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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  • Also - it seems that we need to figure out how quickly you can cycle.   One very 6 months would take for ever to see an effect.   Why not 3 days on and one week off?

    Like
      • Karl
      • Karl.1
      • 1 yr ago
      • Reported - view

      Robert Olin you are making the assumption that more is better? 

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      Karl Voice of reason! I think the best approach is to mimick for now Walter's Longo's fasting protocol  translating it to senolytics on how often depending on your personal physical shape. Once more studies are done, hopefully on monkeys, we will know better on how to proceed with senolytics.

      Like
  • i guess I'm in a hurry.  In two months I'll be 70 and my lower back is killing me.  And that's after back surgery about 2 years ago.    Thanks for the link to Senescent Cell Aging.  Lots of information.  

    Like 2
      • Karl
      • Karl.1
      • 1 yr ago
      • Reported - view

      Robert Olin I don’t mean to rain on your parade. I’m glad you’re here and getting involved in senolytics. There is great potential to slow or reverse aging.  Unfortunately there are very few human studies available on senolytics, so it’s difficult to determine the correct dosage or frequency.

      a few quotes from the recent fight aging newsletter:

      “The growing numbers of senescent cells in older people (and even larger numbers in older obese people) contribute to near all conditions of aging. Removing them has proven to be very beneficial in animal studies, reversing the progression of numerous age-related diseases.

      A global, always-on mechanism to remove senescent cells has been shown to improve health and longevity in mice, but is probably not a good idea for human medicine. Senescence is a harmful process only when it runs awry, when senescent cells accumulate over time. Senescent cells are constantly created in a youthful metabolism, and serve useful purposes in suppression of cancer, wound healing, and other processes. “
       

      so, as with many things in medicine, just because a little is good does not mean more is better. And even if more is better, we don’t know how much more yet.

      Like
      • Michael
      • Michael.1
      • 7 mths ago
      • Reported - view

      Robert Olin "i guess I'm in a hurry" Best anti aging forum line ever! I am so there too.

      Like
  • It would be great to share before and after blood test like JGC  did. Especially so medium and long term tests to see the progress. 

    Like 1
  • This all comes from Dr. Green's site.   https://senolyticstreatment.com/  at bottom of site.  also, EXCLAMATIONS, and clinical trials.

    12. THE NEW ANTI-AGING FORMULA

    Rapamycin

    Dasatinib

    Fisetin

    Zithromycin

    Doxycycline

    Vitamin C

    Metformin

     

    Dose and Interval

    Rapamycin 3-6 mg; once a week

     

    Dasatinib 50 mg capsules;  2 capsules a day for 3 days; once a month to 4 times a year.

     

    Fisetin 100 mg capsules; 1500 mg once a day for 3 days; once a month to 4 times a year; taken with Dasatinib.

    [Quercetin 1000 mg can be use in addition to Fisetin]

     

    Zithromycin 250 mg tablets; 1 tab day for 6 days; once a month. 

     

    Doxycycline 50 mg capsules, 1-2 capsules a day.

     

    Vitamin C capsules; 250-500 mg a day.

     

    Metformin ER, 500 mg 1-4 tabs a day. 

     

    Other valuable drugs:

    Statins

    ARBs (candesartan)

    Tadalafil

    Like
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • 1
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      Van Thanks for the list. I would be careful of the doxycycline. It has side some side effects.

      From Podiatry Today:

      "Researchers have now shown fluoroquinolones triple the risk of tendon rupture and the risks increase with age as well. Over the years, there have been increased reports of tendon rupture and tendinitis with other antibiotics, such as tetracyclines, doxycycline and macrolides (i.e. azithromycin)."

      My dad had bad tendon issues with it. Some people will have tendons snap after taking it, though that was for antibiotic dosing. Just want people to know.

      Like 1
    • Van 

      Other valuable drugs: Statins

      https://www.youtube.com/watch?v=inwfSkSGvQw 

      Enjoy your post Van, they are always very useful. If it's not too much trouble when you get a chance take a look at this video from Dr. David Diamond PHD and post a comment if you don't mind. I'd like to hear your take..

      Like 1
  • @Van interesting  stuff. The doses by themselves seem moderate. That said together it seems a lot. I take 2mg rapamycin from Walmart once a week. Rapamycin by itself has quite an effect on me. Feel a bit like fainting sometimes, my skin itches a bit sometimes, extra thirst, shivers, brain impact during the first couple of nights after taking. Without rapa I’m in very very good physical shape. I’m concerned that without studies on monkeys first to see what this drug cocktail does just from the safety perspective put aside if it does anything for longevity, we are taking too much risk. For our safety I think we should first focus on setting up and sponsoring such studies. 

    Like
    • Joe smith rapa is not very toxic at all - people have tried to OD on it with 100 mg and nothing happened

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      Paul Beauchemin Well, temporary spike in the cholesterol happened in the case you brought up. Basically, young transplant patient tried to kill herself.  That said I do agree that real Rapa (I don't know about that stuff some of people on this forum buy from websites in India or China, etc.) is not very toxic. I wouldn't take it myself otherwise.  That said my sides are real and not imagined. I'm saying that potent drugs have interactions and you need to test them on monkeys first. For instance, Rapa makes it already harder for me to heal quickly. Senolytics remove senescent cells interfering with healing when you take them. Taken together it may overwhelm the system and you may be then walking around scaring people like Dr Peter Attiya does by opening his mouth and showing what Rapa did too him.  So in the summary could you make your point clearer as I'm not getting why you are bringing Rapa lack of toxicity up? (I assume that you are not just trying to dismiss my first-hand experience but trying to say something else?)
       

      Like
    • Joe smith you do know that rapamycin has been taken in daily doses higher than your once per week dose in transplant patients for 2 decades with no issues?

      Like
  • Good point about statins and longevity. Statins work in just a small subset of people with specific type of ldl and then not very well. Basically if your ldl is of smaller type you need something, to reduce it. But this info can only be hypothesized from the standard lipid test. That is if your Hdl and triglycerides  are good, Then your ldl is very likely to be a big fluffy type and hence nothing to worry about. even if it is above 130. That said you really need a specific test for it to know for sure. And yes in cases of  very high triglycerides, high ldl and low hdl, You need to do something and sometimes all you have are statins. Further , Statins may reduce inflammation. But do they do it as well as some other drugs or even aspirin? I doubt it because they really don’t lengthen the lifespan overall in nearly all the cases. The do benefit some though.

    Like 1
      • Van
      • Van
      • 1 yr ago
      • 1
      • Reported - view

      Joe smith Statins save lives my reducing the soft plaque in arteries that break away and cause cloths which cause heart attacks, and strokes         https://www.youtube.com/watch?v=ilu-TiWMmLM

      Like 1
      • Joe smith
      • Joe_smith
      • 1 yr ago
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      Van This video from Dr Brewer is about CIMT testing and plaque/calcium in the arteries and not on the treatment and whether statins OVERALL reduce mortality risk. And yes, I respect Dr. Brewer and it is a good video and yes let’s get CIMT tested. Now, the argument I’m making about the statins goes like this. I'm not at all saying that in all people with atherosclerosis high ldl-c statins are useless. Not at all! What I'm saying is 1) Not all people with high ldl have or will get atherosclerosis. Hence, CIMT test is important to really diagnose 2) If advanced lipid test shows the issue and CIMT indicates problem, then sure take statins. Your case most likely will benefit from them. However, in a subset of such cases, statins won't help much due to the fact that they only lower your overall level of ldl-c. They do nothing for the LDL-c type, you don’t get more larger LDL-cs and fewer smaller LDL-cs with statins. So even though they reduce overall count, you can still get heart attack even with your lowered ldl.  In some cases, PKCS9 inhibitors may be smarter way to go or need to be combined with statins 3) Going back to calcium in your arteries sometimes little K2 can help too. So in summary 1) I’m not condemning statins just pointing pout limitations and the fact that we need better more targeted drugs to save even more lives.  2) If we are going to be taking that drug cocktail for anti-aging and taxing our liver, do statins really make sense in otherwise healthy person- e.g. male with 80 HDL and 100 triglycerides?  Or should we be taking something else? I’m thinking let’s look for something better/different in our drug cocktail. That said, I’m open to data driven science discussion and changing my mind.

      Like 1
      • Van
      • Van
      • 1 yr ago
      • 1
      • Reported - view

      Joe smith You stated:  "This video from Dr Brewer is about CIMT testing and plaque/calcium in the arteries and not on the treatment and whether statins OVERALL reduce mortality risk."

        Here is the video where the trial had to be stopped because there was a 50% reduction in CV events when on Crestor.  Very large trial 17,000+.  90% of all CV events are caused by inflammation which causes the formation of "hot plaque" ie. soft plaque, which will cause the formation of blood clots when it comes in contact with blood stream in artery.  A simple and non-evasive CIMT will tell you if you have soft plaque or not, and if so, you have inflammation, and then you start Crestor, 5 mg. or less to reduce inflammation and reverse that plaque build up. (Dr. Brewer is poster boy for this reversal)  Easy to follow up with another CIMT to judge results.  Not all statins are same in reducing inflammation, low dose Crestor is best.  High statin dose is not needed unless very high LDL of 200+   You are basically treating inflammation, not trying to lower LDL. 

      https://www.youtube.com/watch?v=SWs30V3gDNQ

      Like 1
      • BobM
      • BobM
      • 1 yr ago
      • Reported - view

      Van Hi Van/ Joe/others

      Crestor is interesting. Here is another study:

      https://www.birminghammedicalnews.com/news.php?viewStory=362
      it was a 40mg dose.

      I have been on Lipitor/Atorvastatin for 19 years (now 69),  10mg then 20mg. Lost ALL my weight slowly over that time and controlled my diet to manage adult diabetes. And ate super heart healthy for Last 15+ years. Excellent blood work etc.
      Last month I was not feeling right. Went to ER. I now have 2 stints. I had 95 and 90% blockages. Docs said I had bad genes. 

      Anyway, plaque buildup happens, often in spite of all the healthy things we talk about. More so in men.

      Crestor is very interesting to me and I’m pushing my cardio doc to switch me over from the current 40 mg dose of a Lipitor. this change may have a much greater impact on life extension than many others, for me.

      Although ldl/hdl was excellent, I just do not see that Lipitor/statin was doing much to reduce My plaque or its buildup. I do not see the benefit in continuing it. 

      Your thoughts?

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • 1
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      BobM Please see my other post recent post on the subject. I'd advise that you reach out to Tom Dayspring ASAP. You need solid cardiologist (i'm not) with experience and wisdom to guide you and not somebody blaming "your bad genes" - his contact https://www.doximity.com/pub/thomas-dayspring-md

      Caveat: I don't know Tom Dayspring but I listened to his super technical four episodes and if I were you I would call him ASAP. Second opinion can't hurt.

      Good Luck and Get well!

      Like 1
    • BobM You might want to take these 2 supplements:
      1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566462/
      In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. An adequate intake of vitamin K2 has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K2, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels.
      2. https://pubmed.ncbi.nlm.nih.gov/22260513/
      Nitric oxide (NO) has led a revolution in physiology and pharmacology research during the last two decades. This labile molecule plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. Currently, it is known that NO synthesis occurs via at least two physiological pathways: NO synthase (NOS) dependent and NOS independent. In the former, L-arginine is the main precursor. It is widely recognized that this amino acid is oxidized to NO by the action of the NOS enzymes. Additionally, L-citrulline has been indicated to be a secondary NO donor in the NOS-dependent pathway, since it can be converted to L-arginine.

      What you need to do is intermittent fasting. That is to say, have an early dinner and late breakfast with nothing between dinner and breakfast.

      All the best.
       

      Like
      • Van
      • Van
      • 1 yr ago
      • Reported - view

      BobM   You have really done a lot of things correctly.  Lost weight.  If you blood glucose and insulin resistance is good, then your main problem in my mind is the inflammation in your arteries, and  the genetic factor.  Your doctor put you on the wrong statin, Lipitor very good at reducing LDL, but not so good at reducing inflammation.  If I were you, I would switch to Crestor 5 mg. daily for 3 months then have a CMIT done at once to see a base line, and then another to check if it is working.  ( CMIT will measure your calcified plaque diameter in your artery walls, as well as looking for soft plaque.  If working could possibly lower the dose, if not then up dose. 

      I would not put much faith in your Doctor, this is a fatal mistake on his part to not know about arterial inflammation. (you have stents because of inaccurate treatment)  Should have ordered CMIT as a screening tool, and  a DNA test for genetic screening.  You need a doctor such as Ford Brewer who specializes in Preventive Medicine, and teaches it to other Doc's.  Dr. Brewer has many video's and will also hold an examination of you on line or in his office, and write Rx's.  Licensed in 46 states.  He is up on treating for people like you that have a genetic problem, because he also has bad genes.  I believe you would also  benefit from Rapamycin at your age, you have to slow down the ageing process, and the best way to do that is Mtor inhibition.  At 74 yo, I had a CIMT yesterday, and I have the arteries of a 65 yo,  no soft plaque and calcified plaque was below average.  I take 5 mg crestor daily.   Dr. Brewer has some of his patients on 2.5 mg Crestor 3 X week.

      Here is a video specifically talking about Lipitor, and other Statins.  https://www.youtube.com/watch?v=Yp9nvc65HiQ

      Good Luck!

      Like
      • Van
      • Van
      • 1 yr ago
      • Reported - view

      BobM Bob, forgot to include this video from Dr. Brewer on the "heart attack gene"

      https://www.youtube.com/watch?v=RJrltDmVPuE

      Like
  • @Van i’m not disagreeing with what you just have Just replied with. And yes the most prudent approach would be to reduce inflammation and especially so in cases like diabetes when dealing with arterial plaque formation. And yes I’m quite aware that statin beneficial effects may be due to potential inflammation reduction. And I’m not against people taking statins when prescribed by md to treat arteriosclerosis. I’m just concerned about the use of the statins for anti-aging when you don’t have any underlining conditions. Let’s say Your blood pressure is 100/60 your hdl is 80 your triglycerides are 100. You are healthy. there is no plaque in your arteries. You just happen to be 60,  Is this the best course of actions for you to take statins? I say no. Will you advocate everybody to take statins for anti-aging? I say no way. There is a cost of to taking statins and your liver will pay for it. You may even live shorter if you do. Are there better alternatives? I say yes: cr,if, exercise, sauna, eat your veggies + fatty fish. Why? Because they actually can affect Together your ldl-c  type which statins Can’t do. Statins are just the second gen drugs. We need the third gen ASAP. Now if you are doing senolytics  you must take special ldl-c precautions but we can chat about it some other time.

    Like 1
      • Van
      • Van
      • 1 yr ago
      • 2
      • Reported - view

      Joe smith You are right Joe, Dr. Brewer does not prescribe statins to anyone who does not have inflammation in there body, and evidence of disease and when he does it is usually a very low dose.   Everyone has inflammation in the body, just a matter of degree.  The older you get the more  build of plaque in your arteries.  Babies have plaque in there arteries, and it builds up slowly throughout a persons lifetime.  Because ultrasound is safe, they have scanned children also.   And if you are one of the very few people who can control there weight, exercise properly, have good genetics  then you probably do not need a statin, until your older.   But most of the people on this site are older, and part of the aging process is inflammation.  We have 2 test to measure it.  There are a few people with certain genetic profiles that are unaware of there problem.   CIMT, and urinalysis of the microalbumin/creatine ratio.  Both measure inflammation.  Both are screening tools, but you can also follow your progress on follow up tests.  These tests are non invasive so safe to use.   Inflammation is not localized, it is everywhere. The main driver is insulin resistance.   If you have a problem in your kidneys, you will also have it in your cardio vascular system in the arteries.  The arteries have a Medial layer which is layer that separates the artery wall from the lumen where the blood flows.  Inflammation attacks the Medial layer of the arteries  in the kidney's as well as the arteries throughout the body including the one's supplying blood to the heart.  So two of the main diseases afflicting older people are these two, and you have 2 save and relative inexpensive tests that will let you know where you stand.  At that point you can make a decision how to attack the problem or not.

      Like 2
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • 1
      • Reported - view

      Van Isn't that scary about even children and young men having plaque build up? I blame it on our misguided dietary guidelines that got perverted by the processed food industry and lead us to replace fats and proteins (including healthy ones) with processed carbs (eggs-->cocoa puffs.) Statins are proven to work. Stats show that the number of infarctions is highly reduced nowadays from the pre-statin area. And no it is not due to power and superior taste of cocoa puffs. And yes actually people should get tested and based on the outcome decision needs to be made made jointly with physician on how to proceed. So in summary I'm all for the test based medicine and less is more approach. 

      Like 1
    • Joe smith not sure what you base your statement on "statins are proven to work"

      All the research I've done shows that of 100 people that take statins only one will have a lower risk of a cardio event. No effect for the other 99. They cause lots of muscle problems and on balance don't look like useful drugs to me

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
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      Paul Beauchemin Hey Paul, I'm basing it on guidance opinion of of American College of Cardiology supported  by substantial meta study: https://www.acc.org/latest-in-cardiology/articles/2016/11/17/09/03/summarizing-the-current-state-and-evidence-on-efficacy-and-safety-of-statin-therapy

      "In a meta-analysis of 27 randomized trials and 174,000 participants, for every ~40 mg/dL LDL-C reduction with statin therapy, the relative risk of major adverse cardiovascular events is reduced by ~20-25%, and all-cause mortality is reduced by 10%. More intense statin regimens yield a 15% further proportional reduction in major adverse cardiovascular events compared to less intense regimens."

      Now if you want more color and hear it front the frontlines and get balanced view then check out what Thomas Dayspring, M.D., FACP, FNLA, a world-renowned expert in lipidology said over the course of 4 episodes - https://www.youtube.com/watch?v=xJ6X81Gn83Y He actually practiced in the seventies and saw what went on in the hospitals then.  He provides extremely balanced view where he advocates for small statins + PKCS#9 inhibitors, the view I share. You know no megadoses and being very cautious. 

      I don't want to preach; but, in summary when you make major treatment decisions/statements/give advice make sure that it is data driven and let meta studies like Cochrane review or equivalent guide you. 

      Like 1
      • Iðunn
      • Iunn
      • 1 yr ago
      • 1
      • Reported - view

      Joe smith  @BobM @Gary_Gilley @Paul_Beauchemin @Van This thread is for the use of fiseting for clearance of senescent cells. If you guys want to talk statins, or rapamycin, or sourcing for dasatinib, or anything else, will you please start a new thread for that purpose instead of cluttering up this one with extraneous discussion (and sending everyone on the thread an alert each time)?

      Like 1
      • Van
      • Van
      • 1 yr ago
      • Reported - view

      Paul Beauchemin Paul here is a video about the Jupiter study on "statins are proven to work", but on inflammation not on LDL lowering effect although they do both.  It is the inflammation that kills most people and not usually high LDL.

      https://www.youtube.com/watch?v=SWs30V3gDNQ

      Like
      • Van
      • Van
      • 1 yr ago
      • 2
      • Reported - view

      Joe smith Unfortunately most doc's are trained to treat disease instead of preventing it, and the consequences for many patients is not good.

      Like 2
  • Just wanted people to know. Apparently, people other than just my uncle and I have experienced a decrease in arthritis symptoms with fisetin use. The Navy is sponsoring a study to look at the effects of reducing osteoarthritis using the same dosage as the Mayo Clinic's frailty study. 20mg/kg. I am excited for this research because I have noticed such a big difference in my life, and I hope this will lead to helping more people.

    https://clinicaltrials.gov/ct2/show/NCT04210986?term=Fisetin&draw=2&rank=3

    Like 2
  • @Fairy8i8 Indeed great to see formal study planned but lets' wait for the safety outcome before we start everybody on senolytics. OK?  Now I don't doubt that senolytics remove senescent cells. (And yes, Fisetin appears to be safer than others.) And I have zero doubt about what excessive senescent cells do to our bodies. That said when you remove senescent cells quickly you overwhelm your body regeneration and you may cause fibrosis or worse- https://pubmed.ncbi.nlm.nih.gov/32485135/

    That’s why I suspect our bodies (immune system) are less vigorous in clearing senescent cells as we age. Our body got little to replace it with, so it does a clever evolutionary trick of keeping senescent cells around by making them play some positive role too. If you remove senescent cells and don’t regenerate, this will impact quality of your life down the road. Your regenerations goes downhill after 60…..You are younger, below 40 so your regeneration is still mostly ok.  The senolytic researchers are aware of regeneration  limitation and are working on it to combine it with even better targeted senolytics. All that said low dose Fisetin or Quercetin on daily basis may be harmless and who knows it may help somewhat with slowing down senescence (well the research is encouraging so far).

    So in summary I'm all for slowing down senescence for now but concerned about senolytics even Fisetin in mega does until we have more studies on safety and side-effects. Now if you want to experiment at your own risk with senolytics than I'm ok but please do so in organized manner. Please produce detailed records, like what you took, dosages, when, your hopefully frequent physical exams results, comprehensive blood tests, weight, blood pressure, lipids (if you read the paper i put the link to, you will know why).  Those records will benefit me and others who may build on your own self experiments.  And again than you for sharing good news about the study! 

    Like 1
    • Joe smith Joe, that is a very strange thing to say to fairy8i8. You are giving her permission to use fisetin but then you insist she provides detailed records.  Do you happen to be a politician or something. You seem to like to control others and make decisions for complete strangers for "their own good"

      Can you clarify who are you and why you think it is ok to decide things for other people?

      Like 3
      • Endless
      • Simone_Maher
      • 11 mths ago
      • 1
      • Reported - view

      Joe smith I find your point interesting. Many people into life/health span extension are also trying other pathways/modalities to address this issue. Treating senescence is just one "pillar" of a strategy. Regeneration is just as important...that is where exosomes, peptiedes, red light therapy etc. come into the picture.

      @fairy818

      Like 1
  • You are right regarding scientific aspects of such self experiments.

    For me the first cycle was no fun at all. It involved some stomach pain followed by diarrhea on the first day why i extended the intake for an additional day, and feeling uncomfortable and somehow weaker in general on the next days.

    The only measurable parameter i have is nightly HRV which increased about remarkable 30% since one week compared to my baseline (2 years). Unfortunately, i did not find any studies regarding the intake of senolytics and elevated HRV values. Any hints are welcome. 

    Like
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      Need Help What was your dose and ingestion method? What else do you take?

      Like
  • I believe it's been discussed but with so many thread...........What is a good brand for Fisetin 500 mg tablets or capsules.   I was looking at on on amazon and the comments said it was false advertising and it was in reality only 250 mgs.

    Like
  • Just received my order for Fisetin 50 grams and Dasatinib 5 grams from China.  No problems with Customs was shipped via Fedex.  Fisetin was $2.50 gram including $25 Fedex.  Dasatinib was $20 gram + $25 shipping.  I received exactly 50 grams of Fisetin, and 5.6 grams of Dasatinib.  Over paid for Fisetin, better to order online.  Dasatinib and Rapamycin also are such small amounts that they can ship in an envelope and less likely to have a problem with customs.  Dr. Green is now recommending to take Fisetin and Dasatinib together and you can skip or not quercetin because Fisetin works better.  Green recommends 1500 mg Fisetin x 3 day x quarterly for anti ageing.  I prefer to use Mayo clinic's formula of 20mg/kg.  On July 01, 2020, I will take Fisetin 1700 mg x 3(with olive oil) + Dasatinib 100 mg x 3.(quarterly)  The next week will  take 250 mg Zithromycin x 6 days (quarterly)  Will try taking Vitamin C, 500 mg with all of the above.  These 3 drugs target 3 of the 4 senescent putrid cells, (aka, zombie)  WIll be waiting for a treatment for the 4th. cell type.

    Like
      • JGC
      • JGC
      • 1 yr ago
      • 1
      • Reported - view

      Van 

      What is the contact link for the Chinese firm you dealt with?

      Like 1
  • RAW said:
    As I understand it,  Fisetin does not attack cells of any kind,  it simply removes the covering or "camouflage" coating that hides senescent cells from macrophages and prevents them from being removed by normal autophagy.  ... [I]t seems logical to ingest a large dose of Echinacea to stimulate our immune system about a day in advance of starting a course of Fisetin + lecithin.   Reports indicate that stimulating the immune system causes it to produce more, new macrophages (or microphages in the brain) which should increase the probability of senescent cells being removed during the brief period while they're exposed.  

     There's a lot of misunderstanding here. I don't know where you got the idea that fisetin removes some kind of covering or camouflage from senescent cells, or that it involves the immune system; it is generally accepted that it works in a similiar way to other senolytic compounds: by inhibiting cell-survival pathways that are ramped up in senescent cells. Several such potential pathways have been identified, although none has been shown to be the one (or the main one) responsible.

    Separately from senolytics, the immune system does eliminate some senescent cells, but macrophages aren't  the cell type that does it: natural killer cells are. And autophagy doesn't remove cells: it removes components of cells, such as used and damaged proteins and organelles.

    Like 1
  • Has anyone seen any information that Curcumin and Fisetin counteract each other when used as a senolytic, or their different modalities of actions nullify each other?  I have seen several comments to this effect, but have never seen any literature that cleared this up in my mind.  Any references or thoughts would be welcome.

    Like
    • Dan Nave 

      Hi! I have this link to a paper from 2010 that discuss how to Improv the oral bioavailability of beneficial polyphenols through designed synergies. it is a general paper and not specifically about fisetin. But personally Learned a few things from it. Curcumin is a BCRP inhibitor which also goes for Quercetin. But I don’t have any specific paper about fisetin.  

       

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820202/

       

      I take curcumin a few hours after the Senolytic agent.

      Like
      • garland
      • garland
      • 8 mths ago
      • Reported - view

      Staffan Olsson I have been taking Quercetin along with Fisetin...  when I do my senolytics... should I not combine them? 

      Like
    • @garland  Metabolism is a very complex process and at this stage it is not possible at this stage to say something certain about how fisetin and quercetin influence each others biological actions when they are co-consumed.  But so far the science regarding quercetin seam to favor co-consumption with other substances. if the question is to increase the senolytic effect of fisetin I find that co-consumption with piperine/black pepper is a safer bet.

       

      But then again one has to be humble about this. There are many here who co-consume fisetin with quercetin and report positive effects.

      Like
      • garland
      • garland
      • 8 mths ago
      • Reported - view

      Staffan Olsson Thanks.... am doing bio-peperine with it and it seems to help... 

      Like
      • Dan Nave
      • Dan_Nave
      • 7 mths ago
      • Reported - view

      garland The question here was whether to take Curcumin and Quercetin together.  My feeling is *no* for C + Q, or C + F.

      I would take Quercetin together with Fisetin  though.

      Like
  • Does anyone have an opinion on the new Life Extension product Bio Fisetin? They claim (up to) 25 times availability, which suggests that one capsule with 8 mg of fisetin would be equivalent to 200 mg of plain fisetin. So, potentially a 4 tablet dose for 3 days might have senolytic effects???

     

    Here's a link to the product page:  https://www.lifeextension.com/vitamins-supplements/item02414/bio-fisetin

    Like
      • garland
      • garland
      • 8 mths ago
      • 1
      • Reported - view

      Michael Avenoso I am trying 10 tomorrow to get a dose that seems close to Mayos... I always do at least 2300 mgs when I do senelytics every 2 or 3 weeks. I the past I mixed the Fisetin with olive oil and took it with bioperine pepper. I also took Quercitin and 100 mgs of Dasatinib. The Quercetin was the highly absorbable form from LE> I also took Senolytic Activator from LE each day.  So I am excited to try the new formulation of Fisetin out to see if I notice any difference with it. After all Fisetin is supposed to be the most powerful of them all. I notice all kinds of good effects at high doses from what I did in the past. I am more limber and get in yoga positions i could not get into for years. I have no pain in my body... I feel more clear and alive for sure. Kiind of high on life.... high doses are where it is at if you are not allergic and always talk to your doctor first> I would not do this unless you are under doctors care. 

      Like 1
      • Iðunn
      • Iunn
      • 7 mths ago
      • Reported - view

      Michael Avenoso They don't present any studies showing this improved absorption; I would phone them and ask them for their evidence before taking this statement at face value. JGC 's post above seems to suggest they're just guessing based on a rodent study involving curcumin, not fisetin. In any case, even if it really has 25 times availability, it's more than 25 times more expensive per milligram, so not really an advantage.

      Like
      • JGC
      • JGC
      • 7 mths ago
      • 1
      • Reported - view

      Iðunn 

      I don't think LifeExtension is just guessing based or rodent studies.  As I recall the account I read somewhere, they used the same bio-enhancement coating trick that had been used on curcumin, gave the coated fisetin orally to several human volunteers, and tested the resulting blood-levels of fisetin.  That's where they got the x25 value.  As I recall, when LifeExtension tested the coated curcumin the same way, they got a much bigger (x80?) bioenhancement.

      Like 1
      • Iðunn
      • Iunn
      • 7 mths ago
      • 1
      • Reported - view

      JGC Hm. It'd be great if you could track this down...

      Like 1
      • Iðunn
      • Iunn
      • 7 mths ago
      • Reported - view

      Iðunn Ah: I see you posted it here. Thanks, JGC .

      Like
  • garland   Thanks for your response. I am waiting on the product to arrive. I am going to take a small dose to rule out an allergic response and then try the 4 caps for 3 consecutive days. If I survive that, I'll attempt your heroic dose. :^). I will also take some of the LEF Bio Quercetin with it. If I see any obvious benefits, I'll post them here.

    Like
  • That sounds like a good way to start... give it time to make sure. Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one. I have done Fisetin at least 15 times usually about 2,300 mg... so I started with 8 of the capsules and feel it is very powerful. I feel unbelievably clear headed and full of energy and kind of 'high on life' type of feeling. But again I have done this many times and also with Dasatinib and Quercetin so go slow. You can always wait a couple of weeks and redo at a higher dose. Getting rid of old cells can be very taxing and draining and uncomfortable. But now I am sitting up straight and walking tall with a spark... but I feel this way after doing fisetin each time but this definitely feels more intense and more complete. I will know more after tomorrows when I take another dose.... and after what I feel like in a few days coming down from this session... dont ever over do it... it is not worth it.... there is always time to do another round in a few weeks...

    Like 1
    • garland Sounds like strong effect.  Did you take fisetin alone or did you take it with quercetin?

      Like 1
      • garland
      • garland
      • 8 mths ago
      • 1
      • Reported - view

      Staffan Olsson  see below for a report of my latest experiences. I had a difficult time  sleeping last night ... I take it with Quercetin, Dasatinib and Senoytic activator from LE..with bio peperine .... awesome combo feel alive but it is intense so be careful when you are starting out with Bio Fisetin

      Like 1
  • garland said:
    Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one.

     I wonder if we couldn't do this ourselves by mixing regular fisetin with, say, Guar Gum which is a galactomannan containing gum.  

    Like 1
      • Dan Nave
      • Dan_Nave
      • 8 mths ago
      • Reported - view

      Supplement Facts

      Serving Size 1 vegetarian capsule

      Amount Per Serving
      Proprietary Blend: 44.5 mg
      Providing 18% fisetin (8 mg) [from wax tree extract (stem)], 35% galactomannans (15 mg) [from fenugreek (seed)]  

      Other ingredients: microcrystalline cellulose, vegetable cellulose (capsule), silica, vegetable stearate, soluble fiber, sunflower lecithin.

      Like
      • garland
      • garland
      • 8 mths ago
      • 1
      • Reported - view

      Dan Nave Maybe but it would  be a totally blind experiment... at least with the LE mixture they did some research on it. I also include Bio-Perine with the mixture of Bio-fisetin.... that may help it get into the blood stream as well. But at 10 dollars a bottle with 3 doses per bottle why take a chance. I will be taking 10 capsules for 3 days equivalent to 2000 mg per day... Word to the warning the Bio-fisetin is far more powerful then the regular one according to my experience. So go slow... I started at 8 capsules but i have done these probably close to 15 times in past year and a half... I mix it with 100mgs of Dasatinib and Quercetin..... So if I was starting new I would probably just do 2 or 3 per days to see how I adjust... then the second time increase slightly. 

      Like 1
      • Dan Nave
      • Dan_Nave
      • 8 mths ago
      • 1
      • Reported - view

      garland I'd be more concerned with the Dasatinib.  Anything you do that increases the bioavailability of the polyphenols, including taking more of them, increases the bioavailability of Dasatinib, as they act like CYP3A4 inhibitors themselves.  

      "Dasatinib is a CYP3A4 substrate. Concomitant use of SPRYCEL and drugs that inhibit CYP3A4  may increase exposure to dasatinib and should be avoided."

      "Quercetin, a flavonoid, is an inhibitor of P-glycoprotein-mediated efflux transport, and its oxidative metabolism is catalyzed by CYP enzymes. ... Quercetin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC(50)) of 1.97 μM."

      " In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4."

      etc...

      Like 1
      • garland
      • garland
      • 8 mths ago
      • 1
      • Reported - view

      Dan Nave thanks for the heads up... . However i wonder about that specifically with the Quercetin. I know last year LE suggested heavy doses of Dasatinib (225 mgs) along with heavy doses of Quercetin (2200 mgs).... once a week for 2 weeks to be repeated every 3 to 6 months. I have seen many research studies that have found that Quercetin works much better with Dasatinib then without it. And the combination is better then isolating them. I decided once i was able to finally get DASA to limit it to 3 days of 100 mgs of it because I looked at the research on DASA and found that the 100 mg dose once a day had far less side effects then 200 mgs a day. I am following doctor Green from New York protocol with this combination. Plus I stay away from this for a few weeks. So maybe once every 3 weeks I do this. There is too many unknowns here about Fisetin. Maybe one should not mix it with Quercetin at all. Who knows. What we do know is that researchers have found that Fisetin appears to be the best flavonoid for Senyletics so far.  And I do know that the Quercetin/Dasatinib is the most researched.... so there is something to that combination as well and it is a very powerful combo. By the way I notice that you had quotes around your post ... were you quoting from some source? if so what was the source. I am not disagreeing with you and perhaps one solution is to get rid of Peperine. I added that last year to help absorb fisetin but now with BioFisetin i do not think it is so necessary. 

      Like 1
      • Dan Nave
      • Dan_Nave
      • 8 mths ago
      • Reported - view

      garland Anything that is in quotes is quoted.  You can take a unique portion of the quote or all of it and do a Google search to get the source.  I have stopped including urls as it is easy enough for you to Google it if you want to.

      I am not overly concerned with Quercetin or Fisetin as being a problem.  I am concerned with Dasatinib.  If you take Dasatanib with a lot of these substances over and above what has been used in the trials, you are potentiating the Dasatinib, and that could be a problem.  That is the point that I am trying to make.

      Like
      • garland
      • garland
      • 8 mths ago
      • Reported - view

      Dan Nave Ok now I see what you are saying... but does it make it that much more potent then 100 mgs? I will check out the quotes and see what they are saying.  Again LE had much higher doses that I was using so I felt safe with this dose especially after  reading about the research on Dasatinib which showed the safety of 100mgs of Dasa... however it potency increases dramatically then yes it can be an issue... thanks

      Like
      • garland
      • garland
      • 8 mths ago
      • Reported - view

      Dan Nave  I guess I am confused as to the amount of  DASA to use  now... I had thought that the LE people researched this. Sounds like I should use closer to 50 mg of Dasa when i use the flavonoids... I saw some substances would increase DASA by four or 5 times.... wow.... which researchers should I look at or should I take it at different times. But what about all that research that shows that Dasa and Quercetin should be taken together...

      Like
      • garland
      • garland
      • 7 mths ago
      • 1
      • Reported - view

      Dan Nave  Hello DAN....

      I checked out some of the things that you mentioned. The link below summaries all the research as of May 20th this year . It seems that most studies looked at 50 or 100 mgs of Dasatinib with Quercetin for either 1 day or 3 days or 5 days.  The quercetin is usually heavily dosed. I did not see any studies mixed with Quercetin and Fisetin together however. I think the peperine is something that may put this over the limit, and you maybe correct that the Fisetin may also take this over the limit. The good new is that in none of these studies where Quercetin is combined with Dasatinib. were there any negative side effects related to Dasatinib. I do know one thing that I am feeling better and better and more strong and alive and mentally aware. Next year according to LE they are going to be giving us some new senolytics that we all are looking forward to. So I hope to replace the Dasa with something better. I think that using every 3 weeks or so seems to be canceling out whatever possible negative effects.  You are right they suggest 100 mgs not 200 mgs because side effects go down appreciably with 100mgs a day. So not sure what this means.... so for sure I am getting rid of the Peperine. 

      Like 1
      • Dan Nave
      • Dan_Nave
      • 7 mths ago
      • 1
      • Reported - view

      garland The clinical studies I saw for D+Q used from 50 to 100 mg of Dasatinib with about 1000 mg of Quercetin a day.  One of the studies divided up the Quercetin into 2 doses per day.  Taken for either 2 or 3 days.   I think this is realistic for average weighted people.  In my opinion, there should be no attempt to potentiate the D or Q in this protocol. 

      When I take Fisetin and Quercetin I take 1000 mg each and potentiate the hell out of it by mixing it with oil, including Bioperine, and taking it on an empty stomach.  Fisetin could go up to 1500 mg if you are heavier, or if you want a heavier dose.  I take this for 3 days.  I find that one feels achy, headachy, under the weather for about a week to a week and a half.  After that one feels better than the baseline. This effect seemed to be lasting.  On the other hand, some people report absolutely no negative or positive effects.  Two other people here have done this, one falls into the former category and one into the latter.  

      Like 1
      • garland
      • garland
      • 7 mths ago
      • 1
      • Reported - view

      Dan Nave thanks I have decided to not use the pepper and may take 50mg of dasatinib

      Like 1
      • garland
      • garland
      • 7 mths ago
      • 1
      • Reported - view

      Dan Nave I meant that I will take Dasatinib of 50 mgs in the middle of the three day run thanks to your warnings. Still take it 100 first day and last. I also did the same procedure as yours with Fisetin and the Quercetin with Peperine mixed with OIL.. And I also had some down days but really those have become less and less. Usually just the first day or two.  Compared to the positive changes I get far more of those now.  I have done Fisetin regularly for months now usually every 3 weeks and sometimes 2 weeks. I have added the Dasatinib in the past 3 months and again the first few times I did it I had more negative then I do now.

      There have been so many positive changes ... My prostate problems are far less. Also I am far more limber for yoga and have more energy and clarity of mind. It is almost like I am high in non drug way. So count me as someone who has had very favorable results. I have done Fisetin maybe 15 or more times with Quercitin and 

      Like 1
    • garland Tnx for that dasatinib / quercetin  risk assessment meta study.   Interesting risks of both.  Q may enhance cancer growth, D has water on the lung etc sides.   Any longer term taker of D+Q have comments re their more negative side effects?  I've read re feeling bad as a potential.

      Another issue in play with listing luekemia study side effects is they take D continuously  (?) and may be higher doses (?).  This senolytic oriented meta study didnt list the doses and duration from the studies they pulled the side effects from.

      Like
      • JPA
      • JPA
      • 7 mths ago
      • Reported - view

      Curtis Smith It says Q could be preventative, but in other studies that it could enhance tumorigenesis. Quercetin has been listed by many doctors as a possible prophylactic for Covid-19, but maybe it's not a good idea

      Like
  • Is it best to take the fisetin on an empty stomach? is there a specific diet to follow that is best to be on while taking the fisetin?

    Like
      • JGC
      • JGC
      • 8 mths ago
      • 2
      • Reported - view

      LCM 

          Good question without a good answer.  The published research on Fisetin senolytics is on mice, with the Fisetin added to their mouse-chow, and on human cells, with the Fisetin infused into the cell cultures.

          My wife and I have done 3-day Fisetin sessions in the morning, taking Bio-Perine first (to temporarily shut off digestive enzymes) and then an hour later taking 2 g of Fisetin powder suspended in warm olive oil.  This procedure, however, is not based on research, but is just an educated guess as to how to achieve the best bioavailability.

          I note that Life Extension is now selling Bio-Fisetin, which has been treated with a protective coating (developed in India to boost Curcumin) that is claimed to boost the bio-availability of Fisetin by up to x25.  That can probably be taken any time with water.  We plan to do a 3-day senolytic session with Bio-Fisetin  soon.

      Like 2
      • Dan Nave
      • Dan_Nave
      • 8 mths ago
      • Reported - view

      JGC What do you think about mixing regular fisetin with, say, Guar Gum which is a galactomannan containing gum to simulate the Bio-Fisetin?  Or are they doing some special process to combine them?

      Like
      • JGC
      • JGC
      • 8 mths ago
      • Reported - view

      Dan Nave 

          I ran down the published paper by researchers in India on which the Life Extension technique for increased bio-availability of flavenoids (curcumin, fisetin, quercetin, ...) is based (J Funct Foods. 2015;14:215-225.).  It involves an elaborate procedure for coating  the flavenoid granules with the galactomannan from fenugreek powder.   Therefore, I don't think just mixing fietein with guar gum or fenugreek powder would work.

      Like
      • Chan
      • Chan.1
      • 8 mths ago
      • Reported - view

      JGC Thanks for this.   I spoke out against senolytics previously but I've been trying novusetin and just ordered Bio-Fisetin to try.

      Like
      • Dan Nave
      • Dan_Nave
      • 8 mths ago
      • Reported - view

      JGC Thanks JGC!

      Like
  • I have made a similar experience. Based on nothing but my own personal experience I prefer to take Fisetin on empty stomach in the morning  (after having taken some black pepper or piper longum extract)

     

    Occasionally I have used other substances a few hours (1-3h) after ingesting fisetin. I have used the senolytic activator and curcumin. And those times I have experienced what can be called side effects in the form of Headache.

     

    Next I will order sublingual fisetin gel.

     

    https://alivebyscience.com/liposomal-products/

    Like
    • Staffan Olsson

      regarding the above mentioned product it is important to read their webpage. The research that has been done on sublingual liposomal fisetin is done by comparing administration of intravenous and intraperitoneal free fisetin VS administration of intravenous and intraperitoneal liposomal fisetin.

       

      The bioavailability study does not include the oral route.  That said I still have an interest in the product.

      Like 2
      • Iðunn
      • Iunn
      • 7 mths ago
      • Reported - view

      Staffan Olsson Ding ding! There's a lot of sleight of hand in this company's marketing.

      Like
      • Jennifer Smith
      • We are all responsible for our own health, wealth, and happiness
      • Jennifer_Smith
      • 7 mths ago
      • Reported - view

      Staffan Olsson As a livestock producer I use several medications off label and oral dosing of an injectable is VERY common. I will be looking into this product as well. For now I chew it up (on buttered toast) and swallow my fisetin. 

      Like
  • New study at Mayo using heavy dose of Fisetin on women to study aging bans sirolimus users from participating. ...  Very interesting.  So they feel that sirolimus interferes with some of the effects of Fisetin....

    Like 1
      • Fred Cloud
      • Fred_Cloud
      • 7 mths ago
      • 3
      • Reported - view

      garland No, it doesnt interfere with the effects of fisetin, that is not the concern. Rapamycin can suppress sasp like fisetin so you wouldnt be able to tell if it is the fisetin reducing sasp or the rapamycin.

      Like 3
      • garland
      • garland
      • 7 mths ago
      • Reported - view

      Fred Cloud wow that makes sense

      Like
      • Iðunn
      • Iunn
      • 7 mths ago
      • Reported - view

      garland That doesn't necessarily follow. They may be concerned that a beneficial effect of rapamycin (Sirolimus) may be mistaken for a beneficial effect of fisetin.

      Like
      • Fred Cloud
      • Fred_Cloud
      • 7 mths ago
      • Reported - view

      Iðunn yeah, because rapamycin can suppress senescent cell sasp like fisetin, which is what I said.

      Like
  • This is what brought me here, in a roundabout way. I was looking at investing, playing with stocks. I decided that I not only wanted to invest in the research but I wanted to try and improve my own health. Lots of things I had read over the years all clicked together. Here is to our health, our wealth, and our happiness. 

    "Unity Biotechnology, Inc. is a clinical stage biotechnology company engaged in developing therapeutics to treat ageing related diseases. The Company develops therapeutics for age-associated diseases such as arthritis, vision loss, and cognitive decline. It develops a range of Senolytic medicines that eliminate senescent cells and stop the production of Senescence Associated Secretory Phenotype. Its pipelines of products that target cellular senescence are in its clinical development stage. Its lead products candidates include senolytic molecules, UBX0101 and UBX1967, designed for local treatment for the removal of accumulated senescent cells.UBX0101 is a drug candidate developed for musculoskeletal diseases targeting osteoarthritis. It is a inhibitor of the MDM2/p53 protein interaction that eliminates senescent cells. UBX1967 is targeted at ophthalmologic diseases. It is a senolytic small molecule inhibitor of specific members of the Bcl-2 family of apoptosis regulatory proteins."

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  • Who here has switched to the Bio Fisetin at Life Extension? Supposedly 25x the bio availability...they suggest taking around 7 caps for theoretically a 1400 mg dose. (7 caps x 8 mg x 25 bio availability). If you have switched are  you noticing the same effects as mega dosing regular fisetin? Would be cheap and convenient to use the LE brand.

    Like 1
      • JGC
      • JGC
      • 7 mths ago
      • 3
      • Reported - view

      Endless 
      Last week my wife and I did a 3-day session with 10 caps/day of LE's Bio Fisetin, which should be the equivalent of about 2 grams of Fisetin powder.  I also gave 2 caps/day to my 7 year old Shetland Sheepdog.  I didn't notice much in the way of effects, except for mild diarrhea on day 3.  Previous sessions with Fisetin and D+Q produced more noticeable effects.  This makes me skeptical of their x25 multiplier claim, and I think we will do 15 caps next time.

      Like 3
  • So I have been mixing fisetin with shea butter and applying it to myself. The big thing I notice right off is, it works as a pretty good deodorant. I work hard on the farm so this is no small thing. I did not apply it to my underarms for that reason but I will take it. Can anyone else see my logic in applying it to such a strange place? Does it also make sense to anyone else?

    Like
  • Is anyone concerned that fisetin might be contaminated with the cytotoxin hinokiflavon?

    https://forum.age-reversal.net/t/63bxk5?r=x1ay46

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