Scientists wouldn’t ever have become fascinated with strawberries if it wasn’t for this plant pigment. Meet fisetin: a promising anti-aging compound and a so-called senolytic. It also has anti-inflammatory, antioxidant, and immune-supporting effects, but clinical evidence is lacking. Read on to learn the benefits, food sources, dosage, and side effects of fisetin.
What is Fisetin?
Fisetin is a flavonol, a yellow plant pigment that belongs to the flavonoid group of polyphenols. It gives color to many different fruits and vegetables [1, 2].
Compared to now-famous plant antioxidants like resveratrol and quercetin, fisetin was unfairly ignored for far too long. It wasn’t until recent years that researchers became increasingly interested in its medicinal potential.
Science teams are currently exploring its ability to slow the aging process and extend lifespan – its so-called “senolytic” effects. What’s more, fisetin has powerful anti-inflammatory, antioxidant, and immune-supporting properties [3, 4].
Despite promising animal and cell-based findings, research is still in its early stages. Only a single clinical trial has been conducted with fisetin.
- May protect the brain and improve memory
- Might delay aging
- Helps control blood sugar
- May have anticancer properties
- Protects the liver and heart
- Clinical trials are lacking
- Poorly absorbed
- Possible interactions with blood thinners
- Unknown safety in humans
Many different fruits and vegetables contain fisetin. Food sources with the highest concentration of fisetin include (expressed as ~micrograms of fisetin per gram of freeze-dried food) :
- Strawberries (160)
- Apples (27)
- Persimmons (11)
- Lotus root (6)
- Onions (5)
- Grapes (4)
- Kiwi (2)
It’s also found in mangoes and cucumbers in lower amounts. The listed fisetin levels were measured in freeze-dried foods. Levels may vary in fresh fruits and vegetables and depend on the conditions they’re grown in .
In Japan, the average dietary intake of fisetin is about 0.4 mg/day .
How It Works
Let’s zoom in on how fisetin acts on a cellular level to understand its health benefits. Put your science hat on and get ready to read about some advanced research…
Or if you’d just like the bottom line, skip to the list of benefits below!
To start with, fisetin increases antioxidant defense.
It directly neutralizes free radicals and also increases other powerful antioxidants, such as glutathione, superoxide dismutase, catalase [7, 8, 9].
Secondly, it can block a pathway called NF-κB.
NF-κB is a switch that tells genes to produce inflammatory compounds. An overactive NF-κB response is linked to allergies, autoimmune diseases, and cancer. Plus, fisetin blocks inflammatory enzymes that degrade fatty acids (lipoxygenases) [10, 11, 12, 13, 14, 15].
It also reduces the activity of a group of enzymes (MMPs) that cancers require to spread and invade other tissues [16, 17].
Fisetin also blocks the mTOR pathway.
mTOR’s demands for energy and growth can throw your cells into a frenzy: metabolic waste builds up – and there’s no time to clean it up. An overactive mTOR response is associated with cancer, diabetes, obesity, and neurodegenerative diseases. By blocking this pathway, fisetin helps remove waste and enhance cellular metabolism [18, 19, 20, 21].
And here’s the most intriguing part: blocking mTOR increases longevity. In fact, blocking mTOR is the only intervention that increased lifespan in all organisms studied to-date [22, 23].
This is because once mTOR is blocked, autophagy is activated: a process of recycling damaged cellular components [22, 23].
It’s worth reminding you, however, that the vast majority of fisetin health effects haven’t yet been confirmed in clinical trials.
Health Benefits of Fisetin
Animal and Cellular Research (Lacking Evidence)
No clinical evidence supports the use of Fisetin for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based studies; they should guide further investigational efforts but should not be interpreted as supportive of any health benefit.
Much of the interest in fisetin has centered around its potential to help slow aging and extend a healthy lifespan.
Aging is characterized by the buildup of senescent cells – cells that stop dividing, become damaged, and start releasing inflammatory molecules [24, 25].
As we accumulate more and more of these senescent cells, the body starts being affected. These cells start damaging healthy tissue. They contribute to many age-related diseases – from osteoporosis and cancer to heart and brain diseases [24, 25].
Removing senescent cells calms inflammation, improves physical function, and increases lifespan in animals [24, 25].
Certain plant compounds are able to destroy senescent cells without harming healthy cells. In a 2018 cell-based study of 10 such compounds, fisetin was the most effective one. In old mice, fisetin cleared senescent cells and increased their lifespan by over 10% [26, 4].
Because of this study, researchers got particularly interested in “senolytic” or “senotherapeutic” properties of fiestin.
Fisetin also extended the lifespan of yeast by more than 50% and the lifespan of fruit flies by more than 20% [27, 28].
Because of these promising results, a clinical trial is underway to see if fisetin is effective for reducing inflammation and improving frailty and bone health in elderly people .
2) Diabetes and Its Complications
In multiple animal studies, fisetin restored blood sugar levels of diabetic rats and mice to those of healthy animals. It improved their ability to control blood sugar levels by [30, 31, 32, 33, 34, 35]:
- Increasing insulin levels
- Increasing enzymes that turn sugar into energy
- Removing sugar from the blood to store as glycogen in the liver
- Reducing the liver’s ability to make sugar from lactate and amino acids
Fisetin slowed the progression of cataracts and protected the kidneys of diabetic mice by blocking inflammation and oxidative stress. It also protected the liver of diabetic rats from high blood sugar levels by increasing antioxidant levels [36, 37, 33].
Another complication of diabetes is the hardening of the arteries and heart disease. In a cell study, fisetin prevented high sugar levels from causing inflammation in blood vessels [38, 39].
3) Anticancer Potential
The findings discussed below stem from preliminary clinical research and animal studies. They should guide further investigation but shouldn’t be interpreted as supportive of the anticancer effects until more research is done. Fisetin isn’t approved for cancer prevention or treatment.
Inflammation is linked to colon cancer growth, as well as it’s spread and resistance to chemotherapy. In a clinical study of 37 colon cancer patients undergoing chemotherapy, fisetin (100 mg/day for seven weeks) reduced markers of inflammation (IL-8 and hs-CRP). However, the authors didn’t report the effects on tumor growth and progression .
In rats, fisetin reduced oxidative stress and the growth of liver cancer caused by fungal toxins .
In mice, it prevented the growth of lung cancer and boosted low antioxidant levels caused by a toxin in tobacco smoke. It reduced lung tumor growth by 67% in mice and by 92% when combined with a chemotherapy drug. It also prevented the growth of new blood vessels supplying nutrients to the cancer [42, 43].
Another study found that fisetin reduced tumor growth by 66% in mice with melanoma .
Certain types of prostate cancers are fueled by androgens such as testosterone and dihydrotestosterone (DHT). Fisetin slowed the growth of prostate tumors in mice by blocking the receptors for testosterone and DHT on cancer cells .
Fisetin also protected against kidney damage from chemotherapy in rats by reducing inflammation and boosting antioxidant levels .
In cell studies, fisetin causes programmed cell death and prevents the growth and spread of a variety of cancer cell lines, but this doesn’t imply the actual anticancer effects in living organisms [46, 47, 48, 49, 50, 51, 52, 53, 54].
4) Brain Protection and Mental Health
Older rats given fisetin experienced memory and learning improvements. Cell studies revealed that fisetin activates pathways in the brain involved in storing memories [55, 56].
In another study, fisetin prevented memory loss in mice exposed to toxins .
Fisetin can easily cross the blood-brain barrier in mice. This is important as there is an ongoing debate about whether compounds like fisetin can reach high enough levels in the brain to improve its function [57, 58].
Depression and Anxiety
Fisetin reduced depression and anxiety in mice by increasing levels of serotonin and noradrenaline, neurotransmitters that play key roles in mood [59, 60, 61].
Immune cells in the brain called microglia are overactivated in neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease. This causes inflammation and damage to healthy brain cells. In cells studies, fisetin boosted brain antioxidant levels and prevented microglia from releasing inflammatory compounds in response to bacterial toxins (LPS) [62, 63].
Alzheimer’s disease involves the buildup of amyloid plaques and tau proteins in the brain. Fisetin reduced levels of tau proteins in brain cells by activating a process that removes these harmful proteins (autophagy) .
In mice with amyloid plaques, fisetin improved memory, reduced inflammation, and prevented the loss of brain cell function. in mice with Alzheimer’s, it reduced amyloid plaque buildup and loss of brain cells .
Huntington’s disease is a genetic movement disorder in which brain cells get destroyed. In mice with Huntington’s, fisetin was able to improve declining physical function and increase lifespan .
In amyotrophic lateral sclerosis (ALS), brain cells that control muscles die off. Fisetin improved balance and muscle coordination and increased survival in mice with ALS .
Protection Against Stroke and Toxins
Fisetin protects brain cells and reduces inflammation and damage due to stroke in mice and rats [68, 58, 69].
In another study of rabbits, fisetin prevented loss of balance, lack of energy, and uncontrolled eye movements caused by stroke .
Cell studies show that fisetin reduces the activity of immune cells in the brain that are responsible for the inflammation and brain damage after a stroke [68, 62].
Aluminum is toxic to the brain and has been linked to Alzheimer’s disease. In mice, fisetin reduced inflammation and oxidative stress in the brain caused by aluminum [71, 72].
In cells, fisetin promotes the survival of brain cells by getting rid of damaged or unneeded proteins .
In a mouse model of brain trauma, fisetin prevented seizures by reducing oxidative stress .
Fisetin also reduced seizures and death in mice exposed to chemicals and electric shocks. It did so by increasing levels of the neurotransmitter GABA and reducing oxidative damage in the brain .
5) Heart Health
Fisetin reduced high total and LDL cholesterol and triglycerides in rats fed a high-fat diet. In diabetic rats, it doubled HDL levels and cut LDL cholesterol levels in half. A cell study hinted that fisetin reduces cholesterol by causing more of it to be released in the bile [76, 77, 32].
Cell studies show that fisetin prevents immune cells called macrophages from oxidizing and ingesting LDL cholesterol. When macrophages ingest oxidized LDL, they create fatty plaques that harden the arteries and cause heart disease [78, 79].
Circulation and Blood Pressure
In rats, fisetin improved poor blood flow caused by a high-fat diet .
Test-tube experiments reveal that fisetin helps relax and dilate blood vessels, which helps improve blood flow and reduce blood pressure [81, 82].
Fisetin protected heart cells from oxidative stress and improved heart function in rats with abnormal thickening of the walls of the heart .
It also protected heart tissue and mitochondrial function from damage due to a heart attack in rats .
6) Liver Protection
In mice, fisetin protected the liver from alcohol by helping the animals process it quicker. It also reduced oxidative stress, which prevents damage .
In mice and rats fed high-fat diets, fisetin reduced the buildup of fats in the liver. It works by increasing enzymes that break down fats and reducing enzymes that make new fats [85, 86, 87].
Diabetes often causes nerve damage and pain. Fisetin reduced heightened sensitivity to pain in diabetic mice and in mice with nerve injuries. It lowered oxidative stress and increased serotonin and GABA activity in spinal nerves, which acts to relieve the sensation of pain [59, 88].
8) Bone Loss
Estrogens keep bones healthy. After menopause, low estrogen levels put women at risk of osteoporosis. The rise inflammation due to aging also weakens the bones [89, 90].
Fisetin improved bone density and prevented bone loss in mice with low estrogen levels and inflammation. In cells, it worked by reducing the activity of bone-degrading cells (osteoclasts) [89, 90, 91].
9) Skin Benefits
UV Protection and Skin Aging
Collagen gives structure and elasticity to the skin. In human skin cells, fisetin prevented the breakdown of collagen from UV/sun exposure – a key factor in skin aging. It also reduced inflammation and oxidative stress caused by UV rays .
Applied to the skin of mice, fisetin prevents the abnormal growth of skin cells, DNA damage, and inflammation caused by UVB rays. It also reduces the formation of wrinkles by boosting skin collagen [93, 94, 95].
Skin inflammation in eczema is typically treated with steroid creams, which often have harsh side effects. In one study, it reduced skin inflammation, swelling, and redness in mice with eczema .
10) Microbial Infections
In one study, fisetin helped prevent Listeria infection by interfering with the bacteria’s ability to hide from the immune system .
In another cell study, it was active against two fungi that cause infections in people with weak immune systems (C. gattii and C. neoformans). It impairs the production of a compound fungi need to survive called ergosterol [98, 99].
Fisetin might also help with infections caused by the parasite L. amazonensis. It blocks the activity of arginase, an enzyme the parasite needs to protect itself [100, 101].
IgE antibodies and T immune cells activate mast cells and basophils, which go on to trigger an allergic response. In cell studies, fisetin prevented T cells and IgE from activating these cells and causing inflammation [102, 103, 104].
Similarly, fisetin prevented IgE antibodies from activating mast cells in mice exposed to allergens. In turn, it stopped the release of histamine and other inflammatory compounds .
12) Inflammatory Bowel Disease
In a mouse model of inflammatory bowel disease or IBD, fisetin reduced damage and inflammation in the colon by blocking NF-κB activity and restoring antioxidant levels .
Fisetin Side Effects and Precautions
Keep in mind that the safety profile of fisetin is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one, and you should consult your doctor about other potential side effects, based on your health condition and possible drug or supplement interactions.
Even at high doses, scientists found no evidence of side effects or toxicity in animal studies. Clinical studies, of course, are needed to confirm its safety .
In the lone clinical trial on cancer patients, stomach discomfort was reported in the fisetin group. However, this might not actually be a side effect of fisetin. All patients were receiving chemotherapy and the same stomach complaint was also reported in the placebo group .
Due to the lack of safety data, pregnant women and children should avoid fisetin supplements.
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
The liver uses the same pathway to process fisetin as it does for the blood-thinning agent warfarin (Coumadin). This can, in theory, increase the effects of warfarin [107, 108].
Fisetin substantially reduces blood sugar in diabetic animals. The combination with blood sugar-lowering drugs may further reduce sugar levels [30, 31, 32, 33, 34, 35].
Fisetin Dosage & Supplements
Fisetin supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.
The below doses may not apply to you personally. If your doctor suggests using a grape seed extract supplement, work with them to find the optimal dosage according to your health condition and other factors.
In a clinical study of colon cancer patients, 100 mg/day was effective for reducing inflammation .
In an ongoing clinical trial looking at the effects of fisetin on inflammation, bone health, and frailty in the elderly, fisetin will be used at a high dosage of 20 mg/kg for two consecutive days. This would be around 1,400 mg/day for a 155-lbs person .
We don’t recommend taking such a high dosage until the results of this study are published
Some researchers are doubtful about the benefits of supplemental fisetin since it is poorly absorbed when taken orally.
But there is at least one simple way to, theoretically, increase its absorption: take it with fats. Fisetin is fat-soluble, similar to other flavonoids like quercetin. Fish oil and other oils enhance the bioavailability of quercetin, and they might do the same for fisetin [109, 110].
Even so, new formulations combining fisetin into small fat-like molecules (liposomes) may be the only effective solution. These greatly improve its absorption and anticancer effects. However, they are not yet commercially available [109, 111].
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Users commonly report improvements in focus, memory, and mood.
Many people use fisetin as part of an experimental program or stack to remove senescent cells. It is often paired with other flavonoids such as quercetin for this purpose. Some users reported headaches as a side effect.
Fisetin is a promising senolytic that might help the body get rid of toxic, senescent cells that cause aging. Plus, according to preclinical research, it may protect the brain and heart, improve memory, and combat inflammation and free-radical damage.
Strawberries are by far the best food source of fisetin, followed by apples and persimmons. Keep in mind that research on fisetin’s effects is still in the preliminary stages. Based on what we know, it is probably safe but poorly absorbed from oral supplements. You might improve its absorption by taking it with fats.
Pregnant women and children should avoid fisetin while others should talk to their doctor before supplementing.