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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Ahhhh this is sad news indeed...
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Staffan Olsson Thank you.
There seem to be many natural substitutes for metformin or acarbose, for the calorie-restriction mimetic effect. Berries are more palatable; but leaf powder is cheaper.
Below is another study on mulberry twigs, and a direct comparison with acarbose, on HbA1c levels.
- Qu and colleagues analyzed data from 600 adults who met 1999 WHO diagnostic criteria for type 2 diabetes and had not been treated for diabetes for more than 3 months. Participants were randomly assigned mulberry twig alkaloids (n = 360; 48.6% men; mean age, 55 years) or acarbose (n = 240; 53.2% men; mean age, 54 years) for 24 weeks. Primary endpoint was change in HbA1c compared with baseline. Researchers also assessed adverse events and gastrointestinal disorders.
- At 24 weeks, change in HbA1c was –0.93% (95% CI, –1.03 to –0.83) and –0.87% (95% CI, –0.99 to –0.76) in the mulberry twig alkaloids and acarbose groups, respectively. The least squares mean difference was –0.05% (95% CI, –0.18 to 0.07) between the two groups, with no significant difference on the basis of covariance analysis.
Now to find a rapamycin mimetic, in addition to withaferin, so I can pair them for self-experimentation. Would help if Dr. Miller publishes his study, so dosage can be determined.
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Juan Daw Agreed! To me, while new research such as that conducted by ITP carries some weight, to me it's just another data point. Fisetin still holds other benefits. Plus if you look at ITP's other studies like rapamycin, most people aren't going to run out and buy it. They conduct the study in a controlled environment, and we know it's not ready for prime time until further research is done.
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I'm not convinced. I felt a real difference the first time I did a senolytic dose. I don't think the Mayo would do this study and show improvements before doing this study if there was no effect. I guess we will see in years to come.
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JOHN Agree with you. I saw immediate, quantifiable increase in my exercise performance and qualitative improvement in color vision. Those improvements continue after 1.5 years of continuing Mayo Protocol.
Note that several others on this thread reported similar results.
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JOHN Agreed, I am not convinced either.
There have been so many positive reports from taking fisetin as a senolytic and people are just going to ignore those and listen to the ITP instead? Bizarre. Sure, you could say some of those are possibly placebo effect, but are you saying all of them are placebo? No way. What kind of person rejects every single report of benefits of fisetin that is out there and instead just blindly believes some guy saying their study said it didnt work without even reading the study or anything else? Are people that easily persuaded?
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Peter H. Howe Agreed Peter, there are many reports of positive effects from fisetin out there like yours. It really makes me wonder how people do research on substances. Do they just read a study and reject all other evidence and thats it?
If there is an abundance of positive feedback, then that should be a huge red flag that maybe the study was done incorrectly instead.
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Fred Cloud Forgot to mention that I am 81 yo male. My age ( lots of senescent cells ???) may have contributed to the positive effects that I noticed. I was somewhat impressed as the positive effects were almost immediate--next day after my first treatment. My chinups/pullups increased by 25 % from 20 to 25. My exercise regime had been about the same for the past several years. What I perceived to be increased color vision was also immediate.
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Peter H. Howe Twenty five pullups at any age is impressive. At age 81 its scary!
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Peter H. Howe Great to hear. But even younger people using fisetin on this forum have been getting great results, like fairy8i8 who is 38 years old. I guess I should tell her to ignore all her great results and stop using fisetin because Dr Richard Miller from ITP said so.
fairy8i8 wrote: "I have been taking 1200mg/day of fisetin in a single dose for 2 days (I am 56.8kg). I started doing this monthly over 18 months ago. After about 6 months, I started taking this dose twice a month because I noticed clearance of facial fine lines, which would return after a few weeks. Doing the dose every 2 weeks has kept visible skin indicators of aging decreasing.
At first, I did not think anything of the treatment. I am young (started treatment at age 38), and didn't figure I would see much effect. However, my mother, age 70, has had a nickel sized flat mole on her cheek since her mid 50s. She took 1 round for 2 days, and when I saw her a few months later, the mole was gone, and there were just a few small freckles there. I asked her about it, and she said it disappeared after taking the fisetin. After that, I started to track my own moles. The ones that have appeared over the years have all lightened significantly and diminished in size, and the few I've had since childhood have all lightened to almost skin color.
I have injury onset arthritis in my big toe, and that reduced to nothing (before walking 13 miles, running for 30 minutes on the Great Wall, not having run in almost 10 years, and then getting on a plane 3 hours later made it hurt again). I am recovering from that, but the pain is consistently decreasing again...."
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Fred Cloud What brand are you taking and how much? Thanks, Fred.
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Peter H. Howe will you be my adopted grandfather? You sound awesome
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Michael Look for a brand that uses Novusetin fisetin ingredient. Lately, I have been using Wellness resources brand on amazon because they were offering 250mg caps so you dont have to take as many capsules.
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Fred Cloud
I am among those who have had distinct improvements from fisetin. I have noticed different effects from different formulas. When I (orally) take the fisetin labelled as novousetin from Dr’s best, after a few days I notice distinct physical improvements on muscular strength and when it comes to joint health. When I (orally) take the more bioavailable formula from life extension “bio-fisetin” (a formula created for better absorption in the digestive tract) I notice mental effects - like clarity of mind and an uplifted mood.
I have made my own suppositories based on the Dr’s best brand. But when using those suppositories I do not experience the same effects as I do from orally taken fisetin from Dr’s best.
When it comes to homemade suppositiries I am of course a novice. So that experience does not say much. Just out of curiosity I will make suppositories from the life extension's brand as well.
Ps. In my case I am sure the experience from the Dr’s best formula is not placebo.
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@saxxnviolins Juan Daw My purpose in mentioning dramamine was not to correct anything. The "old" formula contains dimenhydrinate and the "new" contains meclazine. Both are listed as having high anticholinergic activity. From RXFiles.ca: Diseases associated with an essential cholinergic deficit include Alzheimer’s dementia, Lewy body dementia & to some extent other dementias (not frontal). Anticholinergic drugs worsen the deficit & are therefore highly problematic (in older people- my add).
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I have recently stopped taking Fisetin and Quercetin daily (500 mg each) due to severe side effects. My lips became painfully dry and cracked daily for about a month and this had never happened before in my life. This also made them susceptible to bacterial infection and my lips puffed up like a clown. It coincided with my taking Fisetin and Quercetin daily (as per Dr. Sinclair). After taking antibiotics to control the infection, my lips were still very dry cracked and painful. When I stopped taking fisetin and quercetin daily, my lips returned to normal. Has anyone else had a similar physiological response?
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Chris M Sinclair recommends high dose fisetin and Quercetin daily? Thats crazy. Senolytics arent meant to be taken daily long term. They are supposed to be pulsed, once a month at most. Not sure what Sinclair is thinking unless I am missing something, but no wonder you were having symptoms.
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Fred Cloud "Recommend" is not the right word. Sinclair was asked in a recent interview about his daily regime and he confirmed he was taking F+Q in those quantities (he didn't elaborate on the reasons why). He certainly wasn't "recommending" that others follow suit.
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Kaptain Asia I try to follow what the leaders in longevity are doing. I figure that if they are the most knowledgeable people in the world regarding aging, I should do what they do. However, I realize we all have different physiologies and genetic makeups so results may vary. Also, daily F+Q giving me painful cracked lips every day. Is that a sign that the senolytics are working? A bad interaction with one or more of the other 15 supplements that I am taking? or a sign that my genetics are different? I haven't a clue, but the daily pain and inflammation was intolerable for me, so I am going back to pulsing F+Q until I run out and then wait for the Mayo report before I buy any more. I am a little younger than Sinclair so it may be more beneficial when I am older.
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50 year old guy here.
Finally tried the fisetin hit and run regimen. Aimed for 30mg per kg dissolved in warm olive oil. Threw in 400mg of Q on top by taking a bio-available 250mg cap plus 2x the Life Extension Senolytic Activator. This for two days straight.
In preparation I had dropped anything like rapa, aspirin or glynac for 10 days that some here have stated might block results.
Honestly, I feel like I'm using my imagination to say that anything happened. My body temperature may have been half a degree C higher than normal. I might have felt slightly sweaty though it was hot weather anyway. I might have had a vague ache in my left hand finger joints. Now four days later I might have slightly better colour perception in my left eye.
See where I'm going? Really difficult to judge.
When I did a 500mg tolerance test last year, a cup of my black & green tea mix kicked off some sort of immune reaction for a while and the room swam. Much greater dose this time led to maybe something, but possibly nothing.
I will say that since my tolerance test last year I have dosed 100mg fisetin a couple of times a week. I have done a rapamycin protocol for around 2 months. I have done the odd alpha lipoic acid cleanout. Basically I'm not a clean slate when it comes to self experimentation.
However, all in all nothing really to report. I'm getting back on my rapa this afternoon.
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Jack Black Thank you for your report. which brand of fisetin did you use? I have observed different effects from Dr's best fisetin and the life extension brand Bio -fisetin. I got a strong reaction from the Dr’s best fisetin.
And I have noticed a muscular weakness a few days after the fisetin session. And afte these few days of weakness I have experienced increased physical performance (at least when I have used Dr’s best fisetin. )
In a few weeks I will do a new regimen with the Dr’s best Fisetin. It will be interesting to see what (if any) reaction I can observe.
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Staffan Olsson I was using the Dr's Best Fisetin with novusetin. Cut the capsules open to mix into the oil.
Going to try again in a month and I might employ some D at the same time.
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Jack Black I think the novusetin may be at too high of a concentration to dose. I did my first Fisetin dosing using that brand and it made me nauseous. I switched to HumanX Fisetin for massive dosing and I did not have nausea when O repeated the dosing the following month. I did 1.5 g of Fisetin 3 days in a row for each mixed with 500 mg of Quercetin as well as black pepper and tumeric.
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Chris M That's the strange thing, I had the opposite reaction of it being too strong. I was dosing 2600mg per day plus Q on top, and had had a 10mg BioPerine 20 minutes before the Fisetin. Frankly surprised by the lack of experience.
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My first reaction to Novusetin (Drs Best or Swanson) was wonderful. I felt absolutely fantastic for a few days, almost like a drug, and I suddenly had the ability to stay up all night without experiencing discomfort the following day. After not taking senolytics for months I have taken another set of doses. I take all 30 capsules in the bottle once/day with lots of Q and did this 3x in one week. No weakness or nausea. I am noticing a strength increase in the gym. I just added 10-20 lbs to almost everything I do. Also, I do 209 stairs two at a time and for the first time have been able to get through that without pausing. I have to say Novusetin is effective, theoretical absorbability notwithstanding. I'm 70.
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Small update, I noticed today that I didn't have the minor ache in my injured hip joint that I've had since the Fisetin. Maybe that's a sign there has been some clear up this week.
