Home Ingredients Isorhamnetin (Methylated Quercetin)
Antioxidant

Isorhamnetin (Methylated Quercetin)

Evidence Level
Preliminary
6 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Isorhamnetin is a plant flavonol, a methylated form of quercetin (quercetin 3'-O-methyl ether). It occurs in the fruit of sea buckthorn, the leaves of ginkgo, mustard greens and onions, and the body also makes some isorhamnetin from the quercetin in food, so an isorhamnetin conjugate shows up in the blood after an onion meal. What stands out about it as a supplement topic is how little direct human data exists: there are essentially no standalone human trials testing isorhamnetin for a health outcome. The antioxidant, metabolic and blood-vessel findings that get cited all come from test tubes, cell cultures, rats and mice, where it behaves as an antioxidant and shifts several cell-signaling pathways. It is a separate compound from quercetin, which has its own page and its own small human trials. Because the human evidence is preliminary, it is best seen as an early-research antioxidant.

Studied Dose No human dose is established. Most intake is from foods or indirectly from quercetin. Animal studies gave isorhamnetin by mouth at roughly 50 to 100 mg per kg of body weight a day, and a mustard-leaf glycoside at 10 to 20 mg/kg; these are not human doses.
Active Compound Isorhamnetin (3'-O-methylquercetin), a flavonol aglycone; in foods mainly as glycosides such as isorhamnetin-3-O-glucoside.

Benefits

Antioxidant activity in laboratory and animal studies

In test-tube studies isorhamnetin neutralizes free radicals, and in rats it lowered markers of lipid peroxidation, such as thiobarbituric acid-reactive substances, in blood, liver and kidney tissue. These are cell and animal findings. No study has measured an antioxidant effect in people taking isorhamnetin.

Supported by Trial 1, Trial 4

Oxidative stress response in nerve cell studies

In cultured hippocampal nerve cells stressed by high glucose and a period of oxygen and glucose deprivation, isorhamnetin reduced oxidative stress and cell death and raised antioxidant signaling through the Nrf2/HO-1 pathway. This is cell-culture laboratory work; it does not show an effect on memory or brain health in people.

Supported by Trial 3, Trial 1

Glucose uptake in muscle cell and animal studies

In cultured muscle cells, very low concentrations of isorhamnetin increased glucose uptake by moving the GLUT4 transporter to the cell surface via JAK2/STAT signaling, a different route from quercetin. In diabetic rats, a mustard-leaf isorhamnetin glycoside lowered blood glucose. These are cell and animal results only.

Supported by Trial 3, Trial 1

Blood vessel function in isolated artery studies

In rat aortas exposed to angiotensin II, isorhamnetin and quercetin prevented a drop in relaxation, curbed superoxide production and reduced a subunit of the NADPH oxidase enzyme, which the authors linked to better nitric oxide availability. This is isolated-tissue laboratory work, not a blood pressure study in people.

Supported by Trial 2

Inflammation and lipid markers in animal studies

In mice with liver stress from a high dose of acetaminophen, oral isorhamnetin lowered inflammatory signals (TNF-alpha, IL-1beta, IL-6), raised total antioxidant status and improved blood lipid readings. These are animal findings at doses well above dietary intake, and do not establish a benefit in people.

Supported by Trial 4

Mechanism of action

1

Free radical scavenging in the laboratory

In test-tube studies isorhamnetin donates electrons to reactive oxygen species and can bind metal ions, the general way flavonols act as antioxidants. Whether this happens at the very low blood levels reached after food is not known.

2

Activates the Nrf2 antioxidant pathway in cells

In cell studies isorhamnetin switches on Nrf2/HO-1 signaling, which raises the cell's own antioxidant enzymes, and it dampens NF-kB inflammatory signaling. These are laboratory effects that have not been confirmed as clinical outcomes in people.

3

A methylated metabolite of quercetin

The body methylates quercetin to isorhamnetin. After people eat onions, isorhamnetin-3-glucuronide appears in the blood with a longer half-life than quercetin's own conjugates. Dietary isorhamnetin glycosides are also broken down to isorhamnetin in the gut.

4

Low bioavailability limits the lab findings

Like quercetin, isorhamnetin is poorly absorbed and heavily processed by phase II metabolism in the gut and liver, so blood levels after food are below one micromole per liter. That gap between test-tube and body concentrations is why laboratory antioxidant results may not carry over to people.

Clinical trials

1
Isorhamnetin and Diabetic Oxidative Stress (animal and laboratory study)
PubMed

In vivo and in vitro study of an isorhamnetin glycoside from mustard leaf, given orally to rats with streptozotocin-induced diabetes, with antioxidant testing of the released aglycone (Yokozawa et al. 2002, J Agric Food Chem).

Rats with streptozotocin-induced diabetes, plus test-tube antioxidant assays.

Oral isorhamnetin 3,7-diglucoside (10 or 20 mg/kg/day for 10 days) lowered serum glucose and lipid-peroxidation markers in blood, liver and kidney in a dose-dependent way, while the same dose given by injection did little. The authors concluded gut bacteria convert the glycoside to isorhamnetin, which acts as the antioxidant. An animal study, not a human trial.

2
Isorhamnetin and Angiotensin II in Rat Aorta (isolated-tissue laboratory study)
PubMed

Study of quercetin and its methylated metabolite isorhamnetin on endothelial function in rat aortic rings incubated with angiotensin II for 6 hours (Sanchez et al. 2007, J Nutr).

Isolated rat aortic rings (ex vivo), not people.

Angiotensin II reduced acetylcholine-induced relaxation and raised superoxide production and expression of the p47phox NADPH-oxidase subunit. Co-incubation with isorhamnetin or quercetin prevented these changes, pointing to greater nitric oxide availability. A single isolated-tissue experiment; it did not measure blood pressure in animals or people.

3
Isorhamnetin and Muscle-Cell Glucose Uptake (laboratory and animal study)
PubMed

Study of low, physiological concentrations of quercetin and its metabolite isorhamnetin on glucose uptake in L6 muscle cells, with a confirmatory mouse experiment (Jiang et al. 2019, Sci Rep).

Cultured L6 muscle cells, plus mice given quercetin glycoside by mouth.

Isorhamnetin at 1 nanomole per liter increased glucose uptake by moving GLUT4 to the cell surface, mainly through JAK2/STAT signaling, while quercetin used the AMPK route. In mice, oral quercetin glycoside raised GLUT4 at the muscle membrane. Cell and animal findings; isorhamnetin itself was not tested in people.

4
Isorhamnetin in Acetaminophen Liver Stress in Mice (animal study)
PubMed

Study of oral isorhamnetin on lipid, inflammatory and liver markers in mice given a toxic dose of acetaminophen (Gungor et al. 2023, Drug Chem Toxicol).

Mice with acetaminophen-induced liver injury.

Isorhamnetin (50 or 100 mg/kg by mouth) lowered the rise in liver enzymes, reduced TNF-alpha, IL-1beta and IL-6, raised total antioxidant status and improved blood lipids versus untreated animals. The doses are far above dietary intake, and the results are in mice, so they do not establish a benefit in people.

5
Isorhamnetin and Heatstroke Lung Injury in Rats (animal study)
PubMed

Dose-ranging study of oral isorhamnetin on lung inflammation and oxidative stress in rats exposed to a dry-heat environment (Dong et al. 2022, Med Sci Monit).

50 Sprague-Dawley rats in a heatstroke model.

Compared with untreated heatstroke animals, rats given 100 mg/kg/day isorhamnetin for 7 days had less lung tissue damage, lower lung-injury scores and lower levels of phospho-NF-kB, TNF-alpha, IL-1beta, IL-6 and the oxidation marker malondialdehyde. An animal model; no human data.

6
Isorhamnetin as a Quercetin Metabolite in People (human metabolism study)
PubMed

Metabolite profiling of plasma and urine from healthy volunteers over 24 hours after eating onions, using HPLC with mass spectrometry (Mullen et al. 2006, Br J Nutr).

Healthy human volunteers fed lightly fried onions.

Isorhamnetin-3-glucuronide was one of five flavonol metabolites measurable in plasma, with a longer half-life (about 5.3 hours) than the quercetin conjugates. Total urinary flavonol excretion was about 4.7% of intake. This study measured how isorhamnetin is formed and handled in the body; it did not test any health outcome.

Side effects and drug interactions

Common Potential side effects

Isorhamnetin has not been tested for safety in dedicated human trials. What is known comes from its presence in foods and from animal studies, so there is no established safety profile for concentrated supplement doses.
As a close relative of quercetin, it may share quercetin's effects; quercetin at supplement doses can cause nausea, stomach upset, headache or tingling in some people.
No specific data exist for pregnancy or breastfeeding; ask a doctor before use.
Standalone isorhamnetin is an uncommon supplement; most intake comes from foods such as sea buckthorn, onions and leafy greens, or indirectly from quercetin.

Important Drug interactions

No human drug-interaction studies of isorhamnetin have been done.
As a quercetin-type flavonol, it may in laboratory studies affect drug-processing enzymes (such as CYP3A4 and CYP2C9) and the P-glycoprotein transporter; this is the basis of quercetin's cautions with drugs such as warfarin, cyclosporine and digoxin. Tell your doctor if you take prescription medicines.
In animal studies isorhamnetin lowered blood glucose, so if you take glucose-lowering medicines, monitor your blood sugar and talk to your doctor.

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Frequently asked questions about Isorhamnetin (Methylated Quercetin)

Is isorhamnetin the same as quercetin?

No. Isorhamnetin is a methylated form of quercetin (quercetin 3'-O-methyl ether), and the body makes some isorhamnetin from the quercetin in food. It occurs in sea buckthorn, ginkgo leaves, mustard greens and onions, and an isorhamnetin conjugate turns up in the blood after an onion meal. Quercetin is a separate compound with its own page and its own small human trials.

Does isorhamnetin have human trials?

Essentially no. There are no standalone human trials testing isorhamnetin on its own for a health outcome. The antioxidant, metabolic and blood-vessel findings people cite come from test tubes, cell cultures, rats and mice. Review authors have explicitly called for clinical trials to see whether the animal results carry over to people.

What is isorhamnetin studied for?

In the laboratory it behaves as an antioxidant and, in cells and animals, influences glucose handling, blood-vessel cells, inflammation and fat-cell formation. None of this has been shown as a benefit in people, so it is best viewed as an early-research antioxidant rather than a product with proven uses.

How much isorhamnetin should I take?

There is no established human dose. Most people get isorhamnetin from foods or indirectly from quercetin rather than from a standalone product. If you use a supplement that contains it, follow the label and talk to your doctor, especially if you take prescription medicines or are pregnant or breastfeeding.

What is Isorhamnetin?

Isorhamnetin is a plant flavonol, a methylated form of quercetin (quercetin 3'-O-methyl ether). It occurs in the fruit of sea buckthorn, the leaves of ginkgo, mustard greens and onions, and the body also makes some isorhamnetin from the quercetin in food, so an isorhamnetin conjugate shows up in the blood after an onio…

What is Isorhamnetin used for?

Isorhamnetin is researched primarily for Antioxidant. In test-tube studies isorhamnetin neutralizes free radicals, and in rats it lowered markers of lipid peroxidation, such as thiobarbituric acid-reactive substances, in blood, liver and kidney tissue. These are cell and animal findings.

What is the recommended dosage of Isorhamnetin?

The clinically studied dose is No human dose is established. Most intake is from foods or indirectly from quercetin. Animal studies gave isorhamnetin by mouth at roughly 50 to 100 mg per kg of body weight a day, and a mustard-leaf glycoside at 10 to 20 mg/kg; these are not human doses. Always follow the product label and check with a healthcare provider for personal advice.

Is Isorhamnetin safe, and does it have side effects?

For most healthy adults, Isorhamnetin is well tolerated at studied doses. Reported effects can include: Isorhamnetin has not been tested for safety in dedicated human trials. What is known comes from its presence in foods and from animal studies, so there is no established safety profile for concentrated supplement doses. It may also interact with some medications. Isorhamnetin is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Isorhamnetin interact with any medications?

Possible interactions include: No human drug-interaction studies of isorhamnetin have been done. As a quercetin-type flavonol, it may in laboratory studies affect drug-processing enzymes (such as CYP3A4 and CYP2C9) and the P-glycoprotein transporter; this is the basis of quercetin's cautions with drugs such as… If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Isorhamnetin?

NutraSmarts rates the evidence for Isorhamnetin as Preliminary (1 out of 5). It is backed by 6 clinical trials and 10 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(10 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Gong G, Guan YY, Zhang ZL, Rahman K, Wang SJ, Zhou S, Luan X, Zhang H. Isorhamnetin: A review of pharmacological effects. Biomed Pharmacother. 2020;128:110301. doi: 10.1016/j.biopha.2020.110301.PubMedUsed to support: Review describing isorhamnetin as a major active compound of sea buckthorn (Hippophae rhamnoides) fruit and ginkgo (Ginkgo biloba) leaves, with cardiovascular, anti-inflammatory, antioxidant and anti-obesity activities reported mainly in laboratory and animal models through PI3K/AKT, NF-kB and MAPK pathways. The authors note the mechanistic work is limited and lacks detailed validation.
  2. Mullen W, Edwards CA, Crozier A. Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. Br J Nutr. 2006;96(1):107-16. doi: 10.1079/bjn20061809.PubMedUsed to support: In healthy volunteers fed onions, isorhamnetin-3-glucuronide was one of five quercetin-derived flavonol metabolites measurable in plasma, with a longer half-life (about 5.3 hours) than the quercetin conjugates; total urinary flavonol excretion was about 4.7% of intake. Shows isorhamnetin is formed from quercetin and circulates in people; it tested metabolism, not a health outcome.
  3. Kalai FZ, Boulaaba M, Ferdousi F, Isoda H. Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways. Int J Mol Sci. 2022;23(2):704. doi: 10.3390/ijms23020704.PubMedUsed to support: Review of in vitro and in vivo (cell and animal) studies reporting that isorhamnetin lowers glucose, improves oxidative status, reduces inflammation and modulates lipid metabolism in diabetes models by regulating several signaling pathways. No human efficacy trials are described.
  4. Gonzalez-Arceo M, Gomez-Lopez I, Carr-Ugarte H, Eseberri I, Gonzalez M, Cano MP, Portillo MP, Gomez-Zorita S. Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates. Int J Mol Sci. 2022;24(1):299. doi: 10.3390/ijms24010299.PubMedUsed to support: Review of cell and rodent studies on isorhamnetin and body fat: it reduced fat-cell formation at 10 micromoles per liter or higher via PPAR-gamma and Wnt signaling, with limited rodent data. The authors explicitly call for randomized clinical trials to see whether the animal results apply to humans, underlining the absence of human efficacy data.
  5. Sanchez M, Lodi F, Vera R, Villar IC, Cogolludo A, Jimenez R, Moreno L, Romero M, Tamargo J, Perez-Vizcaino F, Duarte J. Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta. J Nutr. 2007;137(4):910-5. doi: 10.1093/jn/137.4.910.PubMedUsed to support: In isolated rat aorta, isorhamnetin and quercetin prevented angiotensin II-induced loss of endothelium-dependent relaxation, reduced superoxide production and lowered overexpression of the p47phox NADPH-oxidase subunit, pointing to improved nitric oxide availability. An ex vivo tissue experiment, not a human study.
  6. Jiang H, Yamashita Y, Nakamura A, Croft K, Ashida H. Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes. Sci Rep. 2019;9(1):2690. doi: 10.1038/s41598-019-38711-7.PubMedUsed to support: In cultured L6 muscle cells, isorhamnetin at 1 nanomole per liter increased glucose uptake by moving GLUT4 to the cell surface mainly through JAK2/STAT signaling, a different pathway from quercetin's AMPK route; a mouse experiment confirmed oral quercetin glycoside raised GLUT4 at the muscle membrane. Cell and animal work; isorhamnetin was not tested in people.
  7. Gungor H, Ekici M, Ates MB. Lipid-lowering, anti-inflammatory, and hepatoprotective effects of isorhamnetin on acetaminophen-induced hepatotoxicity in mice. Drug Chem Toxicol. 2023;46(3):566-574. doi: 10.1080/01480545.2022.2069256.PubMedUsed to support: In mice with acetaminophen-induced liver injury, oral isorhamnetin (50 or 100 mg/kg) reduced the rise in liver enzymes, lowered TNF-alpha, IL-1beta and IL-6, raised total antioxidant status and improved blood lipids. An animal study at doses far above dietary intake.
  8. Dong X, Li JJ, Ma N, Liu AZ, Liu JW. Anti-Inflammatory and Anti-Oxidative Effects of Isorhamnetin for Protection Against Lung Injury in a Rat Model of Heatstroke in a Dry-Heat Environment. Med Sci Monit. 2022;28:e935426. doi: 10.12659/MSM.935426.PubMedUsed to support: In a rat heatstroke model, oral isorhamnetin (best at 100 mg/kg/day for 7 days) reduced lung tissue damage, lung-injury scores, phospho-NF-kB, TNF-alpha, IL-1beta, IL-6 and the oxidation marker malondialdehyde versus untreated animals. An animal study.
  9. Wu Y, Fan L, Wang Y, Ding J, Wang R. Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway. Inflammation. 2021;44(5):1993-2005. doi: 10.1007/s10753-021-01476-1.PubMedUsed to support: In cultured HT22 hippocampal nerve cells under high glucose plus oxygen-glucose deprivation and reoxygenation, isorhamnetin reduced cell death, inflammation and oxidative stress and activated Akt/SIRT1/Nrf2/HO-1 antioxidant signaling; an Akt inhibitor reversed the effect. A cell-culture study.
  10. Yokozawa T, Kim HY, Cho EJ, Choi JS, Chung HY. Antioxidant effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside isolated from mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes. J Agric Food Chem. 2002;50(19):5490-5. doi: 10.1021/jf0202133.PubMedUsed to support: In diabetic rats, an oral isorhamnetin glycoside from mustard leaf (10 or 20 mg/kg/day) lowered serum glucose and lipid-peroxidation markers in blood, liver and kidney dose-dependently, while injection did little; the authors concluded gut bacteria convert the glycoside to isorhamnetin, which acts as the antioxidant. Confirms mustard leaf as a dietary source. An animal and laboratory study.