Scientists wouldn’t ever have become fascinated with strawberries if it wasn’t for this plant pigment. Meet fisetin: a powerful anti-aging compound and a so-called senolytic. It also has anti-inflammatory, antioxidant, and anti-cancer effects. Find out what the latest research says about it and why you might want to get more 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 – it’s so-called “senolytic” effects. What’s more, fisetin has powerful anti-inflammatory, antioxidant, and anti-cancer 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.

Snapshot

PROs

  • Protects the brain and improves memory
  • Might extend lifespan
  • May prevent age-related diseases
  • Controls blood sugar and reduces diabetes complications
  • May fight cancer
  • No known side effects

CONs

  • Not well-studied in humans
  • Poorly absorbed
  • Possible interactions with blood-thinners

Food Sources

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) [5]:

  • 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 [6].

In Japan, the average dietary intake of fisetin is about 0.4 mg/day [3].

Health Benefits

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!

How It Works

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].

There’s more: fisetin blocks the mTOR pathway.

mTOR works as your cells’ central controller. When you get enough nutrients, mTOR tells your body: “All is well, produce energy and grow!”. You would think that mTOR is something you want to be increased, but that’s not usually the case [18].

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 prevent the growth of cancer [19, 20, 21, 22, 19].

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 [23, 24].

This is because once mTOR is blocked, autophagy is activated: a process of recycling damaged cellular components [23, 24].

1) May Fight Aging and Extend Lifespan

Much of the interest in fisetin has centered around its potential to help slow aging and extend a healthy lifespan.

The word senescent simply means “the state of being old.” Aging is characterized by the buildup of senescent cells – cells that stop dividing, become damaged, and start releasing inflammatory molecules [25, 26].

When you’re young, your immune system effectively removes senescent cells. But as you grow older, your immune system becomes less efficient. Senescent cells start gaining traction. They refuse to let the immune system kill them, resisting a healthy process known as apoptosis [25, 26, 4].

As you accumulate more and more of these senescent cells, your whole body starts being affected. These cells start damaging your healthy tissue. They contribute to many age-related diseases — from osteoporosis and cancer to heart and brain diseases [25, 26].

Removing senescent cells calms inflammation, improves physical function, and increases lifespan in animals [25, 26].

Certain plant compounds are able to destroy senescent cells without harming healthy cells. In a 2018 cell study of 10 such compounds (including quercetin), fisetin was the most effective one. In old mice, fisetin cleared senescent cells and increased their lifespan by over 10% [27, 4].

Because of this study, fiestin earned a reputation as one of the most potent and safest “senolytics” or “senotherapeutics.”

Fisetin also extended the lifespan of yeast by more than 50% and the lifespan of fruit flies by more than 20% [28, 29].

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 [30].

Fisetin’s anti-aging effects are exciting but will need to wait and see if they will be confirmed in human trials.

2) May Help with Diabetes and Its Complications

Fisetin restores blood sugar levels of diabetic rats and mice to those of healthy animals. It improves their ability to control blood sugar levels by [31, 32, 33, 34, 35, 36]:

  • 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

Excess sugar in the body can stick to proteins and fats, creating harmful inflammatory molecules called advanced glycation end-products (AGEs). These AGEs play a key role in many different complications of diabetes including cataracts, kidney disease, and nerve damage [37, 38].

Fisetin slowed the progression of cataracts and protected the kidneys of diabetic mice by blocking the formation of AGEs and reducing oxidative stress. It also protected the liver of diabetic rats from high blood sugar levels by increasing antioxidant levels [39, 40, 34].

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, a key step in the development of heart disease [41, 42].

To sum it up, fisetin helps with diabetes by improving blood sugar control and preventing high blood sugar levels from damaging cells and tissues.

3) Anti-cancer Potential

In cell studies, fisetin causes programmed cell death and prevents the growth and spread of a variety of cancers including [43, 44, 45, 46, 47, 48, 49, 50, 51]:

  • Ovarian
  • Prostate
  • Colon
  • Breast
  • Brain
  • Lung
  • Immune cell
  • Leukemia (cancer of the blood and bone marrow)

Fisetin also makes drug-resistant lung cancer cells more vulnerable to chemotherapy [52, 53].

Research in animals confirms the results of cell studies.

In rats, fisetin reduced oxidative stress and the growth of liver cancer caused by fungal toxins [54].

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 [55, 56].

Another study found that fisetin reduced tumor growth by 66% in mice with melanoma [57].

Certain types of prostate cancers are fueled by androgens such as testosterone and dihydrotestosterone (DHT). Fisetin slowed the growth of prostate tumors by blocking the receptors for testosterone and DHT on cancer cells [58].

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, taking 100 mg/day fisetin for seven weeks reduced markers of inflammation (IL-8 and hs-CRP) [59].

Fisetin also protected against kidney damage from chemotherapy in rats by reducing inflammation and boosting antioxidant levels [10].

While fisetin’s broad anti-cancer effects and lack of toxicity are promising, we still can’t say if the results will translate to humans.

4) Brain

Memory and Learning

Older rats given fisetin experienced memory and learning improvements. Cell studies revealed that fisetin activates pathways in the brain involved in storing memories [60, 61].

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 [62, 63].

Depression and Anxiety

Fisetin reduced depression in mice by increasing levels of serotonin and noradrenaline, neurotransmitters that play key roles in mood. It also reduced depression and anxiety in mice caused by nerve pain [64, 65, 66].

It works by blocking the enzyme that breaks serotonin and noradrenaline down (monoamine oxidase or MAO). It may also work by protecting brain cells from damage and oxidative stress [65, 66].

Neurodegenerative Diseases

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 boosts brain antioxidant levels and prevents microglia from releasing inflammatory compounds in response to bacterial toxins (LPS) [67, 68].

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) [69].

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 [70].

Huntington’s disease is a fatal genetic disorder in which brain cells get destroyed. In mice with Huntington’s, fisetin was able to improve declining physical function and increase lifespan [71].

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 [72].

Multiple sclerosis involves the destruction of myelin, an insulating shield that helps brain cells communicate. In a cell study, fisetin prevented immune cells from destroying myelin, suggesting it may be helpful for this disease [73].

Protects Against Stroke and Toxins

Fisetin protects brain cells and reduces inflammation and damage due to stroke in mice and rats [74, 63, 75].

In another study of rabbits, fisetin prevented loss of balance, lack of energy, and uncontrolled eye movements caused by stroke [76].

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 [74, 67].

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 [77, 78].

In another study, fisetin prevented memory loss in mice exposed to toxins. In cells, fisetin promotes the survival of brain cells by getting rid of damaged or unneeded proteins [61, 79].

Seizures

Brain injuries are one of the most common causes of seizures, in which case anti-seizure drugs are often unhelpful. In a mouse model of brain trauma, fisetin prevented seizures by reducing oxidative stress [80].

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 [81].

Fisetin protects the brain by increasing antioxidant levels and reducing oxidative stress and inflammation.

5) Heart Health

Cholesterol

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 [82, 83, 33].

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 [84, 85].

Circulation and Blood Pressure

In rats, fisetin improved poor blood flow caused by a high-fat diet [86].

Cell studies reveal that fisetin helps relax and dilate blood vessels, which helps improve blood flow and reduce blood pressure [87, 88].

In a cell study, fisetin prevented blood cells from clumping together. This suggests it has the potential to reduce blood clots that restrict blood flow [86].

Protects the Heart

Fisetin protected heart cells from oxidative stress and improved heart function in rats with abnormal thickening of the walls of the heart [9].

It also protected heart tissue and mitochondrial function from damage due to a heart attack in rats [89].

Fisetin improves heart health by reducing high cholesterol levels, improving circulation, and protecting the heart from oxidative stress.

6) May Protect the Liver

In mice, fisetin protected the liver from alcohol by helping the animals process it quicker. It also reduced oxidative stress, which prevents damage [90].

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 [91, 92, 93].

7) May Help with Obesity

Mice eating a high-fat diet gained up to 75% less weight when they were given fisetin [94, 86].

Fisetin prevents weight gain by blocking mTOR, reducing the growth of new fat cells. It may also work by increasing adiponectin, a hormone that boosts fat-burning [94, 95].

8) Reduces Pain

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 [64, 96].

9) May Prevent 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 [97, 98].

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) [97, 98, 99].

Due to its strong anti-inflammatory and bone-protective properties, fisetin might help maintain bone health with aging.

10) Skin

UV Exposure

Collagen gives structure and elasticity to the skin. In human skin cells, fisetin prevented the breakdown of collagen from UV exposure – a key factor in skin aging. It also reduced inflammation and oxidative stress caused by UV rays [100].

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 [101, 102, 103].

Fisetin has the potential to protect the skin from excessive sun exposure that causes wrinkles, age spots, and skin cancer.

Eczema

Skin inflammation in eczema is typically treated with steroids creams, which often have harsh side effects. With more research, fisetin may turn out to be a safe anti-eczema remedy. In one study, it reduced skin inflammation, swelling, and redness in mice with eczema [104].

11) Fights Microbes

A couple of studies discovered that fisetin might help fight bacteria, yeast, and even parasites. Unlike prescription drugs, fisetin is safe, and it might be just the compound we need with the rise of superbugs resistant to antibiotics and antifungals.

In one study, it helped prevent Listeria infection by interfering with the bacteria’s ability to hide from the immune system [105].

In another cell study, fisetin 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 [106, 107].

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 [108, 109].

12) May Relieve Allergies

IgE antibodies and T immune cells activate mast cells, which go on to trigger an allergic response. In a cell study, fisetin prevented T cells from activating mast cells and causing inflammation [110, 111].

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 [112].

Another type of immune cell, basophils, also contribute to allergies. Like mast cells, they also release inflammatory cytokines in response to IgE’s encounter with an allergen. In a cell study, fisetin prevented basophils from releasing inflammatory cytokines in response to IgE [113].

Fisetin helps with allergies by preventing key immune cells from causing inflammation.

13) May Help with Inflammatory Bowel Disease

In a mouse model of inflammatory bowel disease (IBS), fisetin reduced damage and inflammation in the colon by blocking NF-κB activity and restoring antioxidant levels [114].

Side Effects, Drug Interactions, Dosage & Limitations

Side Effects & Safety

Scientists are intrigued by fisetin’s outstanding safety. Clinical studies, of course, are needed to confirm it. But even at high doses, scientists found no evidence of side effects or toxicity in animal studies [7].

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 also receiving chemotherapy and the same stomach complaint was also reported in the placebo group [59].

Due to the lack of safety data, pregnant women and children should avoid fisetin supplements.

Drug Interactions

The liver uses the same pathway to process fisetin as it does for the blood-thinning agent warfarin (Coumadin). This can increase the effects of warfarin. Talk with your doctor if you plan to use fisetin in combination with this drug [115, 116].

Fisetin substantially reduces blood sugar in diabetic animals. The combination with blood sugar-lowering drugs may further reduce sugar levels [31, 32, 33, 34, 35, 36].

Dosage & Supplements

In a clinical study of colon cancer patients, 100 mg/day was effective for reducing inflammation [59].

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 [30].

Some people are doubtful about the benefits of supplemental fisetin, since it is poorly absorbed when taken orally. But is at least one simple way to, theoretically, increase its absorption: take it with fats. Fisetin in 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 [117, 118].

Even so, new formulations combining fisetin into small fat-like molecules (liposomes) may be the only effective solution. These greatly improve its absorption and cancer-fighting potential. However, they are not yet commercially available [117, 119].

Limitations and Caveats

Few clinical studies on fisetin exist. The current body of research is limited to animals and cells.

Reviews

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.

Buy Fisetin

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Takeaway

Fisetin is undoubtedly the most promising senolytic. It might help your body get rid of toxic, senescent cells. Plus, it protects the brain, improves memory, and targets anti-inflammatory and antioxidant pathways.

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 very safe but poorly absorbed from oral supplements. You might improve its absorption by taking it with fats (fish oil, olive, or MCT oil).

About the Author

Will Hunter

BA (Psychology)
Will received his BA in Psychology from the University of California, Los Angeles. 
Will's main passion is learning how to optimize physical and mental performance through diet, supplement, and lifestyle interventions. He focuses on systems thinking to leverage technology and information and help you get the most out of your body and brain.

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