We know through written historical accounts that ancient people and not-so-ancient peoples often used plants and herbs to treat sickness. Through years of trial and error, they were able to figure out which plants had healing powers.
What they'd probably stumbled on were plants that had high concentrations of certain natural phenolic compounds, which are more commonly referred to as polyphenols.
Institutionalized medicine didn't pay much attention to them, though, because the things these healers used just didn't work well enough to inspire interest or confidence. No amount of vile-tasting herbal teas was going to fix diabetes, lower body fat, or prevent heart disease.
But science has since been able to identify, extract, and concentrate these plant chemicals and use them in a way that would do all those ancient folk-medicine practitioners proud.
Common examples of these polyphenols include resveratrol, green tea extract, quercetin, caffeic acid, anthocyanins like cyanidin 3-glucoside, and the current darling of the polyphenol world, curcumin.
But a new player is ready to make its entrance and it might eventually rival curcumin in its accomplishments. It's called fisetin, and its list of reported and purported benefits is pretty long.
Like many polyphenols, fisetin seems to be a utility player, playing nutritional shortstop just as well as it plays nutritional right field. One problem, though – even though over 800 studies have been conducted on fisetin, only one of them involved humans. Most of what we know is based on experiments with mice and rats.
Still, if some of the following benefits extend to humans, as they often do with polyphenols in general, then we might really have something:
- Reduces body fat: Mice gained 75% less weight when they were introduced to a high-calorie diet and given fisetin. The thinking is that fisetin may increase levels of the fat-burning hormone adipokinectin.
- Helps regulate blood sugar: Diabetic rats and mice fed fisetin experienced insulin and blood sugar levels compatible with healthy mice. Furthermore, it prevented sugar from bonding with proteins, a process known as glycation that contributes to a host of bad stuff like nerve damage, kidney disease, cataracts, and aging of tissues in general.
- Prevents the growth of various cancers: Like curcumin, fisetin seems to downright hate cancer, holding special grudges against colon, brain, lung, breast, ovarian, pancreatic, and brain cancers. It also seems to protect against prostate cancer by blocking the receptors for DHT.
- Improves memory and learning: Fisetin improved the memory retention and learning abilities of old rats.
- Protects your skin: Fisetin slowed the breakdown of collagen in cells exposed to ultraviolet light.
- Relieves depression and anxiety: Fisetin seems to increase levels of serotonin and noradrenaline, thereby improving mood.
- Helps ameliorate neurodegenerative diseases: Animal models of Alzheimer's, Huntington's, multiple sclerosis, or amyotrophic lateral sclerosis showed marked improvement in such aspects as memory, balance, coordination, and life span when fisetin was introduced.
- Lowers blood pressure: Fisetin dilates blood vessels, thereby allowing blood to flow through the pipes easier.
- Helps you handle booze better: Mice that partied too hard were able to process alcohol better.
- Combats Irritable bowel disease (IBS): When mice with the human equivalent of IBS were given fisetin, inflammation went way down.
- Fights aging in general: Fisetin seems to be a powerful "senolytic" in that it helps the aging body rid itself of senescent cells (cells that stopped dividing) that normally lead to inflammation and reduced lifespan if left to foster.
Like most polyphenols, fisetin is a powerful antioxidant, which explains or partly explains many of its effects.
Secondly, it blocks an inflammatory switch known as NF-kB. Block this protein complex and you help thwart the evil plans of cancers, allergies, and autoimmune diseases.
Fisetin also influences mTOR, a kinase that acts as kind of a cellular switch. Having higher levels of mTOR after a workout is a good thing as it helps you grow muscle, but having perpetually high mTOR levels is associated with a variety of diseases. Fisetin could be used to modulate mTOR levels to your advantage.
Fisetin, like most polyphenols, seems to only have better angels perched on its shoulders in that it doesn't seem to have any negative side effects, even at high doses (at least in animal studies).
Still, pregnant women and children should heed the usual warnings since we don't yet know enough about the substance. The good news is that the Mayo Clinic is currently investigating fisetin in three separate studies involving diabetes, kidney disease, and frailty, so we should have more info on its safety and efficacy soon.
Of all foods analyzed for fisetin levels, strawberries contained the most, but you'd have to eat about 37 of them a day to shoot for the enhanced kidney function seen in one mouse study.
Taking fisetin as a supplement is more realistic and there are currently some offerings on the market, but even so, we're not exactly sure of the optimal dosages need for human health.
The Mayo Clinic studies I mentioned earlier are using doses of between 1,000 and 2,000 mg. daily, which is a hell of a lot. However, in the one human trial that's currently in the literature, just 100 mg. a day proved effective in reducing inflammation in cancer patients.
To further complicate things, fisetin, like many polyphenols, is poorly absorbed, but taking it with fish oil or olive oil might help get it into your system.
Of course, early on, we didn't know to combine curcumin with piperine, or cyanidin 3-glucoside with a self-emulsifying delivery system, to enhance their bioavailability. Science will no doubt soon unlock the key to fisetin's absorption problems, too.
- Khan N et al. A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice. Cancer Res. 2008 Oct 15;68(20):8555-63. PubMed.
- Pal HC et al. Fisetin and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:213-244. PubMed.
- Hunter P. 13 Amazing Fisetin Benefits and Foods, Dosage and Side Effects. Selfhacked. June 8, 2019.
- Robbins P. A healthy-aging superstar you should know about. Bottomline Health. July 2019, Vol 33/No 7
- Park JM et al. Heartwood extract of Rhus verniciflua Stokes and its active constituent fisetin attenuate vasoconstriction through calcium-dependent mechanism in rat aorta. Biosci Biotechnol Biochem. 2016;80(3):493-500. PubMed.
- Prasath GS et al. Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2011 Oct 15;668(3):492-6. PubMed.
- LeBrasseur NK et al. Cellular Senescence and the Biology of Aging, Disease, and Frailty. Nestle Nutr Inst Workshop Ser. 2015;83:11-8. PubMed.