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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@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.
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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?)
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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?
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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.
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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
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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.
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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.
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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?
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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!
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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.
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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!
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BobM Bob, forgot to include this video from Dr. Brewer on the "heart attack gene"
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@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.
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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.
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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.
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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
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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.
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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)?
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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.
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Joe smith Unfortunately most doc's are trained to treat disease instead of preventing it, and the consequences for many patients is not good.
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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
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@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!
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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?
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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
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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.
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Need Help What was your dose and ingestion method? What else do you take?
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