning: don't take BioPerine with any drugs or substances you don't want to magnify.Reply
One concern I have with Fisetin is that it is a PARP1 inhibitor which is needed for DNA repair. PARP1 inhibitors are used for cancer chemotherapy. It would make sense that Fisetin can then induce apoptosis in senescent cells similar to other PARP1 inhibitors killing malignant cells. So a short term course may work in reducing senescent cell burden. But I don’t know whether long term taking of Fisetin is a good idea as it could possibly cause DNA damage in normal cells to accumulate. Fisetin is also a CD38 inhibitor and both CD38 and PARP1 breakdown NAD.Reply
Okay, here's the new Chinese bulk fisetin source from eBAY found by djmichel djmichael and discussed above:
Pure fisetin Powder at a cost of 22 dollars for 10 grams. link attached.
The source is Herba Link and the cost is roughly $50 for 25 grams ($2 a gram). I got a plastic packet today which is 25 grams, and the bulk weight of the plastic resealable packet was 27.2 g including the plastic, so net weight is good. The time from order to receipt was just 4 days.
The source is Chinese. Manufacture date 1/21/2019. There is a certificate of analysis which claims 98.13 % fisetin by HPLC. It's a yellow powder and looks good, no odor. Taste is a bit reminiscent of pine. There is a heavy metal screen and a microbial screen.
It is a true herbal extract, done with water and ethanol. The plant source is stems of Rhus succedanea, the Japanese Wax Tree. This is a rather large and hardy shrub you can read about on Wikipedia. Its coating is the source of a lipid (not a wax) used as part of Japanese lacquer. The more common Linaean name these days is Toxicodendron succedaneum, a name it gets because the the plant is toxic to a number of herbivores. Nevertheless, the Rhus genus plants (many known as "sumacs," from a Syrian word meaning "red"), and anything in the larger Anacardiaceae family, are all quite high in fisetin (which is yellow-- the sumac red color is something else).
R. succedanea (this same wax tree) is the source of fisetin in the Swanson product, too. And I would bet Swanson gets it from the same Chinese source and just encapsulates it, so if you're looking to get out of all risk that way, it won't work.
It isn't clear to me why the wax tree R. succedanea is toxic. Other members of the family, like the infamous poison sumac (perhaps the most poisonous plant in N. America), contain urushiol, the same stuff that makes poison oak and ivy so bad. On the other hand, there are many sumacs with fruits used in spices and dyes, and sumac pink is actually what gives the traditional pink lemonade of colonial days, its color.
The fruit and stems of R. succedanea contains a flavonoid related to fisetin and to apigenin, called hinokiflavone. This stuff may be the toxicity source. It is far more toxic than fisetin, and is fascinating because its cytotoxic properties seem related to why we're interested in fisetin-- it goes to the mitochondria and increases production of reactive oxygen species, and induces apoptosis. It has been tested as an anticarcinogenic in melanoma, and shows some promise. It makes melanoma cells apoptose, with less toxicity in healthy cells.
Somebody badly needs to test hinokiflavone as a senolytic. I can't find that anybody has done so.
Do makers of fisetin from R. succedanea test for hinokiflavone content? They don't say so. Would it show up clearly on HPLC? I don't know. How much more toxic is it? I don't know. So if you are planning on eating fisetin from this source with gravy like mashed potatoes, just remember that there is no such things as a totally pure chemical. Natural product extracts are especially worisome. If you've been getting away with taking grams of Swanson fisetin, it's this same extract, so you're probably fine.
That's all I've been able to find out. I'll update when I have more.
And just for entertainment for this gerontology list, here is a poem about an old cow in the fall, who is tired of life. It was written by Robert Hillyer and was a favorite of my father's. It mentions sumac. It's called "Moo!"
Summer is over, the old cow said,
And they'll shut me up in a draughty shed
To milk me by lamplight in the cold,
But I won't give much for I am old.
It's long ago that I came here
Gay and slim as a woodland deer;
It's long ago that I heard the roar
Of Smith's white bull by the sycamore.
And now there are bones where my flesh should be;
My backbone sags like an old roof tree,
And an apple snatched in a moment's frolic
Is just so many days of colic.
I'm neither a Jersey nor Holstein now
But only a faded sort of cow.
My calves are veal and I had as lief
That I could lay me down as beef;
Somehow, they always kill by halves, -
Why not take me when they take my calves?
Birch turns yellow and sumac red,
I've seen this all before, she said,
I'm tired of the field and tired of the shed
There's no more grass, there's no more clover
Summer is over, summer is over.Reply
Effects of Fisetin dosing over 6 months.
Now in my 5th round of Fisetin dosing over the past 6 months. Some noticeable effects now that were not apparent in the early rounds. Examples below.
I cannot say all effects are direct result of Fisetin, but effects occur immediately on starting a Fisetin round, and then taper off until the next round.
- Improved balance. At age 76 more aware of balance than in younger years. Fisetin seems to improve it. Example: In front of my apartment building are 4 steps, no handrail. So I used to carefully position myself next to a post and hold on before stepping down. After taking a round of Fisetin, no need to do that, just step down. Surprised me. Is it possible Fisetin is the cause of that change?
- Improved mental function. My main mental challenge these days is learning a foreign language; an extremely difficult, Oriental language (Thai). Each time I take a round of Fisetin there is noticeable improvement in my listening comprehension and reading speed. Modest, but noticeable and very welcome.
- Sharper vision. My vision has been steady for many years, but after recent rounds of Fisetin noticeably brighter and sharper. I’ve even gone without glasses a few times.
- Easier urination. An important function for old men. Flow is certainly greater after starting a Fisetin dose.
- Better sleep, but need to sleep and nap a lot more during the 3 days that I take Fisetin.
- Fisetin (Doctor's Best brand), 500 mg. per dose (5 capsules of 100 mg. each) 2x/day, for 3 days: 6 doses for total of 3,000 mg.
- Olive Leaf Extract: 1 capsule
- Bioperine: 10 mg.
- Quercetin: 1,000 mg (2 capsules, 500 mg. each)
- MCT oil: 3,000 mg. (3 capsules, 1,000 mg. each)
- Coconut oil: 1 Tablespoon
- (no DMSO, although would be easy to take along with coconut oil)
Back when first starting Fisetin, I diligently emptied all capsules and mixed with coconut oil before swallowing. But old age is motivating me to simplify things. Now I just swallow the lot of capsules with water or juice.
I'm very interested in comments, critique and others' experiences over several months of Fisetin dosing.Reply
In contrast to my personal observations about Fisetin just above, here is a more rigorous discussion of effects:Reply
I have been taking 1200mg of fisetin in a single dose for 2 days every month. For the last 2 months, I have taken it every 2 weeks because I have liked the effects I have seen and want to see if more frequent doses will increase improvements. I weigh 125 pounds.
The first noticable improvement was not my own, but my mom's. She has had a nickel size flat mole on her cheek for about 15 years. After 2 monthly sessions, it had disappeared and only a light brown freckle the size of a pencil eraser head remains. She has not done more regular sessions. Because of her immediate significant improvement, I started watching my own moles. Ones that have darkened with age have all lightened and decreased in size, though none of mine have disappeared, but I have had them since I was a child where my mom's came in her 50s.
I have injury onset arthritis in my large toe, and the pain has almost completely gone away. While my toe has slowly recovered, the arthritis kept me even from walking more than 30 minutes at a moderate pace without noticable pain for years.
When I take the fisetin, I feel extra tired for a few days and sometimes random aches and pains or muscle soarness, but it goes away after a few days. My husband felt like he had a sunburn the first time he took it (he is fair skinned and burns easily and sometimes blisters). I attribute the pains and soarness to apoptosis and treat it like I do muscle soreness from exercise- in that I try to eat plenty of protein and nutrients to grow new cells and give my body some recovery time.
I am not currently adding in anything to enhance bioavailability because I am seeing impressive results with just the supplement (Swanson brand). Also, at least the high dose study in rats was straight oral gavage, so I don't feel the need to alter treatment.
As a side note, other supplements I have taken for about 4 years: I take 1T of omega3 fish oil daily (4500mg), NAD+ in the form of 2 Elysium pills a day, I have previously taken Mitoq, but haven't for about 4 months, 4000mg VitD, 1000mg VitC, Children's chewable multivitamin, and a probiotic.
I also fast for 18-24 hours once a month from both food and water.
All improvements listed above were after starting Fisetin supplementation about 9 months ago. I would need to do a little more digging for the exact time.Reply