Fisetin is a potent flavonoid that gives fruits like strawberries their vibrant color. This unique pigment had not previously sparked much attention from the scientific community.
Everything changed when researchers found that fisetin was the most potent senolytic agent out of 10 commonly used compounds, including quercetin, resveratrol, and curcumin. Since then, there has been a series of studies, which have paved the way for exciting new human studies.
Learn more about fisetin, one of nature’s unique and promising treatments for disorders caused by aging. We’ll also look at the fisetin supplement’s benefits, side effects, and more in this article.
What is Fisetin?
Fisetin is a special kind of polyphenol that has been linked to numerous longevity benefits in studies on cells and animals. The primary component of fisetin is a flavonoid, a particular type of polyphenol believed to contain powerful antioxidant effects that support healthy aging and disease prevention [1].
The most significant property of fisetin is its ability to behave as a senolytic. It is a compound that can cause natural cellular senescence. This is a process where the cell ages and permanently stops dividing but does not die [2].
Many foods contain fisetin in its natural form. Kiwis, strawberries, and apples are among the most popular fruits.
Benefits of Fisetin Supplements
Fisetin is famous for its effectiveness in preventing cellular senescence, improving brain function, and slowing the growth of cancer cells. However, the flavonoid’s antibacterial properties were highlighted in the first published study on it in 1966 [3].
Let’s look at the benefits of fisetin supplements below.
1. Better Brain Function
Fisetin improves brain health by lowering neuroinflammation, preventing oxidative stress in the brain, and removing senescent cells. In a study published in the journal Molecular Neurobiology, fisetin supplementation significantly improved memory in mice with Alzheimer’s disease. Additionally, it decreased neuroinflammation and suppressed degeneration in the hippocampus, the part of the brain most closely linked to memory and learning [4].
According to another study, fisetin promotes autophagy, our body’s natural recycling process that eliminates unhealthy, damaged, or old cells and cell components to make room for new, healthy ones [5].
2. Reduces Cancer Cell Growth
Fisetin is not yet available for cancer prevention or treatment. But studies on cells and animals suggest that it might prevent the development of cancer cell lines as more study progresses.
Fisetin causes apoptosis, or programmed cell death, in a good deal of cancer cell lines, including those from the larynx, liver, lung, and prostate.
Supplemental fisetin reduces lung tumor cell growth by 67% in a mouse study, and when paired with chemotherapy treatment, this effect is raised to 92% [6].
In mice with melanoma, fisetin decreased tumor growth by 66%, based on another research [7].
Fisetin’s senolytic properties are most likely to be responsible for these possible anti-carcinogenic actions, as some senescent cells may promote cancer cell growth.
3. Removes Dead Cells
Fisetin’s senolytic ability is one of the highlights of many studies.
Cells stop dividing and lose their usefulness when they enter a state of irreversible growth arrest known as cellular senescence.
Senescent cells do not die and depart the body. However, senescent cells do lose function in the body. Instead, they enter a zombie-like state that harms nearby cells and tissues.
The failure of tissues and organs coupled with various age-related disorders is thought to be caused by the inflammatory damage due to senescent cells.
The possibility of eliminating senescent cells from the body by using senolytics is what researchers are now studying and using.
Fisetin was the most successful at removing senescent cells and increasing the survival of the mice by almost 10%, according to a 2018 study that assessed a panel of ten possible senolytics in aged mice [8].
Fisetin even exceeded the performance of widely used antioxidants such as resveratrol, quercetin, and curcumin.
Clinical trials with older persons may determine how flavonoids can support healthy aging. However, most studies on fisetin and senescence used animals or cells that have been treated or cultivated in the lab [9].
Fisetin Side Effects
Researchers are unsure about the long-term side effects of fisetin because it hasn’t been researched as a supplement for a very long time.
However, even at extremely high dosages, fisetin is not hazardous to animals used in experiments.
A Mayo Clinic clinical study analyzing the impact of fisetin on humans discovered no substantial differences in side effects between the control group and colon cancer patients who took 100mg of fisetin for seven weeks [10].
Pregnant women and children should refrain from taking fisetin supplements because there are insufficient safety data available.
Consult your doctor before taking fisetin because it may also intensify the effects of blood thinners or medications that reduce blood sugar.
Dosages
The typical daily dosage for fisetin supplements is between 100 and 500 mg. Meanwhile, in the clinical trial with cancer patients, this dosage administered was 100 mg.
Fisetin is used at a higher dose of 20 mg per kg of body weight for two consecutive days in the ongoing clinical trial examining the effects of fisetin in older people.
How to Find the Best Fisetin Supplements?
When choosing the best fisetin supplements, several factors need careful consideration. Let’s look at these factors before you decide to take fisetin supplements available now in the market.
Form
Topical works best for muscles, skin, and pain relief, while powders, gels, and capsules work best for overall effects.
Bioavailability
Fisetin is often poorly absorbed by the body, although liposomal gels and other innovations improve the body’s capacity to use this nutrient.
Additives
To reduce prices and extend the shelf life of the products, manufacturers frequently add a variety of pointless and unhealthy substances.
Safety
Reputable products must be manufactured in FDA-inspected, cGMP-certified facilities and readily display a certificate of analysis (CoA) proving that their fisetin has undergone independent purity and safety testing.
Bottomline: Fisetin Benefits and Side Effects
Several fruits and vegetables, including strawberries, apples, persimmons, onions, and grapes, contain the plant-based flavonoid called fisetin. Fisetin is a senotherapeutic, which means it has strong senolytic properties that kill senescent cells that can cause aging and disease. It may increase lifespan and health span.
Fisetin has also been explored for its ability to improve brain health, prevent the growth of cancer cells, and fight oxidative stress and inflammation. Since fisetin is a relatively recent addition to the supplement market, further clinical research in humans is still necessary to establish the proper dosage to support its health claims.
Disclaimer: This article is only a guide. It does not substitute the advice given by your healthcare professional. Before making any health-related decision, consult your healthcare professional.
Editorial References And Fact-Checking
- Kozłowska A, Szostak-Wegierek D. Flavonoids–food sources and health benefits. Rocz Panstw Zakl Hig. 2014;65(2):79-85. PMID: 25272572.
- Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536. doi: 10.1111/joim.13141. Epub 2020 Aug 4. PMID: 32686219; PMCID: PMC7405395.
- Gábor M, Eperjessy E. Antibacterial effect of fisetin and fisetinidin. Nature. 1966 Dec 10;212(5067):1273. doi: 10.1038/2121273a0. PMID: 21090477.
- Ahmad A, Ali T, Park HY, Badshah H, Rehman SU, Kim MO. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol. 2017 Apr;54(3):2269-2285. doi: 10.1007/s12035-016-9795-4. Epub 2016 Mar 5. PMID: 26944285.
- Kim S, Choi KJ, Cho SJ, Yun SM, Jeon JP, Koh YH, Song J, Johnson GV, Jo C. Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Sci Rep. 2016 Apr 26;6:24933. doi: 10.1038/srep24933. PMID: 27112200; PMCID: PMC4844953.
- Touil YS, Seguin J, Scherman D, Chabot GG. Improved antiangiogenic and antitumor activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemother Pharmacol. 2011 Aug;68(2):445-55. doi: 10.1007/s00280-010-1505-8. Epub 2010 Nov 11. PMID: 21069336; PMCID: PMC3308124.
- Syed DN, Afaq F, Maddodi N, Johnson JJ, Sarfaraz S, Ahmad A, Setaluri V, Mukhtar H. Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels. J Invest Dermatol. 2011 Jun;131(6):1291-9. doi: 10.1038/jid.2011.6. Epub 2011 Feb 24. PMID: 21346776; PMCID: PMC3166244.
- Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18-28. doi: 10.1016/j.ebiom.2018.09.015. Epub 2018 Sep 29. PMID: 30279143; PMCID: PMC6197652.
- Mayo Clinic, James L Kirkland, MD, PhD, & Sundeep Khosla, MD. (2022, January 11). Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women (AFFIRM). Clinical Trials. Retrieved October 22, 2022, from https://clinicaltrials.gov/ct2/show/NCT03430037
- Farsad-Naeimi A , Alizadeh M , Esfahani A , Darvish Aminabad E . Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food Funct. 2018 Apr 25;9(4):2025-2031. doi: 10.1039/c7fo01898c. PMID: 29541713.
