I took a load of a potential senolytic drug, did lots of bloodwork and got almost nothing.
I am sharing a story of self-experiment with fisetin — a potential health and longevity-boosting drug, belonging to a novel class of senolytic compounds.
I am an enthusiast “biohacker” (whatever this means). I am doing regular health check-ups and bloodwork at least two times a year, monitoring critical health and ageing biomarkers, as well as trying various medical interventions to boost my mental and physical state. Also, I can “almost” be considered a professional, as I am M.Sc. biochemist and a PhD in macromolecular chemistry (this means I try not to do stupid things).
Senotylics have been taking anti-ageing community by storm. Senescence-based theory of ageing is currently considered as one of the most promising approaches to fight some critical manifestations of ageing.
Long story short. There’s a normal ageing process that every cell goes thought. They divide, they live, they die. But, not all of them — sometimes natural mechanism of removing old cells (apoptosis) gets broken and some cells get into the senescence phase. That’s a state of “limbo” — cell continues to live, consume resources, but produces no useful functions and pollutes surrounding space with chemical markers of age. Time goes by, body continues to accumulate those cells and impact becomes more and more visible — ageing.
The idea of senolytic therapy is pretty simple — let’s force those cells to die and remove them out of the body. This should really improve our health.
As I am writing this article Phase I of trials testing a most well-known combination of senolytics is in progress and even some very preliminary results made available.
Recent publication showed that a compound called “fisetin” has very pronounced senolytic properties. A high-dose acute intervention was shown to promote cleansing of senescent cells in mouses and human tissues.
And, by a great coincidence, fisetin is not an extremely expensive research chemical but rather a well-known flavonoid. And you can buy it online as a supplement.
Whaaaat? If this is such a great compound and it’s sold online, why nobody noticed any great health-promoting effects? One of the explanations is simple — the dosage. Researched used much higher doses of fisetin.
Anyway, I decided to give it a try.
Obtaining the compound.
My first attempt to get the compound failed miserably. Famous alibaba.com offered bulk quantitates from a range of suppliers in various forms, purity, etc.
I ordered 500g of 98% fisetin directly from Chinese factory (around USD 500).
It arrived in a few weeks, but customs declined to clear the package with 500g of unknown white powder. What a shame…After some negotiations package went back to China.
Another route was found to be much simpler — fisetin was found as a main and only component of Dr.Best’s Novusetin supplement and sold at iHerb.
The researchers that tested fisetin on mouses used 500mg/kg dosage. The ratio to convert mouse dose to human dose is typically 12.3, so for my weight daily dose was estimated to be:
Daily_dose = 80kg * 500mg/kg * 12.3 = 3250mg = 3.25g
One bottle of Dr. Best Novusetin contains 30 capsules*100mg = 3g. To make life simpler I decided to stick to 3g = 1 bottle as a daily dose. The recommended regimen was taking this dose for 6 days in a row. So, I ordered 6 bottles and they successfully arrived a few weeks later.
I did a traditional bloodwork check-up based on Longevity Panel 1.4, containing major biomarkers a few weeks before I started the experiment.
This is a diagnostic panel developed by Russian longevity community, and I wasn’t able to find an English website to link you, guys. So, here’s my adjusted version of human blood biomarkers for longevity prediction and general health assessment.
- Alanine transaminase
- Vitamin B12
- Vitamin D (calciferol)
- Folic acid
- Ca 2+/Na 2+/K+/Cl-
- Uric acid
- C-reactive proteins
- T3 free / T4 free/ TSH
- Lipid profile + cholesterol
What did I expect from successful treatment? I had no idea, to be honest. Based on preliminary results from a similar experiment going on in Russian biohackers community I was looking for the dramatic change in cystatin C.
During my 6 day treatment, especially on the first and second day, I felt really strange — kind of light-headed and dizzy, also extremely thirsty and dehydrated (signs of dehydration are clearly seen even after two weeks when I did post-intervention checkup).
During the treatment, the most pronounced subjective effect was a change in skin condition. My wife noticed a fast and rapid change in my skin quality just in a few days. It became much firmer, hydrated (despite general dehydration) and smooth. I was very disappointed that I haven’t found a way to quantify this change. My next experiment will definitely include in-depth skin analysis using professional dermatologist equipment.
After two weeks from the last dose, I repeated my bloodwork, just to find that none of the biomarkers changed in a better direction and some just got slightly worse.
Here are my before and after blood biomarkers, with some historical references and comments and and a spreadsheet.
Other people experimenting with fisetin also didn’t noticed any change in blood markers, as well as preliminary results from stage 1 clinical trial of another senolytics regiment (D+Q).
- it takes more time to develope changes in blood
- compound is ineffective in humans
- we should focus more on monitoring functional characteristics, like VO2 max, heart rate variability, pulse wave speed, etc.
- we need more people and more data
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