Fisetin

Health benefits: anti-cancer, anti-inflammatory, anti-oxidant, liver health, may protect against cognitive and neurological disorders such as Alzheimer’s disease

When researchers discovered a positive correlation between strawberry consumption and mental functioning, they set out on a path to discover why. It turns out that strawberries are high in a flavonoid called Fisetin, which is able to cross the blood brain barrier, and research suggests might be responsible for the berries’ apparent brain-health benefits.

Fisetin is naturally found in a number of plants such as the Japanese fruit wax tree (Rhus succedanea), and, in very small amounts, in the already mentioned strawberries, tomatoes, onions and other foods. It has been estimated that a person would have to eat 37 strawberries every day to reach the doses used in animal experiments that showed potential benefits of fisetin. Alternatively fisetin is available as a nutritional supplement from different manufacturers.

Fisetin, like other polyphenols such as resveratrol, is a sirtuin-activating compound and has been shown in laboratory studies to extend the life of simple organisms like yeast, worms, and flies. 

Fisetin has shown anti-cancer activity in studies on cells and model animals conducted in laboratories, and appears to block the PI3K/AKT/mTOR pathway. In lab studies it also has been shown to be an anti-proliferative agent, interfering with the cell cycle in several ways. In studies conducted on cells in a laboratory, fisetin inhibits the activity of several pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and Nuclear factor kappa B. It has also has been shown in lab studies to upregulate glutathione, an endogenous antioxidant. Fisetin also has direct activity as a reducing agent, chemically reacting with reactive oxygen species to neutralize them. Based on lab studies, it appears that fisetin lodges in cell membranes and prevents oxidative damage to lipids in the cell membrane. Finally studies indicate that it protects the liver against alcohol related damage.

It should also be noted that Fisetin, like some other flavonoids, have shown in laboratory experiments to inhibit two enzymes that are critical to proper DNA replication, called topoisomerases I and II.  In recent years, topoisomerases have become popular targets for cancer chemotherapy treatments. It is thought that topoisomerase inhibitors block the ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently leads to apoptosis and cell death. Because of this inhibition, fisetin may also be carcinogenic, although at what levels it could be carcinogenic in humans remains unknown – more about that here.

New and studies in progress are expected to reveal more upsides of Fisetin going forward.