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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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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 ...
https://clinicaltrials.gov/ct2/show/NCT03430037?cond=fisetin&cntry=US&rank=2
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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.
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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.
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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.
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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.
Cheers,
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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 :
- https://www.ncbi.nlm.nih.gov/pubmed/30279143
- The article says the experiment used Fisetin from a company in Houston:
- https://www.selleckchem.com/products/Fisetin(Fustel).html