Herbs & Botanicals · Herbs · Woodland root sold for colds, with no good human trials and several firm safety warnings

Goldenseal

Q: Does goldenseal help with colds or infections?

There is no good human evidence that it does. NCCIH says there is not enough evidence to say goldenseal helps any health condition. Lab studies show germ-slowing in dishes, but that does not mean it works in the body.

Q: Is goldenseal the same as berberine?

No. Berberine is one of goldenseal's alkaloids and is also in other plants. Goldenseal also has hydrastine and canadine, and the amount of berberine in products varies. Almost all the trials with benefits are on purified berberine, so they do not prove goldenseal works.

Q: Can goldenseal interact with my medicines?

Yes. In volunteers, goldenseal supplements reduced CYP2D6 activity by about 40% to 50% and CYP3A4/5 by about 40%, raised midazolam levels by 40% to 60%, and lowered metformin levels. It did not change digoxin much. Purified berberine raised cyclosporine levels in transplant patients. Ask a doctor or pharmacist before combining it with any medicine.

Q: Is goldenseal safe in pregnancy or while breastfeeding?

NCCIH and Health Canada say no: do not use it in pregnancy or while breastfeeding. A rat study found no extra malformations, but the authors say human studies are needed. There are no data on goldenseal in breast milk.

Q: Why is it said to be dangerous for newborns?

In lab tests, berberine pushed bilirubin off its carrier protein, which could raise the risk of newborn jaundice causing brain damage. A review also says berberine can break down red blood cells in babies with G6PD deficiency. Other animal work did not find jaundice, so the evidence conflicts. Official advice is still to avoid it in newborns.

Q: Does goldenseal harm the liver?

It caused liver tumours in rats and mice in two-year National Toxicology Program studies of the whole root powder. That does not show cancer in people. The NIH LiverTox summary for berberine found no clinically apparent liver injury, but the LiverTox page for goldenseal itself was not read.

Q: Does goldenseal affect blood pressure?

No human trial of goldenseal on blood pressure was found. For berberine alone the evidence is limited and inconclusive. Health Canada advises people with a blood pressure or kidney disorder to ask a health professional first.

Q: Does berberine lower blood sugar and cholesterol?

Pooled trials of purified berberine report lower fasting glucose, HbA1c, LDL and triglycerides. The trial quality is mixed and none measured heart attacks. This is berberine, not goldenseal, and goldenseal can lower metformin levels.

Q: Is goldenseal endangered?

It is listed under CITES Appendix II (since 1997, per a US Forest Service bibliography), which controls international trade in wild plants. Wild populations have been greatly reduced by harvesting for the herbal trade and by habitat loss. Cultivated sources take pressure off wild plants.

Q: Are goldenseal products reliable?

Not always. One study found hydrastine from none to 2.93% across products, and only 10 of 17 root products met a proposed standard. Other studies found products made from other plants or mixtures. Results for one product do not apply to another.

Hydrastis canadensis L. · also called Orangeroot, yellow puccoon, yellow root

Goldenseal is a woodland plant of eastern North America whose yellow root and rhizome are dried and sold as powder, extract or tincture. It contains the alkaloids berberine, hydrastine and canadine. It is marketed for colds and infections, but no good human trial shows it works. It changes how the body handles many medicines, and it is advised against in pregnancy, breastfeeding and for infants.

General information, not medical advice. Last substantive update October 25, 2026 · Not medically reviewed. A named clinician has not signed off on this page. How this page is made

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About Goldenseal

Goldenseal (Hydrastis canadensis) is a woodland plant of eastern North America. Its root and rhizome are sold for colds and infections, but no good human trial shows it works. The best-documented findings are about safety: it changes how the body handles many medicines, it should be avoided in pregnancy, breastfeeding and newborns, it caused liver tumours in rodents, and it is over-harvested and often mislabelled. Most "benefit" research is on purified berberine, not goldenseal.

What it is

Goldenseal (Hydrastis canadensis L.) is a perennial forest plant in the buttercup family. It is native to eastern North America. The part used in medicine is the root and rhizome, which is dried and sold as powder, extract or tincture.

Its main active compounds are isoquinoline alkaloids: berberine, hydrastine, canadine and hydrastinine. The same alkaloids, especially berberine, are found in other plants such as barberry, Oregon grape and Coptis.

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Traditional and current uses

Native American peoples used goldenseal for wounds, digestive problems, skin and eye conditions, and as a dye. Folk medicine in the United States added urinary problems and mouth infections. Health Canada lists traditional uses for digestion, as a bitter and as a mild laxative.

Today it is sold for colds, upper respiratory infections, hay fever, diarrhea and constipation. NCCIH says there is not enough evidence to say whether goldenseal helps any health condition, and that no rigorous human studies have looked at it.

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What is in it and how it works

Most of what is known about how goldenseal works comes from test tubes, cells and animals. Berberine and hydrastine slow some germs and some enzymes in dishes. In people, the clearest action is on drug-processing enzymes in the gut and liver, which is why interactions matter.

Goldenseal is not just berberine. In hamsters a goldenseal root extract lowered cholesterol more than pure berberine, and in the human midazolam interaction a model pointed to hydrastine as the main cause. Oral goldenseal may also deliver very little berberine into the blood, so trial results for berberine tablets may not carry over to goldenseal.

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What the research shows

No randomised trial of goldenseal on its own for colds, infections, digestion or any other health use was found. Nothing about goldenseal itself is rated above "insufficient".

The benefit research that exists is on purified berberine. Pooled trials of berberine report lower blood sugar, cholesterol and liver enzymes, and add-on gains in H. pylori treatment and PCOS. The reviewers rate the trials as mixed or low quality, and the evidence here is low certainty at best. Human trials of goldenseal itself are almost all drug-interaction studies in healthy volunteers.

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At a glance

Traditional uses history, not proof

Native American use for wounds, digestive problems, skin and eye conditions (NCCIH, review)
Folk medicine for digestive and urinary complaints and for mouth, skin and eye infections (NTP report)
Traditional herbal use as a digestive bitter and mild laxative (Health Canada)
Used on the skin by nursing mothers for sore nipples (LactMed)

Studied for research

Colds and infections (goldenseal itself), insufficient (no human trial)
Digestive, skin, mouth and eye uses (goldenseal itself), insufficient (traditional only)
Immune and inflammation signals, insufficient (mouse cells only)
Infectious diarrhea and H. pylori, low certainty (purified berberine, not goldenseal)
Blood sugar, cholesterol, fatty liver and waist size, low certainty (purified berberine, not goldenseal)
Blood pressure, insufficient; PCOS, mixed (purified berberine, not goldenseal)

Main compounds

Berberine (a protoberberine alkaloid; 0.82% to 5.86% in 17 root products)
(-)-beta-Hydrastine (0% to 2.93%; likely the main cause of the midazolam interaction)
Canadine (tetrahydroberberine) and hydrastinine
Palmatine (marker for adulteration with Coptis and similar plants)

Common forms

Dried root and rhizome as powder, capsules, tincture or extract (products vary widely in alkaloid content)
Wash or poultice for skin and eyes in traditional use (not tested in trials)
Combination products with other herbs exist but were not evaluated here

Research links: NIH NCCIH: Goldenseal · Health Canada: Goldenseal natural health product monograph (oral) · US National Toxicology Program: Goldenseal root powder feed studies (TR-562) · NIH LactMed: Goldenseal · NIH LiverTox: Berberine · USDA Forest Service: Goldenseal annotated bibliography · Research Library · Genes & Biomarkers Library

The plant and its history

Accepted scientific name: Hydrastis canadensis
Naming authority: L.
Synonyms: Hydrastis trifolia Raf.; Warnera canadensis (L.) Mill.; Warnera diphylla Raf.; Warnera tinctoria Raf.; Warneria canadensis (L.) Mill.; Warneria diphylla Raf.; Warneria tinctoria Raf.
Common names: Goldenseal (en); Orangeroot (en); Yellow puccoon (en); Yellow root (en)
Botanical family: Ranunculaceae (buttercup family)
Classification: Plantae > Tracheophyta > Magnoliopsida > Ranunculales > Ranunculaceae > Hydrastis > Hydrastis canadensis
Native range: Eastern North America. NCCIH says northeastern United States and southeastern Canada; a 2025 paper describes it as native to eastern North America.
Habitat: Moist, rich hardwood forest. In Pennsylvania, the best habitat was forest on moist lower slopes with base-rich bedrock and loamy, slightly acidic to neutral soil (2025 habitat study).
What the plant looks like: Roots: Medicinal part is the root and rhizome (Health Canada source information). Colour and shape details were not read in the sources used.; Stems: Not read in the sources used.; Leaves: Not read in the sources used.; Flowers: Not read in the sources used.; Fruit: Not read in the sources used.
Cultivation: A 2005 USDA Forest Service bibliography says wild supplies are declining, so demand for cultivated roots has grown and propagation research is encouraged. Details not read.
Harvest and processing: Medicinal material is the dried root and rhizome. Not read in more detail.
Look-alikes and adulterants: Name: Other berberine-containing plants (Coptis species, barberry, Oregon grape); Note: These plants contain berberine too. Palmatine, coptisine and jatrorrhizine are alkaloids "native to Coptis spp. and other common goldenseal adulterants" per the analytical paper, and one supplier's goldenseal powder contained them, so it was not pure goldenseal.; Name: Unnamed non-goldenseal species and plant mixtures in commercial products; Note: Metabolomics found commercial "goldenseal" products that came from a non-goldenseal species or a mixture of plants. The abstracts do not name the plants.
Sustainability and conservation: Listed on CITES Appendix II (since 1997 per a USDA Forest Service bibliography; primary CITES record not read). Wild populations have been greatly reduced by harvesting for the herbal trade and habitat loss; a 2025 paper repeats that commercial harvest and habitat loss have led to international conservation concerns. Choose cultivated sources where possible.

Traditional use and history history, not clinical proof

Tradition or era	Documented use	Source
Native American tradition	Used as a coloring agent and as medicine for wounds, digestive disorders, ulcers, skin and eye ailments, and cancer.	Mandal et al. 2020 (PMID 32683037); NCCIH goldenseal page
Folk medicine (United States)	Used for gastrointestinal disturbances, urinary disorders, hemorrhage, and skin, mouth and eye infections and inflammation.	US National Toxicology Program Technical Report 562 abstract (PMID 21372858)
Herbal medicine (Health Canada traditional claims)	Traditionally used in herbal medicine for digestive troubles, as a bitter to aid digestion, and as a mild laxative.	Health Canada NHP monograph, 29 November 2024
Modern marketing (United States)	Sold for colds, upper respiratory infections, hay fever, diarrhea and constipation.	NCCIH (page updated Feb 2025)
Nursing mothers and drug testing	Used on the skin by nursing mothers for sore nipples; also used to try to mask illicit drugs in urine, which appears ineffective with modern laboratory methods.	LactMed goldenseal entry (2025-05-15)
Wikipedia-only or older books	Claims about 19th-century Eclectic medicine and the history of the name were not checked.	NOT verified: not read in any primary or authoritative source for this file

Traditional use shows how a plant was used. It does not show that a supplement works or is safe today.

What is inside, and how it may work

What the plant contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.

Main compounds

Compound	Family	Where it is concentrated	Activity studied	Level of evidence
Berberine PubChem 2353	Protoberberine isoquinoline alkaloid	root and rhizome 0.82% to 5.86% in 17 commercial root products (HPLC)	The best-studied compound. Germ-slowing in lab tests, lowers DNA-repair enzyme activity (topoisomerase) in cells, inhibits CYP2D6 and CYP3A4/5 in lab tests, lowers LDL by raising LDL receptors in liver cells, and displaces bilirubin from albumin in lab tests. ^{10 30 5 1 3}	Laboratory research
(-)-beta-Hydrastine PubChem 197835	Phthalide isoquinoline alkaloid	root and rhizome 0 to 2.93% in 17 commercial root products (HPLC)	Probably the main driver of the midazolam (CYP3A) interaction by time-dependent inhibition in the gut wall, per a modelling study. Inhibits CYP2C9, 2D6 and 3A4/5 in lab tests. Human peak blood level 225 ng/ml after a 2.7 g dose containing 78 mg hydrastine. ^{10 34 30 4 51}	Human data
Canadine (tetrahydroberberine) PubChem 34458	Protoberberine alkaloid	root and rhizome Not read	Raised LDL-receptor expression in liver cells and was resistant to MDR1 efflux, unlike berberine. PubChem lists CID 34458 under the title (+-)-tetrahydroberberine; the exact stereoisomer in goldenseal was not checked. ^{1 5}	Laboratory research
Hydrastinine PubChem 3638	Isoquinoline alkaloid (hydrastine breakdown product)	root and rhizome Not read	Inhibited CYP2D6 in human liver microsomes. A lesser alkaloid. ³⁰	Laboratory research
Palmatine PubChem 19009	Protoberberine alkaloid	root (also in Coptis and other plants) Not read	Caused DNA damage and blocked topoisomerase in human liver cells in the lab. Also a marker of adulteration: palmatine is native to Coptis species and other goldenseal adulterants. ^{5 45}	Laboratory research

Mechanisms, receptors and pathways

Target or pathway	Gene or receptor	What was found	Level
CYP2D6 inhibition	CYP2D6	Goldenseal supplements cut CYP2D6 activity by about 40% to 50% in volunteers; berberine and hydrastinine inhibit it in human liver microsomes. ^{12 14 30}	Human data
CYP3A inhibition in gut wall	CYP3A4/CYP3A5	Midazolam AUC and Cmax rose 40% to 60%; half-life changed little, pointing to gut-wall inhibition mostly by hydrastine. Berberine behaves differently on the two enzymes (inhibits CYP3A4, activates CYP3A5 in the lab). ^{15 34 30}	Human data
Metabolic-intermediate complex formation	CYP2C9, CYP2D6, CYP3A4	Hydrastine formed complexes that lock the enzymes in an inactive state in lab tests. ⁴	Lab
Intestinal uptake transport of metformin	Gut uptake transporters (saturable)	Goldenseal lowered metformin AUC with no change in half-life or kidney clearance, pointing to reduced absorption. ^{33 35}	Human data
P-glycoprotein (digoxin)	ABCB1 / P-gp	Goldenseal was not a potent P-gp modulator in volunteers (digoxin Cmax +14% only). ¹³	Human data
LDL receptor up-regulation	LDLR	Goldenseal root extract raised LDLR expression in liver cells and lowered cholesterol in hamsters, more than pure berberine; canadine contributes. ¹	Animal research
Topoisomerase II inhibition and DNA damage	TOP2	Berberine blocked topoisomerase II and caused DNA damage in human liver cells; proposed link to rodent liver tumours. ^{5 9}	Lab
Macrophage cytokine reduction	TNF, IL6, IL10, IL12	Goldenseal lowered four cytokines in toxin-stimulated mouse macrophages. ⁶	Lab
Antifungal activity	Not identified	Root ethanol extract slowed growth of three fungi from diseased American ginseng; this is a plant-disease study, not a human infection study. ¹¹	Lab
Bilirubin displacement from albumin	Serum albumin	Berberine displaced bilirubin about tenfold more strongly than phenylbutazone (molar basis) in the lab and raised free bilirubin in adult rats. ³	Lab

Absorption, metabolism and elimination

Absorption: Oral berberine is poorly absorbed (bioavailability under 1% in the review; low in humans). NCCIH says oral goldenseal may absorb very little berberine. Hydrastine reached a peak of 225 +/- 100 ng/ml about 1.5 hours after a 2.7 g supplement dose (78 mg hydrastine) in 11 volunteers.
Distribution: For berberine the liver is the main site of distribution (review).
Metabolism: Hydrastine is broken down rapidly and extensively, by reduction, demethylation, hydroxylation and conjugation (glucuronide and sulfate). Some metabolites may be active. Berberine is demethylenated, reduced, then glucuronidated, sulfated and methylated; CYP2D6 matters for berberine metabolism in women but not men.
Elimination: Hydrastine half-life 4.8 +/- 1.4 hours. For berberine, faecal excretion (11% to 23%) exceeds urine or bile, though a major metabolite goes mostly in urine.
Bioavailability: Berberine under 1% (review); females had a 2.8-fold higher berberine AUC and 3.6-fold higher Cmax than males in one study.

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Isolated compounds versus whole extracts

Goldenseal is not just berberine. In hamsters, a goldenseal root extract lowered cholesterol more than pure berberine, and canadine and other compounds contributed. In the human midazolam interaction, a model implicated hydrastine more than berberine. For safety, the rodent liver tumours were found with whole goldenseal root powder, and a cell study ties DNA damage to berberine content. Meanwhile, almost all the human benefit trials (blood sugar, lipids, PCOS) used purified berberine, and the purified-berberine cyclosporine trial cannot be assumed to give the same size effect for goldenseal. NCCIH warns berberine results may not apply to oral goldenseal because it may absorb little berberine.

Nutritional composition

No vitamin or mineral role for goldenseal was found in the sources read. It is used for its alkaloids, not as a food. Not added to the nutrient graph.

13benefits and uses looked at

55studies and sources checked

Low certaintybest evidence rating found

13lab markers tracked in trials

1 mixed findings6 low certainty6 not enough evidence

What was looked at

The 13 benefits and uses checked for Goldenseal, each with how strong the evidence is. Tap one to open it.

Colds, flu and other infections (goldenseal itself)Not enough evidence
Digestive complaints (goldenseal itself)Not enough evidence
Wounds, skin, mouth and eye uses (goldenseal itself)Not enough evidence
Immune and inflammation signals (lab only)Not enough evidence
Infectious diarrhea (berberine alone)Low certainty
Stomach infection with H. pylori (berberine added to antibiotics)Low certainty
Blood sugar in type 2 diabetes (berberine alone)Low certainty
Cholesterol and blood fats (berberine alone)Low certainty
Cholesterol (goldenseal root extract, animal and cell work)Not enough evidence
Blood pressure (berberine alone)Not enough evidence
Fatty liver (berberine alone)Low certainty
Polycystic ovary syndrome (berberine alone or as add-on)Mixed findings
Waist size and body weight (berberine alone)Low certainty

Lab markers tracked in the studies

Stool volume in acute diarrheaH. pylori eradication rateInflammation signals in mouse immune cells (TNF-alpha, IL-6, IL-10, IL-12)Fasting blood glucoseHbA1cLDL cholesterolTriglyceridesTotal cholesterolHDL cholesterolALT and AST (liver enzymes)Total testosterone (in PCOS)Waist circumferenceSystolic blood pressure

What is Goldenseal good for?

The main proposed uses and how strong the human evidence is for each. "Low" means small or inconsistent studies, and "insufficient" means there is not enough to judge. Nothing about goldenseal itself is rated above "insufficient". Rows marked "berberine" describe purified berberine, which is one compound in goldenseal, and do not show that goldenseal works. Goldenseal is also advised against in pregnancy and breastfeeding. Ask a doctor or pharmacist about amounts and products.

Colds, flu and other infections (goldenseal itself)Not enough evidenceGoldenseal is sold for colds and infections, but no good human trial shows it works. NCCIH says there is not enough evidence for any health condition. The only support is traditional use and lab-dish work, such as a study showing a root extract slowed three plant-disease fungi. Digestive complaints (goldenseal itself)Not enough evidenceTraditional herbal medicine used goldenseal for digestion, and Health Canada lists those traditional uses. No human trial of goldenseal for any digestive problem was found. Wounds, skin, mouth and eye uses (goldenseal itself)Not enough evidenceFolk medicine used goldenseal on wounds and on skin, mouth and eye problems. No trial was found. Do not put products in the eyes unless a doctor says so. Immune and inflammation signals (lab only)Not enough evidenceIn mouse immune cells in a dish, goldenseal lowered four inflammation signals. There is no animal or human study behind this, so it is not a health benefit yet. Infectious diarrhea (berberine alone)Low certaintyOne 1987 trial in 165 adults found a single dose of purified berberine cut watery diarrhea from E. coli (42% had stopped by 24 hours versus 20%). The effect in cholera was slight. This is berberine on its own, not goldenseal. Stomach infection with H. pylori (berberine added to antibiotics)Low certaintyIn trials from China, adding berberine to standard antibiotics raised the clearance rate (about 22% higher chance in one review) and cut side effects. This is berberine plus antibiotics, not goldenseal. Antibiotic treatment must be guided by a doctor. Blood sugar in type 2 diabetes (berberine alone)Low certaintyPooled trials of purified berberine found lower fasting glucose (0.82 mmol/L), HbA1c (0.63 percentage points) and after-meal glucose. Trial quality is mixed. Goldenseal itself has not been shown to do this, and it can lower metformin levels. Cholesterol and blood fats (berberine alone)Low certaintyPooled trials of purified berberine found lower LDL, total cholesterol and triglycerides. The reviewers describe low methodological quality. None measured heart attacks or strokes. Cholesterol (goldenseal extract, animal and cell work)Not enough evidenceA goldenseal root extract lowered cholesterol in hamsters more than pure berberine did. No human test of goldenseal for cholesterol was found. Blood pressure (berberine alone)Not enough evidenceEvidence that berberine lowers blood pressure is limited and inconclusive; a placebo-controlled pooled analysis found no clear effect. Goldenseal was not tested. Fatty liver (berberine alone)Low certaintyA 2024 pooled analysis of 10 small trials found berberine lowered liver enzymes and blood fats in fatty liver disease. This does not cancel the liver tumours seen in rodents fed whole goldenseal root. Polycystic ovary syndrome (berberine alone or as add-on)Mixed findingsReviews found berberine lowered testosterone in women with PCOS, but live birth was not clearly improved. One review found higher pregnancy rates as an add-on. Goldenseal is advised against in pregnancy. Waist size and body weight (berberine alone)Low certaintyPooled placebo-controlled trials found a small fall in waist size (about 3 cm) and BMI with berberine.

Benefits, one by one

Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.

Colds, flu and other infections (goldenseal itself)

Not enough evidence

Goldenseal is widely sold for colds and infections, but no good human trial shows it helps. The only support is traditional use and lab work.

3 studiesRoot and rhizome as powder, tincture, extract or capsule; products va…

Studies, doses and limits

What the trials found

No randomised trial of goldenseal itself was found for this use. NCCIH states there is not enough evidence to say whether goldenseal helps any health condition and that no rigorous human studies have looked at it. A 2020 critical review of goldenseal listed antimicrobial effects among many lab-based findings and called for large randomised trials. Oral goldenseal may deliver very little berberine into the blood, so berberine results may not carry over (NCCIH).

Results

No human efficacy results exist. Lab only: goldenseal root ethanol extract at 2% slowed growth of three plant-disease fungi by 86.0%, 94.9% and 39.1%.

Why this rating

No human trial of goldenseal alone for colds or infections was found. The lab results are not about human infections.

Form and dose studied

Root and rhizome as powder, tincture, extract or capsule; products vary widely in berberine and hydrastine content.

Who was studied

Adults (traditional use)

Limits

The one pointer is traditional use. Lab results cannot be assumed to work inside the body, because goldenseal alkaloids are poorly absorbed.

Why researchers looked

Goldenseal root is one of the best-known American herbs sold for colds, sore throats and infections. Its alkaloids (berberine, hydrastine) kill or slow some germs in lab dishes.

Traditional use

Native American peoples used goldenseal for many ailments including wounds, digestive problems, skin and eye conditions. In the United States today it is marketed for colds and upper respiratory infections.

Proposed mechanism Laboratory research

Lab tests show goldenseal alkaloids can slow some bacteria and fungi in a dish. One new lab study showed a goldenseal root extract slowed three fungi from sick American ginseng plants. These are petri-dish results and do not show that goldenseal treats infections in people.

A proposed mechanism does not show that the effect happens in people.

Goldenseal can change how the body handles many medicines (see the Safety tab). It should not be used in pregnancy or breastfeeding, or given to infants.

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Digestive complaints (goldenseal itself)

Not enough evidence

Goldenseal has a long traditional use for upset stomach and gut infections, but there is no good human trial of goldenseal for any digestive problem.

3 studiesDried root and rhizome in powders, extracts and tinctures.

Studies, doses and limits

What the trials found

No randomised trial of goldenseal itself was found for this use. The 2020 critical review lists gastrointestinal protective effects among lab findings only.

Results

No human efficacy results for goldenseal.

Why this rating

Traditional use only; no human trial of goldenseal found.

Form and dose studied

Dried root and rhizome in powders, extracts and tinctures.

Who was studied

Adults (traditional use)

Limits

Traditional claims are not proof. Quality varies between products.

Why researchers looked

Health Canada's monograph lists traditional herbal-medicine use of goldenseal as a bitter to aid digestion and as a mild laxative.

Traditional use

Health Canada lists traditional herbal-medicine uses for digestive troubles. NCCIH says today it is marketed for diarrhea and constipation, among other things.

Proposed mechanism Pharmacological theory

Not established for goldenseal. Berberine, one of its main alkaloids, has been studied for gut infections (see the separate entries for berberine alone).

A proposed mechanism does not show that the effect happens in people.

Berberine-containing herbs can cause gut side effects such as constipation or diarrhea (umbrella review of berberine).

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Wounds, skin, mouth and eye uses (goldenseal itself)

Not enough evidence

Goldenseal has been used on wounds, skin, mouth and eyes in folk medicine. No trial of goldenseal for these uses was found.

3 studiesWashes, poultices and powders (traditional).

Studies, doses and limits

What the trials found

No randomised trial of goldenseal itself was found for this use. (The review of goldenseal alkaloids also mentions possible light-related toxicity in lab studies.)

Results

No human efficacy results.

Why this rating

Traditional use only; no human trial found.

Form and dose studied

Washes, poultices and powders (traditional).

Who was studied

Adults (traditional use)

Limits

No trial data. Putting a berberine-rich product on broken skin or eyes has not been shown safe or effective.

Why researchers looked

Traditional medicine used goldenseal for wounds, skin and eye ailments; the NTP report describes folk use for mouth, skin and eye infections.

Traditional use

NCCIH and the 2020 critical review both describe wound, skin and eye uses in traditional medicine.

Proposed mechanism Laboratory research

Lab studies show the alkaloids are germ-slowing in a dish and may react to light (phototoxic in test systems). Neither shows a skin benefit in people.

A proposed mechanism does not show that the effect happens in people.

Lab studies report light sensitivity of goldenseal alkaloids (review). Avoid putting products in the eyes unless a doctor advises.

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Immune and inflammation signals (lab only)

Not enough evidence

In mouse cells, goldenseal dampened inflammation signals. This has not been tested in people.

1 studiesTwo commercial goldenseal preparations (details not in the abstract).

Studies, doses and limits

What the trials found

No human study. The only study found used two commercial goldenseal preparations on mouse cells (J774A.1). Goldenseal did little to resting cells.

Results

Lab cells only: reduced four cytokines in stimulated mouse macrophages.

Effect sizes as reported

Dose-dependent reductions in TNF-alpha, IL-6, IL-10 and IL-12 (in mouse cells).

Why this rating

Mouse cells in a dish; no animal or human data in this file.

Form and dose studied

Two commercial goldenseal preparations (details not in the abstract).

Limits

Cell findings often do not carry over to people.

Why researchers looked

Goldenseal is called an immune stimulant. A lab study asked what it actually does to immune cells.

Traditional use

The lab paper describes goldenseal as a Native American plant used as an immune stimulant.

Proposed mechanism Laboratory research

In mouse macrophages stimulated with a bacterial toxin, goldenseal lowered TNF-alpha, IL-6, IL-10 and IL-12 in a dose-related way. The authors suggest this may limit symptoms indirectly. This is a cell-dish finding.

A proposed mechanism does not show that the effect happens in people.

No safety information from this study.

⁶

Infectious diarrhea (berberine alone)

Low certainty

An old trial of purified berberine found it reduced watery diarrhea from E. coli in adults, with little effect on cholera. This is berberine, not goldenseal.

2 studiesBerberine sulfate, a purified alkaloid, at doses used in the trial (s…

Studies, doses and limits

What the trials found

Important: this result is for berberine on its own (a purified compound), not for goldenseal root. Goldenseal contains berberine, but a goldenseal product has other compounds, and the amount of berberine varies between products. In a 1987 randomised trial of 165 adults with acute diarrhea from enterotoxigenic E. coli (ETEC) or cholera, a single dose of berberine sulfate cut stool volume in ETEC diarrhea in all three 8-hour periods (P under .05); 42% of treated ETEC patients had stopped by 24 hours versus 20% of controls. In cholera the effect was slight (2.22 versus 2.79 litres in the second 8 hours), and berberine plus tetracycline did no better than tetracycline alone. No side effects were noted.

Results

Fewer watery stools in ETEC diarrhea; slight effect in cholera, not additive to an antibiotic.

Effect sizes as reported

ETEC diarrhea stopped at 24 h: 42% vs 20% (P<.05). Cholera 8-hour stool volume 2.22 vs 2.79 L (P<.05).

Why this rating

A single old trial with short follow-up, in a setting different from most readers' lives; the abstract does not give trial quality.

Form and dose studied

Berberine sulfate, a purified alkaloid, at doses used in the trial (see the abstract).

Who was studied

Adults with acute watery diarrhea from ETEC or cholera

Limits

One trial; berberine alone, not goldenseal; short follow-up. Modern oral rehydration remains the standard care for watery diarrhea.

Why researchers looked

Berberine slows fluid loss from the gut in lab work, so it was tested in diarrhea caused by bacterial toxins.

Traditional use

Not documented in the sources read.

Proposed mechanism Pharmacological theory

Berberine is thought to reduce the gut secretion triggered by bacterial toxins (the trial title calls it an antisecretory drug). The abstract does not give a proven mechanism.

A proposed mechanism does not show that the effect happens in people.

No side effects were noted in the trial. Berberine can cause constipation or diarrhea in other settings.

^{40 25}

Stomach infection with H. pylori (berberine added to antibiotics)

Low certainty

In trials from China, adding berberine to standard antibiotic treatment raised the chance of clearing H. pylori and cut side effects. This is berberine plus antibiotics, not goldenseal and not berberine alone.

3 studiesBerberine alone in an add-on regimen.

Studies, doses and limits

What the trials found

Important: this result is for berberine on its own (a purified compound), not for goldenseal root. Goldenseal contains berberine, but a goldenseal product has other compounds, and the amount of berberine varies between products. Two meta-analyses of randomised trials found adding berberine to triple therapy raised eradication: RR 1.22 (95% CI 1.16 to 1.27; 13 articles) in the first, and RR 1.18 (1.12 to 1.24) by breath test and 1.23 (1.13 to 1.34) by biopsy in the second. Side effects were also lower (RR 0.65 and OR 0.59). An umbrella review of berberine also lists H. pylori infection among outcomes affected. The authors of the second review still call for better-designed trials.

Results

Higher eradication rates and fewer side effects when berberine was added to standard triple therapy.

Effect sizes as reported

Eradication RR 1.22 (1.16 to 1.27); RR 1.18 (1.12 to 1.24) breath test; RR 1.23 (1.13 to 1.34) biopsy.

Why this rating

Trials were from China, berberine was an add-on to antibiotics, and the authors of the reviews call for better-designed trials. No GRADE rating is given in the abstracts.

Form and dose studied

Berberine alone in an add-on regimen.

Who was studied

Adults with H. pylori infection, in China

Limits

Does not show that goldenseal helps H. pylori. Antibiotic treatment is needed; berberine alone was not tested for eradication in these reviews.

Why researchers looked

H. pylori causes stomach ulcers. Berberine is a germ-slowing alkaloid so it has been added to treatment regimens.

Traditional use

The 2019 meta-analysis describes berberine-containing quadruple therapy as being used in China.

Proposed mechanism Preliminary mechanism

Berberine slows H. pylori in lab dishes; how much this explains the trial results is not established.

A proposed mechanism does not show that the effect happens in people.

Berberine can interact with some medicines (see Safety tab). Treatment should be directed by a doctor.

^{20 22 25}

Blood sugar in type 2 diabetes (berberine alone)

Low certainty

Pooled trials of purified berberine found lower blood sugar in people with type 2 diabetes. No trial of goldenseal has shown this.

4 studiesBerberine tablets or capsules, alone or with diabetes drugs; amounts …

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. A 2022 meta-analysis of 37 randomised trials (3,048 people with type 2 diabetes) found berberine lowered fasting glucose by 0.82 mmol/L (95% CI -0.95 to -0.70), HbA1c by 0.63 percentage points (-0.72 to -0.53) and 2-hour glucose by 1.16 mmol/L (-1.36 to -0.96), without more total adverse events or significantly more hypoglycemia (RR 0.48, 0.21 to 1.08). A 2015 meta-analysis of 27 trials reached a similar direction, but berberine alone was not clearly different from standard diabetes drugs. A 2025 meta-analysis of placebo-controlled trials in metabolic syndrome found fasting glucose fell 0.515 mmol/L (-0.847 to -0.183). An umbrella review lists glucose and insulin resistance among significantly affected outcomes.

Results

Lower fasting glucose, HbA1c and after-meal glucose in pooled trials.

Effect sizes as reported

FPG WMD -0.82 mmol/L; HbA1c WMD -0.63%; 2hPBG WMD -1.16 mmol/L (37 trials); MetS FPG WMD -0.515 mmol/L.

Why this rating

Most trials are from China with mixed quality; reviewers ask for better trials. The abstracts do not give GRADE ratings. Not tested with goldenseal.

Form and dose studied

Berberine tablets or capsules, alone or with diabetes drugs; amounts vary between trials.

Who was studied

Adults with type 2 diabetes or metabolic syndrome

Limits

Does not show goldenseal lowers blood sugar. Goldenseal can lower metformin levels in the blood (see Safety tab).

Why researchers looked

Berberine is one of the most-studied plant compounds for blood sugar, mostly in China.

Traditional use

The 2015 meta-analysis describes berberine as frequently used in China as an extra treatment for type 2 diabetes, high blood fats and high blood pressure. Goldenseal is sold in supplements with similar claims (NCCIH lists other uses).

Proposed mechanism Preliminary mechanism

Lab work suggests berberine may increase insulin release only when sugar is high, and improve insulin sensitivity. The reviews do not prove which mechanism explains the trial results.

A proposed mechanism does not show that the effect happens in people.

Berberine may add to the effect of diabetes drugs; goldenseal lowered metformin blood levels by about 23% in healthy adults (ratio 0.77). People on diabetes medicine should ask a doctor before adding either.

^{48 24 27 25}

Cholesterol and blood fats (berberine alone)

Low certainty

Pooled trials of purified berberine found lower LDL, total cholesterol and triglycerides. Goldenseal has only been tested for this in animals.

4 studiesBerberine capsules or tablets; amounts vary between trials.

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. A 2018 meta-analysis of 16 randomised trials (2,147 people) found total cholesterol fell 0.47 mmol/L (95% CI -0.64 to -0.31), LDL-C 0.38 mmol/L (-0.53 to -0.22) and triglycerides 0.28 mmol/L (-0.46 to -0.10), with a small HDL-C rise of 0.08 mmol/L when berberine was used alone, and no significant difference in adverse events. The authors rated the trials high in clinical variation and low in methodological quality. The 2025 placebo-controlled meta-analysis found triglycerides -0.367 mmol/L, LDL-C -0.495 mmol/L and total cholesterol -0.451 mmol/L, with no significant effect on HDL-C.

Results

Lower LDL, total cholesterol and triglycerides in pooled trials; HDL-C result mixed.

Effect sizes as reported

TC MD -0.47; LDL-C -0.38; TG -0.28 mmol/L (2018); TG -0.367; LDL-C -0.495; TC -0.451 mmol/L (2025).

Why this rating

The 2018 reviewers describe high heterogeneity and low methodological quality of the included trials; the 2025 review notes the need for better randomised trials.

Form and dose studied

Berberine capsules or tablets; amounts vary between trials.

Who was studied

Adults with raised blood fats or metabolic syndrome

Limits

Lower cholesterol is a marker, not proof of fewer heart attacks; none of these trials measured heart events.

Why researchers looked

Berberine raises the number of LDL receptors in liver cells, which helps clear LDL cholesterol from the blood.

Traditional use

The 2018 review calls berberine widely used in China as an alternative treatment for high blood fats.

Proposed mechanism Laboratory research

In lab work, berberine stabilises the messenger RNA for the liver LDL receptor so liver cells clear more LDL.

A proposed mechanism does not show that the effect happens in people.

Not applicable to goldenseal; see Safety tab for medicine interactions.

^{23 27 24 25}

Cholesterol (goldenseal root extract, animal and cell work)

Not enough evidence

In hamsters and liver cells, a goldenseal root extract lowered cholesterol more than pure berberine. No human test was found.

2 studiesGoldenseal root extract (animal doses).

Studies, doses and limits

What the trials found

Cell and hamster study only (2006). The goldenseal root extract lowered plasma cholesterol and LDL-C in high-cholesterol hamsters and was reported as more active than pure berberine.

Results

Lower cholesterol in hamsters; no human results.

Effect sizes as reported

Reported as greater than pure berberine; numbers not in the abstract.

Why this rating

Cells and hamsters only. No human trial of goldenseal for cholesterol was found.

Form and dose studied

Goldenseal root extract (animal doses).

Who was studied

Hamsters and liver cells

Limits

Animal results often do not carry over to people.

Why researchers looked

A research group asked whether goldenseal, which contains berberine plus other alkaloids, beats pure berberine.

Traditional use

Not a traditional use.

Proposed mechanism Laboratory research

The extract raised liver LDL-receptor expression in HepG2 cells. The authors identified canadine and two other compounds as further LDL-receptor boosters and found goldenseal seems to contain natural blockers of a drug-pumping protein (MDR1), which let berberine work better.

A proposed mechanism does not show that the effect happens in people.

Not applicable.

^{1 29}

Blood pressure (berberine alone)

Not enough evidence

The evidence that berberine lowers blood pressure is limited and inconclusive. Nothing was found for goldenseal itself.

3 studiesBerberine alone or in mixtures.

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. A 2021 systematic review of 5 randomised and 2 non-randomised trials (614 people) found berberine plus amlodipine was not better than amlodipine alone; berberine beat metformin on systolic pressure by 11.87 mmHg (95% CI -16.64 to -7.10). Two multi-ingredient products lowered blood pressure but not clearly because of berberine. The reviewers call the evidence limited, low quality and inconclusive. A 2025 placebo-controlled meta-analysis found no significant effect on systolic or diastolic blood pressure. A 2015 meta-analysis said berberine with lifestyle change or drugs tended to lower pressure more than those alone.

Results

Mixed and inconclusive; the placebo-controlled pool found no effect.

Effect sizes as reported

SBP -11.87 mmHg vs metformin (CI -16.64 to -7.10); no significant effect vs placebo in the 2025 meta-analysis.

Why this rating

Highly varied trials, low quality, no heart events measured.

Form and dose studied

Berberine alone or in mixtures.

Who was studied

Adults with high blood pressure or metabolic syndrome

Limits

Goldenseal was not tested for blood pressure. Health Canada advises people with a blood pressure or kidney disorder to ask a health professional first.

Why researchers looked

Berberine is sold for heart and blood-pressure health, and some trials measured blood pressure.

Traditional use

Berberine herbs are used for heart and blood-vessel conditions in Chinese medicine.

Proposed mechanism Pharmacological theory

Not established.

A proposed mechanism does not show that the effect happens in people.

Berberine may add to blood-pressure drugs; do not stop or change blood-pressure medicine without a doctor.

^{43 27 24}

Fatty liver (berberine alone)

Low certainty

A pooled analysis of 10 small trials found berberine lowered liver enzymes and blood fats in non-alcoholic fatty liver disease. It is not a goldenseal result.

1 studiesBerberine, various amounts.

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. A 2024 meta-analysis of 10 randomised trials (811 people) found berberine lowered ALT (SMD -0.72, 95% CI -1.01 to -0.44), AST (SMD -0.79, -1.17 to -0.40), GGT, triglycerides, total cholesterol, LDL-C, insulin resistance (HOMA-IR) and BMI. HDL-C did not change significantly. Only mild gut side effects were reported. The review calls berberine a possible add-on treatment.

Results

Liver enzymes, blood fats, insulin resistance and BMI improved in pooled small trials.

Effect sizes as reported

ALT SMD -0.72; AST SMD -0.79; GGT SMD -0.62; HOMA-IR SMD -1.56.

Why this rating

Small trials from the same region; the abstract does not give quality ratings. Liver enzymes are markers, not liver outcomes.

Form and dose studied

Berberine, various amounts.

Who was studied

Adults with non-alcoholic fatty liver disease

Limits

Berberine alone. A separate safety note: whole goldenseal root caused liver tumours in rodents (see Safety tab).

Why researchers looked

Fatty liver goes with insulin resistance and high blood fats, which berberine is studied for.

Traditional use

Not a traditional use.

Proposed mechanism Pharmacological theory

Not established.

A proposed mechanism does not show that the effect happens in people.

This benefit result does not cancel the animal liver findings for goldenseal root.

³⁶

Polycystic ovary syndrome (berberine alone or as add-on)

Mixed findings

Reviews of trials in women with PCOS found berberine lowered testosterone and improved insulin resistance, but live birth was not clearly improved.

2 studiesBerberine, alone or added to drugs.

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. A 2019 meta-analysis of 12 randomised trials found no solid evidence berberine improved live birth; it was lower than with letrozole (RR 0.61, 0.44 to 0.82). Berberine lowered total testosterone (MD -0.34, -0.47 to -0.20) and the LH/FSH ratio (MD -0.44, -0.68 to -0.21) versus placebo or no treatment, and total cholesterol and waist versus metformin. A 2024 meta-analysis of 10 trials (713 women) found berberine added to Western medicine raised ovulation (RR 1.41, 1.26 to 1.60) and clinical pregnancy (RR 1.96, 1.59 to 2.41). Goldenseal products are advised against in pregnancy by NCCIH and Health Canada (see the Safety tab), so any use for fertility should be supervised by a doctor.

Results

Lower androgens and better insulin markers; live birth not clearly better; add-on trials show higher pregnancy rates.

Effect sizes as reported

Total testosterone MD -0.34 (-0.47 to -0.20); clinical pregnancy RR 1.96 (1.59 to 2.41) as add-on; live birth vs letrozole RR 0.61.

Why this rating

The two reviews disagree on fertility outcomes: one found no evidence for live birth, one found higher pregnancy rates as an add-on. Many trials are from China.

Form and dose studied

Berberine, alone or added to drugs.

Who was studied

Women with PCOS

Limits

Berberine alone. NCCIH and Health Canada advise against goldenseal in pregnancy.

Why researchers looked

PCOS goes with insulin resistance and high androgens, so berberine has been tested as a metformin-like option.

Traditional use

Not a traditional use.

Proposed mechanism Pharmacological theory

Not established; possibly through insulin sensitivity.

A proposed mechanism does not show that the effect happens in people.

Pregnancy and newborn warnings apply (see Safety tab).

^{16 47}

Waist size and body weight (berberine alone)

Low certainty

Pooled placebo-controlled trials found a small drop in waist size and BMI with berberine.

3 studiesBerberine capsules.

Studies, doses and limits

What the trials found

Important: this is berberine on its own, not goldenseal root. The 2025 meta-analysis of placebo-controlled trials found waist circumference fell 3.27 cm (95% CI -4.818 to -1.722) and BMI fell 0.435 kg/m2 (-0.856 to -0.013). In PCOS, waist fell versus metformin but BMI did not (MD -0.03, -0.46 to 0.39). An umbrella review lists body measures among affected outcomes.

Results

Small drop in waist size and BMI.

Effect sizes as reported

Waist WMD -3.270 cm; BMI WMD -0.435 kg/m2.

Why this rating

BMI change is small and borderline; the abstracts give no quality ratings.

Form and dose studied

Berberine capsules.

Who was studied

Adults with metabolic syndrome features

Limits

Not a goldenseal result.

Why researchers looked

Berberine is marketed for weight loss, so reviews checked waist and BMI.

Traditional use

Not a traditional use.

Proposed mechanism Pharmacological theory

Not established.

A proposed mechanism does not show that the effect happens in people.

See Safety tab.

^{27 47 25}

Connections to the rest of health

How Goldenseal connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.

Explore every connection: goals, body systems, organs, symptoms, genes

Kind of connection Connected to Search

A. Wellness goals

Connected to	Kind of connection	Evidence status	Context	Studies
Immune Support	Traditional use	Not enough evidence	Colds, flu and other infections (goldenseal itself): Goldenseal is widely sold for colds and infections, but no good human trial shows it helps. The only support is traditional use and lab work.	^{31 29 11}
Digestive Support	Traditional use	Not enough evidence	Digestive complaints (goldenseal itself): Goldenseal has a long traditional use for upset stomach and gut infections, but there is no good human trial of goldenseal for any digestive problem.	^{31 17 29}
Gut Health	Traditional use	Not enough evidence	Digestive complaints (goldenseal itself): Goldenseal has a long traditional use for upset stomach and gut infections, but there is no good human trial of goldenseal for any digestive problem.	^{31 17 29}
Healthy Skin	Traditional use	Not enough evidence	Wounds, skin, mouth and eye uses (goldenseal itself): Goldenseal has been used on wounds, skin, mouth and eyes in folk medicine. No trial of goldenseal for these uses was found.	^{31 29 32}
Inflammation Balance	Preliminary mechanism	Not enough evidence	Immune and inflammation signals (lab only): In mouse cells, goldenseal dampened inflammation signals. This has not been tested in people.	⁶
Immune Support	Preliminary mechanism	Not enough evidence	Immune and inflammation signals (lab only): In mouse cells, goldenseal dampened inflammation signals. This has not been tested in people.	⁶
Digestive Support	Potential benefit	Low certainty	Infectious diarrhea (berberine alone): An old trial of purified berberine found it reduced watery diarrhea from E. coli in adults, with little effect on cholera. This is berberine, not goldenseal. Stomach infection with H. pylori (berberine added to antibiotics): In trials from China, adding berberine to standard antibiotic treatment raised the chance of clearing H. pylori and cut side effects. This is berberine plus antibiotics, not goldenseal and not berberine alone.	^{40 25 20 22}
Gut Health	Potential benefit	Low certainty	Infectious diarrhea (berberine alone): An old trial of purified berberine found it reduced watery diarrhea from E. coli in adults, with little effect on cholera. This is berberine, not goldenseal. Stomach infection with H. pylori (berberine added to antibiotics): In trials from China, adding berberine to standard antibiotic treatment raised the chance of clearing H. pylori and cut side effects. This is berberine plus antibiotics, not goldenseal and not berberine alone.	^{40 25 20 22}
Blood Sugar Balance	Demonstrated clinical effect	Low certainty	Blood sugar in type 2 diabetes (berberine alone): Pooled trials of purified berberine found lower blood sugar in people with type 2 diabetes. No trial of goldenseal has shown this.	^{48 24 27 25}
Metabolic Health	Demonstrated clinical effect	Low certainty	Blood sugar in type 2 diabetes (berberine alone): Pooled trials of purified berberine found lower blood sugar in people with type 2 diabetes. No trial of goldenseal has shown this.	^{48 24 27 25}
Cholesterol Balance	Demonstrated clinical effect	Low certainty	Cholesterol and blood fats (berberine alone): Pooled trials of purified berberine found lower LDL, total cholesterol and triglycerides. Goldenseal has only been tested for this in animals.	^{23 27 24 25}
Heart Health	Demonstrated clinical effect	Low certainty	Cholesterol and blood fats (berberine alone): Pooled trials of purified berberine found lower LDL, total cholesterol and triglycerides. Goldenseal has only been tested for this in animals.	^{23 27 24 25}
Cholesterol Balance	Preliminary mechanism	Not enough evidence	Cholesterol (goldenseal root extract, animal and cell work): In hamsters and liver cells, a goldenseal root extract lowered cholesterol more than pure berberine. No human test was found.	^{1 29}
Blood Pressure Support	Potential benefit	Not enough evidence	Blood pressure (berberine alone): The evidence that berberine lowers blood pressure is limited and inconclusive. Nothing was found for goldenseal itself.	^{43 27 24}
Heart Health	Potential benefit	Not enough evidence	Blood pressure (berberine alone): The evidence that berberine lowers blood pressure is limited and inconclusive. Nothing was found for goldenseal itself.	^{43 27 24}
Liver Support	Potential benefit	Low certainty	Fatty liver (berberine alone): A pooled analysis of 10 small trials found berberine lowered liver enzymes and blood fats in non-alcoholic fatty liver disease. It is not a goldenseal result.	³⁶
Metabolic Health	Potential benefit	Low certainty	Fatty liver (berberine alone): A pooled analysis of 10 small trials found berberine lowered liver enzymes and blood fats in non-alcoholic fatty liver disease. It is not a goldenseal result. Waist size and body weight (berberine alone): Pooled placebo-controlled trials found a small drop in waist size and BMI with berberine.	^{36 27 47 25}
Womens Wellness	Potential benefit	Mixed findings	Polycystic ovary syndrome (berberine alone or as add-on): Reviews of trials in women with PCOS found berberine lowered testosterone and improved insulin resistance, but live birth was not clearly improved.	^{16 47}
Hormone Balance	Potential benefit	Mixed findings	Polycystic ovary syndrome (berberine alone or as add-on): Reviews of trials in women with PCOS found berberine lowered testosterone and improved insulin resistance, but live birth was not clearly improved.	^{16 47}
Fertility Support	Potential benefit	Mixed findings	Polycystic ovary syndrome (berberine alone or as add-on): Reviews of trials in women with PCOS found berberine lowered testosterone and improved insulin resistance, but live birth was not clearly improved.	^{16 47}
Weight Management	Potential benefit	Low certainty	Waist size and body weight (berberine alone): Pooled placebo-controlled trials found a small drop in waist size and BMI with berberine.	^{27 47 25}

B. Body systems

Connected to	Kind of connection	Evidence status	Context	Studies
Immune System	Biological association	Not enough evidence	Studied for: Colds, flu and other infections (goldenseal itself) Studied for: Immune and inflammation signals (lab only)	^{31 29 11 6}
Respiratory System	Biological association	Not enough evidence	Studied for: Colds, flu and other infections (goldenseal itself)	^{31 29 11}
Digestive System	Biological association	Not enough evidence	Studied for: Digestive complaints (goldenseal itself) Studied for: Infectious diarrhea (berberine alone)	^{31 17 29 40 25 20 22}
Integumentary System	Biological association	Not enough evidence	Studied for: Wounds, skin, mouth and eye uses (goldenseal itself)	^{31 29 32}
Endocrine System	Biological association	Low certainty	Studied for: Blood sugar in type 2 diabetes (berberine alone) Studied for: Polycystic ovary syndrome (berberine alone or as add-on)	^{48 24 27 25 16 47}
Metabolism Weight	Biological association	Low certainty	Studied for: Blood sugar in type 2 diabetes (berberine alone) Studied for: Cholesterol and blood fats (berberine alone)	^{48 24 27 25 23 36 47}
Cardiovascular System	Biological association	Low certainty	Studied for: Cholesterol and blood fats (berberine alone) Studied for: Cholesterol (goldenseal root extract, animal and cell work)	^{23 27 24 25 1 29 43}
Hepatic System	Biological association	Low certainty	Studied for: Fatty liver (berberine alone)	³⁶
Reproductive System	Biological association	Mixed findings	Studied for: Polycystic ovary syndrome (berberine alone or as add-on)	^{16 47}

D. Symptoms

Connected to	Kind of connection	Evidence status	Context	Studies
Colds and upper respiratory infections	Traditional use	Not enough evidence	Sold for colds; no human trial found. Preparation or compound: Goldenseal root	^{31 29}
Infectious diarrhea	Potential benefit	Low certainty	One 1987 trial; ETEC diarrhea stopped sooner. Preparation or compound: Berberine sulfate (not goldenseal)	⁴⁰

E. Health conditions

Connected to	Kind of connection	Evidence status	Context	Studies
Pregnancy and breastfeeding	Contraindication	Low certainty	Avoid, per NCCIH and Health Canada. Preparation or compound: Goldenseal root; berberine	^{31 17 7}
Newborn jaundice and kernicterus	Adverse effect or risk	Low certainty	Bilirubin displacement in lab and rats; human evidence conflicting. Preparation or compound: Berberine	^{3 18 26 49}
Helicobacter pylori infection	Potential benefit	Low certainty	Higher eradication in pooled Chinese trials. Preparation or compound: Berberine added to triple therapy	^{20 22}
Type 2 diabetes	Potential benefit	Low certainty	Lower fasting glucose and HbA1c in pooled trials. Preparation or compound: Berberine (not goldenseal)	^{48 24}
High cholesterol and blood fats	Potential benefit	Low certainty	Lower LDL, total cholesterol and triglycerides in pooled trials. Preparation or compound: Berberine (not goldenseal)	^{23 27}
High blood pressure	Potential benefit	Not enough evidence	Limited, inconclusive evidence. Preparation or compound: Berberine (not goldenseal)	⁴³
Fatty liver disease	Potential benefit	Low certainty	Lower ALT and AST in 10 small trials. Preparation or compound: Berberine (not goldenseal)	³⁶
Polycystic ovary syndrome	Potential benefit	Mixed findings	Lower testosterone; live birth not clearly improved. Preparation or compound: Berberine (not goldenseal)	^{16 47}
Newborn jaundice	Adverse effect or risk	Low certainty	Bilirubin displacement in lab and rats; human data conflicting. Preparation or compound: Berberine	^{3 18 26}

I. Biomarkers

Connected to	Kind of connection	Evidence status	Context	Studies
Stool volume in acute diarrhea	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	⁴⁰
H. pylori eradication rate	Biological association	Low certainty	Measured in trials: raised. A lab change is not the same as a health benefit.	^{20 22}
Inflammation signals in mouse immune cells (TNF-alpha, IL-6, IL-10, IL-12)	Biological association	Not enough evidence	Measured in trials: lowered. A lab change is not the same as a health benefit.	⁶
Fasting blood glucose	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{48 27}
HbA1c	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{48 35}
LDL cholesterol	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{23 27}
Triglycerides	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{23 27 36}
Total cholesterol	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{23 27}
HDL cholesterol	Biological association	Mixed findings	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{23 27 36}
ALT and AST (liver enzymes)	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{36 28}
Total testosterone (in PCOS)	Biological association	Mixed findings	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{47 16}
Waist circumference	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{27 47}
Systolic blood pressure	Biological association	Not enough evidence	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{43 27}

J. Genes, receptors and enzymes

Connected to	Kind of connection	Evidence status	Context	Studies
CYP2D6	Preliminary mechanism	Human	Inhibited by goldenseal in people; gene variants change berberine metabolism in women.	^{12 53}
CYP3A4 / CYP3A5	Preliminary mechanism	Human	Inhibited in gut wall; berberine inhibits CYP3A4 and activates CYP3A5 in the lab.	^{34 30}
CYP2C9	Preliminary mechanism	Lab	Inhibited by hydrastine in lab tests.	^{4 30}
LDLR	Preliminary mechanism	Animal	Up-regulated in liver cells by goldenseal extract.	¹
TOP2 (topoisomerase II)	Preliminary mechanism	Lab	Inhibited by berberine in liver cells.	⁵
SLC22A1 (OCT1)	Preliminary mechanism	Human	Berberine is an OCT1 substrate in the lab, but OCT1-poor people showed no difference in berberine levels.	⁵³

K. Biological pathways

Connected to	Kind of connection	Evidence status	Context	Studies
Inflammatory cytokines (TNF, IL-6)	Preliminary mechanism	Lab	Lowered in toxin-stimulated mouse cells.	⁶

L. Active compounds

Connected to	Kind of connection	Evidence status	Context	Studies
Berberine	Biological association	In vitro	The best-studied compound. Germ-slowing in lab tests, lowers DNA-repair enzyme activity (topoisomerase) in cells, inhibits CYP2D6 and CYP3A4/5 in lab tests, lowers LDL by raising LDL receptors in liver cells, and displaces bilirubin from albumin in lab tests. Preparation or compound: root and rhizome	^{10 30 5 1 3}
(-)-beta-Hydrastine	Biological association	Human	Probably the main driver of the midazolam (CYP3A) interaction by time-dependent inhibition in the gut wall, per a modelling study. Inhibits CYP2C9, 2D6 and 3A4/5 in lab tests. Human peak blood level 225 ng/ml after a 2.7 g dose containing 78 mg hydrastine. Preparation or compound: root and rhizome	^{10 34 30 4 51}
Canadine (tetrahydroberberine)	Biological association	In vitro	Raised LDL-receptor expression in liver cells and was resistant to MDR1 efflux, unlike berberine. PubChem lists CID 34458 under the title (+-)-tetrahydroberberine; the exact stereoisomer in goldenseal was not checked. Preparation or compound: root and rhizome	^{1 5}
Hydrastinine	Biological association	In vitro	Inhibited CYP2D6 in human liver microsomes. A lesser alkaloid. Preparation or compound: root and rhizome	³⁰
Palmatine	Biological association	In vitro	Caused DNA damage and blocked topoisomerase in human liver cells in the lab. Also a marker of adulteration: palmatine is native to Coptis species and other goldenseal adulterants. Preparation or compound: root (also in Coptis and other plants)	^{5 45}

Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 25, 2026).

Evidence at a glance: what changed in 13 lab markers

Tap a number to show only those markers. Counts are markers, not people.

Hormonal1 Metabolic51 Organ function1 Other311

The evidence

The research centre for Goldenseal. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.

Evidence by outcome

Colds, flu and other infections (goldenseal itself) 3 studies Not enough evidence Digestive complaints (goldenseal itself) 3 studies Not enough evidence Wounds, skin, mouth and eye uses (goldenseal itself) 3 studies Not enough evidence Immune and inflammation signals (lab only) 1 study Not enough evidence Infectious diarrhea (berberine alone) 2 studies · 165 people in trials Low certainty Stomach infection with H. pylori (berberine added to antibiotics) 3 studies Low certainty Blood sugar in type 2 diabetes (berberine alone) 4 studies Low certainty Cholesterol and blood fats (berberine alone) 4 studies Low certainty Cholesterol (goldenseal root extract, animal and cell work) 2 studies Not enough evidence Blood pressure (berberine alone) 3 studies Not enough evidence Fatty liver (berberine alone) 1 study Low certainty Polycystic ovary syndrome (berberine alone or as add-on) 2 studies Mixed findings Waist size and body weight (berberine alone) 3 studies Low certainty

Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).

How we rate evidence

High certainty

Several well-run trials or reviews agree; further research is unlikely to change the picture much.

Moderate certainty

Good trials point the same way, but some doubt remains.

Low certainty

Small, short or inconsistent trials. The finding could change with better research.

Very low certainty

Very little or very weak human data. Treat as a possibility only.

Mixed findings

Trials or reviews disagree with each other.

Not enough evidence

Not enough human research to say either way.

Evidence against

Good research found no benefit, or found harm.

We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We searched PubMed, read the NCCIH goldenseal page, the Health Canada goldenseal monograph and a US Forest Service bibliography, and checked plant names in GBIF and the NCBI taxonomy and compounds in PubChem. Only abstracts were read for nearly all studies. Some sources were not verified: the NIH LiverTox page for goldenseal and the full LactMed and LiverTox pages (only short summaries were read through PubMed because the site blocked access), the CITES record itself, the EMA herbal medicines list, the ESCOP monograph, the German Commission E, and the WHO and FDA statements. Berberine-only studies are labelled as berberine and are not treated as goldenseal evidence. Certainty ratings are the compiler's own reading, not formal grades. No study is cited that we could not verify.

Study library: every study we checked 55

Design Research type Plant part Year from Search

Study	Design	People	Product, dose, length	Result
Abidi 2006 The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms. J Lipid Res · PMID 16885565 · DOI	Animal research animal	Human liver cells (HepG2) and high-cholesterol hamsters	Goldenseal root extract, berberine and canadine root · vs Pure berberine	The goldenseal root extract raised LDL-receptor expression in liver cells and lowered blood cholesterol and LDL-cholesterol in high-cholesterol hamsters, more than pure berberine did. Canadine was identified as another active compound. Reported as greater than pure berberine; numbers not in abstract Methods, limits and funding Outcomes: LDL receptor in liver cells; blood cholesterol in hamsters Limitations: Cells and hamsters only; no human test of goldenseal for cholesterol was found. Funding and conflicts: Not stated in the abstract Read: abstract
Adiwidjaja 2022 Physiologically based pharmacokinetic model predictions of natural product-drug interactions between goldenseal, berberine, imatinib and bosutinib. Eur J Clin Pharmacol · PMID 35048143 · DOI	Other in-vitro	Computer model (no participants)	Goldenseal extract and high-dose berberine, modelled Modelled doses Model	The model predicted about a twofold rise in bosutinib exposure with goldenseal, and no important change for imatinib. It also reproduced the known effects on midazolam, indinavir, cyclosporine and digoxin. Bosutinib AUC ratio about 2 (5th to 95th percentile 1.4 to 3.1) (1.4 to 3.1) Methods, limits and funding Outcomes: Predicted effect on bosutinib and imatinib exposure Limitations: A prediction only. The authors say it needs checking in real studies. Funding and conflicts: Not stated in the abstract Read: abstract
Chan 1993 Displacement of bilirubin from albumin by berberine. Biol Neonate · PMID 8513024 · DOI	Laboratory research animal	Lab protein-binding tests and adult rats	Berberine (isolated alkaloid) 10 and 20 micrograms/g by injection daily 1 week (rats) · vs Untreated rats	In the lab, berberine pushed bilirubin off albumin about ten times more strongly than phenylbutazone. In adult rats, it lowered bilirubin binding and raised free and total bilirubin. The author advised avoiding berberine-rich herbs in jaundiced newborns and pregnant women. Roughly tenfold stronger bilirubin displacement than phenylbutazone (molar basis) Methods, limits and funding Outcomes: How tightly bilirubin binds to albumin Limitations: Lab and adult-rat study; no newborn data in this paper. Funding and conflicts: Not stated in the abstract Read: abstract
Chatterjee 2003 Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos · PMID 14570772 · DOI	Laboratory research in-vitro	Human liver microsomes and lab enzymes	Goldenseal extract, berberine and hydrastine unspecified Lab concentrations Lab test	The extract inhibited CYP2C9, 2D6 and 3A4. Hydrastine formed a complex that locks CYP2C9, 2D6 and 3A4 in an inactive state. Berberine IC50 about 45 uM on CYP2D6; hydrastine IC50 about 25 to 30 uM on CYP3A4 activity Methods, limits and funding Outcomes: Inhibition of CYP2C9, CYP2D6, CYP3A4 Limitations: Test-tube study. Funding and conflicts: Not stated in the abstract Read: abstract
Chen 2013 Mechanism study of goldenseal-associated DNA damage. Toxicol Lett · PMID 23747414 · DOI	Laboratory research in-vitro	Human liver cancer cells (HepG2) in the lab	Five goldenseal alkaloids and commercial goldenseal extracts unspecified Lab concentrations Lab test	Berberine, then palmatine, caused the most DNA damage. Berberine blocked topoisomerase II. Commercial goldenseal extracts also caused DNA damage, more with more berberine. DNA damage correlated with berberine content Methods, limits and funding Outcomes: DNA damage and topoisomerase activity Limitations: Cell-culture study; does not show harm in people. Funding and conflicts: Not stated; US FDA research centre authors Read: abstract
Clement-Kruzel 2008 Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts. J Med Food · PMID 18800897 · DOI	Laboratory research in-vitro	Mouse macrophage cells	Two commercial goldenseal preparations (and astragalus) unspecified Lab concentrations Lab test · vs Untreated cells	Goldenseal did little to resting macrophages. In cells stimulated with a bacterial toxin it lowered TNF-alpha, IL-6, IL-10 and IL-12 in a dose-related way. Dose-dependent reductions in four cytokines Methods, limits and funding Outcomes: TNF-alpha, IL-6, IL-10, IL-12 Limitations: Mouse cells in a dish; no human data. Funding and conflicts: Not stated in the abstract Read: abstract
Drugs and Lactation Database (LactMed) 2025 Goldenseal (LactMed) LactMed (NIH) · PMID 30000926	Authoritative guidance	Breastfeeding mothers and infants (guidance)	Goldenseal (Hydrastis canadensis) root root	No data on goldenseal compounds in breast milk or on safety in nursing mothers. Berberine can displace bilirubin from albumin, causing concern for newborns, but how much reaches the infant is unknown. Most sources advise avoiding exposure of newborns to goldenseal, including through breastfeeding. Guidance Methods, limits and funding Outcomes: LactMed summary on goldenseal in breastfeeding (page dated 2025 May 15) Limitations: Summary text read from the PubMed record; the full LactMed page was not opened. Funding and conflicts: US NIH (NICHD) Read: abstract
Dumitru 2026 Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review. Pharmaceuticals (Basel) · PMID 42653808 · DOI	Systematic review mixed	Narrative review of berberine-drug interactions	Berberine Various Various	Berberine is poorly absorbed yet can interact with CYP3A4, CYP2D6, CYP2C9 and transporters, and may add to the effects of blood sugar, blood pressure and QT-interval drugs. The clinical anchor is the cyclosporine increase in kidney-transplant recipients. Product quality varies and European limits differ widely. Narrative; no pooled numbers Methods, limits and funding Outcomes: Mechanisms and risk grouping of interactions Limitations: Narrative review (not a systematic search with pooled data); interactions are documented in humans for only a few drug pairs. Funding and conflicts: No conflicts declared Read: abstract
Dunnick 2011 Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle. Toxicol Pathol · PMID 21300790 · DOI	Other animal	Rats and mice from the 2-year NTP studies	Goldenseal root powder (and milk thistle extract) root See NTP report 2 years · vs Untreated feed	Main finding was more liver tumours in rats and mice on goldenseal. The authors suggest berberine (or its breakdown product berberrubine) blocking topoisomerase may play a part, and that the fate of the active compounds is similar in humans and rodents, but say more work is needed. Liver tumours increased in rodents Methods, limits and funding Outcomes: Review of the 2-year NTP findings Limitations: Interpretation by the NTP authors; human relevance not established. Funding and conflicts: US government authors (NIEHS) Read: abstract
Edwards 2003 Variations in alkaloid content of herbal products containing goldenseal. J Am Pharm Assoc (2003) · PMID 12836794 · DOI	Other	20 20 commercial goldenseal products bought from pharmacies and health food shops (17 root, 3 herb)	Commercial goldenseal products root and herb · vs Proposed USP standards	Hydrastine ranged from 0 to 2.93% and berberine from 0.82% to 5.86% in root products. Only 10 of 17 met the proposed USP standard. Five had little or no hydrastine and unusual patterns. Products labelled "herb" had about a quarter of the alkaloid of root products. Hydrastine 0 to 2.93%; berberine 0.82 to 5.86%; 10 of 17 met proposed USP Methods, limits and funding Outcomes: Hydrastine and berberine content by HPLC Limitations: Paper published in 2003, so products may not reflect the current market. Funding and conflicts: Not stated in the abstract Read: abstract
Gao 2024 Goldenseal (Hydrastis canadensis L.) Extracts Inhibit the Growth of Fungal Isolates Associated with American Ginseng (Panax quinquefolius L.). Molecules · PMID 38338301 · DOI	Laboratory research in-vitro	Three fungi from diseased American ginseng plants	Goldenseal root and leaf extracts (ethanol or water) root and leaf 2% extract Lab test · vs Untreated cultures	Goldenseal root ethanol extract at 2% blocked growth of A. panax by 86.0%, F. sporotrichioides by 94.9% and P. nanjingensis by 39.1%. Water and leaf extracts were weaker. Inhibition 86.0%, 94.9%, 39.1% Methods, limits and funding Outcomes: Fungal growth inhibition Limitations: Plant-disease fungi on a petri dish. It tells us nothing about infections in people. Funding and conflicts: No conflicts declared Read: abstract
Gurley 2005 In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther · PMID 15900287 · DOI	Controlled trial	12 Healthy adult volunteers (6 women), crossover with 30-day washouts	Goldenseal supplement (Hydrastis canadensis), root or rhizome product; exact product and dose not given in the abstract unspecified 28 days · vs Each person measured before and after (baseline); other herbs tested in the same people	Goldenseal cut CYP2D6 and CYP3A4/5 activity by about 40%. Black cohosh weakly lowered CYP2D6 (about 7%). Kava lowered CYP2E1. Valerian had no effect. CYP2D6 phenotype ratio difference -0.228; CYP3A4/5 difference -1.501 (about 40% inhibition each) (CYP2D6 -0.268 to -0.188; CYP3A4/5 -1.840 to -1.163) Methods, limits and funding Outcomes: Activity of four drug-processing enzymes (CYP1A2, 2D6, 2E1, 3A4/5), measured with probe drugs Limitations: Small study in healthy adults; measured enzyme activity with probe drugs, not patient outcomes. Product dose not in the abstract. Funding and conflicts: Not stated in the abstract Read: abstract
Gurley 2007 Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos · PMID 17079360 · DOI	Controlled trial	20 Healthy adult volunteers, with rifampin and clarithromycin as positive controls	Goldenseal supplement (Hydrastis canadensis), root or rhizome product; standardised, 3210 mg daily unspecified 3210 mg daily 14 days · vs Own baseline; kava kava; rifampin and clarithromycin as controls	Goldenseal did not meaningfully change digoxin levels, apart from a 14% rise in peak concentration. Rifampin and clarithromycin changed digoxin strongly, as expected. Goldenseal: Cmax +14%; no other significant change Methods, limits and funding Outcomes: Digoxin blood levels (a P-glycoprotein drug) Limitations: Healthy adults, one product. Says nothing about other P-glycoprotein drugs. Funding and conflicts: Not stated in the abstract Read: abstract
Gurley 2008 Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res · PMID 18214849 · DOI	Controlled trial	16 Healthy adult volunteers (8 women), separate studies for each herb pair	Goldenseal supplement (Hydrastis canadensis), root or rhizome product (a standardised extract) unspecified 14 days · vs Own baseline; milk thistle, black cohosh, kava, St. John's wort and echinacea tested too	Goldenseal cut CYP2D6 activity by about 50%. The five other extracts did not. About 50% CYP2D6 inhibition by goldenseal Methods, limits and funding Outcomes: CYP2D6 activity from the debrisoquine urine ratio Limitations: Healthy adults, a single probe drug. Funding and conflicts: Not stated in the abstract Read: abstract
Gurley 2008 Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther · PMID 17495878 · DOI	Controlled trial	16 Healthy adult volunteers, crossover with 30-day washout	Goldenseal supplement (Hydrastis canadensis), root or rhizome product (a standardised supplement) unspecified 14 days · vs Kava kava arm; each person compared with their own baseline	Goldenseal raised midazolam exposure: AUC 175.3 versus 107.9 ng x h/ml (after versus before), half-life 3.15 versus 2.01 h, clearance fell from 1.26 to 0.81 l/h/kg. Kava did not change midazolam. AUC(0-infinity) 107.9 +/- 43.3 before vs 175.3 +/- 74.8 ng x h/ml after Methods, limits and funding Outcomes: Midazolam (a CYP3A drug) blood levels before and after goldenseal Limitations: Healthy adults, one probe drug, no patient outcomes. Funding and conflicts: Not stated in the abstract Read: abstract
Ha 2024 Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials. Explore (NY) · PMID 39236662 · DOI	Meta-analysis	713 10 randomised trials in women with PCOS and reduced fertility	Berberine added to Western medicine Various Various · vs Western medicine alone	Added berberine improved ovulation rate (RR 1.41), clinical pregnancy rate (RR 1.96), endometrial thickness, and lowered LH and total testosterone. FSH did not change significantly. Clinical pregnancy RR 1.96 (1.59 to 2.41) Methods, limits and funding Outcomes: Ovulation, clinical pregnancy, endometrial thickness, hormones Limitations: Chinese trials with berberine as an add-on; authors call for more trials. Funding and conflicts: Not stated in the abstract Read: abstract
Health Canada 2024 Health Canada Natural Health Product monograph: Goldenseal (Hydrastis canadensis), oral · Source	Authoritative guidance			Monograph dated 29 November 2024. Source material: root and rhizome. Uses are traditional-medicine claims (for example for digestive complaints). Cautions: ask a health care practitioner before use if you have a kidney or blood pressure disorder. Contraindication: do not use if pregnant or breastfeeding. Direction: take a few hours before or after other medicines. The monograph says "No statement required" for known adverse reactions. Methods, limits and funding Read: full-text (PDF)
Ho 1996 Traditional Chinese medicine and treatment of neonatal jaundice. Singapore Med J · PMID 9104069	Systematic review	Twenty Chinese-language reports (1973 to 1989) of herbs used for newborn jaundice	Chinese herbs for newborn jaundice, including Coptis (huang-lian, a berberine herb) rhizome Various Various	Coptis was used in 4 of 20 centres. The review states berberine can cause severe acute hemolysis in babies with G6PD deficiency. It notes phototherapy is well established, reducing the need for drug treatment. Descriptive Methods, limits and funding Outcomes: Which herbs were used and what is known about them Limitations: Narrative review of older reports. The abstract gives no primary data on hemolysis. Funding and conflicts: Not stated Read: abstract
Houston 2025 Identification of Goldenseal (Hydrastis canadensis L.) Habitat and Indicators in Pennsylvania, USA: The Influence of Climate and Site on In Situ Conservation of an Edge of Range Plant Species. Ecol Evol · PMID 40027423 · DOI	Other	Goldenseal habitat in Pennsylvania (51 occurrence points, 28 field plots)	Wild goldenseal plants whole plant	The paper states that commercial harvesting for the medicinal plant trade and habitat loss have led to international conservation concerns. In Pennsylvania the best habitat was moist forest on base-rich bedrock. Habitat model Methods, limits and funding Outcomes: Habitat suitability and conservation guidance Limitations: Regional study; does not give national population counts. Funding and conflicts: No conflicts declared Read: abstract
Hu 2019 The Efficacy of Berberine-Containing Quadruple Therapy on Helicobacter Pylori Eradication in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Front Pharmacol · PMID 32116685 · DOI	Meta-analysis	Adults with Helicobacter pylori infection in China (13 articles)	Berberine added to standard triple therapy (quadruple therapy) Various Various · vs Standard triple therapy	Adding berberine raised eradication (RR 1.22, 95% CI 1.16 to 1.27), ulcer healing (RR 1.15), symptom relief (RR 1.11) and cut side events (RR 0.65). Eradication RR 1.22 (1.16 to 1.27) Methods, limits and funding Outcomes: H. pylori eradication, ulcer healing, symptoms, side effects Limitations: Trials from China only; abstract does not rate trial quality; berberine was added to antibiotics, so this says nothing about berberine or goldenseal on its own. Funding and conflicts: Not stated in the abstract Read: abstract
Jahnke 2006 Developmental toxicity evaluation of berberine in rats and mice. Birth Defects Res B Dev Reprod Toxicol · PMID 16634078 · DOI	Animal research animal	Pregnant rats and mice	Berberine chloride dihydrate (isolated alkaloid) in feed or by gavage Rats up to 1,313 mg/kg a day in feed; 1,000 mg/kg a day by gavage Rats gestation days 6 to 20; mice days 6 to 17 · vs Untreated feed	Rats: lower mother weight gain at 531 mg/kg a day; lower fetal weight at the top feed dose; developmental NOAEL 1,000 mg/kg a day by gavage. Mice: 33% of treated mothers died at the top dose and fetal weight fell 5 to 6% at 1,000 mg/kg a day. Fetal weight down 5 to 6% in mice at 1,000 mg/kg a day Methods, limits and funding Outcomes: Maternal and fetal harm Limitations: Animal study at very high doses, berberine alone. Funding and conflicts: US government authors (NIEHS) Read: abstract
Jiang 2018 Berberine Combined with Triple Therapy versus Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials. Evid Based Complement Alternat Med · PMID 30410559 · DOI	Meta-analysis	Adults with H. pylori infection	Berberine combined with triple therapy Various Various · vs Triple therapy	Eradication improved (urea breath test subgroup RR 1.18, 95% CI 1.12 to 1.24; biopsy subgroup RR 1.23, 1.13 to 1.34). Total adverse effects were lower (OR 0.59). Trial sequential analysis suggested the result was stable. The authors still call for better-designed trials. RR 1.18 (breath test) and 1.23 (biopsy) (1.12 to 1.24; 1.13 to 1.34) Methods, limits and funding Outcomes: H. pylori eradication; adverse effects Limitations: Berberine as an add-on to antibiotics; trial quality limited per the authors. Funding and conflicts: Not stated in the abstract Read: abstract
Ju 2018 Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine · PMID 30466986 · DOI	Meta-analysis	2147 16 randomised trials in people with high blood fats	Berberine (isolated alkaloid) Various Various · vs Control	Total cholesterol fell 0.47 mmol/L, LDL-C 0.38 mmol/L and triglycerides 0.28 mmol/L; HDL-C rose 0.08 mmol/L when berberine was used alone. No significant difference in adverse events. TC MD -0.47; LDL-C -0.38; TG -0.28 mmol/L; HDL-C +0.08 (TC -0.64 to -0.31; LDL-C -0.53 to -0.22; TG -0.46 to -0.10; HDL-C 0.03 to 0.12) Methods, limits and funding Outcomes: Total cholesterol, LDL-C, triglycerides, HDL-C, adverse events Limitations: The authors report high clinical heterogeneity and low methodological quality in most trials. Funding and conflicts: Not stated in the abstract Read: abstract
Lan 2015 Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol · PMID 25498346 · DOI	Meta-analysis	2569 27 randomised trials in type 2 diabetes, high blood fats and high blood pressure	Berberine (alone or added to usual drugs or lifestyle change) Various Various · vs Placebo, lifestyle change or drugs	Berberine with lifestyle change or with drugs lowered glucose, lipids and blood pressure more than lifestyle change or drugs alone. Berberine alone was not clearly different from oral diabetes drugs. No serious adverse reaction was reported in the 27 trials. The authors say the quality of the studies limits confidence. Direction of effect only; no pooled numbers in the abstract Methods, limits and funding Outcomes: Glucose, lipids and blood pressure; serious adverse reactions Limitations: Limited quality of included studies per the authors; older review (2015). Funding and conflicts: Not stated in the abstract Read: abstract
Li 2023 Berberine and health outcomes: An umbrella review. Phytother Res · PMID 36999891 · DOI	Systematic review	11 meta-analyses of randomised trials of berberine (umbrella review)	Berberine (isolated alkaloid) Various Various · vs Controls in the included trials	Berberine significantly affected glucose, insulin resistance, lipids, body measures, inflammatory markers, colorectal adenomas and H. pylori infection. Common side effects were gut symptoms such as constipation and diarrhea. The authors call for better-quality trials. They graded evidence with AMSTAR-2 and GRADE; the abstract does not give the grades. Significant effects reported; no pooled numbers in abstract Methods, limits and funding Outcomes: Glucose, lipids, weight, inflammation, colorectal adenoma, H. pylori; common side effects Limitations: Review of reviews; the abstract gives no GRADE results and notes the included meta-analyses need better methods. Berberine, not goldenseal. Funding and conflicts: Not stated in the abstract Read: abstract
Linn 2012 Berberine-induced haemolysis revisited: safety of Rhizoma coptidis and Cortex phellodendri in chronic haematological diseases. Phytother Res · PMID 22002596 · DOI	Case series Not stated in the abstract	20 Patients with chronic blood diseases who took Coptis and/or Phellodendron in a Chinese herbal mix (a subset of a single-arm study)	Rhizoma coptidis and Cortex phellodendri (berberine herbs) in decoctions rhizome and bark Traditional amounts in a herbal mix 1,055 patient-days (coptis) and 1,252 (phellodendron) · vs Single arm	Organ toxicity, electrolytes, bilirubin No organ toxicity or electrolyte problem. Transient bilirubin rise in 3 people with thalassaemia, with no worsening of anaemia. The literature review found conflicting evidence on berberine causing newborn jaundice and kernicterus. These two herbs have been banned in Singapore for three decades. (No organ toxicity in 20 patients) Methods, limits and funding Outcomes: Reviewed also the literature on newborn jaundice Funding and conflicts: No newborns were studied, so it says nothing about newborns. Small single-arm study. Read: human
Liu 2025 Efficacy and safety of berberine on the components of metabolic syndrome: a systematic review and meta-analysis of randomized placebo-controlled trials. Front Pharmacol · PMID 40740996 · DOI	Meta-analysis	Adults with metabolic syndrome features; placebo-controlled randomised trials	Berberine (isolated alkaloid) Various Various · vs Placebo	Berberine lowered triglycerides (-0.367 mmol/L), fasting glucose (-0.515 mmol/L) and waist (-3.27 cm), plus LDL-C, total cholesterol, BMI and 2-hour glucose. No significant effect on HDL-C or blood pressure. No significant safety difference from placebo. Short courses (90 days or less) worked better for HDL-C and LDL-C than long ones. TG WMD -0.367 mmol/L; FPG -0.515; waist -3.270 cm (TG -0.560 to -0.175; FPG -0.847 to -0.183; waist -4.818 to -1.722) Methods, limits and funding Outcomes: Triglycerides, fasting glucose, waist, LDL-C, blood pressure Limitations: Number of trials not in the abstract; authors call for better randomised trials. Registered CRD42024588614. Funding and conflicts: Authors declare no conflicts Read: abstract
LiverTox (NIDDK) 2020 Berberine (LiverTox) LiverTox (NIH) · PMID 33242239	Authoritative guidance	Adults (guidance on liver injury)	Berberine (found in goldenseal, barberry, Oregon grape)	Berberine has not been linked to serum aminotransferase elevations during therapy or to clinically apparent liver injury. Guidance Methods, limits and funding Outcomes: LiverTox summary on berberine (page dated 2020 Oct 6) Limitations: Summary read from the PubMed record only; the full LiverTox page (including likelihood score) was not opened because the site blocked automated access. This is about berberine, not goldenseal root. Funding and conflicts: US NIH (NIDDK) Read: abstract
Mandal 2020 Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues. Pharmacol Res · PMID 32683037 · DOI	Systematic review mixed	Narrative review of goldenseal and its alkaloids (lab, animal and some human data)	Goldenseal and its alkaloids rhizome Various Various	The authors list antimicrobial, anti-inflammatory, lipid-lowering, blood-sugar-lowering, antioxidant and other effects, mostly from berberine research. They also note possible nerve, liver and light-sensitivity toxicity. They state large randomised double-blind clinical studies of goldenseal and its main alkaloids are needed. Narrative review Methods, limits and funding Outcomes: Efficacy and toxicity Limitations: Narrative review; mostly lab and animal evidence. Funding and conflicts: Not stated in the abstract Read: abstract
McDonald 2020 Modulation of Major Human Liver Microsomal Cytochromes P450 by Component Alkaloids of Goldenseal: Time-Dependent Inhibition and Allosteric Effects. Drug Metab Dispos · PMID 32591416 · DOI	Laboratory research in-vitro	Human liver microsomes and lab enzymes	Berberine, (-)-beta-hydrastine and hydrastinine from goldenseal Lab concentrations Lab test	Berberine inhibited CYP2D6 and CYP3A4/5. Hydrastine inhibited CYP2C9, CYP2D6 and CYP3A4/5. Hydrastinine inhibited CYP2D6. These are time-dependent (grow with exposure) inhibitions. Examples: berberine on CYP2D6 KI 2.7 uM; hydrastine on CYP3A4/5 KI 28 uM Methods, limits and funding Outcomes: Inhibition of CYP enzymes Limitations: Test-tube study. Real-life effect depends on how much reaches the gut and liver. Funding and conflicts: Not stated in the abstract Read: abstract
NCCIH 2025 NIH NCCIH: Goldenseal · Source	Authoritative guidance			NCCIH (page updated February 2025): not enough evidence to say goldenseal helps any condition; no rigorous human studies; small short studies of about 3 g a day showed no serious harm but long-term safety is unknown; goldenseal may change how the body handles many medicines (metformin levels fell about 25% in one NCCIH-funded study); some products contain unlisted herbs; do not use in pregnancy or breastfeeding or give to infants because berberine can harm newborns. Methods, limits and funding Read: full-text (web page)
National Toxicology Program 2010 Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser · PMID 21372858	Animal research animal	Male and female F344/N rats and B6C3F1 mice; 2 weeks, 3 months and 2 years	Goldenseal root powder in feed root Up to 25,000 ppm in feed (about 1,175 to 1,340 mg/kg a day in rats at the top dose) 2 weeks, 3 months, 2 years · vs Untreated feed	Clear evidence of carcinogenic activity in male and female rats (liver adenoma; combined adenoma or carcinoma in males). Some evidence in male mice (hepatoblastoma, multiple adenoma). No evidence in female mice. Liver cell enlargement and damage in rats and male mice. Not mutagenic in bacteria and no increase in micronuclei in mouse blood. Liver adenoma significantly increased at 25,000 ppm in rats of both sexes Methods, limits and funding Outcomes: Survival, weights, liver pathology, tumours, genetic toxicity Limitations: Rodent feeding study with whole root powder at high daily doses. Not proof of cancer in people. Funding and conflicts: US National Toxicology Program (government) Read: abstract
Nguyen 2021 Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail. Clin Pharmacol Ther · PMID 33174626 · DOI	Controlled trial	16 Healthy adult volunteers, probe-drug cocktail	Goldenseal extract standardised to berberine unspecified · vs Own baseline	Goldenseal raised midazolam AUC (ratio 1.43), lowered metformin AUC (ratio 0.77), and did not change rosuvastatin or furosemide. Metformin half-life and kidney clearance did not change, so the effect is thought to be on absorption. Midazolam AUC ratio 1.43; metformin AUC ratio 0.77 (Midazolam 1.35 to 1.53; metformin 0.71 to 0.83) Methods, limits and funding Outcomes: Blood levels of several probe drugs (midazolam, rosuvastatin, furosemide, metformin) Limitations: Healthy adults; the authors say the model predictions did not match all results. Funding and conflicts: Authors declare no competing interest Read: abstract
Nguyen 2023 An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations. J Pharmacol Exp Ther · PMID 37541764 · DOI	Other	Healthy adults (human data) plus lab enzyme tests and a computer model	Goldenseal, berberine and (-)-beta-hydrastine unspecified Single 3 g dose, or 1 g three times a day for 6 days Acute and 6 days · vs Own baseline	Goldenseal raised midazolam AUC and peak by 40% to 60% after both single and repeated doses. Half-life rose little, which points to the gut wall rather than the liver. The model named (-)-beta-hydrastine as the main cause. Midazolam AUC and Cmax +40% to +60% Methods, limits and funding Outcomes: Midazolam AUC and Cmax; enzyme tests; modelling Limitations: Mixes human data with lab and modelling results; the number of participants is not in the abstract. Funding and conflicts: Not stated in the abstract Read: abstract
Nguyen 2025 The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose-Dependent: A Three-Arm Crossover Study in Adults With Type 2 Diabetes. Clin Transl Sci · PMID 39943692 · DOI	Controlled trial	Adults with type 2 diabetes already stable on metformin (500 to 2550 mg a day)	Goldenseal (botanical product) taken with metformin unspecified · vs Open-label three-arm crossover (low, moderate and high metformin dose groups); registered NCT05081583	Overall no clinically meaningful change in metformin exposure (AUC ratio 0.93). But metformin AUC fell about 20% in the low-dose group, 14% in the moderate-dose group and 0% in the high-dose group. HbA1c fell from 6.8% to 6.5% on average, whatever happened to metformin levels. Metformin AUC geometric mean ratio 0.93 (0.86 to 1.01 (predefined no-effect range 0.80 to 1.25)) Methods, limits and funding Outcomes: Metformin blood levels (AUC); exploratory HbA1c Limitations: Open-label, no placebo; HbA1c was exploratory; number of participants is not in the abstract. Funding and conflicts: Authors declare no conflicts of interest Read: abstract
Nie 2024 The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. J Transl Med · PMID 38429794 · DOI	Meta-analysis	811 10 randomised trials in non-alcoholic fatty liver disease	Berberine (isolated alkaloid) Various Various · vs Control	Berberine lowered ALT (SMD -0.72), AST (SMD -0.79), GGT, triglycerides, total cholesterol, LDL-C, HOMA-IR and BMI. HDL-C did not change significantly. Only mild gut side effects were reported. ALT SMD -0.72; AST SMD -0.79 (ALT -1.01 to -0.44; AST -1.17 to -0.40) Methods, limits and funding Outcomes: ALT, AST, GGT, lipids, HOMA-IR, BMI Limitations: Small trials; the abstract does not give trial quality. Registered CRD42023462338. Funding and conflicts: Authors declare no competing interests Read: abstract
Predny 2005 Goldenseal (Hydrastis canadensis): an annotated bibliography · Source	Authoritative guidance			USDA Forest Service (Predny and Chamberlain, 2005): goldenseal has been listed under CITES Appendix II since 1997; rising consumption and habitat loss have greatly reduced wild populations; cultivation research and consumer education are recommended. Methods, limits and funding Read: summary-only (web page)
Qiu 2009 Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res · PMID 19370549 · DOI	Animal research animal	Rats	Berberine 30 and 100 mg/kg 2 weeks · vs Untreated rats	Berberine raised the absorption of oral digoxin and cyclosporine A in a dose-related way (cyclosporine AUC up 62% and 96%) by blocking P-glycoprotein in the gut. No significant change in CYP3A activity or in carbamazepine levels. CsA AUC +62% (30 mg/kg) and +96% (100 mg/kg) Methods, limits and funding Outcomes: Blood levels of carbamazepine, digoxin and cyclosporine A Limitations: Rats; the CYP3A result differs from the human kidney-transplant result. Funding and conflicts: Not stated in the abstract Read: abstract
Quiroz-Delfi 2024 Non-targeted chemical analysis of consumer botanical products labeled as blue cohosh (Caulophyllum thalictroides), goldenseal (Hydrastis canadensis), or yohimbe bark (Pausinystalia yohimbe) by NMR and MS. Anal Bioanal Chem · PMID 37910202 · DOI	Other	Consumer products labelled blue cohosh, goldenseal or yohimbe bark	Commercial goldenseal products (among others) unspecified · vs Principal component analysis	Each product group had several outliers. Some findings supported and some refuted that a product was authentic. Not given as a number in the abstract Methods, limits and funding Outcomes: Chemical fingerprinting by NMR and mass spectrometry Limitations: The abstract does not say how many goldenseal products were outliers. Funding and conflicts: No conflicts declared Read: abstract
Rabbani 1987 Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. J Infect Dis · PMID 3549923 · DOI	Controlled trial	165 Adults with acute diarrhea from enterotoxigenic E. coli (ETEC) or cholera	Berberine sulfate (isolated alkaloid, not goldenseal) 400 mg once (ETEC and cholera); 1200 mg plus tetracycline in a cholera group Single dose, followed 24 hours · vs Control patients (and tetracycline alone in the combination group)	ETEC: stool volumes were lower than controls in each of three 8-hour periods, and 42% vs 20% had stopped by 24 hours (P<.05). Cholera: small drop in stool volume in the second 8 hours (2.22 vs 2.79 litres, P<.05); no added benefit over tetracycline alone. No side effects noted. ETEC diarrhea stopped at 24 h: 42% vs 20% Methods, limits and funding Outcomes: Stool volume; diarrhea stopped at 24 hours Limitations: Old trial, berberine sulfate alone, short follow-up. Funding and conflicts: Not stated in the abstract Read: abstract
Rad 2017 Toxicology effects of Berberis vulgaris (barberry) and its active constituent, berberine: a review. Iran J Basic Med Sci · PMID 28656087 · DOI	Systematic review mixed	Animal, cell and human reports on barberry and berberine	Barberry (Berberis vulgaris) and berberine mixed Various Various	Toxicity depends on route and dose. Reported effects include stomach and gut upset, immune, nerve and heart toxicity, light sensitivity and jaundice in a dose-dependent way. The authors advise caution in pregnancy, in newborns and in G6PD deficiency, and with drugs processed by CYP enzymes. Narrative review, no pooled numbers Methods, limits and funding Outcomes: Toxicity review Limitations: Narrative review of mixed-quality sources; about barberry and berberine, not goldenseal. Funding and conflicts: Not stated in the abstract Read: abstract
Sandhu 2003 Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol · PMID 14551183 · DOI	Controlled trial	10 Healthy adult volunteers, crossover (before and after)	Goldenseal root root 1140 mg twice daily 14 days · vs Own baseline	No significant change in indinavir peak concentration (11.6 vs 11.9 mg/L) or oral clearance (26.8 vs 23.9 mg x h/L), half-life or time to peak. The authors concluded an interaction was unlikely. This result differs from the midazolam studies of other goldenseal products. No significant difference Methods, limits and funding Outcomes: Indinavir (a CYP3A4 drug) blood levels Limitations: Only 10 people and one drug. The abstract does not explain why this result differs from the other CYP3A studies, so it should not be read as proof that goldenseal is safe with CYP3A drugs. Funding and conflicts: Not stated in the abstract Read: abstract
Suadoni 2021 Berberine for the treatment of hypertension: A systematic review. Complement Ther Clin Pract · PMID 33461163 · DOI	Systematic review	614 5 randomised and 2 non-randomised trials in people with high blood pressure	Berberine (alone or in multi-ingredient products) Various Various · vs Amlodipine, metformin, placebo or no treatment	Berberine plus amlodipine was not better than amlodipine alone. Against metformin, berberine lowered systolic pressure by 11.87 mmHg. Two multi-ingredient products lowered pressure but effects could not be tied to berberine. The authors call the evidence limited, low quality and inconclusive. No trial measured heart events or long-term harms. SBP -11.87 mmHg vs metformin (-16.64 to -7.10) Methods, limits and funding Outcomes: Blood pressure Limitations: Highly varied trials; no meta-analysis possible; low quality. Funding and conflicts: Not stated in the abstract Read: abstract
Wallace 2018 Detection of adulteration in Hydrastis canadensis (goldenseal) dietary supplements via untargeted mass spectrometry-based metabolomics. Food Chem Toxicol · PMID 30031041 · DOI	Other	35 35 commercial Hydrastis canadensis products	Commercial goldenseal supplements unspecified · vs Principal component analysis against the main group	Several products stood out from the main group. The outliers were confirmed as coming from a non-goldenseal species or a mixture of plant materials. Several outlier products; exact number not in abstract Methods, limits and funding Outcomes: Detection of non-goldenseal material by LC-MS metabolomics Limitations: Method paper; the abstract does not give how many products were adulterated. Funding and conflicts: No conflict of interest declared Read: abstract
Weber 2003 Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers. J Agric Food Chem · PMID 14640583 · DOI	Other	3 Goldenseal root powder from three commercial suppliers	Goldenseal root powder root	All three lots had goldenseal alkaloids. Material from one supplier also contained palmatine, coptisine and jatrorrhizine, so it was not pure goldenseal. The authors judged alkaloid content the best marker for goldenseal. One of three suppliers' lots was impure Methods, limits and funding Outcomes: Chemical comparison (HPLC, GC-MS, LC-MS) Limitations: Only three lots, tested for NIEHS toxicity work. Funding and conflicts: Not stated in the abstract Read: abstract
Wu 2005 Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol · PMID 16133554 · DOI	Controlled trial	104 Kidney-transplant recipients taking cyclosporine A (52 on berberine, 52 not); 6 of them in a separate pharmacokinetic study	Berberine alone (isolated alkaloid, not goldenseal) 0.2 g three times a day 3 months (12 days in the pharmacokinetic part) · vs Cyclosporine without berberine	Cyclosporine trough levels were 29.3% higher in the berberine group than in the no-berberine group at the end. In 6 patients, cyclosporine AUC rose 34.5% and clearance fell 40.4%. No effect on liver or kidney tests was seen. CsA trough 29.3% higher; AUC +34.5%; CL/F -40.4% Methods, limits and funding Outcomes: Cyclosporine A blood levels; liver and kidney tests Limitations: Berberine alone, not goldenseal, so the size of the effect with goldenseal is not known. The pharmacokinetic part had only 6 people. Funding and conflicts: Not stated in the abstract Read: abstract
Xie 2019 The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials. Evid Based Complement Alternat Med · PMID 31915452 · DOI	Meta-analysis	12 randomised trials in women with PCOS	Berberine (isolated alkaloid) Various Various · vs Placebo, metformin, letrozole or no treatment	No solid evidence berberine improved live birth. Live birth was lower than with letrozole (RR 0.61, 0.44 to 0.82). Berberine lowered total testosterone and the LH/FSH ratio versus placebo or no treatment, and total cholesterol and waist versus metformin. Gut side effects were not more common than with placebo. Live birth vs letrozole RR 0.61 (0.44 to 0.82) Methods, limits and funding Outcomes: Live birth, androgens, LH/FSH, lipids, waist, side effects Limitations: Varied comparators; small numbers per outcome. Funding and conflicts: Authors declare no conflicts Read: abstract
Xie 2022 Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol · PMID 36467075 · DOI	Meta-analysis	3048 Adults with type 2 diabetes, 37 randomised trials	Berberine (alone or with oral diabetes drugs) Various Various · vs Control or standard care	Fasting glucose fell 0.82 mmol/L, HbA1c 0.63 percentage points and 2-hour glucose 1.16 mmol/L. Total adverse events were not higher; hypoglycemia risk was not significantly higher (RR 0.48, 0.21 to 1.08). The effect was larger in people with higher starting glucose. FPG WMD -0.82 mmol/L; HbA1c WMD -0.63%; 2hPBG WMD -1.16 mmol/L (FPG -0.95 to -0.70; HbA1c -0.72 to -0.53; 2hPBG -1.36 to -0.96) Methods, limits and funding Outcomes: Fasting glucose, HbA1c, 2-hour glucose; adverse events, hypoglycemia Limitations: Mostly Chinese databases; trial quality and heterogeneity are not reported in the abstract. Registered CRD42021292975. Funding and conflicts: Authors declare no conflicts Read: abstract
Yang 2008 A research on the erupted fetal diseases caused by traditional Chinese drugs--discussion from the issue that Chinese goldthread rhizome is prohibited in Singapore. J Tradit Chin Med · PMID 19004212 · DOI	Animal research animal	Pregnant rats and mice; newborn rats; mouse red blood cells	Coptis rhizome and berberine rhizome · vs Untreated animals	The authors found no induction of newborn jaundice in the animals and no effect on G6PD activity of mouse red cells. They say fetal toxicity of such drugs should be studied further. No jaundice induction seen in animals Methods, limits and funding Outcomes: Newborn jaundice and G6PD activity Limitations: Animal data; the abstract gives no numbers. Conflicts with the older bilirubin-displacement findings. Funding and conflicts: Not stated Read: abstract
Yao 2005 A reproductive screening test of goldenseal. Birth Defects Res B Dev Reprod Toxicol · PMID 16193497 · DOI	Animal research animal	Pregnant rats; rat embryos in culture	Goldenseal (ethanol-based preparation) unspecified 65 times the human dose by mouth Gestation days 1 to 8 or 8 to 15 · vs Ethanol only	No increase in pre- or post-implantation loss, fetal weight change or malformations in live rats. Rat embryos grown in the lab with goldenseal added did show toxicity. The authors suggested poor gut absorption explains the gap and that human pharmacokinetic studies are needed. No malformation increase in live rats Methods, limits and funding Outcomes: Pregnancy losses, fetal weight, malformations Limitations: Rats only; the authors say human data are needed to confirm. Funding and conflicts: Not stated in the abstract Read: abstract
p25609220 Hydrastine pharmacokinetics and metabolism after a single oral dose of goldenseal (Hydrastis canadensis) to humans. · Source	Pharmacokinetic study			Methods, limits and funding Read: abstract
p36221815 Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review. · Source	Review mixed			Methods, limits and funding Read: abstract
p39488825 Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. · Source	Pharmacokinetic study			Methods, limits and funding Read: abstract
s-gbif-hydrastis-canadensis GBIF Backbone: Hydrastis canadensis L. (usageKey 3033110) · Source	Authoritative guidance plant			Methods, limits and funding Read: full-text (API)
s-ncbi-taxonomy-13569 NCBI Taxonomy: Hydrastis canadensis (taxid 13569) · Source	Authoritative guidance plant			Methods, limits and funding Read: full-text (API)

What we do not know yet

What the evidence supports: goldenseal lowers the activity of CYP2D6 and CYP3A4/5 and lowers metformin levels in volunteers; purified berberine raises cyclosporine levels in transplant patients.
What the evidence supports: pooled trials of purified berberine report lower blood sugar, LDL cholesterol, triglycerides and liver enzymes. These are berberine results, with mixed trial quality.
What is uncertain: whether goldenseal itself helps any health condition. No randomised trial of goldenseal for colds, infections, digestion or any other use was found.
What is uncertain: the indinavir study found no change, which differs from the midazolam studies, and the reason is not explained in the abstracts.
What is uncertain: newborn jaundice risk from berberine. Lab and rat work shows bilirubin displacement; other animal work and a small adult series found no problem.
What is uncertain: whether the rodent liver tumours matter for people. There are no human cancer data, and LiverTox's goldenseal page was not read.
What is missing: long-term human safety, effects in older adults and in people with illness, and the size of the cyclosporine effect with goldenseal rather than berberine.
What is missing: heavy-metal, pesticide and microbe testing of products, and human photosensitivity data.
What is missing: goldenseal-specific blood pressure data.
Not verified directly: the CITES primary record (listing year taken from a US Forest Service bibliography), the EMA herbal list, ESCOP, FDA, Commission E and WHO statements, and the LiverTox goldenseal page.

How new research is added

New studies are found by a saved PubMed search and are placed in a review queue. A person reads each one before it changes any evidence rating or safety wording. New publications never change ratings automatically.

Lab markers

What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".

Hormonal 1

▼

Total testosterone (in PCOS)

Lowered in trials

The main male-type hormone, raised in many women with PCOS.

Mixed findings

Results and what it means

Why it was measured

Marker of androgen excess in PCOS.

Statistical vs. clinical meaning

Hormone markers fell, but live birth was not clearly improved in one review.

Safety implication

Pregnancy cautions apply.

Study	Result	People	Product
⁴⁷	MD -0.34 (-0.47 to -0.20) vs placebo or no treatment	Women with PCOS, 8 trials	Berberine
¹⁶	SMD -0.70 (-1.02 to -0.39) as add-on; LH WMD -2.07 U/L	Women with PCOS, 10 trials	Berberine added to Western medicine

^{47 16}

Metabolic 6

▼

Fasting blood glucose

Lowered in trials

Blood sugar after not eating overnight.

Low certainty

Results and what it means

Why it was measured

Basic marker in diabetes trials.

Statistical vs. clinical meaning

Statistically significant; mixed trial quality.

Safety implication

Can add to diabetes drugs; watch for low sugar when combined (not significantly more in one review).

Study	Result	People	Product
⁴⁸	WMD -0.82 mmol/L (95% CI -0.95 to -0.70) vs control	Adults with type 2 diabetes, 37 trials	Berberine
²⁷	WMD -0.515 mmol/L (-0.847 to -0.183) vs placebo	Adults with metabolic syndrome features	Berberine

^{48 27}

▼

HbA1c

Lowered in trials

Average blood sugar over about 3 months.

Low certainty

Results and what it means

Why it was measured

Standard long-term diabetes marker.

Statistical vs. clinical meaning

A clear marker, but trial quality is mixed.

Safety implication

The goldenseal-metformin trial saw HbA1c fall from 6.8% to 6.5% on average (exploratory, no placebo), which should not be credited to goldenseal.

Study	Result	People	Product
⁴⁸	WMD -0.63 percentage points (-0.72 to -0.53)	Adults with type 2 diabetes	Berberine

^{48 35}

▼

LDL cholesterol

Lowered in trials

The cholesterol carried in LDL particles.

Low certainty

Results and what it means

Why it was measured

Main lipid target for heart risk.

Statistical vs. clinical meaning

Marker only; trials did not measure heart events.

Safety implication

None specific.

Study	Result	People	Product
²³	MD -0.38 mmol/L (-0.53 to -0.22)	Adults with dyslipidaemia, 16 trials	Berberine
²⁷	WMD -0.495 mmol/L (-0.714 to -0.276)	Metabolic syndrome features	Berberine

^{23 27}

▼

Triglycerides

Lowered in trials

A type of fat in the blood.

Low certainty

Results and what it means

Why it was measured

Common lipid marker.

Statistical vs. clinical meaning

Consistent direction across three reviews.

Safety implication

None specific.

Study	Result	People	Product
²³	MD -0.28 mmol/L (-0.46 to -0.10)	Dyslipidaemia	Berberine
²⁷	WMD -0.367 mmol/L (-0.560 to -0.175)	Metabolic syndrome features	Berberine
³⁶	SMD -0.59 (-0.86 to -0.31)	Fatty liver disease	Berberine

^{23 27 36}

▼

Total cholesterol

Lowered in trials

All cholesterol in the blood.

Low certainty

Results and what it means

Why it was measured

Common lipid marker.

Statistical vs. clinical meaning

Consistent direction.

Safety implication

None specific.

Study	Result	People	Product
²³	MD -0.47 mmol/L (-0.64 to -0.31)	Dyslipidaemia	Berberine
²⁷	WMD -0.451 mmol/L (-0.631 to -0.271)	Metabolic syndrome features	Berberine

^{23 27}

↕

HDL cholesterol

Mixed results in trials

The "good" cholesterol carried in HDL particles.

Mixed findings

Results and what it means

Why it was measured

Lipid marker.

Statistical vs. clinical meaning

One review found a small rise, two found no significant change.

Safety implication

None specific.

Study	Result	People	Product
²³	MD +0.08 mmol/L (0.03 to 0.12) when berberine alone	Dyslipidaemia	Berberine alone
²⁷	No significant effect	Metabolic syndrome features	Berberine vs placebo
³⁶	Not significant (P=0.11)	Fatty liver disease	Berberine

^{23 27 36}

Organ function 1

▼

ALT and AST (liver enzymes)

Lowered in trials

Enzymes that leak into blood when liver cells are stressed; used as liver markers.

Low certainty

Results and what it means

Why it was measured

Marker in fatty liver trials and also a safety check.

Statistical vs. clinical meaning

Enzyme lowering in fatty liver; not evidence about whole goldenseal root.

Safety implication

A LiverTox summary says berberine has not been linked to enzyme rises or clinically apparent liver injury. Whole goldenseal root caused liver tumours in rodents (Safety tab).

Study	Result	People	Product
³⁶	ALT SMD -0.72 (-1.01 to -0.44); AST SMD -0.79 (-1.17 to -0.40)	Non-alcoholic fatty liver disease, 10 trials	Berberine

^{36 28}

Other 5

▼

Stool volume in acute diarrhea

Lowered in trials

The amount of watery stool passed over a set time, a direct measure of fluid loss in diarrhea.

Low certainty

Results and what it means

Why it was measured

Main outcome in the berberine diarrhea trial.

Statistical vs. clinical meaning

Statistically significant (P<.05) but from one trial; for cholera the gain was slight.

Safety implication

Fluid and salt replacement is the standard treatment for watery diarrhea.

Study	Result	People	Product
⁴⁰	ETEC diarrhea: stool volumes lower than controls in three consecutive 8-hour periods; cholera: 2.22 vs 2.79 L in the second 8 hours	Adults with ETEC diarrhea or cholera	Berberine sulfate, single oral dose (berberine alone)

⁴⁰

▲

H. pylori eradication rate

Raised in trials

The share of treated people in whom the stomach infection is no longer detected after treatment, tested by breath test or biopsy.

Low certainty

Results and what it means

Why it was measured

Main outcome of the berberine add-on reviews.

Statistical vs. clinical meaning

Eradication is a clinical result, but trials were from China and are add-on designs.

Safety implication

See interaction notes for berberine on the Safety tab.

Study	Result	People	Product
²⁰	RR 1.22 (95% CI 1.16 to 1.27) for eradication with berberine added to triple therapy	Adults with H. pylori, 13 articles	Berberine plus triple therapy (berberine as add-on)
²²	RR 1.18 (1.12 to 1.24) by urea breath test; RR 1.23 (1.13 to 1.34) by biopsy	Adults with H. pylori	Berberine plus triple therapy

^{20 22}

▼

Inflammation signals in mouse immune cells (TNF-alpha, IL-6, IL-10, IL-12)

Lowered in trials

Small proteins released by immune cells that drive inflammation.

Not enough evidence

Results and what it means

Why it was measured

Used in a lab study to see what goldenseal does to immune cells.

Statistical vs. clinical meaning

Cell-dish result only; no human data.

Safety implication

None known from this study.

Study	Result	People	Product
⁶	Dose-dependent reductions in TNF-alpha, IL-6, IL-10 and IL-12 in stimulated mouse macrophages	Mouse macrophage cell line (J774A.1)	Two commercial goldenseal preparations

⁶

▼

Waist circumference

Lowered in trials

Distance around the waist; a rough measure of belly fat.

Low certainty

Results and what it means

Why it was measured

Component of metabolic syndrome.

Statistical vs. clinical meaning

Small drops; quality mixed.

Safety implication

None specific.

Study	Result	People	Product
²⁷	WMD -3.270 cm (-4.818 to -1.722)	Metabolic syndrome features	Berberine vs placebo
⁴⁷	MD -2.74 cm (-4.55 to -0.93) vs metformin	Women with PCOS	Berberine vs metformin

^{27 47}

↕

Systolic blood pressure

Mixed results in trials

The upper number in a blood pressure reading.

Not enough evidence

Results and what it means

Why it was measured

Heart and stroke risk marker.

Statistical vs. clinical meaning

Reviewers call the evidence inconclusive.

Safety implication

Do not stop blood pressure medicine without a doctor.

Study	Result	People	Product
⁴³	Berberine vs metformin: -11.87 mmHg (-16.64 to -7.10); berberine plus amlodipine not better than amlodipine alone	Hypertension, 7 trials	Berberine
²⁷	No significant effect vs placebo	Metabolic syndrome features	Berberine

^{43 27}

Safety

What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.

Main points to know 6

Goldenseal can change how the body handles many medicines. This is the best-documented risk. In healthy volunteers, goldenseal supplements cut the activity of two drug-processing enzymes, CYP2D6 (about 40% to 50%) and CYP3A4/5 (about 40%), and raised blood levels of the test drug midazolam by 40% to 60%. In people with type 2 diabetes and in healthy adults, goldenseal lowered metformin levels (ratios 0.93 overall, 0.77 in healthy adults, with the biggest drop at low metformin doses). It did not meaningfully change digoxin, rosuvastatin or furosemide, and one small study found no change in indinavir. Purified berberine raised cyclosporine levels by about 30% in kidney-transplant patients. Anyone on prescription medicine, especially a drug with a narrow safe range, should ask a doctor or pharmacist first. Controlled trial ^{12 14 15 33 35 13 42 46 34}
Avoid in pregnancy, while breastfeeding and in newborns. NCCIH says pregnant or breastfeeding women should not use goldenseal and it should not be given to infants, because berberine can harm newborns. Health Canada's monograph says do not use if pregnant or breastfeeding. LactMed says there are no data on goldenseal in breast milk, that berberine can push bilirubin off albumin (a worry for newborns), and that most sources advise avoiding exposure of newborns. A rat study found no extra malformations at 65 times the human dose, but the authors say human studies are needed, so this does not make it safe. Authoritative guidance ^{31 17 7 50}
Newborn jaundice and kernicterus (berberine). Berberine pushed bilirubin off its carrier protein in lab tests and raised free bilirubin in adult rats. A review of Chinese reports says berberine can cause severe red-blood-cell breakdown in babies with G6PD deficiency. Other work does not agree: a small adult study found no organ toxicity from berberine herbs, and an animal study found no jaundice induced in newborn rats. Singapore has banned two berberine herbs for decades over this concern. The evidence is conflicting, but because newborn brain damage from jaundice is serious, official guidance is to avoid it. Laboratory research ^{3 18 26 49 41 7}
Liver: tumours in rodents, no clear human liver injury signal for berberine. In two-year US National Toxicology Program studies, goldenseal root powder in feed caused liver tumours in rats and mice (clear evidence in rats, some evidence in male mice). The NTP authors suggest berberine blocking an enzyme called topoisomerase may be involved. These are high-dose animal studies and do not show cancer in people. The NIH LiverTox summary for berberine says it has not been linked to liver enzyme rises or clinically apparent liver injury. LiverTox's own goldenseal page was not read. Animal research ^{32 9 5 28}
Blood pressure and kidneys. Health Canada's monograph tells people with a kidney or blood pressure disorder to ask a health professional before use. No human trial of goldenseal on blood pressure was found. For berberine alone, trial evidence on blood pressure is limited and inconclusive, and a review notes berberine could add to blood pressure drugs. Authoritative guidance ^{17 43 8}
Over-harvesting and mislabelled products. Goldenseal is a wild forest plant listed under CITES Appendix II (since 1997 according to a US Forest Service bibliography), and wild populations have been greatly reduced by harvesting and habitat loss. Product quality is a problem too: in one check, hydrastine ranged from none to 2.93% and only 10 of 17 root products met a proposed standard, and metabolomics studies found commercial products made from other plants or mixtures. Authoritative guidance ^{37 19 10 44 39}

Side effects 6

Effect	How often	Severity and recovery	Evidence
No serious harm in small, short human studies NCCIH says about 3 g a day in small short-term studies caused no serious harm. Long-term safety is unknown.	Not established	not applicable not applicable	Authoritative guidance ³¹
Constipation or diarrhea and other gut upset (berberine) An umbrella review of berberine trials lists gut symptoms such as constipation and diarrhea as the common side effects; fatty-liver trials reported mild gut effects. Frequency is not given in the abstracts.	Not established	mild not stated	Meta-analysis ^{25 36}
Higher blood levels of other medicines (interaction) See the interactions section. These are measured blood-level changes in volunteers and patients, not reports of harm.	Not established	could be serious with narrow-range drugs not stated	Controlled trial ^{12 15 46}
Possible lower metformin levels In healthy adults metformin exposure fell 23%. In people with type 2 diabetes the overall change was within the no-effect range, but exposure fell about 20% at low metformin doses.	Not established	could affect blood sugar control not stated	Controlled trial ^{33 35 31}
Red-blood-cell breakdown and jaundice in G6PD-deficient newborns (berberine) Stated by a review of older Chinese reports; another review finds the evidence conflicting. No frequency is available.	Not established	severe not stated	Case series ^{18 26}
Light sensitivity, nerve toxicity (possible, lab based) Reviews list possible phototoxic, neurotoxic and hepatotoxic activity from lab and animal work. No confirmed human cases were found in the sources read.	Not established	unknown unknown	Laboratory research ^{29 41}

Liver

Human evidence: the NIH LiverTox summary for berberine says it has not been linked to serum enzyme rises or clinically apparent liver injury, and a berberine meta-analysis in fatty liver found ALT and AST fell. In kidney-transplant patients on berberine plus cyclosporine for three months no change in liver tests was seen. Animal evidence for whole goldenseal is different: in the 2-year NTP rat and mouse feeding studies, goldenseal root powder increased liver adenomas (and adenoma or carcinoma combined in male rats), with liver cell enlargement and degeneration at lower doses. An NTP-related review and a cell study point to berberine blocking topoisomerase II and damaging DNA in liver cells. The human relevance of these animal findings is not established. LiverTox's own goldenseal page was not read. ^{28 36 46 32 9 5}

How often. No case reports of goldenseal liver injury were found in the sources read, and no frequency is available. This does not prove none exist.

Monitoring. No monitoring protocol exists. People with liver disease, or who take medicines that can affect the liver, should ask a doctor before using goldenseal.

This is a safety connection. It is not evidence that Goldenseal supports liver health.

Medicines and supplements 9

With	Why it matters	Importance	Evidence	What to do
Drugs broken down by CYP2D6 pharmacokinetic (enzyme inhibition)	Goldenseal alkaloids (berberine, hydrastine, hydrastinine) inhibit CYP2D6 in lab tests, and goldenseal supplements cut CYP2D6 activity by about 40% to 50% in volunteers.	Could raise blood levels of medicines that rely on this enzyme. The size depends on the drug and the person (CYP2D6 gene type also varies).	Controlled trial Moderate certainty ^{12 14 30 4}	Ask a doctor or pharmacist whether any medicine you take is processed by CYP2D6.
Midazolam and other CYP3A4/5 drugs pharmacokinetic (enzyme inhibition)	Hydrastine is the main driver by time-dependent inhibition of gut-wall CYP3A, with berberine playing a smaller part, according to a modelling study.	Midazolam blood exposure rose 40% to 60% after a single dose and after repeated doses.	Controlled trial Moderate certainty ^{15 12 33 34}	Ask a doctor or pharmacist about any medicine processed by CYP3A.
Indinavir pharmacokinetic	Expected from CYP3A4 inhibition.	In 10 healthy volunteers, goldenseal root changed none of the measured indinavir values. This differs from the midazolam studies and is a small study.	Controlled trial Low certainty ⁴²	A null result in 10 people does not make goldenseal safe with HIV medicines; ask a pharmacist.
Cyclosporine (and tacrolimus-type transplant drugs) pharmacokinetic	Berberine alone raised cyclosporine levels in kidney-transplant patients; the authors point to CYP3A4 inhibition, and a rat study points to P-glycoprotein in the gut.	In a randomised trial, cyclosporine trough levels ended 29.3% higher with berberine, and AUC rose 34.5% in 6 patients. This was berberine alone; goldenseal contains less berberine and other alkaloids, so the size for goldenseal is unknown.	Controlled trial Moderate certainty ^{46 38 2}	People on transplant drugs should not add goldenseal or berberine unless their transplant team agrees.
Metformin pharmacokinetic (absorption)	Goldenseal appears to block a saturable gut transport step for metformin; half-life and kidney clearance did not change.	Metformin exposure fell by 23% in healthy adults (ratio 0.77, CI 0.71 to 0.83). In people with type 2 diabetes the overall ratio was 0.93 (0.86 to 1.01), but exposure fell about 20% at low and 14% at moderate metformin doses and not at high doses. NCCIH says this could weaken blood sugar control.	Controlled trial Moderate certainty ^{33 35 31}	People on metformin should ask their doctor before using goldenseal and should not change metformin on their own.
Digoxin pharmacokinetic (P-glycoprotein)	Tested as a P-glycoprotein substrate.	Goldenseal (a standardised supplement) raised digoxin peak concentration by 14% but changed no other measure. A rat study found berberine raised oral digoxin absorption in a dose-related way.	Controlled trial Low certainty ^{13 38}	No large effect was seen with goldenseal, but check with a pharmacist if you take digoxin.
Rosuvastatin and furosemide pharmacokinetic (transporters)	Tested as transporter probe drugs.	No effect of goldenseal on either drug in 16 healthy volunteers.	Controlled trial Low certainty ³³	No action needed from this result alone; ask a pharmacist.
Bosutinib and imatinib (cancer drugs) pharmacokinetic (computer prediction)	Modelled CYP3A inhibition by hydrastine and berberine.	A computer model predicted about a twofold rise in bosutinib exposure with goldenseal, and no important change for imatinib. Not yet confirmed in people.	Pharmacological theory Not enough evidence ²	People on targeted cancer drugs should ask their oncology team before using goldenseal.
Diabetes drugs, blood pressure drugs and QT-prolonging drugs pharmacodynamic (added effect)	A 2026 narrative review says berberine may add to blood sugar, blood pressure and QT-interval effects of drugs.	Mainly theoretical for goldenseal; human data for berberine are limited.	Pharmacological theory Not enough evidence ^{8 43}	Tell your doctor if you use berberine-containing supplements together with such drugs.

Who should check first 7

Situation	Advice	Evidence
Pregnancy	Do not use (NCCIH, Health Canada). Rodent data are reassuring at one dose but incomplete, and berberine is a concern for newborns.	Authoritative guidance ^{31 17 50 21}
Breastfeeding	Do not use (NCCIH, Health Canada). LactMed says most sources advise avoiding exposure of newborns, though how much berberine reaches the infant is unknown.	Authoritative guidance ^{31 17 7}
Babies and infants, especially newborns with jaundice	Do not give to infants (NCCIH). Berberine can displace bilirubin from albumin.	Authoritative guidance ^{31 3 7}
G6PD deficiency (for babies, and caution for anyone)	A toxicity review advises caution with berberine in G6PD deficiency; ask a doctor.	Case series ^{41 18}
Taking cyclosporine, other transplant drugs, or other medicines with a narrow safe range	Avoid unless the prescriber agrees; levels can change.	Controlled trial ^{46 12}
Taking metformin or other diabetes medicine	Ask a doctor first; goldenseal lowered metformin levels in studies.	Controlled trial ^{33 35}
Kidney or blood pressure disorder	Health Canada's monograph says ask a health professional before use.	Authoritative guidance ¹⁷

Overdose, product quality and regulators

Summary. The main toxicity signal is liver tumours in rodents fed goldenseal root powder for two years. No human toxicity trial exists. Human studies (NCCIH) point to no serious harm in small short-term use.

Animal. NTP, F344/N rats and B6C3F1 mice, up to 2 years: liver enlargement and liver cell changes from 2 weeks; liver adenomas in rats of both sexes, and adenoma or carcinoma combined in male rats, at the top feed level (about 1,175 to 1,340 mg/kg a day); hepatoblastoma and multiple adenomas in male mice; none in female mice. A separate developmental study of berberine in rats and mice found maternal weight and fetal weight effects at very high doses and deaths in 33% of treated female mice.

Human doses studied. Short human studies gave goldenseal supplements for up to 28 days to healthy volunteers (for example 3,210 mg a day for 14 days; 1,140 mg twice a day for 14 days; a single 2.7 g or 3 g dose). NCCIH describes about 3 g a day for short periods as causing no serious harm. These studies measured blood levels of other drugs and were not designed to find rare harms.

High dose or long term signals. Long-term human safety is unknown. Rodent liver findings came from daily lifelong feeding.

Overdose response. No overdose data were found in the sources read.

Genotoxicity. The NTP found goldenseal root powder not mutagenic in bacteria and no increase in micronucleated red cells in mouse blood after 3 months. In cultured human liver cells, berberine and palmatine caused DNA damage by blocking topoisomerase II, and commercial goldenseal extracts did too, in line with their berberine content.

Toxic plant parts. Not documented as a poisoning risk in the sources read. Supplements use the root and rhizome; in one check, products labelled "herb" (above-ground parts) had about a quarter of the alkaloid content of root products.

Goldenseal products are sometimes not what the label says. Roots from other berberine plants, other plants or mixtures have been found, and alkaloid content varies widely.

Alkaloid content varies. In 20 products, hydrastine ranged from 0 to 2.93% and berberine from 0.82% to 5.86%. Only 10 of 17 root products met proposed USP standards. Five had little or no hydrastine and unusual patterns. ¹⁰

Mixed with look-alike alkaloid plants. Powder from one of three suppliers also contained palmatine, coptisine and jatrorrhizine, which come from other berberine plants (such as Coptis), so it was not pure goldenseal. ⁴⁵

Non-goldenseal species and mixtures. LC-MS metabolomics of 35 commercial products found several outliers that came from a non-goldenseal species or a mixture of plant materials. An NMR and mass-spectrometry survey of products labelled blue cohosh, goldenseal or yohimbe also found outliers in each group. ^{44 39}

NCCIH warning. NCCIH notes some commercial products contain unlisted herbs or ingredients. ³¹

Heavy metals and pesticides. Not searched in this round; no goldenseal-specific data were read.

Body	Action	Date
NIH NCCIH (United States)	Says there is not enough evidence to say goldenseal helps any condition; advises against use in pregnancy and breastfeeding and in infants; warns of drug interactions and mislabelled products. source	Page updated February 2025
Health Canada (Canada)	Natural Health Product monograph for oral goldenseal root and rhizome: traditional uses only; do not use in pregnancy or breastfeeding; ask a professional first if you have a kidney or blood pressure disorder; take a few hours apart from other medicines. source	29 November 2024
US National Toxicology Program (United States)	Technical Report 562: clear evidence of carcinogenic activity (liver) in rats, some evidence in male mice, no evidence in female mice, feed studies of goldenseal root powder. source	2010
NIH LiverTox (berberine) (United States)	Berberine not linked to serum aminotransferase elevations or clinically apparent liver injury. source	2020-10-06
NIH LactMed (United States)	No data on goldenseal in breast milk; most sources advise avoiding exposure of newborns. source	2025-05-15

When to get medical help

Yellow skin or eyes, poor feeding or unusual sleepiness in a newborn who has been exposed to goldenseal (through breast milk or directly): get medical help at once.
Swelling of the face or throat, trouble breathing, or a spreading rash after taking it: stop and get emergency help.
Signs that another medicine is building up (for example for a transplant, heart or seizure medicine): new tremor, severe nausea, irregular heartbeat, confusion, or sedation: contact your doctor or pharmacist.
Blood sugar swings or new symptoms in someone with diabetes who has started it: contact your doctor.
Dark urine, severe belly pain or yellowing of the skin in an adult: stop and see a doctor.

Stop the supplement and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.

General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.

Frequently asked questions

Does goldenseal help with colds or infections?

There is no good human evidence that it does. NCCIH says there is not enough evidence to say goldenseal helps any health condition. Lab studies show germ-slowing in dishes, but that does not mean it works in the body.

^{31 29 11}

Is goldenseal the same as berberine?

No. Berberine is one of goldenseal's alkaloids and is also in other plants. Goldenseal also has hydrastine and canadine, and the amount of berberine in products varies. Almost all the trials with benefits are on purified berberine, so they do not prove goldenseal works.

^{10 1 34 31}

Can goldenseal interact with my medicines?

Yes. In volunteers, goldenseal supplements reduced CYP2D6 activity by about 40% to 50% and CYP3A4/5 by about 40%, raised midazolam levels by 40% to 60%, and lowered metformin levels. It did not change digoxin much. Purified berberine raised cyclosporine levels in transplant patients. Ask a doctor or pharmacist before combining it with any medicine.

^{12 14 15 33 35 13 46}

Is goldenseal safe in pregnancy or while breastfeeding?

NCCIH and Health Canada say no: do not use it in pregnancy or while breastfeeding. A rat study found no extra malformations, but the authors say human studies are needed. There are no data on goldenseal in breast milk.

^{31 17 7 50}

Why is it said to be dangerous for newborns?

In lab tests, berberine pushed bilirubin off its carrier protein, which could raise the risk of newborn jaundice causing brain damage. A review also says berberine can break down red blood cells in babies with G6PD deficiency. Other animal work did not find jaundice, so the evidence conflicts. Official advice is still to avoid it in newborns.

^{3 18 26 49 7}

Does goldenseal harm the liver?

It caused liver tumours in rats and mice in two-year National Toxicology Program studies of the whole root powder. That does not show cancer in people. The NIH LiverTox summary for berberine found no clinically apparent liver injury, but the LiverTox page for goldenseal itself was not read.

^{32 9 28 5}

Does goldenseal affect blood pressure?

No human trial of goldenseal on blood pressure was found. For berberine alone the evidence is limited and inconclusive. Health Canada advises people with a blood pressure or kidney disorder to ask a health professional first.

^{17 43 27}

Does berberine lower blood sugar and cholesterol?

Pooled trials of purified berberine report lower fasting glucose, HbA1c, LDL and triglycerides. The trial quality is mixed and none measured heart attacks. This is berberine, not goldenseal, and goldenseal can lower metformin levels.

^{48 23 27 35}

Is goldenseal endangered?

It is listed under CITES Appendix II (since 1997, per a US Forest Service bibliography), which controls international trade in wild plants. Wild populations have been greatly reduced by harvesting for the herbal trade and by habitat loss. Cultivated sources take pressure off wild plants.

^{37 19}

Are goldenseal products reliable?

Not always. One study found hydrastine from none to 2.93% across products, and only 10 of 17 root products met a proposed standard. Other studies found products made from other plants or mixtures. Results for one product do not apply to another.

^{10 45 44 39}

Is goldenseal approved by European or US regulators?

In the United States it is sold as a dietary supplement, which needs no pre-market proof of safety or effectiveness. Health Canada has a monograph of traditional uses. No EU (EMA/HMPC) herbal monograph was found, but the EMA list was not searched directly, so that is "not found" rather than "none exists".

^{17 7 31}

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Editorial transparency

Written by: AlternativeMed editorial team. Research compiled with AI assistance, then checked against PubMed records.
Medical review: None. This page has not been reviewed by a physician or pharmacist.
First published: 2026-10-25
Last substantive update: 2026-10-25
How we research: We searched PubMed, read the NCCIH goldenseal page, the Health Canada goldenseal monograph and a US Forest Service bibliography, and checked plant names in GBIF and the NCBI taxonomy and compounds in PubChem. Only abstracts were read for nearly all studies. Some sources were not verified: the NIH LiverTox page for goldenseal and the full LactMed and LiverTox pages (only short summaries were read through PubMed because the site blocked access), the CITES record itself, the EMA herbal medicines list, the ESCOP monograph, the German Commission E, and the WHO and FDA statements. Berberine-only studies are labelled as berberine and are not treated as goldenseal evidence. Certainty ratings are the compiler's own reading, not formal grades. No study is cited that we could not verify.
How we rate evidence: See "How we rate evidence" in the Evidence tab.
Independence: No product is promoted on this page. No affiliate links are shown. If one is added later it will be labelled and kept apart from the evidence.

Sources 55

Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.

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Adiwidjaja J, Boddy AV, McLachlan AJ. Physiologically based pharmacokinetic model predictions of natural product-drug interactions between goldenseal, berberine, imatinib and bosutinib.. Eur J Clin Pharmacol. 2022. PMID 35048143. DOI 10.1007/s00228-021-03266-y. (abstract)
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Gurley BJ, Swain A, Hubbard MA, et al.. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo.. Clin Pharmacol Ther. 2008. PMID 17495878. DOI 10.1038/sj.clpt.6100222. (abstract)
Ha S, Song X. Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials.. Explore (NY). 2024. PMID 39236662. DOI 10.1016/j.explore.2024.103040. (abstract)
Health Canada. Health Canada Natural Health Product monograph: Goldenseal (Hydrastis canadensis), oral. . 2024. (full-text (PDF))
Ho NK. Traditional Chinese medicine and treatment of neonatal jaundice.. Singapore Med J. 1996. PMID 9104069. (abstract)
Houston E, Burkhart EP, Zuiderveen G, et al.. Identification of Goldenseal (Hydrastis canadensis L.) Habitat and Indicators in Pennsylvania, USA: The Influence of Climate and Site on In Situ Conservation of an Edge of Range Plant Species.. Ecol Evol. 2025. PMID 40027423. DOI 10.1002/ece3.71050. (abstract)
Hu Q, Peng Z, Li L, et al.. The Efficacy of Berberine-Containing Quadruple Therapy on Helicobacter Pylori Eradication in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.. Front Pharmacol. 2019. PMID 32116685. DOI 10.3389/fphar.2019.01694. (abstract)
Jahnke GD, Price CJ, Marr MC, et al.. Developmental toxicity evaluation of berberine in rats and mice.. Birth Defects Res B Dev Reprod Toxicol. 2006. PMID 16634078. DOI 10.1002/bdrb.20075. (abstract)
Jiang X, Jiang C, Huang C, et al.. Berberine Combined with Triple Therapy versus Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials.. Evid Based Complement Alternat Med. 2018. PMID 30410559. DOI 10.1155/2018/8716910. (abstract)
Ju J, Li J, Lin Q, et al.. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials.. Phytomedicine. 2018. PMID 30466986. DOI 10.1016/j.phymed.2018.09.212. (abstract)
Lan J, Zhao Y, Dong F, et al.. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension.. J Ethnopharmacol. 2015. PMID 25498346. DOI 10.1016/j.jep.2014.09.049. (abstract)
Li Z, Wang Y, Xu Q, et al.. Berberine and health outcomes: An umbrella review.. Phytother Res. 2023. PMID 36999891. DOI 10.1002/ptr.7806. (abstract)
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LiverTox (NIDDK). Berberine (LiverTox). LiverTox (NIH). 2020. PMID 33242239. (abstract)
Mandal SK, Maji AK, Mishra SK, et al.. Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues.. Pharmacol Res. 2020. PMID 32683037. DOI 10.1016/j.phrs.2020.105085. (abstract)
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Quiroz-Delfi GO, Rider CV, Ferguson SS, et al.. Non-targeted chemical analysis of consumer botanical products labeled as blue cohosh (Caulophyllum thalictroides), goldenseal (Hydrastis canadensis), or yohimbe bark (Pausinystalia yohimbe) by NMR and MS.. Anal Bioanal Chem. 2024. PMID 37910202. DOI 10.1007/s00216-023-05004-y. (abstract)
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Wu X, Li Q, Xin H, et al.. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study.. Eur J Clin Pharmacol. 2005. PMID 16133554. DOI 10.1007/s00228-005-0952-3. (abstract)
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Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of goldenseal.. Birth Defects Res B Dev Reprod Toxicol. 2005. PMID 16193497. DOI 10.1002/bdrb.20055. (abstract)
. Hydrastine pharmacokinetics and metabolism after a single oral dose of goldenseal (Hydrastis canadensis) to humans.. . . (abstract)
. Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review.. . . (abstract)
. Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.. . . (abstract)
. GBIF Backbone: Hydrastis canadensis L. (usageKey 3033110). . . (full-text (API))
. NCBI Taxonomy: Hydrastis canadensis (taxid 13569). . . (full-text (API))

Where to buy

Check the label first. Whatever you buy, look for these:

The plant part and the extract type or ratio on the label
A standardized amount of the active compounds, where relevant
A third-party testing mark (USP, NSF or ConsumerLab)
Interactions: ask a pharmacist if you take medicines, are pregnant or have a medical condition

Talk to a pharmacist or doctor before you start any supplement, especially if you take medicines. See the Safety tab for interactions.

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Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.