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Research on a flavonoid called fisetin, which contributes to the pigment of fruits and vegetables like apples, cucumbers, grapes, onions, persimmons and strawberries, has been called out for its potential antiaging properties. In experiments performed on lab mice, fisetin was shown to eliminate senescent cells, which accumulate as you age and can be harmful to your body.
While fisetin was discovered years ago, it is one of many diet-derived antioxidants being increasingly investigated for its health-promoting effects. As a plant-based flavonoid, fisetin can be consumed for long periods of time without any known adverse effects. Let’s take a closer look at this promising plant pigment.
What Is Fisetin?
If you’ve not yet heard of fisetin, you are not alone. After all, there are about 6,000 flavonoids from which to choose and each of them contributes to the colorful pigments of fruits, vegetables, herbs and medicinal plants.1 Beyond their role in producing pigments, flavonoids are also antioxidants.
With the continued focus on the value of antioxidants, individual flavonoids are increasingly being recognized for the positive effects they can have on human health. Now, a study published in EBioMedicine2 suggests consuming fisetin at high levels may help you live a longer, healthier life.
In fact, the research, which involved lab mice, suggests the consumption of fisetin may extend your life by as much as 10 percent. Researchers from Scripps Research Institute, Mayo Clinic and University of Minnesota evaluated 10 flavonoids to determine their senolytic activity, calling out fisetin as the most potent.
Fisetin Is Prized for Its Role in Killing Senescent Cells
Though you may not have heard of them, senescent cells are cells that through oxidative damage and aging have lost their ability to reproduce. The study authors defined senescence as a “tumor-suppressor mechanism activated in stressed cells to prevent replication of damaged DNA.”3
They note past studies involving genetic and pharmacologic approaches have shown senescent cells to play a causal role in accelerating aging and age-related diseases. In fact, before putting fisetin to the test, the scientists published research in Aging Cell in 2015 highlighting the flavonoid quercetin for its senolytic activity.4,5
When administered with the chemotherapy drug dasatinib, quercetin was shown to improve age-related conditions such as cardiovascular disease, frailty and osteoporosis. About those results, the study authors said, “The combination of dasatinib and quercetin was effective in eliminating senescent MEFs (mouse embryonic fibroblasts).
In vivo, this combination reduced senescent cell burden in chronologically aged, radiation‐exposed and progeroid [syndrome-affected] mice.”6 The researchers also noted “the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.”7
In terms of underscoring the value of senolytics like fisetin, another study, published in July 2018, affirmed that “senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health[span] and life span in old mice.”8
Fisetin Shown to Promote Longer Healthspans in Lab Mice
Scientists are interested in fisetin mainly for its usefulness in eliminating senescent cells, an action that could encourage antiaging and promote longer, healthier lives. Senior study author Laura Niedernhofer, director of the Institute on the Biology of Aging and Metabolism at the University of Minnesota (UM), told Newsweek:9
“We’re looking for drugs that can kill these damaged senescent cells that are very toxic to our bodies and accumulate as we get older. It turns out that fisetin is a natural product that actually we were able to show very selectively and effectively kills these senescent cells, or at least dials back their bad secretions or inflammatory proteins.”
According to Newsweek, as senescent cells accumulate in your body, they can cause both inflammation and tissue degradation.10 Acting as a senolytic agent, fisetin may be able to kill senescent cells in humans just as it has been shown to do in aging mice.
Paul Robbins, Ph.D., UM professor of biochemistry, molecular biology and biophysics and associate director of the Institute, commented:11
“The mice reached an extension of life span and healthspan of over 10 percent, that’s pretty remarkable. At the dose we used, the question is if we could give them a lower dose or more infrequently. That’s a theoretical advantage of using these types of drugs that can clear the damaged cells — you can use them intermittently.”
Fruits and Vegetables Containing Fisetin
Even though fisetin is naturally occurring in a number of fruits and vegetables, you will likely not be able to obtain therapeutic amounts of this flavonoid from food alone. While scientists continue working out the proper dosing for fisetin, there is, however, little harm in — and possibly much benefit to — adding some of these fisetin-containing foods to your diet:12,13
Fisetin in micrograms/gram (g)
Cucumber (with skin)
As you can see, strawberries are by far the best food source of fisetin, but you’d need to eat about 37 whole berries to get a decent amount of benefits. (One supplement brand, which I cannot endorse, even uses the wording “37 strawberries” in their product name.) Obtaining an optimal amount of this, or other flavonoids, from food sources is, unfortunately, not always realistic.
While a small 1998 Japanese study14 estimated the average daily intake of fisetin to be just 0.4 milligrams (mg) in that country, figures are not yet available to track fisetin consumption by Americans. Additionally, recommended dietary intakes for fisetin do not exist.
For now, as noted by Robbins, knowing that fisetin can have a positive impact on damaged cells is good news even as more work, including a series of human medical trials, is needed.
He stated, “These results suggest that we can extend the period of health — termed ‘healthspan’ — even toward the end of life. But there are still many questions to address, including the right dosage, for example.”15
Some of the Health Benefits of Fisetin
As noted in the Journal of Nutritional Science, the interest in the health-boosting effects of flavonoids, including fisetin, continues to grow. The study authors asserted:16
“Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their antioxidative, anti-inflammatory, antimutagenic and anticarcinogenic properties, coupled with their capacity to modulate key cellular enzyme function.”
Already, a number of fisetin supplement brands exist, touting some of the health benefits noted below.17 To date, fisetin has been shown to:
Encourage anti-inflammatory action — Fisetin has been shown to suppress the production of inflammatory cytokines. While noting a flavonol-rich compound containing fisetin could be a potential therapeutic agent in the treatment of inflammatory conditions, one group of study authors noted:18
“In experimental inflammation-related models, flavonol-rich RVHxR (Rhus verniciflua Stokes) and fisetin have shown significant anti-inflammatory activities on vascular permeability, leukocyte migration and cellular immunity.
Also, flavonol-rich RVHxR and fisetin treatments significantly reduced the incidence and severity of [the] collagen-induced arthritis model.
These results suggest RVHxR and its major compound fisetin have shown potent suppressive effects on some inflammatory cytokines/chemokines and angiogenic factor in [Interleukin 1 beta]-stimulated rheumatoid arthritis FLS (fibroblast-like synoviocytes) and inflammatory in vivo models.”
Help prevent cancer — Given its well-known anti-inflammatory, antioxidant and antiproliferative properties, fisetin can play a role in helping to prevent cancer. To date, among other effects, fisetin has been shown to:
Activate particular signaling pathways to induce cell death (apoptosis) in cervical cancer cells19
Inhibit melanoma cell growth22
Inhibit bone-damaging glycation — Glycation, a process in which sugar molecules bond to certain proteins and lipids in your body, results in bone-damaging Advanced Glycation End (AGE) products.
According to natural health expert Vivian Goldschmidt, founder of the Save Institute, a branch of which focuses on osteoporosis prevention, these molecules destroy collagen, the cartilage-like material that gives your bones tensile strength.24 Due to its beneficial interaction with proteins found in your body, one study indicates fisetin arrests the glycation process.25
Maintain your glutathione levels — According to a 2009 study published in the journal Genes & Nutrition, fisetin has been shown to help maintain your glutathione levels, particularly during times of increased oxidative stress.26
The study authors stated, “Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant.”27 Goldschmidt asserts glutathione “has the most electrons of any antioxidant, so it can ‘donate’ more of these electrons to free radicals in order to neutralize them.”28
Protect your brain function — A 2014 study published in Aging Cell29 suggests fisetin may have the ability to stave off age-related memory associated with Alzheimer’s disease and other types of dementia. The researchers suggested fisetin can act on many of the target pathways implicated in Alzheimer’s disease.
They also found oral administration in mice aged 3 to 12 months prevented the development of learning and memory deficits. The study authors suggested “our results demonstrate fisetin, a compound that activates multiple, well-defined neuroprotective pathways, may provide a new approach to the treatment of [Alzheimer’s disease].”30
As noted in the featured video, fisetin is one of the few substances capable of crossing your blood-brain barrier. (Curcumin, a polyphenol with neuroprotective qualities, is another.)
Slow the progression of Huntington’s disease — In animal studies, fisetin has been found to slow the progression of Huntington’s disease, an ultimately fatal neurodegenerative disorder characterized by cognitive, motor and psychiatric symptoms.
Pathways implicated in the disease include those involving mitogen-activated protein kinase signaling and, particularly, the Ras-extracellular signal-regulated kinase (Ras-ERK) cascade. Based on 2011 experiments involving three disease models, fisetin was shown to reduce the impact of the mutant huntingtin gene.31
The study authors noted both fisetin and resveratrol activated the ERK pathway, “thus suggesting that polyphenols and/or their derivatives might be useful for the treatment of [Huntington’s disease].”32
Stabilize resveratrol — Similar to other flavonoids, fisetin has been shown to inhibit the hepatic and duodenal sulphation of resveratrol,33 thus improving the bioavailability of this powerful anti-inflammatory polyphenol found in red wine and the skins of certain fruits.
Says Goldschmidt, “Fisetin acts as a shield for resveratrol, slowing its breaking down and being metabolized in the liver. Thus, fisetin actually increases the amount of resveratrol in the blood.”34
What’s Next for Fisetin?
Fisetin is currently undergoing clinical trials at Mayo Clinic, which means some more conclusive information about recommended dosing could become available at some point in the future. One of the current trials35 seeks to evaluate markers of frailty and inflammation, as well as bone resorption and insulin resistance in older postmenopausal women.
The study involves 40 women, ages 70 to 90, who are affected by gait disturbance. Half of the women are receiving an oral dose of 20 mg of fisetin per kilogram of body weight per day for two consecutive days, for two consecutive months, while the other half is receiving a placebo according to the same time schedule.
The trial began in February 2018 and will conclude in June 2020. According to the researchers, “Positive results of this study would lead to the development of a larger clinical trial examining the effects of this intervention on age-related dysfunction.”36
Given the many health benefits of fisetin, I highly recommend you regularly add a serving of organic strawberries (or another fisetin-containing food) to your diet. Given the fact a 1-cup serving (152 g) of strawberry halves contains just 3.8 g of fructose, you can easily incorporate this delicious, nutritious fruit into your eating plan and still moderate your fructose levels.
As you may recall, I advise you limit fructose from all sources, including whole fruit, to 25 mg a day if you are healthy and less than 15 mg if you are dealing with a chronic illness like cancer or diabetes.
Also, when buying strawberries from the store, keep in mind conventional varieties are sprayed with a number of toxic pesticides, including chemicals known to cause cancer and reproductive damage, so be sure to purchase organic and wash them well before eating.
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