Supplement: Fisetin & Quercetin

What It Is

Fisetin and quercetin are flavonoids, the colored plant compounds spread across fruits and vegetables. Quercetin is the most abundant flavonol in the ordinary diet, richest in capers, kale, onions, apples, and berries. Fisetin is rarer, turning up in strawberries, persimmons, grapes, and apples. Both act as antioxidants in the test tube. What put them on supplement shelves is a second lab property: they can act as senolytics, compounds that clear senescent cells.

Anatomy of the Practice

1In cells and in animals

At the high, intermittent doses used in laboratory research, both flavonoids can push senescent cells toward death. Fisetin carried this furthest in animals, lowering senescence markers across tissues and extending life in aged mice. This is the mechanism the supplements are sold on, and the evidence for it is almost all in cells and animals.

2In the human bloodstream

Getting these compounds into the blood is the bottleneck. Quercetin is poorly and variably absorbed. In one human study no free quercetin reached the blood at all: only its modified metabolites, and how much showed up depended on the form eaten. Fisetin is thought to share this low bioavailability.

3Over weeks of quercetin

Given to people for weeks at gram-level doses, quercetin produces modest shifts. The effect appeared in people whose blood pressure was already high, and not in those already in range.

What It Does

Fisetin's animal result has no finished human trial behind it. Quercetin's measured effects, strongest first:

• Blood pressure: pooled across seven randomized trials in 587 people, about 3 mmHg off systolic, 2.6 off diastolic: concentrated at 500 mg daily and up, mostly where pressure was already high.
• Colds: no drop across a 1,002-person trial, though fit adults 40 and over taking 1,000 mg logged 31 percent fewer sick days.
• Endurance: a very small edge, around 2 percent.
• Allergy and immunity: still mostly cell-and-animal data.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

How it works

Quercetin was one of the first senolytics identified, paired with dasatinib in the researchModerate · mixed

In plain terms

Quercetin war eine der ersten Verbindungen, die gefunden wurde, um die Überlebensprogramme abzuschalten, die abgenutzte Zellen am Leben halten.

In detail

By mapping the pro-survival networks senescent cells depend on, researchers identified quercetin, alongside dasatinib, as one of the first senolytic compounds, able to block those survival signals so senescent cells undergo the programmed death they had resisted. The selectivity is partial and differs by cell type, and the intermittent research doses are far larger than nutritional supplement doses.

Who this may not transfer to:Mechanism from cell work; research doses far exceed supplement doses.

The study · 1

Zhu 2015, Aging Cell · Aging Cell, 2015

Quercetin is poorly absorbed; no free compound reached the blood in 12 volunteersModerate · mixed

In plain terms

Quercetin is absorbed poorly and unevenly; it never showed up in the blood as the free compound, and how much got in depended on the form eaten.

In detail

In a four-way crossover of 12 healthy volunteers, no free quercetin appeared in plasma at all, only glucuronide metabolites, and peak levels differed several-fold depending on the sugar form and food matrix, being far higher from onion and quercetin-4-glucoside than from rutin or buckwheat tea. A small pharmacokinetic study measuring blood levels, not a health outcome; it defines the absorption constraint, not any benefit.

Who this may not transfer to:Small pharmacokinetic study; defines the absorption limit, not a health outcome.

The study · 1

Graefe 2001, Journal of Clinical Pharmacology · J Clin Pharmacol, 2001

Fisetins gesundheitliche Vorteile sind bisher nur in Zell- und Tierstudien dokumentiertPreliminary · mixed

In plain terms

Fisetins berichtete gesundheitliche Vorteile stammen fast ausschließlich aus Labor- und Tierarbeiten, nicht aus abgeschlossenen menschlichen Studien.

In detail

Übersichtsarbeiten zu Fisetin beschreiben seine antioxidative, entzündungshemmende und zytoprotektive Aktivität aus Zell- und Tierexperimenten. Die dokumentierten Gesundheitseffekte der Verbindung befinden sich im präklinischen Stadium, wobei menschliche Wirksamkeit für die behaupteten Ergebnisse noch nicht in abgeschlossenen Studien belegt wurde. Eine Übersichtsarbeit fasst präklinische Befunde zusammen und kann keinen menschlichen Nutzen zeigen; sie wird hier für das Stadium der Evidenz zitiert, nicht für einen Effekt beim Menschen.

Who this may not transfer to:Cell and animal evidence; not yet shown in completed human trials.

The study · 1

Khan 2013, Antioxidants & Redox Signaling · Antioxid Redox Signal, 2013

Heart And Vascular

Quercetin lowered blood pressure about 3 mmHg, mostly at 500 mg a day or moreModerate

In plain terms

Across the trials, quercetin took a few points off blood pressure, mostly when the dose was 500 mg a day or higher.

In detail

Pooling seven randomized controlled trials in 587 patients, quercetin lowered systolic blood pressure by 3.04 mmHg and diastolic by 2.63 mmHg. The effect was significant in trials using doses of 500 mg a day or more and not significant below that. A small evidence base of seven trials, with the reduction concentrated at higher doses and largely in people whose pressure was already raised.

Who this may not transfer to:Effect largest in people with raised blood pressure and at 500 mg a day or more.

The study · 1

Serban 2016, Journal of the American Heart Association · J Am Heart Assoc, 2016

Respiratory Infection

Quercetin did not cut colds overall; fit adults 40 and over on 1000 mg had 31% fewer sick daysModerate · no effect

In plain terms

Quercetin did not cut colds across everyone in the trial, though older, fitter people on the higher dose reported fewer and milder sick days.

In detail

In a randomized trial of 1002 adults taking 500 or 1000 mg a day of quercetin for twelve weeks, there was no reduction in upper respiratory tract infection rates for the group as a whole. A subgroup of physically fit people aged 40 and over on 1000 mg had 31% fewer sick days and 36% lower symptom severity. The overall result was null; the benefit came from a post-hoc subgroup, which is a lead to test, not a confirmed effect.

Who this may not transfer to:Null overall; benefit only in a post-hoc subgroup of fit adults 40 and over.

The study · 1

Heinz 2010, Pharmacological Research · Pharmacol Res, 2010

Cardiorespiratory Fitness

Quercetin gave about a 2% edge in endurance, a real but tiny effectEmerging

In plain terms

Quercetin gave a real but tiny edge in endurance exercise, on the order of 2%.

In detail

A meta-analysis of eleven trials in 254 people, at a median dose of 1000 mg a day, found quercetin produced a statistically significant improvement in endurance capacity and VO2max, but the effect size was between trivial and small, equating to roughly a 2% gain over placebo. The pooled effect is between trivial and small, and study results were mixed, so any practical benefit for a given person is minor.

Who this may not transfer to:Statistically real but between trivial and small for any one person.

The study · 1

Kressler 2011, Medicine & Science in Sports & Exercise · Med Sci Sports Exerc, 2011

Longevity And Mortality

Fisetin verlängerte die Lebensdauer bei alten Mäusen, das stärkste Senolytikum der getesteten FlavonoidePreliminary

In plain terms

Fisetin räumte abgenutzte Zellen ab und verlängerte das Leben bei alten Mäusen stärker als die anderen getesteten Pflanzenflavonoide.

In detail

Im Vergleich mit einem Panel von Flavonoiden war Fisetin das stärkste Senolytikum. Bei alten Mäusen reduzierte es Seneszenzmarker in mehreren Geweben und verlängerte die mediane und maximale Lebensdauer, auch wenn es im späteren Leben begonnen wurde. Die Dosen waren hoch im Verhältnis zu dem, was die Ernährung liefert, das Ergebnis ist bei Mäusen, wo Langzeitbefunde oft nicht auf Menschen übertragen werden, und ein Supplement in nutritiven Dosen ist nicht die getestete Intervention.

Who this may not transfer to:Result is in aged mice; longevity findings often fail to transfer to people.

The study · 1

Yousefzadeh 2018, EBioMedicine · EBioMedicine, 2018

Immune Function

Quercetin calms allergy and inflammation in the lab, with few human trials yetPreliminary

In plain terms

In the lab quercetin calms the cells that drive allergy and inflammation, though this has mostly not been carried into human trials.

In detail

Quercetin stabilizes mast cells and inhibits histamine release, lowers pro-inflammatory cytokines and leukotrienes, and shifts the Th1/Th2 balance, mechanisms relevant to allergic rhinitis and asthma. Most of this evidence is from cell and laboratory models, not clinical trials. Predominantly mechanistic and in-vitro evidence; controlled human trials in allergic rhinitis are few, so the clinical size of any effect is not established.

Who this may not transfer to:Mostly cell and laboratory models; controlled human allergy trials are few.

The study · 1

Mlcek 2016, Molecules · Molecules, 2016

How It Works

The whole idea rests on senescence. As tissue ages, some cells stop dividing but do not die, and they secrete inflammatory signals that irritate the healthy tissue around them. Senolytics remove those cells selectively. Quercetin was one of the first two compounds identified this way, found by mapping the survival networks that senescent cells depend on. Fisetin was then singled out as the most potent natural senolytic in a panel of flavonoids tested.

The catch is the dose. The doses that cleared senescent cells in a dish or a mouse were large and taken in bursts, hard to reach in a person on daily capsules. So the mouse longevity results and the modest human quercetin numbers are two separate findings, not a single one. The clinical work pairing quercetin with the prescription drug dasatinib, and the first small human trials, sits on the senolytics page.

Cellular senescence is one recognized hallmark of aging.

Getting It Right

Ways to Do It

Most of what these two have to offer comes from food, and the food is pleasant to eat. The supplement rungs are for specific targets, and the higher ones belong in a conversation with a clinician.

1

Eat the foods that carry themFreeEasy

A diet with fruit, vegetables, and tea supplies both flavonoids, in the whole-food form the body absorbs well. That is the sensible starting point for most people who are not chasing a specific number.

2

A quercetin supplement, if blood pressure is the target$Easy

The blood-pressure trials that showed an effect used doses of 500 mg a day or more. If lowering blood pressure is your aim, that is the studied range. Decide it with your doctor, who can track your numbers.

3

Take it with food to help the low absorption$Easy

Because quercetin is poorly absorbed, taking it with a meal that has some fat in it is a simple way to help. Some products use forms meant to improve uptake, such as a phytosome or an enzymatically modified version; the human outcome data behind those forms are limited.

4

Fisetin, as a deliberate self-experiment$ to $$Easy

Fisetin's senolytic and longevity evidence is animal-only, and its human trials have not reported. If you choose to try it, the footing is simple: you are running an experiment on yourself, testing an effect no completed human trial has measured. It should not displace the habits that do have human evidence behind them, such as exercise and sleep.

5

Choose a third-party-tested product$Easy

Supplements are loosely regulated. An independent testing mark such as NSF or Informed Choice tells you the capsule holds what the label says.

Go Deeper

• Senolytics: the drug-based clinical side of clearing senescent cells, and the early human trials.
• The biology of aging: where cellular senescence sits among the hallmarks of aging, and why the anti-aging compounds as a group are earlier-stage than the marketing suggests.

The Chinese Medicine View

Fisetin and quercetin were isolated by modern chemistry, so the classical Chinese pharmacopoeia never named them. It has no channel, temperature, or flavor for a purified flavonoid. The tradition can only speak to the foods these compounds come from, not the isolated flavonoid.

Traditionally the two sit in different food categories. The fruits that carry fisetin are read as generating fluids and gently nourishing, the kind offered to someone dry or depleted. The pungent plants richest in quercetin belong to the acrid, warming flavors the tradition links with moving Qi and dispersing, a different job entirely. That the same class of compound appears in foods read so differently is a caution against treating a flavonoid as one traditional entity. The tradition reads the whole food, not an isolated compound.

Where the two views meet is one idea: the right amount depends on the person. A tradition that gives a moistening fruit to someone dry, and a warming onion to someone else, would not hand everyone the same daily dose of a concentrated isolate. It matches the food to the individual.

Cautions For This Practice

Extra restraint

Everything to be aware of is here, in one place. This practice suits most healthy people; a few situations call for real care.

Quercetin up to 1000 mg a day is usually well tolerated, with kidney and drug-interaction cautions

A safety review found that reported adverse effects from supplemental quercetin, commonly sold at up to 1000 mg a day, have been infrequent and mild, but adequate data for high doses beyond twelve weeks are lacking. Animal studies flagged potential to worsen a predamaged kidney and to alter the bioavailability of certain drugs. The kidney and tumor-promotion signals come from animal studies, and long-term high-dose human data are not available, so risk in specific groups is inferred, not measured.Andres 2018, Molecular Nutrition & Food Research

Quercetin can change how your medications work

Quercetin affects some of the enzymes and transporters that clear other drugs, so it can alter the blood levels of medicines a person already takes. If you are on prescription drugs, have a pharmacist or clinician check for interactions before starting a supplement dose.

High-dose quercetin and the kidneys

A safety review flagged that in animal studies quercetin could worsen damage in an already-injured kidney. If you have kidney disease, reduced kidney function, or take medication that affects the kidneys, raise a quercetin supplement with your doctor before starting. For those groups it is a check-first step, and often still fine after that check.

It can lower blood pressure

The measured blood-pressure effect is the reason to watch for overlap with medication. If you already take drugs for high blood pressure, adding quercetin could stack with them, so tell your doctor and keep an eye on your numbers.

Long-term high-dose safety is not well mapped

Quercetin supplements are commonly sold at up to 1,000 mg a day, and reported side effects at those doses have been infrequent and mild. Data past about twelve weeks are limited. Safety across years of use has not been established, so the studied range is the sensible ceiling.

Research senolytic doses were far larger than the amounts sold as supplements

The senescent-cell clearance seen in research used big, burst doses whose benefit and safety in healthy people are not established. Buying fisetin or quercetin at ordinary nutritional amounts is a different thing, and copying a trial with very large doses is not supported by current evidence.

Pregnancy and breastfeeding

Supplemental doses of either flavonoid above what food provides have not been well studied in pregnancy or breastfeeding. Without that evidence, food-level amounts are the safe assumption, and a supplement is a discussion to raise with your doctor.

Start slow, be smart, read the research, and consult a professional if you have any concerns. This is here to inform your choice, not make it for you.

Common Questions

Does fisetin actually slow aging?

Not that anyone has shown in a person. The lifespan gain is a mouse result, and such findings often fail to carry to humans, whose metabolism, dosing, and lifespan differ. Fisetin's efficacy trials in people have not reported, so no finished study yet weighs on human aging.

The lifespan gain is a mouse result, and such findings often fail to carry to humans, whose metabolism, dosing, and lifespan differ.

Does quercetin lower blood pressure?

Modestly, and mainly if your pressure is already high. The trials used concentrated supplement doses. Eating a few more onions or apples is a different quantity, and has not been tested the same way.

Is quercetin safe?

For most people at usual supplement amounts, it is well tolerated. The everyday quercetin in onions, apples, and tea raises no safety question at all; the cautions attach to the concentrated capsule doses. If you have kidney disease or take a prescription drug it might interact with, check with a pharmacist or doctor before a first supplement dose.