What is the metabolism of quercetin?

November 27, 2025 •

4 min read

Despite its numerous health benefits, the bioavailability of quercetin is relatively low, typically less than 10%. This is largely due to its extensive metabolism within the human body after consumption, a complex process that converts it from its initial form found in foods into various conjugated metabolites. Understanding this metabolic pathway is crucial for appreciating how quercetin's potential therapeutic effects are mediated throughout the body.

Quick Summary

This article details the comprehensive metabolic journey of quercetin, from intestinal absorption through hepatic processing, and its interaction with gut microbiota. It explains how this flavonoid is converted into more water-soluble conjugates like glucuronides and sulfates, which circulate and are eventually excreted. Factors influencing its bioavailability and the biological activity of its metabolites are also covered.

Key Points

Low Bioavailability: The low water solubility and extensive metabolism of quercetin result in low bioavailability, limiting its direct physiological effects.
Glycoside Absorption: Quercetin is most commonly consumed as glycosides, which are more readily absorbed in the small intestine, while other forms like rutin are processed by gut bacteria in the colon.
Phase II Conjugation: Absorbed quercetin undergoes rapid and extensive Phase II metabolism in the small intestine and liver, primarily through glucuronidation and sulfation, to form water-soluble conjugates.
Metabolite Circulation: The circulating forms of quercetin in the plasma are predominantly conjugated metabolites, not the parent aglycone form.
Gut Microbiota's Role: Unabsorbed quercetin is catabolized by gut bacteria into smaller phenolic acids, which can also be absorbed and contribute to the overall metabolic profile.
Excretion Pathways: Conjugated metabolites are efficiently excreted from the body via bile and urine with the help of specific efflux transporters in the liver and kidneys.
Altered Bioactivity: The conjugation of quercetin can alter its biological activity, meaning the metabolites, not the parent compound, are often responsible for its health effects in the body.

What Happens to Quercetin After You Consume It?

Quercetin, a potent flavonoid, is consumed predominantly in foods as glycosides, which means it is attached to sugar molecules. The way these sugar groups are attached dictates its initial absorption pathway. Once ingested, quercetin undergoes a complex metabolic journey in the gut and liver, transforming into various metabolites that ultimately circulate in the body. These transformations are vital because they drastically alter the compound’s solubility and biological activity.

The Intestinal Phase: Absorption and Microbial Action

Before entering the bloodstream, quercetin must be absorbed through the gastrointestinal tract. This process differs depending on whether it is in its glycoside form or as the sugar-free aglycone.

Absorption of Quercetin Glycosides:

Small Intestine Absorption: Some quercetin glycosides, particularly those bound to glucose (like isoquercetin), can be absorbed intact into the small intestinal cells via specific sodium-dependent glucose transporters (SGLT1). The enzyme lactase-phlorizin hydrolase (LPH) on the intestinal brush border can also deglycosylate certain quercetin glycosides, allowing the freed aglycone to be absorbed by passive diffusion.
Colonic Metabolism: Other quercetin glycosides, such as rutin (quercetin-3-O-rutinoside), are not readily hydrolyzed in the small intestine due to their specific sugar type. Instead, they travel to the colon where the resident gut microbiota breaks them down.

Role of the Gut Microbiota:

The gut microbiota plays a crucial role in metabolizing unabsorbed quercetin compounds. These bacteria perform deglycosylation and further cleave the flavonoid structure, leading to the formation of smaller phenolic acids and aromatic compounds. These catabolites can then be absorbed by the colon and undergo further Phase II metabolism in the liver before excretion.

The Hepatic Phase: Extensive Phase II Metabolism

After absorption, whether as an aglycone or a microbial metabolite, the compound travels via the portal vein to the liver, the primary site of Phase II metabolism. Here, enzymes conjugate the compounds to make them more water-soluble for easier excretion.

Glucuronidation: This is one of the most significant metabolic pathways for quercetin. Enzymes called UDP-glucuronosyltransferases (UGTs) attach glucuronic acid molecules to the hydroxyl groups of quercetin. The most common glucuronidation sites are the 3, 7, 3', and 4' positions, resulting in various quercetin-glucuronide conjugates, which are the predominant forms found circulating in the bloodstream.
Sulfation: Another key Phase II reaction involves sulfotransferases (SULTs) attaching a sulfate group, primarily at the 3'-position. Sulfation, along with glucuronidation, increases the compound's hydrophilicity.
Methylation: Catechol-O-methyltransferase (COMT) enzymes can add a methyl group to the catechol ring of quercetin, forming methylated derivatives like isorhamnetin and tamarixetin. Methylation reduces the antioxidant activity but may increase other biological effects and lipophilicity.

The Excretion Process

After metabolism in the liver, the water-soluble conjugated quercetin metabolites are either secreted into the bile, leading to elimination via feces, or enter the systemic circulation to be excreted by the kidneys into urine. Efflux transporters such as Multidrug Resistance-associated Proteins (MRPs) and Breast Cancer Resistance Protein (BCRP) play a critical role in moving these metabolites out of the liver and kidneys.

Factors Influencing Quercetin Metabolism

Various factors impact the absorption and metabolism of quercetin, contributing to its low and variable bioavailability.

Food Matrix: The food source significantly affects absorption. Quercetin glucosides from onions, for instance, are better absorbed than rutin from black tea or apples. The presence of fat can also improve bioavailability.
Molecular Form: The initial molecular structure matters. Quercetin aglycone (the sugar-free form) is poorly soluble and less bioavailable than its glycoside counterparts in supplements.
Gut Microbiota Composition: The specific composition of an individual’s gut bacteria influences the type and quantity of quercetin metabolites produced in the colon, as different bacteria possess different deglycosylating enzymes.

Comparison of Quercetin vs. Metabolites


Feature	Quercetin Aglycone	Conjugated Metabolites (e.g., glucuronides)
Water Solubility	Very low	High
Antioxidant Activity	High, especially scavenging reactive oxygen species	Variable, often lower but still significant
Absorption Site	Mainly passive diffusion in the small intestine, but poor due to hydrophobicity	More effectively absorbed in the intestine and colon after microbial action
Bioavailability	Low	The primary form available in circulation for biological activity
Primary Metabolic Pathways	Phase II (glucuronidation, sulfation, methylation) in the liver and enterocytes	Excretion via kidneys or bile
Biological Target Interaction	Primarily studied in vitro; high potency but may not reflect in vivo action	Act as modulators or precursors, affecting physiological processes from the bloodstream

Conclusion

The metabolism of quercetin is a sophisticated process involving intricate interactions in the gut and liver, profoundly influencing its bioavailability and ultimate health effects. The initial glycoside form, its interaction with gut microbiota, and rapid Phase II conjugation into more water-soluble metabolites all play a role in its systemic fate. While the parent quercetin compound shows strong activity in lab settings, its physiological effects largely depend on the concentration and biological activity of its conjugated metabolites circulating in the bloodstream. Research continues to explore these metabolic intricacies to develop more effective quercetin-based nutraceuticals with enhanced bioavailability.

Disclaimer: The information in this article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before taking any supplements or making changes to your diet.

Frequently Asked Questions

After ingestion, quercetin is absorbed in the gut, but most of it is rapidly metabolized in the intestinal walls and liver into water-soluble conjugates like glucuronides and sulfates. It is these metabolites that circulate in the body, not the original quercetin.

Quercetin's bioavailability is low primarily because of its poor solubility in water and its rapid, extensive Phase II metabolism by enzymes in the intestine and liver, which convert it into less active, water-soluble metabolites for excretion.

Yes, the form of quercetin significantly affects absorption. Glycosides (quercetin with sugar molecules attached), like those found in onions, are generally better absorbed than the sugar-free aglycone form found in many supplements.

The gut microbiota metabolizes unabsorbed quercetin glycosides that reach the colon. Bacteria break down these compounds into smaller phenolic acids and other catabolites, which are then absorbed and further metabolized.

The main metabolites of quercetin in humans are glucuronide and sulfate conjugates, with limited methylation also occurring. These hydrophilic conjugates are the primary forms found in the bloodstream.

No, conjugation can alter the biological activity of quercetin. While some metabolites, like certain quercetin-glucuronides, retain significant antioxidant or other activities, they may differ in potency and mechanism compared to the parent quercetin compound.

The water-soluble conjugated metabolites of quercetin are eliminated from the body through excretion. The liver secretes them into the bile, and the kidneys excrete them in the urine.

Some studies suggest that consuming quercetin with fats can increase its bioavailability by improving its absorption in the intestine. Additionally, newer formulations like nanosuspensions are being developed to improve oral absorption.