In recent decades, obesity and diabetes have emerged as twin epidemics, creating a global health crisis. Amidst this backdrop, nature offers a glimmer of hope in the form of fisetin-a potent, yet lesser-known antioxidant found in many fruits and vegetables. Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. Its potency surpasses that of many other flavonoids, giving fisetin an edge in research studies focused on its health benefits.
What is Fisetin?
Fisetin is a polyphenol flavonoid that occurs naturally and is highly regarded for its powerful antioxidant properties. This unique compound can be found in a variety of foods. Among the richest sources are strawberries, which have been lauded for their high fisetin content. Additionally, this flavonoid is present in certain nuts and wines. Fisetin belongs to the polyphenol family of compounds, specifically the flavonoids, which are found in a number of fruits and vegetables and give many of them their vibrant colors. The body loves flavonoids not only for their powerful antioxidant properties, but also because they help your body function more efficiently and offer protection from many of the potentially harmful pathogens, toxins and stressors that can trigger must-to-avoid inflammatory reactions.
Fisetin and Weight Loss: Targeting mTORC1 Signaling
Obesity, characterized by excessive fat accumulation, is more than just a cosmetic concern. When individuals gain excessive weight, especially in the form of visceral fat around internal organs, it can lead to a state of chronic low-level inflammation. Over time, this inflammatory environment can impair insulin signaling, giving rise to insulin resistance-a hallmark of Type 2 diabetes. In essence, obesity sets the stage for inflammation, and this inflammation, in turn, paves the way for diabetes.
One of the mechanisms by which fisetin may aid in weight loss is through the regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis.
Studies have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. Fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner.
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Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling.
Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. It also efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity.
Additional Mechanisms Supporting Weight Management
Beyond mTORC1 signaling, fisetin may contribute to weight management through other mechanisms:
- Inhibiting Adipocyte Differentiation: Research has demonstrated that fisetin can inhibit the growth and differentiation of adipocytes (fat cells), potentially preventing excessive fat accumulation.
- Boosting Metabolic Rate: Fisetin may boost metabolic rate by influencing certain cellular pathways associated with energy expenditure.
- Metabolic Support: Fisetin may be helpful in controlling metabolic issues and weight gain, based on an animal study that reported 75% less weight gain when fed a high-fat diet in tandem with fisetin. Though here too, research is in early stages, the potential upsides for those with metabolic concerns is significant.
Fisetin's Broader Health Benefits
Fisetin's benefits extend far beyond weight management, encompassing a wide range of health-promoting properties:
1. Anti-Inflammatory Action
Inflammation, while a natural response to injury or pathogens, can become problematic when chronic. Studies have shown that fisetin can inhibit the production and release of pro-inflammatory cytokines, molecules that intensify inflammation.
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2. Enhancing Insulin Sensitivity
Research indicates that fisetin can enhance insulin sensitivity, ensuring that glucose is efficiently taken up by cells and utilized for energy. Yes, research indicates that fisetin can enhance insulin sensitivity, helping cells more effectively take up and utilize glucose. Preliminary studies suggest that fisetin may improve insulin sensitivity and assist in regulating blood sugar levels, making it a potentially valuable resource for those with diabetes.
3. Neuroprotection
Research has demonstrated that fisetin can enhance memory, support neuron survival, and reduce the risk of neurodegenerative diseases. For those with diabetes, where cognitive decline is a potential complication, fisetin’s neuroprotection might be especially significant. In the lab, multiple studies have looked at the anti-aging effects of fisetin. Among the most exciting recent findings is fisetin’s potentially neuro-protective effects, which could be beneficial for preventing age-related cognitive decline and neurodegenerative diseases such as Alzheimer's and Parkinson's. Showing additional promise are animal studies that have shown fisetin to be helpful in reducing amyloid plaque buildup and protective against the loss of healthy brain cells. Though the research continues to work its way up the line from animal to human studies, the current thinking is that fisetin’s anti-inflammatory and potentially cancer-preventing powers all play a key role in keeping the brain healthy - making it a potential boon to the body from head to toe, regardless of where you are in the aging process.
4. Kidney Protection
The kidneys, our natural filtration system, often bear the brunt of metabolic diseases like diabetes.
5. Cardiovascular Support
Cardiovascular health is paramount, especially in the context of obesity and diabetes which can elevate heart disease risks. It helps in reducing arterial inflammation and improving endothelial function, which is vital for proper blood vessel dilation. Some research even points towards its potential in limiting cholesterol accumulation, thereby preventing plaque buildup in arteries. Fisetin's anti-inflammatory properties and ability to reduce cholesterol levels and blood pressure levels may improve heart health, while its antioxidant effects may protect against oxidative stress. In animal studies, findings indicated that fisetin also helped improve heart function and hearth tissue health following cardiac events.
6. Promoting Longevity
The quest for longevity is as old as humanity itself, and fisetin offers a glimpse of hope in this journey. Fisetin has shown the ability to slow down this process by enhancing the activity of sirtuins, proteins linked to cellular longevity. This not only supports overall health but can also extend lifespan at the cellular level. While there are a number of factors at play, in large measure, fisetin is thought to combat the effects of aging by helping to reduce the amount of free radicals in the body, and, an added bonus, may also help boost the effects of other antioxidants in the body. Those trouble-making free radical molecules can inflict oxidative harm on your cells and set the table for more rapid aging and many age-related illnesses - so the fewer free radicals on the loose the better. Fisetin fights back, scavenging excess free radicals, providing antioxidant protection for your cells which, in turn, helps slow down the aging process. What’s more, studies have shown that fisetin stimulates sirtuins, those essential proteins responsible for promoting cellular health and extending lifespan. By activating sirtuins, fisetin enhances natural cell repair processes to promote longevity.Fisetin has got a lot to give in the youth-preserving department.
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7. Addressing Non-Alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent, especially among those with obesity and diabetes. By modulating lipid metabolism, fisetin can reduce fat accumulation in liver cells, a primary hallmark of NAFLD.
8. Cancer Prevention
Research has shown that fisetin can hinder the growth of cancer cells and promote cell death in breast, prostate, and colon cancers. The thinking is that it’s antioxidant boosting and anti-inflammatory properties make it well suited to fight cancer cell growth.
9. Skin Health
Its antioxidant abilities may allow fisetin to shield the skin from damage caused by UV radiation and environmental toxins, thereby promoting skin health and potentially reducing signs of aging. Also based on animal study results, fisetin has been shown to be helpful for the treatment of inflammatory skin issues like eczema.
10. Pathogen-Fighting
Studies suggest that fisetin may also have antimicrobial properties, as well as anti-bacterial, anti-fungal and anti-parasitic effects.
11. Improving Physical Function and Reducing Senescent Cells
Central to age-related decline are what scientists call senescent cells - cells that accumulate in tissues and release harmful molecules that contribute to inflammation and organ damage. Senescent cell accumulation accelerates the aging process and leads to age-related conditions like muscle weakness.
Among the various senolytics being investigated, a naturally occurring compound called fisetin has garnered significant attention. Fisetin is a flavonoid, a type of plant pigment found in many fruits and vegetables. Strawberries contain the highest concentration of fisetin (160 µg/g), but you’d need to eat a lot of them to get a therapeutic dose.
A new study published in Aging Cell delves into the exciting findings surrounding fisetin’s impact on physical function and cellular aging in mice. This study offers compelling preclinical evidence that fisetin could be a powerful tool in our quest for healthier, more active later years. The researchers in this study orally administered fisetin to old mice using an intermittent treatment schedule - one week on, two weeks off, then one week on again. The results were promising, as researchers observed significant improvements in the physical function of old mice treated with fisetin. Specifically, these mice showed a reduction in frailty, a state of increased vulnerability to adverse health outcomes. The fisetin-treated old mice also demonstrated a notable increase in grip strength, an indicator of muscle strength and physical capability. Moreover, in humans, a stronger grip predicts a longer life.
Interestingly, fisetin had no discernible effects on young mice, reinforcing the idea that its benefits are specifically related to combating age-associated cellular changes. By analyzing the gene expression in the quadriceps muscles of the mice, the researchers found that fisetin treatment led to a reduction in the expression of genes associated with cellular senescence, supporting the idea that fisetin is indeed working by clearing senescent cells and reducing their harmful impact on muscle tissue.
A compelling aspect of the study was a comparison between fisetin and other established senolytic approaches. The study compared fisetin’s effects to the genetic clearance of senescent cells, which involved using genetically modified mice (p16-3MR mice) where senescent cells are specifically removed. This method is considered a gold standard for demonstrating the benefits of senescent cell clearance. Remarkably, the improvements in frailty and grip strength observed with fisetin treatment were comparable to those achieved through both genetic clearance and treatment with ABT-263. This comparability is particularly exciting given the potential side effects associated with some synthetic drugs. Fisetin, being a natural flavonoid found in foods, may offer a potentially safer and more accessible alternative for targeting cellular senescence in aging populations.
While this study primarily focused on muscle and physical function, the same research group showed that intermittent supplementation with fisetin improves arterial function in old mice. Considering that senescent cells accumulate in multiple organs during aging, one could imagine the possibility of fisetin improving multiple age-related diseases. This research provides compelling preclinical evidence for fisetin as a powerful natural senolytic.
Incorporating Fisetin into Your Diet
Incorporating fisetin into your diet is both simple and enjoyable, given its presence in various delicious foods. To get your dose, the top edible sources are:
- Strawberries at the forefront: Among the richest sources of fisetin, strawberries can be enjoyed fresh in salads, smoothies, or as a standalone snack. Strawberries contain the highest concentration of fisetin (160 µg/g)
- Apples and grapes: An apple a day could provide you with a decent fisetin dose. Similarly, grapes-especially the skin-contain this beneficial compound.
- Vegetable inclusions: Cucumbers and onions, while lesser known for their fisetin content, are great sources.
- Sip on wine: Red wine, in moderation, can provide a dose of fisetin.
- Other sources: Cucumber, Onions, Lotus root, Kiwi fruit, Persimmons and grapes are also good sources of fisetin but keep in mind they are also high in sugar, so go easy, and instead focus on lower sugar fruit like strawberries and apples.
Fisetin Supplements
If ensuring daily fisetin intake is challenging, consider high-quality supplements. Supplements are another way to boost intake of this potent compound. When choosing a fisetin supplement, opt for reputable brands that use high-quality ingredients and follow recommended dosage guidelines. As always, be sure to get also the go-ahead from your doc first, and have them check for your specific needs, conditions and any contraindications for prescriptions you may be taking. Assuming you’ve got the all clear, a 100 mg daily supplement should suffice.