What is Fisetin?
Fisetin is a flavonol, a chemical that belongs to the flavonoid group of polyphenols. Fisetin is a type of plant pigment that gives color to many fruits and vegetables [1, 2].
- Fisetin Encourages New Brain Growth
Out of a number of studied flavanoids, fisetin was found to be the most effective at causing new brain growth .
One of the reasons fisetin possesses so many brain-boosting effects is because it is able to cross the blood-brain barrier .
Fisetin Improves Memory
Fisetin supplementation increases the strength of long term memory pathways (by modifying ERK signaling and increasing BDNF), so it might be useful for memory disorders like Alzheimer’s [5, 6].
Fisetin Protects Against Brain Degeneration
Fisetin has been shown to regulate a number of pathways (e.g. antioxidant & mitochondrial function) that are implicated in age-related decline in brain health . One mechanism by which fisetin might protect against degenerative brain conditions is by activating certain transcription factors such as Nrf2 that increase the cellular levels of glutathione – a key cellular antioxidant that has protective effects on nerve cells [8, 91].
Fisetin protects nerve cells from oxidative stress. Oxidative death is one of the many factors associated with cognitive decline, stroke, Alzheimer’s, and Parkinson’s disease .
Moreover, Fisetin limits the accumulation of harmful compounds (phosphorylated tau) that accumulate in the brain and cause Alzheimer’s disease .
Alzheimer’s is characterized by an accumulation of amyloid beta. Fisetin has been found to protect the brain of mice against damage caused by effects of these usually neurotoxic compounds .
In fact, fisetin was convincingly shown to reduce the impact, and slow the progression of, Huntington’s disease in animal models (by activating the ERK cascade) [13, 14].
Fisetin is a potentially useful supplement for decreasing inflammation in microglia – immune cells that exert neurotoxic effects and are often activated in neurodegenerative conditions (see Dr. Younger speak about Microglia) .
Fisetin Decreases Brain Damage After Stroke
In one study, mice treated with fisetin showed a reduction in behavioral abnormalities after a strokecompared to the untreated mice .
Another study confirmed that fisetin helps to protect whichever part of the brain is starved of blood flow during a stroke .
Ten flavonoids including fisetin were tested for their ability to protect brain cells against glutamate toxicity. Fisetin was one of four that were found to increase antioxidant defenses enough to limit toxicity .
Fisetin Minimizes Brain Damage From Injury
Traumatic epilepsy is a condition of repeated seizures after a head injury. One study showed that epileptic rats experienced less brain damage from their seizures when given fisetin – probably because Fisetin inhibits oxidative stress . Rodents that were given a high dose of fisetin (50mg/kg of body weight) had a significantly better neurological function and reduced brain swelling after brain injury – maybe because fisetin inhibits TLR 4/NF-κB mediated inflammatory pathways .
Fisetin is Neuroprotective
Fisetin exerts neuroprotection against Aluminium chloride induced brain pathology [21, 22].
Fisetin decreases elevated levels of ammonia in the blood (hyperammonemia) that might affect vital brain functions in hyperammonemic rats .
Fisetin promotes nerve cell survival from trophic factor (helping molecules that allow neurons to develop and maintain connections with their neighbors) withdrawal by the enhancement of proteasomal activity .
Fisetin increases SIRT1, a protein linked to longevity that has been shown to be neuroprotective.
- Fisetin May Treat Depression
Fisetin is a potent anti-depressant that can increase serotonin and noradrenaline in mice (by inhibiting MAOA) . Fisetin-treated mice demonstrated fewer symptoms of depression and anxiety as a result of pain .
Fisetin’s anti-depressant effects can be enhanced with 5-HTP .
- Fisetin Has Anti-Inflammatory Properties
Fisetin inhibits the activity of lipoxygenases (enzymes that act on fatty acids), thereby reducing the production of pro-inflammatory compounds (eicosanoids) and their by-products [28, 29].
Fisetin may be a promising candidate in the treatment of inflammatory bowel disease (IBD) .
Treatment with fisetin suppresses activation of mast cells, demonstrating its potential use as an anti-inflammatory .
High blood sugar in diabetics can cause inflammation of the blood vessels and lead to serious damage. These inflammatory processes are inhibited by treatment with fisetin (possibly via inhibition of the HMGB1 signaling pathway) [32, 33].
Fisetin can relieve allergic reactions by inhibiting inflammatory cytokine production (IL-4 and IL-13) by Basophils .
Fisetin was found to be an effective treatment for Eczema in animals as it reduced the presence of inflammatory cytokines, eosinophils, mast cells and T-cells (CD4+ & CD8+) that are typically found in atopic dermatitis skin lesions .
- Fisetin May Prevent and Treat Cancer
The following studies are performed in animals and/or cells…Speak to your doctor if you have cancer.
Fisetin induces cell death and inhibits the growth of various types of cancers (e.g. melanoma, pancreatic cancer, colon cancer, lung cancer, and prostate cancer) .
Numerous studies have concluded that fisetin should be developed for cancer treatments that have proved resistant to chemotherapy [37, 36].
Fisetin inhibits the pathways responsible for cell growth and survival that are overactive in cancer patients .
Fisetin inhibits the ability of cancer cells to invade healthy tissues .
Fisetin inhibits cell proliferation and causes programmed death of chronic myeloid leukemia (white blood cell cancer) cells and possibly other leukemias [40, 41].
Treatment with fisetin was able to kill acute monocytic leukemia cells by increasing levels of nitric oxide and Ca(2+) and activating pathways of apoptosis (cell death) .
Aflatoxin is one of the most potent carcinogens known to man. Fisetin was found to reverse oxidative damage in the livers of rats with aflatoxin-induced cancer . Treatment with fisetin reduced tissue lesions and lipid peroxidation in the lungs of mice exposed to Benzo(a)Pyrene (a carcinogenic chemical) .
A diet rich in fisetin might help prevent and treat prostate cancer (by inhibiting urokinase plasminogen activator, altering genes that regulate cell cycles, and causing cancer cell death) [45, 46, 47].
Fisetin might exert anti-cancer effects by inhibiting the mTOR pathway .
Fisetin inhibits MMP-1 activity, which regulates important enzymes in cancer growth .
Fisetin is such a promising anti-cancer agent because it appears to inhibit and kill cancers without severely affecting the surrounding normal cells – probably because it is able to identify the unique cell-signaling pathways used by cancer cells [49, 50, 51].
- Fisetin Improves Blood Flow & Lowers Blood Pressure
Fisetin lowers the clumping together (coagulation) of blood cells in mice and, thus, lowers the chance of blockages 
By inhibiting Ca(2+) signaling, Fisetin helps reverse vasoconstriction caused by the release serotonin and phenylephrine .
Fisetin was able to reverse bad circulation in mice caused by a high-fat diet .
A rodent study found that Fisetin relaxes drug-induced contractions of blood vessels and, thus, lowers blood pressure. This action occurs regardless of blood vessel function .
- Fisetin May Help Treat Diabetes
Fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and, therefore, may have potential therapeutic use for the treatment of diabetic complications .
Diabetic mice fed a diet high in Fisetin stayed diabetic, but the kidney abnormalities normalized .
Fisetin administration normalized the increased levels of lipid content in blood, liver, and kidney in drug-induced diabetic rats .
In diabetic mice, Fisetin reduced the expected formation of cataracts .
Fisetin increases HDL and lowered LDL in diabetic rats .
Fisetin reduced anxiety-related behaviors in diabetic mice.
Fisetin improved mitochondrial function in diabetic rats .
Fisetin maintains stable blood glucose levels by increasing insulin sensitivity, resulting in a lower HbA1C [60, 61, 62]. Fisetin regulates carbohydrate metabolism by modulating the key regulatory enzymes in the liver and kidney tissues of diabetic rats .
- Fisetin May Extend Lifespan
A number of studies have found that fisetin activates SIRT-1, a gene that has been repeatedly associated with long lifespan; in fact, it is often referred to as the longevity gene [63, 64, 65].
Dietary supplementation with a strawberry extract (which is said to have the highest levels of fisetin) improved the performance of rats in a rodent model of accelerated aging .
- Fisetin May Lower Body Weight
In mice, fisetin supplementation reversed the weight gain caused by a high-fat diet .
Mice that underwent fisetin treatment had less weight increase than mice that did not undergo treatment .
Fisetin prevents diet-induced obesity by regulating cell growth .
In one study, mice were subjected to pain by altering their sciatic nerves. Mice treated with fisetin experienced less pain than the untreated mice .
Fisetin treatment can delay or lower the heightened sensitivity to pain associated with type 1 diabetes .
Fisetin’s pain reducing effects can be enhanced with 5-HTP .
In mice with estrogen deficiency or inflammation, the consumption of fisetin resulted in less bone density loss. Bone mineral density and bone markers positively correlated with the amount of fisetin consumed .
Therefore, fisetin might be an effective tool for preventing age-related or inactivity-related (e.g. when injured) loss of bone density.
- Fisetin Protects Skin From Sun Damage
Fisetin lowers the expression of various genes associated with skin aging (COX-2, MMP-1, MMP-3, MMp-9) that are usually induced by UVB exposure .
Fisetin inhibits UVB-induced collagen degradation – a key factor in skin aging .
Fisetin reduced the cellular levels of UV-induced reactive oxygen species, prostaglandin E2, and nitric oxide generation .
- Fisetin Prevents Toxicity
A study found that drug-induced kidney toxicity was lower in rats given fisetin via inhibiting Nf-kB and activating antioxidant defense . As such, it might be a wise idea to take fisetin if you are taking any substance that affects the kidneys, such as pain medications, alcohol, antibiotics, and laxatives .
- Fisetin Helps Maintain Energy Levels
Fisetin is able to enhance and maintain ATP levels during oxidative stress , by maintaining ATPase activity .
- Fisetin Can Treat Infections
Fisetin is a promising anti-fungal that is less toxic than prescription ones [73, 73].
One study found that fisetin was antifungal and might be a useful therapeutic treatment for cryptococcosis infections .
Fisetin inhibits Listeria infection .
Fisetin inhibits arginase, a key enzyme in the Leishmania amazonensis infection and, therefore, could be used as a food supplement in Leishmaniasis treatment .
- Fisetin is a Mast Cell Inhibitor and Can Help Histamine Intolerance
Fisetin has been found to reduce the activation of mast cells [35, 31].