Fisetin ( + quercitin)
Among flavonoids, fisetin appears to be an effective senolytic:
"Fisetin appears about as effective in mice as any of the current top senolytics, such as the chemotherapeutics dasatinib and navitoclax."
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.
-
Rob8311 Thanks for all the information. Much appreciated.
It turns out that heart disease was a misdiagnosis on my dog. He has now been confirmed with a diagnosis of acute myloid leukemia. He had to stay over 2 nights in an emergency vet care centre as his condition had deteriorated quite rapidly.
He has been home for about a week now after being given the L-asparaginase enzyme. My brother and I have been giving him some CBD oil and Fisetin. For the first few days his condition had improved dramatically. Eating more, drinking more and trying to walk more (his hind leg seems to have been affected by the cancer). His breathing had also improved. However for the last 2 days, he seems to have gone downhill again. He seems more tired than the previous days and breathing a little more rapidly and heavier. He has just gone in for another dose of the L-asparaginase enzyme and we are awaiting his blood test results tomorrow. I have all my fingers crossed right now.
-
HD I can completely identify...
Forgive me if I am muddying the waters, but you might want to visit http://dognasalcancertreatmentforlucy.blogspot.com/. It's just a guy who saved his dog and compiled a ton of anti-cancer info. I notice that research on alpha-lipoic acid is showing it to be good against leukemia. His idea is to throw everything that has been shown to enhance the immune system and/or have anti-cancer properties at the cancer. An odd thing I found was research into a possible remedy called DMAPT, and a particular study mentioned dasatinib (talked about a lot here) as being able to cause molecular remission, whatever that is, in myeloid leukemia (http://www.bloodjournal.org/content/128/22/4242?sso-checked=true).
-
I found a new source of pure Fisetin. It is a company on ebay who advertised 98% pure Fisetin Powder at a cost of 22 dollars for 10 grams. link attached.
-
djmichel Good find. Although the effects of PARP inhibitors and pro-apoptotic agents is likely to be mixed, I am encouraged that life time feeding, at least in this preliminary report, found life extension in wild-type mice. That might increase confidence to use it at least short term in healthy humans.
We may find eventually that fisetin (and perhaps tocotrienols) forms the base of our “senolytic pyramid” or stack.
Always use the least toxic stuff for that!
-
HD Rob8311 This is a late response but I find this "simple practice guide for dose conversion between animals and human"educational and useful.
-
Rob8311 Dear Rob, how do you feel about your dogs on Fisetin? I have a 10 years old lab, he started to hurt from arthritis, so I consider treating him with Fisetin. And how are you?
-
Andriy Urenov Doing OK, thanks. Still grieving. They did fine on fisetin. You can also give fish/krill oil (with breakfast and dinner) and anti-inflammatories like curcumin (prefer Theracurmin). Also really helpful are cold laser treatments if you can find a vet that offers them. It helped so much with inflammation (both me and my dogs) that I bought one!
-
Rob8311 Thank you Rob! I gave my dog first course of fisetin (36 mg/kg x 2 days) and in few days will have the second round. As far as i see he is doing better, more active. Also I am giving him CurcuBrain for like 2 months. I thinks it also helps. Now reading on red light. Which wavelength do you use?
-
Andriy Urenov Hi Andry. You have a lucky dog! My laser uses 637nm for red but the range is 600-660nm. Near IR (800-860nm) is better for most applications, but red helps more with skin and circulation. Look into the Avant LZ30Z at coldlasers.org or wherever. I know it is expensive but was the best $6K I ever spent. I now consider it almost as essential as having a car! Besides incredible anti-inflammatory capability and tissue regeneration, if you apply it shortly after a muscle injury, whiplash, or a burn you will annihilate the after effects. A whiplash that could lead to permanent damage will be gone the next day. You won't have pain or blisters following a fairly serious burn. I used to get arthritis in my knees that would make it almost impossible to go down on one knee. After 5 minutes with the laser I could do burpees! It was short term relief in that case, but still... My dogs would stop limping. I am saving for a more powerful EvoLaser to reduce treatment times. I am not wealthy, but after being initially skeptical I am sure I will always own at least one cold laser.
-
Rob8311 Hi Rob! Still on here, would like to ask you some questions!
-
Arizona Kid Sure
-
Rob8311 Do you have an email? Wanted to ask you questions about protocols for dogs. My 13 year old is having dementia signs. I have her on rapa but wanted to add Choline, melatonin and fisetin.
-
Arizona Kid heavy metal toxticity from vaccins. long road ahed with chelation is the cure
-
Burgundy Summer for my dog? I don’t think she had many vaccines
-
Rob8311 Do you have an email Rob :)?
-
Arizona Kid one would be enough, they are loaded with mercery, lead n alumium. a animal doc i know also said this is the reason. old humans fall apart from the metal toxticity and the same is with animals
-
Arizona Kid Send me a message - click on pic circle.
-
-
I've been taking 1 quercetin and 1 fisetin in my daily supplement regime. I'm considering joining the self experimenters/testers here, but the problem is I wonder how much change I'll be able to show since I'm already doing many of these (e.g. NAD+, quercetin, fisetin, fasting, etc)
-
And they used human adipose tissue explants (voluntary liposuction!) to see if results translated. They did!
-
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.
-
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.
-
Fred Yeganeh - As I understand it, Fisetin probably induces apoptosis (in cancer cells, senescent cells, and possibly persistent myofibroblasts) primarily by inhibiting antiapoptotic Bcl-2 family proteins, including Bcl-xL.
-
-
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!"
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. -
A great review of Fisetin as senolytic agent.
https://brain.forever-healthy.org/display/EN/Fisetin+Senolytic+Therapy
-
Steve Harris said:
Summer is over, summer is over.Wonderful post above from Steve Harris I'd give it 5 "likes" if that was possible.
