Quercetin and fisetin are natural compounds known as flavonoids, which are found in many plants and contribute to their vibrant colors, thereby protecting the plants from environmental factors such as UV rays and pests.
Quercetin is predominantly found in apples and green tea, and you can get fisetin in your diet by eating strawberries and persimmons. Both compounds are best known for their strong antioxidant support and senolytic properties.
Senolytic compounds are studied for their ability to help clear the body of senescent cells — cells that no longer work properly but just won't die like normal, worn-out cells should. High amounts of these senescent cells can lead to problems like chronic inflammation, slower tissue repair, weakened immune system, and faster aging.
Fisetin vs. Quercetin
Both fisetin and quercetin have been shown in lab and animal studies to target senescent cells, helping the body's natural process of clearing them out without harming surrounding healthy cells.
Let's look at how these two natural compounds stack up against each other.
|
Feature |
Fisetin |
Quercetin |
|
Senolytic Strength |
Shown to clear a wider range of senescent cells on its own [1] |
More effective when combined with another senolytic compound, such as fisetin or the drug dasatinib [2] |
|
Lifespan Impact |
Significantly increased lifespan in mouse models [3] |
No clear lifespan extension on its own. |
|
Solo Use |
Effective as a standalone senolytic compound, it's also used for antioxidant support. |
It's less effective on its own for senolytic purposes, but it's used to support a healthy inflammatory response with allergy symptoms [4]. |
|
Additional effects |
Anti-oxidant support, healthy inflammatory response, neuroprotective |
Anti-oxidant support, healthy inflammatory response, histamine-support |
|
Safety & Accessibility |
Safe in small doses for everyday use, and it's well-tolerated. Naturally found in strawberries, most fisetin supplements are made from the Japanese Wax Tree for its high concentration. Supplements are common and fairly accessible through specialty online stores. |
Safe for daily use and well-tolerated. Naturally found in foods, but not in high concentrations. Quercetin supplements are widely available through specialty online stores. |
Which is a Better Senolytic Compound?
Based on the available research, fisetin is currently considered the more effective senolytic compound than quercetin. Unlike quercetin, you don't need to stack fisetin to produce targeted senolytic effects. On its own, it's been found to support a longer health span in murine model studies and clears a broader range of senescent cells.
Quercetin supplements still seem helpful, but it's best when combined with other compounds like fisetin or dasatinib (a prescription medication).
Chemical Structure and Properties
Fisetin's chemical formula is C₁₅H₁₀O₆.
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It has two aromatic (benzene) rings, one oxygen-containing central ring, and four hydroxyl groups (–OH), which give it antioxidant potential.
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Fisetin is fat-soluble, so taking the compound with food helps it cross the cell membranes and potentially the blood-brain barrier.
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Fisetin has a moderate bioavailability unless you get a supplement formulated with bioavailability enhancers like liposomes.
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Fisetin can enter cells and bind to proteins or enzymes involved in cell survival. In studies, it has also been seen to trigger apoptosis (programmed cell death) in senescent cells by activating stress-response pathways [5].
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Some of the fisetin benefits have been studied to support discomfort through interactions with pro-inflammatory markers like NF-κB and SASP.
Quercetin's chemical formula is C₁₅H₁₀O₇.
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It's also a flavonol similar to fisetin with a three-ring backbone, but it has five hydroxyl groups (more than fisetin), making it slightly more hydrophilic (water-soluble).
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Quercetin is notorious for its low bioavailability without enhancements like liposomes.
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Quercetin has been shown to suppress inflammatory signaling, protect the body from oxidative damage, and aid in clearing senescent cells [6].
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On its own, quercetin is less selective in killing senescent cells, which is why it's often combined in senolytic formulas.
The slight differences in the chemical structure, particularly in the number and placement of hydroxyl groups, affect how these compounds interact with cell membranes, enzymes, and signaling pathways. This is why fisetin is more effective at targeting senescent cells, while quercetin is more complementary.
Side Effects of Quercetin vs Fisetin
Quercetin and fisetin are considered safe when taken at typical supplement doses — but they might have different side effect profiles, depending on the dose and the individual response.
Quercetin Side Effects
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Mild headaches
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Upset stomach
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Tingling and numbness (rare and only at very high doses)
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Kidney stress (above 1000 mg/day for long periods) [7]
The long-term safety of taking quercetin at high doses hasn't been well studied. It's often combined with other ingredients, such as bromelain or liposomes, to improve absorption and reduce gastrointestinal side effects.
Fisetin Side Effects
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Upset stomach (rare but can happen in higher doses above 1000 mg)
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Fatigue or brain fog, especially with "hit-and-run" senolytic protocols — taking higher doses 1-3 days consecutively and then pausing for weeks to allow the body to finish clearing out senescent cells and recover.
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Mild headaches
Animal studies using high doses of fisetin (20 mg/kg) showed no significant toxicity signs [8]. And while human safety data is limited, short-term use of fisetin seems safe and well-tolerated.
In the case of both compounds, the side effects are mild and temporary. To reduce the chances of side effects, you should start with lower doses or opt for liposomal formulations that are much gentler on the digestive system.
Fisetin is a Stronger Senolytic Compound
Fisetin stands out as the more powerful and practical option for its genotypic effects. However, both compounds' respective health benefits could significantly add to wellness stacks focused on healthy inflammation and antioxidant support.
Research shows that fisetin on its own works well to support the body's process of clearing out senescent cells, while quercetin tends to work well as a complementary compound. Combining fisetin and quercetin may synergistically promote cellular health. They target different signaling pathways and influence various cell types, making them a powerful duo.
If you're trying to keep your supplement routine simple or are on a budget, fisetin is a better pick overall. It's more versatile, doesn't require stacking, and has more consistent results in animal studies in reducing senescent cells and improving health markers.
In user forums like Reddit, many people report noticeable benefits from fisetin, especially when taken in high doses, such as short bursts (hit-and-run method). For those looking for additional anti-inflammatory support with allergy symptoms, quercetin might be a beneficial compound to look into.
Resources:
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Huard, C. A., Gao, X., Dey Hazra, M. E., Dey Hazra, R. O., Lebsock, K., Easley, J. T., ... & Huard, J. (2023). Effects of Fisetin treatment on cellular senescence of various tissues and organs of old sheep. Antioxidants, 12(8), 1646.
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Lee, E., Carreras-Gallo, N., Lopez, L., Turner, L., Lin, A., Mendez, T. L., ... & Dwaraka, V. B. (2024). Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions. Aging (Albany NY), 16(4), 3088.
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Yousefzadeh, M. J., Zhu, Y. I., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., ... & Niedernhofer, L. J. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18-28.
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Mlcek, J., Jurikova, T., Skrovankova, S., & Sochor, J. (2016). Quercetin and its anti-allergic immune response. Molecules, 21(5), 623.
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Park, B. S., Choi, N. E., Lee, J. H., Kang, H. M., Yu, S. B., Kim, H. J., ... & Kim, I. R. (2019). Crosstalk between fisetin-induced apoptosis and autophagy in human oral squamous cell carcinoma. Journal of Cancer, 10(1), 138.
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Aghababaei, F., & Hadidi, M. (2023). Recent advances in potential health benefits of quercetin. Pharmaceuticals, 16(7), 1020.
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Mount Sinai. (n.d.). Quercetin. Mount Sinai Health Library. https://www.mountsinai.org/health-library/supplement/quercetin
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Hassan, S. S. U., Samanta, S., Dash, R., Karpiński, T. M., Habibi, E., Sadiq, A., ... & Bungau, S. (2022). The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Frontiers in Pharmacology, 13, 1015835.
