Fisetin

What it is

Like quercetin, fisetin belongs to the flavonols. In the diet, it is found in fruit and vegetables such as strawberries, apples, persimmons and onions. For supplements and studies, fisetin is extracted in high purity from plants, for example from the bark of the smoke tree or from Rhus succedanea.

Unchanged fisetin is poorly absorbed from the gut. In a study with 15 healthy people, pure fisetin reached only very low blood levels. A special hydrogel formulation brought a 26.9-fold larger amount into the blood. However, the study comes from the manufacturer of this formulation. In practice this means: how much fisetin from a capsule reaches the tissue depends strongly on the preparation.

How it is supposed to work

Senescent cells are cells that no longer divide but also do not perish. They accumulate with age and release inflammatory substances that damage the surrounding tissue. Senolytics are meant to send these cells selectively into programmed cell death. The mouse data fit a so-called hit-and-run principle: even short or intermittent administration lowered senescence markers.

In 2018, a research group led by Laura Niedernhofer and Paul Robbins tested 10 flavonoids on aged mouse and human cells. Fisetin was the most effective. In mice with accelerated aging and in old normal mice, it lowered senescence markers in several tissues. In human adipose tissue in the laboratory, it reduced senescence in a subset of cells. Given late in life, fisetin extended the average and the maximum lifespan of the animals. Almost all of the enthusiasm for fisetin rests on this study.

What self-measurements show

Anyone taking fisetin cannot measure senescence in their own body, and self-tests for biological age are not a reliable substitute. In a small pilot study with 10 adults over 50, biological age measured this way fell in 4 people and rose in 5. Telomere lengths did not change. The authors therefore advise against taking fisetin as an anti-aging agent until larger studies are available. Above all, the study shows how difficult it is to judge an effect without a comparison group.

What the studies show

The 2018 mouse study

Of 10 flavonoids tested, fisetin proved to be the most potent senolytic. It lowered senescence markers in several organs of mice with accelerated aging and of old wild-type mice, improved tissue health and extended average and maximum lifespan, even though treatment began only late in life. The authors saw this as a good basis for human studies.

The independent replication in the ITP

The Interventions Testing Program tests longevity interventions at three sites using genetically heterogeneous mice. Fisetin was fed from an age of 20 months, either continuously or alternating 3 days on and 11 days off; the content in the feed was 99 percent of the target. Lifespan was not extended in either sex. The senescence marker p16 rose with age in kidney, brain and liver, but did not fall under fisetin. The measurements were made by the same laboratory that had co-authored the 2018 study.

Fisetin in knee osteoarthritis

In this randomized, quadruple-blind study, 75 people with knee osteoarthritis received fisetin on 2 days at a time, each followed by a break, or placebo. The primary endpoint was safety over a mean of 12 months: 28 people under fisetin and 33 under placebo had side effects, no difference. The senescence-associated inflammation markers did not differ either. The results have so far been published only in the trial registry.

Fisetin in colorectal cancer during chemotherapy

37 patients received fisetin or placebo double-blind for 7 weeks, starting one week before chemotherapy. In the fisetin group, IL-8, hs-CRP and the enzyme MMP-7 fell. In direct comparison with placebo, only the decline in IL-8 was significant. Clinical endpoints such as response or survival were not examined.

Where the data stop

The decisive claim, that fisetin removes senescent cells in humans, has not been shown to this day. The only randomized study with registered senescence markers, the osteoarthritis study with 75 participants, found no difference from placebo. The Mayo Clinic study AFFIRM in 40 older women has been running since February 6, 2018; its estimated completion is 11/2027. A sister study with older adults is also still open.

The foundation in animals has also become shakier. In the independent testing program, fisetin did not extend life and did not lower senescence markers, even though the content in the feed was correct. The positive human studies are small, short and measure blood values such as IL-8 or IL-6 instead of frailty, disease or lifespan. A frequently cited study on knee osteoarthritis, ROPE, was never conducted; it is listed as withdrawn in the registry.

Status, approval and legal

Isolated fisetin with at least 98 percent purity from the bark of the smoke tree was classified in the EU as a novel food following an inquiry to the Czech authority and is not authorized. The entry in the European Commission's Novel Food Catalogue dates from April 14, 2026. As a food supplement, the pure substance therefore may not be marketed in the EU. There is no approved medicinal product, and no authorized health claims either. Fisetin is not on the WADA Prohibited List. Because fisetin is not an approved active substance, Biohacking Kompakt does not give a dosage.

Safety

Safety data exist only from small, short studies. There, fisetin was well tolerated: in the osteoarthritis study with 75 participants, side effects were no more frequent than under placebo, and none were reported in an absorption study with 15 healthy people or in a pilot study with 10 adults. There is no upper limit from EFSA, BfR or NIH, and no official safety assessment either. Interactions with medicines, for example with anticoagulants, have not been studied in humans. Data are lacking for pregnancy, breastfeeding and children. Anyone who has cancer or is being treated for it should take fisetin only within a study or after consulting a physician, because an intervention in cell programs cannot be assessed there.

Sources

• Yousefzadeh et al., EBioMedicine 2018
• Harrison et al., GeroScience 2024 (ITP)
• ClinicalTrials.gov NCT04210986, fisetin in knee osteoarthritis
• ClinicalTrials.gov NCT03430037, AFFIRM
• Farsad-Naeimi et al., Food Funct 2018
• Wang et al., Clin Appl Thromb Hemost 2019
• Alipour et al., J Int Soc Sports Nutr 2026
• Krishnakumar et al., J Nutr Sci 2022
• Lee & Burns, Altern Ther Health Med 2024
• European Commission, novel food status (catalogue)