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Fisetin: A Game-Changing Phytonutrient for Optimal Health and Longevity

The Bioregulatory Medicine Institute

fruits and vegetables that contain fisetin

Have you heard of fisetin?  It's got quite the reputation for being a powerhouse supplement with tons of benefits. It's an antioxidant, neuroprotective, anti-inflammatory, anti-cancer, and even senolytic - it can selectively zap dysfunctional cells.


Longevity researchers often consider it one of the most significant supplements older adults can take –except that they're still figuring out the best way to take it.

Where Is Fisetin Found Naturally? 

It's found in strawberries (the highest food source), apples, persimmons, onions (especially parts close to the skin), grapes, kiwis, a few other fruits and vegetables, and some trees and shrubs. However, the amounts in these natural sources are so low in fisetin, supplementation is most likely the best option for reaping the benefits of this powerful phytonutrient.  

To put things in perspective, you would have to consume about five cups of strawberries a day just to reach the same amount found in a 100 mg fisetin supplement, and an incredible amount of them to reach the 20 mg/kg dose that is common in many of the research studies.  

What Exactly is Fisetin? 

Fisetin is a polyphenol, a subclass of flavonoids, and more specifically categorized as a flavanol. Quercetin also belongs to this same flavanol subclass. Together, these compounds are among the most potent found on Earth. 


 Fisetin is a Powerful Antioxidant 

There is a lot of talk these days about antioxidants. That’s because oxidative stress in our bodies is associated with chronic diseases such as cancer, cardiovascular disease, and neurodegenerative disorders.  


Oxidative stress refers to harmful free radical molecules in our bodies that are unstable because they do not have an equal number of electrons. Antioxidants, like fisetin, neutralize these dangerous free radicals by donating an electron to make them stable. Reducing excess free radicals results in less stress and inflammation in the body. 


However, fisetin's antioxidant properties extend beyond scavenging free radicals, involving complex pathways unfamiliar to most of us. 


Fisetin’s Superpowers 

Research is also discovering that fisetin may offer other powerful superpowers such as senolytic properties, anti-inflammatory, antimicrobial, and anticancer properties, which can potentially offer therapeutic benefits for a wide range of conditions.  


Fisetin is the Most Potent Senolytic 

Recent studies are pointing to fisetin as potentially the strongest senolytic among flavonoids. This is pretty interesting, especially with all the recent research looking into senolytics and how they might impact our longevity. 

So, being senolytic basically means a molecule like fisetin can target and get rid of those pesky senescent cells, the ones that refuse to die. In young folks, our immune system usually takes care of these troublemakers, sometimes called "zombie cells." But as we get older, these senescent cells stick around, piling up and wreaking havoc by spewing out toxins and sparking inflammation. That's where fisetin comes in handy – it's effective at clearing out these troublemakers, especially in high doses. 

Studies on mice have found that fisetin could actually help older mice live longer. We're talking mice that are equivalent in age to a 75-year-old human. So, for the elderly, this supplement looks like it could be a real game-changer. 

Fisetin’s Anti-Inflammatory Properties 

Let's talk about how fisetin can help calm things down in the body with its anti-inflammatory properties. It's been shown to have some pretty cool anti-inflammatory powers, like putting the brakes on the production of pro-inflammatory molecules and pathways that can lead to chronic inflammation.  

Now, chronic inflammation is a big player in a bunch of diseases, like arthritis, Alzheimer's, and even some cancers. By keeping inflammation in check, fisetin might just help lower the risk of these conditions and give our immune system a boost. 


Fisetin shows Promise with Neurodegenerative Diseases 

In addition to its antioxidant and anti-inflammatory effects, fisetin has shown promise in combating neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Research indicates that fisetin may help protect neurons from damage, reduce the accumulation of toxic protein aggregates, and enhance cognitive function. These findings suggest that fisetin could be a valuable ally in the fight against age-related cognitive decline and neurodegeneration. 


Fisetin Anti-Cancer Properties 

Moreover, fisetin has been investigated for its potential anticancer properties. Studies have demonstrated that fisetin can inhibit the proliferation of cancer cells, induce apoptosis (programmed cell death), and suppress tumor growth in various cancer types, including breast, prostate, colon, and lung cancer, but the precise impact and related molecular mechanism of fisetin on migration and invasion is still unknown.  

Additionally, fisetin may enhance the efficacy of conventional cancer therapies while reducing their toxic side effects, making it an attractive adjuvant to cancer treatments. 


Fisetin’s Other Potential Properties 

Fisetin appears to be helpful for other health conditions too. It shows promise in aiding recovery from ischemic strokes and other traumatic brain injuries, mitigating the severity of osteoarthritis at specific doses, potentially restoring gut health, lowering serum cholesterol levels, enhancing skin conditions, and exhibiting potential antifungal properties against Candida. 


However, fisetin has not been extensively studied, and therefore the ideal way to supplement it has not been established. Currently there is a lot of controversy surrounding who should and should not take it. For starters, it should not be taken by children or pregnant women. It should also probably not be taken by healthy individuals under 50 years of age.  


However, for healthy individuals over 50 or 60 years of age, there may be some fantastic benefits to supplementing with fisetin, but there is so much uncertainty about how to take fisetin.  


People vary in their fisetin supplementation routines, with some taking a daily dose of 100 mg, others opting for 500 mg, and some choosing intermittent supplementation a few days a week or only a few times per year. 


 What Researchers Have Discovered Thus Far 

The studies that have been conducted so far, seem to indicate that low doses (1-3 mg/kg/day) or roughly 68 - 200 mg/day for a 150-pound person does not push the senescent cells to die. Instead, the low dose seems to rejuvenate the old cells, similar to what researchers discovered in a 2022 study with resveratrol.  


Therefore, low dosing of fisetin may be best for combating inflammation, supporting metabolic health, and for mild age-related cognitive decline. 


On the other hand, studies also seem to indicate that high doses (20 mg/kg) probably benefit older people by reducing the senescent cells, and in patients with cancer.  


Dosing Approaches 

To get an idea of what some researchers are thinking, the best approach might be for people over 55 or 60 years of age to consider taking fisetin intermittently, such as four times a year (quarterly) for a day or two, at a high dose – “a hit-and-run” approach. This recommendation stems from findings in human adipose tissue lab tests and mouse studies, indicating that senescent cells can be eliminated with a brief exposure (just four hours) with a high dose of fisetin.  


Considerations For Taking Fisetin 

The caution surrounding the use of senolytic compounds arises from considering the reasons behind cellular senescence and their functional role. Scientists think that senescent cells enter a dormant state to prevent the replication of damaged DNA, serving as a protective mechanism against cancer.  


Additionally, these cells are believed to contribute to healing processes. This cautious approach towards daily senolytic supplements is influenced by the complex functions senescent cells serve in the body. 


General Guidelines to Consider: 

  • If you're under 50 or 60, it might be wise to hold off on taking this supplement until more research is done, especially beyond 2024. 

  • When choosing a supplement, opt for a reputable brand. 

  • Consider intermittent supplementation. 

  • Take the fisetin supplement with a meal that contains fat, as it is not soluble in water. 

  • Always consult your doctor before starting any supplementation regimen. 

  • When possible, prioritize consuming polyphenols in their natural form by selecting supplements that list the plant source as an ingredient. 

  • Purchase organic fruits and vegetables when you can. Especially those on the “Dirty Dozen” list.  

  • For individuals dealing with serious conditions like neurodegenerative diseases or cancer, fisetin might be worth considering. 


More Research is Needed 

So, while fisetin looks super promising, we still need more research to really nail down its full potential and figure out the best ways to use it. Right now, there are clinical trials happening to see how well fisetin supplements work in people, which should give us a better idea of what it can do for our health. Meanwhile, scientists are also looking into other similar compounds like quercetin and resveratrol, trying to come up with solid guidelines. 

But here's the exciting part: fisetin is this natural powerhouse that could do wonders for us. It's got all these cool properties like being an antioxidant, anti-inflammatory, neuroprotective, and even anti-cancer. And get this – you can find it in everyday foods like strawberries, apples, onions, and grapes. So, adding more of these into your diet might just give you a little dose of fisetin's health-boosting benefits. 

As we keep digging into the research, fisetin seems like it could be a real game-changer for our health and longevity, so stay tuned.  


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