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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That's an interesting point. I found an article HERE that discusses the effect of grapefruit juice. It says: "Compounds in grapefruit called furanocoumarin chemicals are the cause of the increased medication potency. These chemicals interact with the cytochrome P450 3A4 (CYP3A4) enzyme, found in the small intestine and liver, which partially inactivates many medications under normal circumstances." One can click at the bottom of the document to get a document entitled "Appendix 1: Grapefruit Interacting Drugs and Associated Oral Bioavailability, Adverse Event(s), Risk Ranking and Potential Alternative Medications". It lists the reaction risk of combining grapefruit juice with Dasatinib as "High". I don't see any flavenoids on the list.
On that basis, I would say that combining D+Q with grapefruit juice is risky.
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Dan Nave
You probably only remove a small fraction of senescent cells per cycle.
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Robert Olin In vivo experiment with Zithromycin cleared 97%. Then takes it weeks to build back up. https://senolyticstreatment.com/
Four major senescent cell types
The three senolytics we use use are:
Dasatinib
Zithromycin
Fisetin.
Quercetin is very similar to Fisetin; but Fisetin is better.
The four major senescent cells types and the drug used to target them are:
Adipocytes: Dasatinib
Fibroblasts: Zithromycin
Endothelial cells: FisetinReplyForward
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Van
So can anyone here report results from having used Zithromycin as a senolytic? In particular, its effect on skin tone from clearing senescent fibriblasts in aging skin?
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JGC I have only done one round of azithromycin so far and I can tell a shift in my skin tone. I was thinking that since the skin circulation is normally pretty low and sluggish I figured I would do something to compensate. So the last day of the round I induced a niacin flush to dilate the capillaries and increase blood flow to the skin tissue and expose it to higher rates of azithromycin and increase senolytic action. There has been a shift in my skin tone to a healthier glow like you get when you put lotion on. I do niacin flushes a couple of times a year and have never had this effect happen afterwards. I have also taken azithromycin in the past but dont remember it changing my skin tone. Hope this helps.
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Fred Cloud
Thanks, Fred. That's very useful info. Where/how did you get the azithromycin? Did you have a prescription? And what dose did you use in the senolytic sessions?
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JGC I took 500mg because that is what the tabs were, I have seen mention of using 250mg and I could have broken them in half but decided not to. I did also have the post senolytic hunger effect too. No prescription. I order most of my drugs from india. I have never had any issues, customs even opened the box last time and saw what it was, innocent stuff and sealed it back up and sent it on to me.
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Fred Cloud
From which pharmacy in India did you order your azithromycin? On March 21, 2020, I ordered some Zithromax for $85.35 from the Online Drugstore, and it has never arrived. Their support page claims the shipment is delayed because of the cancellation of international flights, but even with that the 11+ week delay seems excessive.
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JGC Things are getting delayed. I ordered something 2 months ago and they cancelled it. I ordered again last month and it hasnt shipped. So I think everyone is having issues. Send me a PM if you still want my source.
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JGC
My order of Zithromax from the Online Drugstore finally arrived two weeks ago, after a 3 month + delay. I guess one just has to be patient in this era for the Plague.
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I'm sort of surprised that everyone seems to be just swallowing these capsules (fisetin and quercetin) presumably with water. Since these substances aren't very water soluble it would seem that they aren't being fully absorbed. The research papers that I have seen dissolve them in Phosal which is phosphatidylcholine with propylene glycol. It does seem that they dissolve in oil as well. I emptied my capsules into a bowl and mixed the powders with 1 tablespoon of olive oil. It seemed to dissolve quite well. I also feel that it absorbed well as I experienced definite effects when drinking caffeinated beverages (tea) and also some joint and bone pain and general discomfort or malaise for a few days after the doses.
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Dan Nave As long as they make it into your intestines, they should work fine.
The alternative is to do what Dave Asprey and Joe Mercola discussed on the Bulletproof podcast, and put them into a suppository. Which is gross. But it seems to work.
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FYI, Drs Best Fisetin is now available next day from Amazon. About $14.15 or so.
My previous source, Lucky Vitamin, stopped working. Site would not take an order for weeks. I called and emailed, then gave up on them.
I’ve now completed my 5th dosing. Once a month schedule. 1200mg (for my 135lb weight). I will continue this for now.
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BobM
I notice that Amazon also has Trillium powder-form Fisetin for $59.88 for 50 grams. That's about $0.12 for 100 mg, as compared to $0.47 per 100 mg from Drs Best. Further, if you are going to dissolve it in olive oil (see above), having it already in powder form is an advantage, provided you have a good digital scale to measure the dose.
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JGC
It is not clear how much fisetin is in this product. They do not rate it or guarantee it. It may be better to buy from Alibaba if you want bulk fisetin.
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Dan Nave
Have you bought supplements from Alibaba? How does the payment arrangement work?
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JGC
I bought my fisetin from Swansonvitamins.com. It cost $11 to $12 something for 30 100mg capsules. I have been happy with purchases from swanson.
I have never purchased from Alibaba. I don't really know but I would try to make sure I was purchasing from a reputable manufacturer with a physical presence, and I would also be prepared to lose my payment.
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Dan Nave
I just ordered 100 gm of >98% pure powdered Fisetin from VitaSpace for $190 plus $6 shipping. That's $0.19 for 100 mg, still a lot better than $0.47 per 100 mg from Drs Best. Further, it's already in powder form, removing the need for breaking open capsules before dissolving in olive oil.
The Trillium-brand Fisetin powder from Amazon is cheaper by about a factor of 2, but the purity is not specified.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/
The original study bring forward some ideas. The reserchers show that curcumin is one of the few substances (besides fisetin) that have a proven but smaller senolytic effect. I can only speculate if curcumin, in combination with fisetin, Bioperine and quercetin, could bring some extra benefit. Maybe curcumin can complement fisetin by penetrating tissues where fisetin is less effective? This is a very speculative question but I will test it.
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Staffan Olsson Do you plan to take the circumin with water or dissolve it in oil as some have recommended for fisetin-bioperine?
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Staffan Olsson Don It's important to note that curcumin has only been shown to be senolytic in cell culture models: there is no evidence at all that taking it as a supplement kills senescent cells in vivo.
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Staffan Olsson
I decided to add curcumin to my fisetin+quercetin+black pepper dissolved in olive oil for my second trial (one month after the first one). I decided to add it based on the paper:
https://www.mdpi.com/2077-0383/8/4/433/htm
Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro
o-Vanillin, apparently, is a metabolite of Curcumin.
This combo is kicking my *ss... It may be because I was just coming off a cold that I caught from my grandson last weekend, but I had major joint pain as well as a piercing pain in my left eye and sinus all night, etc... Feeling reasonably good at present though, but still feel a bit "off" like I did with the original formulation. With my original dose I felt a reasonable amount of joint and bone pain mostly about the third and fourth day after starting the dosage. (I took approx. 1 gram of each substance dissolved in oil with 1/4 tsp of freshly ground black pepper, on an empty stomach, for three consecutive days. The first time the pain was mostly in and around the joints of the knees, femurs, backbone, shoulders and elbows.
Interestingly, this time I only have the joint and bone pain in the knees and lower legs and ankles, particularly the left knee which always had the worst arthritic tendency.
I was really feeling pretty good, very good actually, just before catching the cold, so I think the initial dose had a really beneficial effect on my joints. I still get around normally, but seem to have arthritic or rheumatic tendencies, and it runs in the family as well. I'm hoping this protocol will reduce those tendencies, and from the way I was feeling a few weeks after the first dose, I think it has.
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Don I plan to dissolve it with oil. Avaocado oil is my first choice. I try to incorporate more avacado oil in my lifestyle (mostly on salads) so it might just as well be used as a dissolvent to.
https://www.lifeextension.com/Magazine/2015/10/Avocados-Super-Enhanced-Carotenoid-Absorption/Page-01
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Iðunn Thank you for the reminder. We are in uncharterd territory here, but that the territorry where selfexperimentation usually is.
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Staffan Olsson Sure, but you want to be experimenting based on plausible preliminary data 😉. It's one thing to see something like fisetin — which has substantial senolytic effects and low toxicity in mice — and gamble that it may have similar effects in humans; it's quite another to make a similar gamble based on cells in a test tube, with none of the complex metabolism to which curcumin is subject (leading to its extremely low bioavailability). For all we know, something about curcumin or its in vivo metabolites might block the senolytic effects of fisetin — for instance, by competing for access to cellular transporters, altering membrane characteristics necessary for its uptake, or by affecting its metabolism or disposition.
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Iðunn if, like its said in this thread, the structure of fisetin and quercetin is very close to each other they might just as well end up competing for transporters.
I see that Dan Nave already have tried the combo with interesting reactions.
Curcumin in a dose of 400 mg BCM-95 is a part of my daily program. it has wonderful effects on my body and on my mind. After 15 years of selfexperimentation I think I have found a few substances that have a robust and excellent effect (Both short term and long term) on me. Curcumin is one of them and that might lead me into a wishful thinking that curcumin not only might be taken with fisetin but that curcumin also might increase the senolytic effect.
I will use two protocolls. First without curcumin and then with curcumin.
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