Fisetin ( + quercitin)

Among flavonoids, fisetin appears to be an effective senolytic:

https://www.fightaging.org/archives/2018/10/animal-data-shows-fisetin-to-be-a-surprisingly-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.

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  • How much fisetin is required? It seems to come in 100mg capsules.

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  • 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. 

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      • Rob8311
      • Rob8311
      • 7 mths ago
      • Reported - view

      David Michel Not sure that trying to notice how you feel is the best course.  I just had blood taken and want to see liver values change (ALT, AMY, ALKP) because fisetin helps with liver oxidative stress, and also a decrease in systemic inflammation (measured by CRP, C-Reactive Protein).  If we can see evidence that our organs are in better shape, that's a big plus.  Two grams 2x looks reasonable.  I have been watching some friends take bottles of 100mg fisetin and can't help but think their results (mild but positive) are suggestive of doses that are too conservative. I wouldn't be surprised if more is better.  Most fisetin out there is Novusetin by Cyvex, so whether you get Doctor's Best or Swanson you are basically getting the same stuff.  Incidentally, my two elderly dogs (who have also had blood drawn prior) have shown slightly more energy, mobility, and calmness (and slight stomach upset) after 800mg fisetin over 3 days.  Doing another course now with them and will check blood values for all of us in a month or so.  A friend recommended LE CRP and chem/CBC blood tests.  I can afford those but not the recommended $695 tests.

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      • Rob8311
      • Rob8311
      • 7 mths ago
      • Reported - view

       Rob8311 Is the Trillium 50g of fisetin?  It says it is 5 herbs.

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      • djmichel
      • CDR Phx
      • djmichel
      • 7 mths ago
      • Reported - view

      Rob8311 My Trillium Fisetin does not indicate 5 herbs,  it does say it is from Gleditsia thorn  powder. 

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      • djmichel
      • CDR Phx
      • djmichel
      • 7 mths ago
      • 1
      • Reported - view

      Rob8311 Yes I agree with you, it would be nice to be able to afford all the recommended tests.  However I will, as you, have to follow my normal every six months test that my Doctor will recommend.  But because I can't afford a regular regime of 700 dollar tests, and hoping that I will be selected for some study is unreasonable to me, so I cautiously self experiment after reading all I can and approaching with an open mind.   While I have recently tried several protocols I do wonder if there is some synergistic effect.   I have recently noticed very positive results from my D+C protocol last month. 

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      • Rob8311
      • Rob8311
      • 7 mths ago
      • Reported - view

      David Michel  Guess I looked up the wrong one, sorry.  Great to know you had a good result from D+Q, the next thing I will try.  I wonder if using BioPerine to boost bioavailability would help with fisetin.  It is used with the flavonoid curcumin.

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    • djmichel Note the stuff from Trillium is not 100% fisetin, but raw fisetin-containing herb (Gleditsia thorn powder). It might be anywhere from 10% to 50% fisetin. Or less than 10%, since Trillium doesn't actually test it, and it's not standardized. It's a rather severe case of "deception by unclear labeling."

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      • djmichel
      • CDR Phx
      • djmichel
      • 6 mths ago
      • Reported - view

      Steve Harris Thanks for the info....do you have another source?

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    • djmichel Not immediately. I had been using Swanson's, but that's already been mentioned.

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    • Rob8311 You're a bold man feeding that much bioflavonoid to a dog. Dog's don't have primate livers, and things like chocolate are quite toxic for them. It's hard to know what a dog's metabolism is going to do with a basic plant extract.

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      • Rob8311
      • Rob8311
      • 6 mths ago
      • Reported - view

      Steve Harris If you are implying I am bold because there was no risk to me, or assuming I didn't consider toxicity before trying this, your point would have been equally effective without the sarcasm.  I read everything I could get my hands on, consulted with an expert in the senolytic field, and agonized over the dosage.  There seems little point in taking a risk with a dose which will make you wonder later on whether you gave enough to make a difference.  Since animal data was what started the interest in fisetin, primate comparisons don't seem applicable.  Also, do you know what a large amount of bioflavonoid is?  I spend countless hours looking into ways to keep my dogs youthful, and since they are 15 and 16 with an expected lifespan of about 13, I might be doing OK.  Some possible fisetin benefits I weighed against the risk:  heart health, improvements in throat tissue, healthier kidneys, healthier skin, better immune system without senescent T cells, less systemic inflammation, and less oxidative stress on the liver (mentioned in the latest study), to name just a few.  So far I have noticed they have a mild increase in energy and mobility and fast hair regrowth.  I had blood data taken from both dogs before fisetin that I will be comparing against soon.

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    • Rob8311 I mean "bold" by feeding some stuff to your dogs which has never been fed to dogs before (at least not in the recorded science literature--I cannot find one report of dogs and fisetin). You really need some regular lab tests (liver and kidney) and a dose-escalation study for that.

      Senolytics are from animal data, but those animals are RODENTS. Which are omnivores and famously capable of eating just about anything, quite like pigs and humans. But animals differ in their sensitivity to plant products, which is why rabbits and ruminants can feast on the nightshade plants and berries that would kill you or me. And humans and rodents can eat all the chocolate, garlic, onions, grapes and raisins that we like, and we have a good tolerance to ethanol, but these things are toxic (sometimes astonishingly toxic) to meat-eating cats and dogs, which cannot easily metabolize things like thiosulfate, caffeine, theobromine, and the like.

      Here's another one: xylitol which is used as an artificial sweetener, is tolerated by rats and mice, who eat as much as they like. As do your kids on Halloween. But just a few candies can take out your dog.

      So you never know. Dogs cannot eat many raisins and grapes, but apparently tolerate grapeseed extract. And sillymarin and some citrus bioflavonoids. So you got away with fisetin, it appears. But don't ever think that just because rats eat something in a study, and you eat it in unregulated pills from the supplement company, that you can feed the stuff to Rover. Next time, especially with plant-based products, you may guess wrong.

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      • Rob8311
      • Rob8311
      • 6 mths ago
      • Reported - view

      Steve Harris Sorry if I overreacted, and I appreciate your concern for my dogs.  However, "got away with fisetin" doesn't describe the situation for me.  My view of old age is there is less to lose and more to gain with experimentation.  We should set our risk levels according to our philosophy of life.  My dogs, fortunately or unfortunately for them, as my wards, will experience my level of risk.  I think a chance to recapture some lost youth is worth considerable risk when the alternative is an uncomfortable decline.  My dogs are at a very advanced age, but are surprisingly full of life because of some of the things I have tried.  We are at a point in history where to wait for studies to guide our choices will often mean missing opportunities completely.  It is possible I added 10% or more to their lifespan and improved their healthspan, which would be amazing. If they were younger it would be a different calculation.  Caution should inform our decisions, but at least for me should not be the only factor.

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      • cacarr
      • cacarr
      • 6 mths ago
      • Reported - view

      Rob8311 Steve Harris

      For what it's worth, itchy dogs are quite regularly fed quercetin (no proper studies, but a plausible mechanism) -- which is very close to fisetin. 

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      • Ellie
      • Ellie
      • 3 mths ago
      • 1
      • Reported - view

      Rob8311 I think it was you, Rob, who turned me onto fisetin and LDN and Tagamet for my dog with cancer. (diagnosis 17 months ago, now).  I find balancing the risk vs potential benefit pretty straight forward for a dog (age ten and a half, life expectancy 9-11) with cancer--it changes the ratio considerably.  I gave him 800 mg for three days.  After that I started Tagamet.  When those were tolerated, started 2 mg ldn.  I do not know which of those have made the difference, but his activity is way up, and he appears to feel much better.  The recent vet visit told me the tumors had not grown in 7 month with my nutritional supplements he got (Omega 3, minerals, vit D, lots of antioxidants) and he's also now on rapamycin.  Careful reading of all the info, but I figure he has nothing to lose and a lot to gain potentially.

       

      On another note I finally tool 1200 mg fisetin myself, for three days.  It seemed to make me very tired, dragging even.  Short term tho.

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      • cacarr
      • cacarr
      • 3 mths ago
      • Reported - view

      Ellie - I would not be surprised if senolytic cell ablation can cause some fatigue -- maybe proportionate to the quantity of cells undergoing apoptosis. Seems plausible.

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      • Rob8311
      • Rob8311
      • 3 mths ago
      • Reported - view

      Ellie That is really cool! One caution is if the benefit is from the LDN and you stop it, the disease may resume its course. That's because the LDN will no longer fill the receptors that control proliferation. Just for kicks, visit http://dognasalcancertreatmentforlucy.blogspot.com/. Tippner is not a web designer (!) but he saved his dog Lucy and lists a ton of anti-cancer possibilities without taking great care to credit the source (innocently I believe). He mentions some Chinese tumor busters and just about everything else. Reading his blog helped inspire me not to give up. I would say one you can add with little risk is hemp-based CBD oil. My pups get it every day in their food.

      cacarr is right.  An exec at one of the senolytic companies told me that temporary flu-like symptoms are likely.  These will vary from person to person.

      Perhaps apropos of little, except to show that doctors don't know everything: My 15 year old dog ShuShu went in for her 2 year pacemaker (for SSS) checkup, which involved an ECG. The cardiologist came in and told me the pacemaker is working great and ShuShu's mild valve disease is stable. Then she gets a funny look on her face, and says, although ShuShu had a somewhat dilated heart at our last checkup, it has returned to its normal size!!!  She said dogs with heart disease aren't expected to improve.  Although she is probably thinking there was some measurement error, I am sure it was either the fisetin treatment or IV stem cells or both.  She clearly had no place in her world for such an occurrence and wasn't even curious about what might have caused it.  She just told me to keep doing what I'm doing!  When they tell you there's no hope, like with cancer, Cushings, heart disease, disc disease, etc., there are always things to try if you don't give up.

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      • Ellie
      • Ellie
      • 3 mths ago
      • Reported - view

      Rob8311 

      Thanks for the link!  Yes, I figured that most of what I am doing (for both of us) is going to be for life.  The nutritional things I gave to the dog (Omega3, antioxidants, vit D, few herbs etc) for about a year kept the tumors static but they did not regress.  Thuse I am grateful for the 'big guns' (rapamycin, LDN, Fisetin, and tagamet) and figure they are forever.  The cost has reached the point of "nothing new now" especially on top of all meat diet for the dog.  Keeping on keeping on, and at least he is feeling good regardless of the disease, at a pont most have succumbed.  Appreciate the help!

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      • HD
      • quartz_mitten
      • 1 mth ago
      • Reported - view

      Rob8311 How did you work out the Fisetin dosage for your dogs? My elderly dog has recently been diagnosed with heart disease and I'm wanting to try and give him Fisetin to see if it would help. My dog weighs around 11.5kg, so trying to work out what dosage I should be giving him.

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      • Rob8311
      • Rob8311
      • 1 mth ago
      • 1
      • Reported - view

         HD I used 20 mg/kg for 2 or 3 days as in the Mayo study.  First I would try a smaller dose to make sure he tolerates it.

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    • HD Allometric scaling (converting doses between one species and another based on body size differences) is not an exact science. But the factor for converting between dogs and humans is typically taken to be 1.8; that is: to get the dog dose from an appropriate human dose, multiply by 1.8. If 20 mg/kg bodyweight is the right dose for a human (myself, I used 35 mg/kg bodyweight), then the dose for a dog, based on the (of course somewhat arbitrary) factor of 1.8 would be 36 mg/kg bodyweight.

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      • HD
      • quartz_mitten
      • 1 mth ago
      • Reported - view

      BrianMDelaney Rob8311

      Thanks for the advise. Much appreciated. I will give this a go and see if it makes a difference for my elderly dog.

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      • Rob8311
      • Rob8311
      • 1 mth ago
      • Reported - view

      HD For heart disease (my dog has a pacemaker for sick sinus syndrome, and also has slight myxomatous mitral and bicuspid valve disease) you might want to consider Hawthorn, d-ribose, and CoQ10.  ShuShu gets a 50mg Quinogel (water soluble CoQ10 for her mitochondrial health) with every meal, a sprinkle of Hawthorn phytosome once per day and a sprinkle of d-ribose with meals (I notice a definite energy pickup with this).  These should be harmless, but do your own research and talk to your vet.

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      • HD
      • quartz_mitten
      • 1 mth ago
      • Reported - view

      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.

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      • Rob8311
      • Rob8311
      • 1 mth ago
      • Reported - view

      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).

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  • 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)

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  • And they used human adipose tissue explants (voluntary liposuction!) to see if results translated.  They did!

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  • 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.

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  • 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. 

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      • cacarr
      • cacarr
      • 3 mths ago
      • Reported - view

      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. 

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