Fisetin is a bioactive flavonoid molecule that is available as a dietary supplement. Known for its wide range of benefits, fisetin has been studied for its potential to protect brain cells, fight cancer, combat oxidative stress, and reduce inflammation.
These pharmacological effects make it an exciting compound for those interested in enhancing their overall well-being. Keep reading to learn more about fisetin.
Fisetin Rich Foods
Fisetin is a plant-derived metabolite classified as a flavonoid, commonly found in various fruits and vegetables, including:
- strawberries,
- apples,
- persimmons,
- grapes,
- onions,
- kiwis,
- cucumber (1).
Why Is Fisetin So Powerful?
Fisetin stands out for its ability to selectively target key biological processes that are essential for maintaining balance and overall health. Oxygen radicals can damage critical components of our cells, such as:
- lipids,
- proteins,
- carbohydrates,
- DNA.
An imbalance between antioxidants and these oxygen molecules results in oxidative stress. This oxidative stress is associated with the development of various diseases, including:
- diabetes,
- vision impairments,
- neurodegenerative disorders,
- cancer,
- aging (1).
Fisetin is a compound that easily dissolves in fats, allowing it to pass through cell membranes, build up inside cells, and provide strong antioxidant benefits (1).
Fisetin - Antioxidant Protection Against Cancer
Recent in vivo studies with animal cancer models have shown that fisetin possesses powerful anti-cancer properties, significantly slowing the growth of several types of cancer cell models, including:
- breast cancer,
- prostate cancer,
- colorectal cancer,
- lung cancer,
- melanoma/skin cancer,
- bladder cancer,
- leukemia (2).
Fisetin could help slow the growth of tumor cells by targeting critical cellular pathways and controlling important enzymes and transcription factors. One significant mechanism of fisetin appears to be blocking the mTOR pathway. This and other mechanisms are crucial in disrupting tumor growth (3). However, much more research is needed to be able to conclude anything about fisetin's effect on actual human tumors.
Learn more about the mTOR pathway and its importance in longevity in our article: "Are AMPK and mTOR pathways the molecular key to longevity?".
Fisetin Targets Inflammation
Chronic inflammation can significantly contribute to the development of aging and various diseases (4).
Research shows that fisetin demonstrates strong anti-aging effects in living organisms. Both acute and long-term (dietary) treatments with fisetin have been shown to reduce signs of cellular aging and related inflammation in multiple tissues, making it a promising supplement for those looking to support their longevity and overall health (4).
A phase 2 placebo-controlled pilot study is currently exploring whether fisetin can help delay, prevent, or treat complications from COVID-19 in elderly patients. This research has the potential to significantly improve the approach to managing COVID-19-related health issues (5).
Fisetin Protects Heart Health
In vitro and in vivo studies have shown that fisetin provides strong cardio-protection, especially against myocardial ischemia-reperfusion (I/R) injury. By boosting mitochondrial health, fisetin enhances energy production and helps the heart remain resilient under stress (6,7).
Fisetin is well-tolerated by humans even at higher doses, and shows no visible toxic effects. This is why fisetin has a lot of potential in future cardiovascular treatments and prevention of heart tissue damage (7).
Fisetin - Side Effects
Studies consistently show that fisetin is non-toxic, even at high doses. In animal research, fisetin was well-tolerated at doses up to 2000 mg/kg body weight when administered orally. Long-term studies (90 days) with fisetin supplementation at 0.05% in the diet revealed no toxic effects or organ damage (8).
In a newer clinical study, two minor gastrointestinal issues were noted; one instance of bloating and one of reduced appetite. These effects were not considered serious, and passed quickly (8).
The consistent absence of severe or moderate adverse events in this and previous studies underscores fisetin's potential as a safe and effective supplement (8).
As a natural compound found in everyday fruits and vegetables, fisetin’s safety profile supports its potential use in supporting healthy aging, even in elderly individuals (4). While ongoing and completed pilot studies continue to explore its benefits, comprehensive human trials with extensive results are still in progress.
Fisetin - Dosage
Since there is no clear consensus on the optimal daily dosage of fisetin, dosages can vary depending on the specific formulation and intended use. Supplement dosages range from 100 mg to 500 mg per day. Some studies have used fisetin at 200 mg/day for lower doses and up to 800 mg/day for higher doses (9).
For most people, a typical starting dose is around 100-250 mg daily, which most of the studies considered safe and effective for general health and wellness.
References:
1. Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013 Jul 10;19(2):151-62. doi: 10.1089/ars.2012.4901.
2. Imran M, Saeed F, Gilani SA, Shariati MA, Imran A, Afzaal M, Atif M, Tufail T, Anjum FM. Fisetin: An anticancer perspective. Food Sci Nutr. 2020 Nov 25;9(1):3-16. doi: 10.1002/fsn3.1872.
3. Qaed E, Al-Hamyari B, Al-Maamari A, Qaid A, Alademy H, Almoiliqy M, Munyemana JC, Al-Nusaif M, Alafifi J, Alyafeai E, Safi M, Geng Z, Tang Z, Ma X. Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies. Glob Med Genet. 2023 Aug 9;10(3):205-220. doi: 10.1055/s-0043-1772219.
4. 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.
5. Verdoorn BP, Evans TK, Hanson GJ, Zhu Y, Langhi Prata LGP, Pignolo RJ, Atkinson EJ, Wissler-Gerdes EO, Kuchel GA, Mannick JB, Kritchevsky SB, Khosla S, Rizza SA, Walston JD, Musi N, Lipsitz LA, Kiel DP, Yung R, LeBrasseur NK, Singh RJ, McCarthy T, Puskarich MA, Niedernhofer LJ, Robbins PD, Sorenson M, Tchkonia T, Kirkland JL. Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era. J Am Geriatr Soc. 2021 Nov;69(11):3023-3033. doi: 10.1111/jgs.17416
6. Prem PN, Sivakumar B, Boovarahan SR, Kurian GA. Recent advances in potential of Fisetin in the management of myocardial ischemia-reperfusion injury-A systematic review. Phytomedicine. 2022 Jul;101:154123. doi: 10.1016/j.phymed.2022.154123
7. Shanmugam K, Boovarahan SR, Prem P, Sivakumar B, Kurian GA. Fisetin Attenuates Myocardial Ischemia-Reperfusion Injury by Activating the Reperfusion Injury Salvage Kinase (RISK) Signaling Pathway. Front Pharmacol. 2021 Mar 8;12:566470. doi: 10.3389/fphar.2021.566470.
8. Krishnakumar IM, Jaja-Chimedza A, Joseph A, Balakrishnan A, Maliakel B, Swick A. Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study. J Nutr Sci. 2022 Sep 9;11:e74. doi: 10.1017/jns.2022.72.
9. Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, Ness TJ, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). Int J Environ Res Public Health. 2021 Mar 3;18(5):2483. doi: 10.3390/ijerph18052483.
