Fiestin 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.
Thank you for the info. My understanding is the Fisetin should be taken with quercetin?
I have been taking only 100mg Fisetin + 500mg quercitin daily for about 2 weeks. Can't say I have noticed any changes. Except, I did have a short duration vagus nerve zinger that included a hot flash, dizziness, nausea, near faint, and SURPRISE! Lasted only 30 seconds or so but scared the heck out of me. It occurred on the 3rd day of my 5 day fast.
Would like to read more on dosage, duration, and results from others?
Bloodwork Results of Two Fisetin Sessions
As I stated in my first post on this topic, in the past two months my wife and I have taken two massive doses of Fisetin in an effort to clear our senescent cells. We did bloodwork arranged by Life Extension on October 22 before the first session and again on December 17 after the second session. Our goal was to determine if the Fisetin sessions had a measurable effect on our fitness, as measured by the bloodwork results. We analyzed our result values in three ways: (1) using the Aging AI website, (2) using the Young.AI website, and (3) using a calculation of Levine Phenotypic Age done with a spreadsheet that I have posted elsewhere on this site. I note that the Levine age is always close to the calendar age because the latter is one of its most important input factors. The table below summarizes the results:
Interestingly, following the Fisetin sessions my Aging AI age dropped by 8 years and my Young.AI age dropped by 3 years, but my Levine Phenotypic Age actually increased by 3 years. I think that this is because at the time of the second bloodwork I had a big bruise on my left leg from a collision with a chair in the dark a few days earlier. The inflammation from this bruise probably somewhat increased my c-reactive protein, my white blood cell count, and the blood geometry factors, all of which will increase the Levine age.
Therefore, my wife's numbers are probably more relevant. Her aging AI age dropped by 5 years, her Young.AI age dropped by 11 years, and her Levine age dropped by 1.4 years. My conclusion that the Fisetin sessions did have an observable (but not large) effect on our overall fitness, as reflected by the bloodwork.
Soon we will undertake two similar sessions with D+Q, and we will report any bloodwork changes after those.
Thank you for sharing your results and also look forward to the D+Q tests!
In my case I have noticed large variations in the aging.ai results in time (~10 years) and always wondered how I can disentangle the effect from the error. v1.0 and v3.0 have also resp. an intrinsic MAE of 5.5 and 5.9 years. To understand a bit more I did try an ANOVA test which might show a little effect (only with v1.0) in lowering the aging.ai in recent years and I (would like to :-)) associate this to a regular use of metformin. Coincidence or not, I am also looking at senolytics and might try the new LEF formulation.
Good luck for your tests!
Fisetin vs. D+Q
My wife and I have been starting our new senolytic doses on the 22nd of the month. In October and November, we took large doses of Fisetin, as reported above.
Today at 10 AM on empty stomachs, we took 200 mg of Dasatinib, 2,400 mg of Quercetin, and 10 mg of BioPerine. I'll report any side effects that we observe.
We plan to repeat this in a week, on the 29th. After that, we'll do bloodwork yet again and report any changes.
Do you feel that the fiestin was more effective taken on an empty stomach? I've been on the life extension " version of the synolitic therapy, for over one month, and have noticed subtle yet profound changes. ( without the potential added benefit of taking on empty stomach) from now moving forward......
D+Q+P Side Effects?
I do seem to notice some side effects from our D+Q+P (Dasatinib+Quercetin+Piperine) senolytic dose, taken about 24 hours ago. I had early morning stomach cramps and a mild headache, along with a mild feeling of unwellness (as if I was coming down with the flu). My temperature, however, is normal.
I take this as an indication that the D+Q+P treatment is dealing with some senescent cells in my lower digestive system and also has penetrated the blood-brain barrier. My wife has not experienced any similar symptoms.
You might know about already, I did not: clinical trial to follow at Mayo. I might start with Fisetin after the first results appear, will see ...
JGC stomach upset is likely just side effect of the pills, you need better biomarkers to test for senolytic effects. I'm putting a list up in a WIKI here in the near future. Clearing senescent cells involves a lot of recycling (e.g. the Golgi apparatus) which isn't something you generally feel, but there surely are parts that are discarded in your urine. I hypothesize that testing your urines specific gravity is a way to check - however during ad libitum feeding you need a baseline, and it might well be lost in that baseline level (lost in the noise).
For example during a fast, at day 5 is when it's clinically been measured that heavy senolytic activity occurs. Indeed during my last fast at day 4.5 my urine turned from clear to dark yellow and the specific gravity went from negligible to more than my test stick could measure (> 1.03) - in both cases the only other measured value was high ketone bodies (of course)*. I take this as significant senolytic activity, and is the only non invasive way of testing senolytic effects I can think of and I'm fairly confident of it, but this is just a hypothesis.
Note also this has to be calibrated to a given amount of hydration. I carefully measure my daily intake of steam-distilled water at 170 oz, and have that same level of hydration during a fast. Being dehydrated will also drive up your specific gravity.
* it also had a peculiar odor. Normally my urine smells 'green and spicy' from the vegan diet and supplements I take. During a fast in the early part it becomes clear as water with no odor, until day 4-5. Also to be clear my hypothesis is that the specific gravity is measuring the presence of discarded senolytic junk, which is why it's important (for measuring) to separate from the normal feeding activity.
My Fisetin experiment:
First day 500 mg; no side effects. 2nd day 1000mg; no effects. 3rd day 1200mg; no effects. 4th day 1200mg with 20mg BioPerine; no side effects.
Following week noted increased energy, less lower back discomfort, and less/no arthritis in hand.
Will repeat Fisetin after 3~4 week interval. Certainly easier than 5 day water only fast.
This week will start Metagenics' SPM Active pills for 3 weeks. Pill is supposed to provide "resolvins" to help reduce my chronic inflammation.
And then back to 5 day water fast again.
Senolytic Bloodwork Results from 2 Fisetin and 3 D+Q+... Sessions
A while back I reported on the bloodwork results for my wife (PBC) and I (JGC) taken before and after two large-dose sessions of Fisetin. After that we had rwo sessions of 100 mg Dasatinib + 1000 mg Quercerin + 10 mg Bioperine a week apart, followed in a week with 100 mg Dasatinib + 1000 mg Quercerin + 1000 mg Fisetin + 10 mg Bioperine. In each of these sessions, the Bioperine, which is supposed to suppress the action of P-glycoprotein that normally gives drugs a short half-life in the bloodstream, an hour before the other items to give it a chance to do its work. After the last of these sessions we had more bloodwork to observe ant effects of the treatments. The spreadsheet image belowshows the results, and analyzed using three methods of estimating "blood age".
The bottom line seems to be that (a) there is a certain amount of "noise" in bloodwork (not surprising) and small difference are probably fluctuations, and (b) the D+Q sessions didn't do much that the Fisetin Sessions had not already accomplished. For the December bloodwork I had a big bruise on my leg that I speculated had increased my Levine age. That seems to have been borne out, in that it dropped by 3 years in the new bloodwork.
I have Osteoarthritis around my knees. I started taking D+Q three months ago (70mg of D and 1,000mg of Q for three consecutive days / month). For the first two months, I felt fever around the knees a few days after the dosage. Actually, the knee temperature got 1.5 degrees celsius higher than that of thigh. It means that the inflammation around the knees got higher. I guess my immune system attacked the senescent cells.
However, my knees are much improved now. I feel no pain anymore when I go down the stairs. I am very impressed by the result.
I am wondering if your blood age would be younger if you had the blood work weeks after you took the senolytics.
Have you considered doing a purity analysis of the Fisetin supplements that have been mentioned in the Forum like Doctor's Best, Swanson, Rejuvenation Therapeutics. Maybe we could fund a comparative analysis to the Fisetin used in the Fisetin article :
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.
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.
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.
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.
The F + Q + C (at approx. 1 gm each, in oil) + black pepper (approx. 1/2 tsp) seemed to be a little extreme for me, possibly because of the 50% increase of the quantity of senolytics taken with the addition of the 1 gm of curcumin. Lots of aches and pains for up to 2 weeks and taking longer to return to normal than the first time last month with just F + Q + black pepper. I also noticed lack of healing for a couple of small issues during the protocol. I wouldn't want to do this again for perhaps 6 months. I feel I got very good absorption and duration doing it this way. Joints seem good and there is a definite reduction of spider veins. Who knows if the benefits are deeper than that, time will tell...
When doing Fisetin and Quercetin senolytic doses consider dissolving the powders in oil before taking. You could try with or without black pepper or piperine, etc. to see if that makes a difference. F + Q are not water soluble and I think dissolving them in oil increases their uptake massively. I don't think one absorbs much of the F + Q without dissolving it in oil.
For daily supplementation, you might be fine just taking a pill without the oil.
Piperine is supposed to increase absorption massively (2,000% for Curcumin) and keep the liver from quickly metabolizing them. F + Q + Curcumin are all substances that are affected by piperine according to my reading.
My advice is not to massively increase the dosages of these substances if you are going to use these mechanisms to increase their absorption and action. I used only 1 gram of each for 3 days, seeing definite effects. (Weight of approx. 77kg) I saw more effect when adding the Curcumin to the F + Q.
Mechanism of piperine action:
"In general, it inhibits drug metabolizing enzymes, stimulates absorption by stimulating gut amino acid transporters, inhibits the cell pump responsible for drug elimination from cells and inhibits intestinal production of glucuronic acid.
It may increase the absorption of drug in the GIT, or inhibit enzymes responsible for drug metabolism, especially in the liver when the drug passes through the liver after absorption from GIT. Oral administration of piperine in rats strongly inhibited the hepatic arylhydrocarbon hydroxylase and UDP-glucuronyltransferase activities.
Another study demonstrates that piperine modifies the rate of glucuronidation by lowering the endogenous UDP-glucuronic acid content and also by inhibiting the transferase activity.
Piperine inhibits human P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Both the proteins contribute to a major extent to first-pass elimination of many drugs.
Some of the metabolizing enzymes inhibited or induced by piperine include CYP1A1, CYP1B1, CYP1B2, CYP2E1, CYP3A4 etc. Most of the drugs metabolized by these enzymes will therefore be influenced by bioenhancers."
I like olive oil, but I have used other oil such as you would have in your kitchen for baking etc. Surprisingly, with the Fisiten and Quercetin it wasn't bad tasting and none of that unpleasantness you might get from just eating a tablespoon of oil...
Personally, I am somewhat leery of ingesting PG and PEG.