In a world of fly-by-night discoveries that never quite pass scientific muster, it’s easy to become jaded about research claiming to have finally identified a “fountain of youth.” But scientists really have identified something incredible. A naturally occurring flavonoid called fisetin offers us the chance to live longer, healthier lives. And this healthy-aging superstar is found most abundantly inside a beloved food—luscious red strawberries—and, to a lesser extent, in other fruits and vegetables including apples, grapes, kiwis, tomatoes, cucumbers and onions.

A new era of research: Even though most people have never heard of fisetin, the National Institutes of Health’s database of scientific literature lists nearly 800 studies that have investigated its power to help fight age-related ills ranging from cancer and Alzheimer’s disease to arthritis and glaucoma. While most of these studies have been conducted on animals, scientists are confident enough to now conduct research on humans to test fisetin’s power in fighting such age-related health problems as diabetes, kidney disease and frailty. 

To learn more about this remarkable plant compound and how it could benefit you, Bottom Line Health spoke with Paul D. Robbins, PhD, a leading authority on fisetin and a co-senior author of an extensive research paper on the subject that was published in The Lancet’s EBioMedicine.

FISETIN VS. “ZOMBIE CELLS”

You might be wondering how a simple plant compound (polyphenol) can have such powerful effects. To understand how fisetin confers so many health-promoting gifts, you need to think about aging on a cellular level.

At this very moment, if you are older, some of your cells are undergoing an aging process known as cellular senescence, in which cells with damage stop dividing. These rogue cells—called senescent cells—are present in different organs and even circulating in your body in a sort of “living dead” state…like zombies. Even though these cells are not performing normal cell functions, they’re also not dying like they’re supposed to. They just hang around, releasing factors that cause inflammation and tissue destruction, making it harder for healthy cells, including stem cells, to do their jobs. These zombie cells are a natural enemy of youth and vibrant health.

As if that’s not bad enough, these cells accelerate aging in other ways. The factors the zombie cells release “infect” other cells around them, turning perfectly healthy cells into zombie cells. And the more zombie cells you have in your body, the faster you age…both inside and out.

This is where fisetin enters the picture. Fisetin has numerous healthy-aging effects, including a senolytic (senescence-destroying) function, slaying those zombie cells and letting the healthy cells thrive. Fewer zombie cells means healthier, slower aging. That’s one way fisetin works to reverse the signs and symptoms aging and chronic disease.

Age is no barrier: Best of all, fisetin is believed to confer these benefits, even when treatment was started in old age.

HOW THE EVIDENCE STACKS UP

Fisetin has been investigated as a healing agent for numerous age-related health problems. In animal research, fisetin has shown positive results in helping to improve…

• Arthritis. The flavonoid slowed cartilage destruction and relieved swollen joints in arthritic mice, according to research published in 2017 in International Immunopharmacology.

• Memory. Fisetin prevented the death of brain cells and significantly improved memory in mice with Alzheimer’s disease, another 2017 study, published in Molecular Neurobiology, found.

• Liver damage. When mice were injected with an overdose of acetaminophen, fisetin prevented the drug’s liver-damaging effects, shows a study published in 2019 in Phytomedicine.  

Now scientists are forging ahead by testing fisetin’s antiaging effects in research involving humans.

For example, even though there were no big headlines, fisetin was shown to have impressive anti-inflammatory effects in a study involving people with colorectal cancer. In this research, which was published in 2018 in Food & Function, 37 patients who were undergoing chemotherapy for colorectal cancer received either a 100-mg fisetin supplement or a placebo daily. After seven weeks, two inflammation markers—interleukin (IL)-8 and C-reactive protein—reduced significantly in the fisetin group.

Takeaway: Because inflammation plays a role in the spread of cancer and chemotherapy resistance, the researchers concluded that fisetin could be an “antitumor agent” for colorectal patients. Even though this study didn’t delve into fisetin’s antiaging properties, it did point to its safety and a reasonable dosage for people to take in supplement form.

Meanwhile, a three-week pilot study involving 14 older adults with lung disease tested an agent with fisetin-like mechanisms of action—a senolytic drug called DQ (a combination of the chemotherapy agent dasatinib and quercetin, a flavonoid similar to fisetin). After taking the drug three days a week for three weeks, the study participants significantly improved when performing physical function tests, such as walking speed and walking distance, according to the research that was published in 2019 in The Lancet’s EBioMedicine. This finding mirrored earlier research in mice that found DQ improved age-related conditions including frailty, osteoporosis and cardiovascular disease.

Takeaway: DQ has important senolytic effects but comes with side effects, such as respiratory symptoms and heartburn. Researchers recognized that fisetin works in a similar way to DQ, but possibly without side effects.

In a study published in 2018, also in The Lancet’s EBioMedicine, 10 flavonoids were tested head-to-head. Fisetin won hands down for its senolytic effects. In addition, when the researchers tested fisetin in naturally old and artificially aged mice, it was found to restore healthy tissue function…increase glutathione (the body’s master antioxidant)…reduce inflammation markers…and extend the animals’ healthy lifespan by 10% to 15%.

THE “ANTIAGING COCKTAIL”

Senescence, the cellular dysfunction described above, is one of many factors that contribute to aging. The best “antiaging cocktail” will also trigger the repair of stem cells, which have the remarkable ability to develop into many cell types, improve function of mitochondria (the “powerhouses” of cells) and reduce damaging proteins in the brain. Fisetin appears to be unique in providing all of these benefits, researchers have found.

To further investigate fisetin’s healthy-aging power, researchers from Mayo Clinic are recruiting older adults for three separate clinical trials looking at its effects on diabetes, kidney disease and frailty. If you’d like to participate, go to ClinicalTrials.gov and search “fisetin” under “Other Terms.” These studies will use intermittent treatment with high-dose fisetin (with average daily doses of approximately 1,000 mg to 2,000 mg) in order to clear the zombie cells. We don’t know what those results will be. When there’s news to share, we’ll be sure to report it.

In the meantime, if you’re eager to get more of this remarkable plant compound, here are some facts to consider. While fisetin is found in many food sources (as described above), researchers who conducted a study at the Salk Institute that was published in 2011 in PLOS ONE estimated that humans would need to eat 37 strawberries a day to derive the enhanced kidney function that was identified in diabetic mice fed a fisetin-enriched diet.

To increase your odds of getting a meaningful dose of fisetin as the research unfolds, you can ask your doctor about taking a fisetin supplement. Such a supplement is available in 100-mg capsules from online retailers and supplement stores.