
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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I received an email recently from age reversal and it had a link to a video in which Bill Falloon gave an updated presentation. In one of the slides shown in the video it showed the senolytic as dasatinib quercetin and fisetin. That's the first I've seen him include fisetin with dasatinib. I believe they are using combo for there study. Does anyone know what dosage they are recommending?
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Karl Thanks. I am aware of that study. I looking for the dosage that Life Extension is using in its study wherein they use Fisetin and dasatinib and quercitin. I've attached a slide from the video where Bill Falloon mentions it. The slide is at 29:30 of the video which is at :
https://www.youtube.com/watch?v=fPH0sBfUK5U&feature=youtu.be
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For group informational purposes. I completed my first experiment with fisetin this weekend. I weigh 157 lbs. Took 2 grams of Swanson fisetin and 2 capsules of Life Extension Senolytic Activator. No particular reason to add that other than I had ordered ten boxes some time ago, so I had it and just threw it into the mix. I took this same cocktail over three days. No dramatic effects were experienced. Noticeably, a parallel to fasting where you feel a bit "charged" or mildly antsy and just want to do something. I do have some non-arthritis joint pain in my back and hip and I was surprised to note that it eliminated that short term. The following day it was back again. Alleviated with second and third doses also. This leads me to suspect an analgesic mechanism rather than a curative effect. Also, just to note previously I had taken 8 of the LEF senolytic activator capsules and felt like I had five cups of coffee, short-lived jitters. But no pain relief.
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Dan said:
For example during a fast, at day 5 is when it's clinically been measured that heavy senolytic activity occurs.What's your evidence for this? I'm not aware of any evidence for fasting actually killing senescent cells, let alone a specific time-course.
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Latest Senolytic Sessions with Fisetin
It has been 6 months since we last did senolytics with Fisetin and D+Q, and our body load of senescent cells has probably built up again, so it's time for more sessions. This time, in the lead-up to this, I've been experiencing lower back pains and a "wry-neck" problem on the right side of my neck that interferes with sleeping and limits the amount I can turn my head while driving. Popping Advil and Tylenol doesn't help much. These are likely to be aspects of age-related inflammation (I'm 85), so I was curious as to whether the new senolytic session would have any impact on these symptoms.
Yesterday and today my wife Pauline and I took 10 mg of BioPerine at 8 AM followed by 2 grams of Fisetin powder stirred into warm Trader Joe's extra-virgin olive oil at 9 AM. The olive oil was put in a shot glass, heated in the microwave for 30 seconds, then put on a small digital scale while the yellow Fisetin powder was spooned in until an added weight of 2 grams was reached. The result was stirred until the yellow powder was either dissolved or suspended in the oil, forming an unsavory-looking opaque green liquid. This was drunk as thoroughly as possible, and the residue in the glass was scooped out with bread fragments and eaten, until the glass was clean.
My observation this afternoon is that my back pains are gone and my stiff neck is much better, but not completely gone. I also feel more energetic and alert. This time (see previous reports above) there were no flu-like symptoms or other observed negative side effects, at least so far.
We're doing AKC competition dog agility with our Shetland Sheepdog Taliesin at a facility north of Seattle this weekend, so I will also be able to observe how the senolytics affects our performance (which was a mediocre 7 Qs out of 16 runs last weekend). We plan one more Fisetin session tomorrow, followed by two D+Q+F+P sessions, to be done in the next two weeks.
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I've tried several combinations of Fiestin with various supplements. Initial trial was with Fisetin and Qurecetin. 2 grams of each, twice a day for three days. Learned that Quercetin has no senolytic value so switched to using Fisetin with Echinacea as an immune system booster on the assumption that it would increase microglia activity. No immediate changes noted. Third trial, added Lecithin to the combination on the assumption that an emulsifier would increase the adsorption of Fisetin. Noted improvements in cogitative functions, ambition, physical condition over next several weeks. Now seems to have leveled off. Wish someone would devise a simple means of measuring the senescent cells concentration and / or removal effectiveness.
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Fisetin + Hydroxypropyl-Beta-Cyclodextrin?
Some of you may understand more about the arcane subject of biochemistry and molecular structure than does a simple-minded nuclear physicist like me, so perhaps you can answer a question about Cyclodextrins.
Beta-Cyclodextrin
Cyclodextrins are a family of non-toxic glucose-based molecules (alpha, beta, gamma, ...) shaped like doughnuts. They are hydrophylic (water-seeking) on the outside and hydrophobic and lipophylic in the doughnut hole. I have read that these properties can be used to increase the bioavailability of water-insoluble supplements like the flavenoid curcumin. It's a bit more complicated than that, however, because beta-cyclodextrin, which is about the right size for transporting such insoluble molecules, is so tightly bound that it also has water solubility problems. Fortunately, this can be fixed by hanging a propylene molecule on the basic beta-cyclodextrin molecule to make water soluble hydroxypropyl-beta-cyclodextrin.
The supplement manufacturer Nature's Essentials of Suwanee, GA actually sells boosted versions of the supplements Tumeric/Curcumin, Resveratrol, and Melatonin that have hydroxypropyl-beta-cyclodextrin included for increased bioavailability. I have bought and am taking these boosted supplements daily. Unfortunately, Nature's Essentials does not sell versions of the senolytic flavenoids fisetin and/or quercetin that have been similarly boosted.
So my question is, if I buy some hydroxypropyl-beta-cyclodextrin powder, mix it with fisetin or quercetin powder, and take this as a senolytic, will that have the desired boosted bioavailibility? Or does one have to do some further chemistry to thread the flavenoid molecule into the doughnut hole?
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Partial Answer
I found a paper by some researchers in Thailand in which they actually do a computer simulation to investigate how Fisetin threads through the hole in Beta-Cyclodextrin and how this effect the interaction with water. There are four possible configurations, and they calculate their relative probability of formation. Apparently cofigurations II and III are the most soluble because the "B" region is more enclosed. Here's a figure:
The bottom line seems to be that mixing Cyclodextrin and Fisetin in an aqueous solution does produce dual molecules with improved water solubility. They use unmodified Beta-Cyclodextrin, not Hydroxypropyl-Beta-Cyclodextrin, and they do not give any solubility values, but after all, its a simulation.
On this basis, I just ordered some Beta-Cyclodextrin and some 2-Hydroxypropyl-Beta-Cyclodextrin from Amazon. I intend to do some self-experiments with the aqueous mix, and maybe try it with Quercerin also.
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I don't think there's any evidence that piperine/BioPerine enhances the absorption of flavonoids generally — just curcumin. Or do you know of any? And the mechanism isn't really understood, so it's hard to make strong predictions. Bath1 Best Bathroom shower wall panels
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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.
I don't try to increase bioavailability. I just pop 12 pills, usually Swanson, with a glass of water. I usually have it coincide with a 24 hour spiritual fast of no food or drink each month, taking it before start and then after. I take the second round of the month either in the morning or evening, basically whenever I remember, so sometimes it's on an empty stomach, sometimes not, but I eat often, so usually I have some food in me.
My results have been obvious enough and consistent enough with just taking the pills that I feel no need to try to improve bioavailability. (I do take a tablespoon of omega 3 fish oil every day, so that could help!) I don't always take them together, but as I said, I have personally seen a big difference in fine lines and wrinkles before taking fisetin and after, regardless of when I take it.
My uncle started taking 1500mg/day for 2 days each month, and he loves it. He has arthritis in his fingers, and he said that buttoning his top collar button was always really painful, but now it is no longer painful. I didn't tell him about my arthritis before he asked what I thought of fisetin (I didn't know he was taking it). I am usually very conservative in telling others about self-experimentation because I believe it's best done by those who read the studies and understand the risks rather than someone who just takes the word of a friend or family member.
My husband takes it with me. He finishes the bottle- 1800mg/day for 2 days every 2 weeks. He grimaces every time I hand him the bottle and a glass of water, but he takes it. He had severe sepsis a year ago last December where he was a day away from dying before diagnosed. Since then, we started him up a few months later on fisetin again. He said his muscles felt sore like after a good weightlifting workout, but that was his only side effect.
For reference, I also take 4500mg omega-3 daily as indicated above, Ellysium (NR), and just in May started taking 1 pill of Jarrow's Broccomax and 1 pill of Biotivia's Pteromax daily. I added the last 2 in order to promote daily mild stimulation of the NRF2 pathway and its cellular antioxidant properties, but also because when my husband and I took Pteromax and Mitoq 7 years ago, we noticed that neither of us got sunburned, and my husband normally burns very easily. We stopped taking Pteromax because it became unavailable for a while. Mitoq alone didn't have the same effect. We later added Biotivia's Trans resveratrol, and that didn't have the same effect either. We dropped the Trans resveratrol and only took Mitoq for a while, but stopped that shortly after starting fisetin, mostly because of cost and not seeing as significant results as with fisetin. With Pteromax again available, I decided to try it for the summer and see if it has a similar sun protective effect like we experienced before, since I mildly burned my face a few weeks ago on a hike and was reminded of the need for sun protection.
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This encompasses 3 senolytics, Fistein, Azithromycin, and Dasatinib.
Dr. Green has a new website targeting https://senolyticstreatment.com/. He points out that there are 4 different types of senolytics. (zombie cells) and there are different treatments which target each one. He suggests using Fistein 1500 mg x 3 consecutive days x every 3 months for aging purposes. (they are using 20mg/kg in Mayo Clinic trials x 2 consecutive days in elderly patients, as yet unpublished results) Azithromycin 500 mg x 3 spread over 1 week x every 3 months. (targets fibroblast) Dasatinib 100 mg x 3 consecutive days x every 3 months. He has set up a compounding pharmacy to make Dasatinib affordable for his patients. I order powder from China. The frequency is more often for treating specific diseases. He believes that Rapamycin slows down senescence, but cannot remove them. Please refer to his website for additional info.
The following is an interview by Dr. Blagosklonny for his Aging article.
Aging, COVID-19 and more Interview with Alan S. Green, M.D., who practices medicine in New York state, and who, in 2016, began to treat patients with rapamycin (Sirolimus), an anti-aging drug. Interview was taken via email on March 31, 2020, by Editor Dr. Blagosklonny for the journal Aging. Question 1: How many patients and for how long have you treated with rapamycin? Answer 1: Patient number 1 is myself, treated for 4 years. An additional 480 patients treated from 3 years to present. Question 2: Rapamycin (Sirolimus) and its analog Everolimus are FDA-approved drugs used in millions of patients with several severe diseases for many years. Based on a few murine models, some people believe that rapamycin may have unacceptable side effects, even though rapamycin extended the health span and life span of mice in these studies. Have you noticed side effects in your patients? Answer 2: Rapamycin in older persons is very beneficial for the brain, heart, muscle, joints, insulin sensitivity, decreasing visceral fat, and prevention various age-related diseases. Rapamycin is a very potent drug and good results dependent on proper dose and interval. My patients show good results with sirolimus [rapamycin] 2 to 8 mg once a week. Major side effect in that range is decrease in activity innate immune system. To extent chronic inflammation is harmful in aging, this is generally beneficial. The basic researchers I follow are Matt Kaeberlein and Veronica Galvan who have recently shown excellent protection against normative aging in heart (dogs) and brain (rats). I have observed those same beneficial results in older humans. Question 3: Z-pak (Azithromycin) that you prescribed to your patients (just in case of possible bacterial complications) is now considered a promising drug to treat COVID-19. Would you like to comment? Also, it was published in Aging by Sargiacomo et al, that Azithromycin and hydroxychloroquine are senolytics, drugs that selectively kill senescent cells. Answer 3: A natural tension always exists between treating physicians who use standard of "reasonable degree of medical certainty" and government scientists who use standard of "definitive proof" and dismiss anything short of definitive proof as "anecdotal". (Perfect is the enemy of Good). As regards recent paper in Aging by Sargiacomo et al, that was an extraordinary important paper connecting COVID-19, aging, senescent cells and senolytics. In 2017 paper, Blagosklonny noted role of Doxycycline and other antibiotics as anti-aging drugs. Azithromycin looks like major drug in prevention and treatment COVID-19. I use same dose used in Cystic fibrosis study (500 mg 3 times a week) in which Azithromycin appears to be acting as senolytic.
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Hello Van. Thanks for this info. Are you able to advise the name of your Chinese supplier for dasatinib? Being in Canada, I cannot see, or be prescribed drugs by Dr. Green and don't know of any age-reversing docs up here. At the moment I am using several "natural" products that replicate a natural rapalogue from Germany as well as berberine/PQQ, Niagen and resveratrol. Due to almost daily migraines, I cannot fast beyond 12 hours. Applying apocynin to specific areas but not seeing or feeling any difference. My main problem seems to be lack of energy, which I attribute to having a few too many zombies. Many thanks!
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I ordered my Dasatinib and Fisetin powders from the following Alibaba supplier. https://hhdpharm.en.alibaba.com/company_profile.html?spm=a2700.galleryofferlist.0.0.362a73f6ugETpH#top-nav-bar. Used Emily. This is the same supplier that furnished Rapa for other members in this forum. Need to make sure that you get 98% Fisetin vs 50%. Both are sold. Dasatinib is 99% only, I believe. I paid $245 for 5 grams Dasatinib, and 50 grams of Fisetin. That includes $50 Fedex shipping. So cost is Dasatinib = 120/5= $24 gram Fisetin = 120/50 = $2.40 gram. This includes shipping. Saved on shipping by ordering both at same time. This does not include Visa CC charge of 3% = $7.20 which is really the cheapest way to pay, and you have CC guarantees. Will update group once I receive it. Noticed that Fisetin on line is starting to get expensive vs just a few months ago. The word is getting out. It takes around 5 grams for one quarterly dose of Fisetin, so those little 30 tab bottles (100mg) they sell are worthless, and expensive. I had no problem with receiving my Rapa order from China which was only a business size envelope delivered by Fedex, but this one is going to be larger. Will have to wait and see. For those without experience using powders, this is the way to go. Buy a jewelers scale that measures to .001 gm. = 1 mg. for about $30. Usually includes calibration weights. The lower the max weight, the more accuracy you get. Mine has a max weight of 20 grams, but goes to 1/1000. You only need to weigh once a week for Rapa and quarterly for senolytics.
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A UK doctor did his evaluation of the best sulforaphane to purchase: https://www.youtube.com/watch?v=qAb1eQbRAe0&t=18s
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David H
Dr Brad Stanfield (New Zealand) is great and I follow him as well. My comment to him was the same as on this thread. You just can't read ingredient list and believe manufacturer. The supplements in the US are unregulated; hence, no oversight and you need the third-party testing. With respect to Dr. Rhonda Patrick's second statement about efficacy, it is not her personal opinion but it is indeed fact and test based. It came from Jed Fahey at John Hopkins. Basically it seems that Dr. Patrick first sprouted her broccoli then she became too busy and started uing BroccoMax instead. At this point she may have made a few statements about it but then subsequently checked with Dr Fahey and found out what's really in the product and changed her mind on it. The moral of the story: don't put any supplement or medicine in your mouth unless manufacturing monitored by FDA / equivalent reg body in other countries or reliable lab tested.
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I need some help on this topic. My aim is to take take 1.5 g of Fisetin on 3 consecutive days.
Today was the first day. I took 15 capsules a 100 mg after a 20h water fast with 2 spoons of native olive oil, a capsule of curcumin containing perperin and an omega-3 capsule. First i wanted to dissolve Fisetin within the olive oil but seeing the small capsules i thought just to swallow it with oil, no problem. Afterwards i ate 500g of strawberries and ate as usual 1 h later.
So far i recognized some slight stomach pain. Any hints how to improve the intake besides dropping the strawberries? Should i dissolve Fisetin completely in some oil? Take everything on an empty stomach or after a meal, at the beginning of a fast or at the end, or split the intake?
Thank you in advance.
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I'm about to try fisetin. Has anyone used that available on Amazon (Axe-NIC)? It says Pharma Grade, not for human consumption. The Philly company won't ship to Canada. Any Canadians here? The RevGenetics 500 is $99 for us on Amazon plus $10.99 shipping. I just lost my account due to the virus, so don't want to go overboard on something that's encapsulated and costs much less over the border. Thanks all.