Goldenseal (Hydrastis canadensis)

Hydrastis canadensis
Evidence Level
Preliminary
2 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

Goldenseal is a North American woodland plant whose root and rhizome contain berberine — the same isoquinoline alkaloid found in berberis, barberry, and Chinese goldthread. No published clinical trial has tested goldenseal itself for infection, immune function, digestion or blood sugar. The human studies that exist are drug-interaction studies, and they show goldenseal inhibits the CYP3A4 and CYP2D6 enzymes that clear a large share of prescription medicines. Claims made for goldenseal are extrapolated from isolated berberine, which is studied at 1,000 to 1,500 mg per day: a 500 to 1,000 mg serving of goldenseal root contains roughly 10 to 40 mg of berberine, so it does not deliver anything close to a berberine trial dose. Wild goldenseal is listed on CITES Appendix II, so choose cultivated, sustainably sourced root.

Studied Dose No efficacy trial has established a dose. Human studies gave about 3 g/day of a standardized goldenseal root supplement for 14 to 28 days, and those measured drug metabolism, not a health outcome.
Active Compound Berberine (roughly 2 to 4 percent of dried root), hydrastine (roughly 2 to 4 percent) and canadine. At those concentrations, 500 to 1,000 mg of root powder supplies about 10 to 40 mg of berberine, far below the 1,000 to 1,500 mg per day used in berberine clinical trials.

Benefits

Antimicrobial activity in laboratory tests only

Berberine, one of goldenseal's alkaloids, inhibits a range of bacteria, fungi and protozoa in culture, and goldenseal extracts do the same in petri-dish tests. The published goldenseal work on immune function and respiratory infection is limited to laboratory studies and one study in rats; there is no controlled study in people. Nothing here has been shown to shorten a cold or clear an infection in a person, and berberine is poorly absorbed from the gut, under 5 percent, so blood levels after a goldenseal capsule are low.

Digestive use rests on isolated berberine, not on goldenseal

A 1987 randomized trial in Bangladesh gave 165 adults with acute infectious diarrhea a single 400 mg dose of isolated berberine sulfate. In the E. coli group, 42 percent had stopped having diarrhea at 24 hours versus 20 percent of controls; in the cholera group the effect was slight, and adding 1,200 mg of berberine to tetracycline gave no reduction in stool output over tetracycline alone. That was purified berberine at a dose a goldenseal capsule does not contain, given to patients with acute tropical infections. Goldenseal itself has never been tested for diarrhea.

Blood sugar: no goldenseal trial has measured it

Isolated berberine at 1,000 to 1,500 mg per day lowers fasting glucose and HbA1c in trials in type 2 diabetes. Goldenseal has never been tested against blood sugar, and it does not supply that amount of berberine. What goldenseal has been shown to do is reduce the absorption of metformin: in a study in 16 healthy adults it cut metformin exposure by about 23 percent, and in a crossover study in adults with type 2 diabetes exposure fell about 20 percent at metformin doses of 500 to 750 mg per day, though across all metformin doses the overall change was small enough to sit inside the no-effect range. Anyone taking a diabetes medicine should treat goldenseal as a possible interaction rather than a blood sugar aid.

Mucous membrane tonic: a traditional use, not a tested one

Nineteenth-century eclectic physicians used goldenseal as an astringent wash and tonic for inflamed mucous membranes, which is why it still appears in cold and sinus formulas. No study has measured mucus, congestion, sinus symptoms or gut inflammation in people taking goldenseal. Treat this as tradition, not as a demonstrated effect.

Mechanism of action

1

Berberine AMPK activation in cell and animal work

In cell and animal work, berberine activates AMP-activated protein kinase (AMPK) by inhibiting mitochondrial Complex I, which increases glucose uptake and fatty acid oxidation and damps NF-kB signalling. This is berberine pharmacology at concentrations reached with isolated berberine supplements. It has not been shown to occur after a goldenseal dose.

2

Antimicrobial membrane disruption

Berberine inserts into bacterial DNA, inhibiting topoisomerase II and DNA gyrase required for replication. Additionally, berberine disrupts bacterial membrane integrity, inhibits bacterial adhesion to epithelial cells, and reduces biofilm formation — providing several antimicrobial mechanisms in culture against gram-positive and gram-negative organisms. These are concentrations achieved in a test tube, not levels reached in blood after swallowing goldenseal.

3

Hydrastine mucosal astringency

Hydrastine is goldenseal's second major alkaloid and was historically used as a vasoconstrictor. The astringent, secretion-drying effect attributed to it comes from traditional practice rather than from measurement, and no study has compared goldenseal with isolated berberine for any mucosal condition.

Clinical trials

1
Isolated berberine, not goldenseal: 1987 randomized trial in acute infectious diarrhea
PubMed

Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K. J Infect Dis 1987;155(5):979-84 (PMID 3549923). Randomized controlled trial of berberine sulfate in 165 adults in Bangladesh with acute diarrhea from enterotoxigenic E. coli or Vibrio cholerae: a single 400 mg oral dose versus untreated control, and 1,200 mg plus tetracycline versus tetracycline alone in the cholera arms.

165 adults in Bangladesh with acute infectious diarrhea, given isolated berberine sulfate rather than goldenseal.

In the E. coli group, mean stool volumes were lower than controls over the three 8-hour periods after dosing, and 42 percent versus 20 percent of controls had stopped having diarrhea at 24 hours. In cholera the effect was slight, and 1,200 mg of berberine added to tetracycline produced no reduction in stool output over tetracycline alone. There was no placebo arm; the comparison was against untreated controls. The paper's own conclusion was that berberine is effective for E. coli diarrhea but that its activity against cholera is slight and not additive with tetracycline. This tested purified berberine sulfate at a dose roughly ten to forty times what a standard goldenseal capsule contains.

2
Not a clinical trial: no goldenseal efficacy study has been published

This is a summary of the published literature, not a study. Searching PubMed for goldenseal or Hydrastis with the clinical-trial filter returns six records, all of them drug-interaction pharmacokinetic studies. Searches for goldenseal with immune, common cold or upper respiratory outcomes return only laboratory work, one study in rats, and drug-interaction studies.

None. No people were studied, because no such trial exists.

Claims that goldenseal raises secretory IgA or natural killer cell activity come from traditional use, cell studies and one study of antibody production in rats, not from human trials. Goldenseal extracts do inhibit bacteria in culture. Berberine is poorly absorbed orally, under 5 percent, so blood levels after a goldenseal capsule are low. A 2020 critical review of goldenseal in Pharmacological Research concluded that large randomized double-blind clinical studies still need to be conducted on goldenseal supplements and their main alkaloids.

Side effects and drug interactions

Common Potential side effects

GI effects (nausea, vomiting, diarrhea) at high doses. In the US National Toxicology Program two-year feeding studies, goldenseal root powder caused liver tumours in rats of both sexes and in male mice, with liver cell enlargement in every exposed group of rats; it was not mutagenic, and there was no such effect in female mice. Those were dietary doses many times a human serving, but the liver was the target organ at every exposure level, so open-ended daily use is not advisable.
Uterine stimulant — contraindicated during pregnancy
May cause skin and mucous membrane yellowing at very high doses (berberine pigment)
Not recommended for infants: berberine displaces bilirubin from albumin, which can raise the risk of kernicterus in a newborn

Important Drug interactions

Drug metabolism, and this is goldenseal's biggest practical risk. In controlled studies in healthy adults, 14 to 28 days of standardized goldenseal inhibited CYP3A4/5 and CYP2D6 activity by about 40 percent and raised exposure to the test drug midazolam by 43 to 62 percent. Between them these two enzymes handle a large share of prescription medicines, including several statins, calcium channel blockers, benzodiazepines, and some antidepressants and antipsychotics, whose levels can rise. For codeine and tramadol the effect runs the other way: CYP2D6 has to convert them into their active form, so blocking it can leave them working less well. Ask a prescriber or pharmacist before taking goldenseal with any prescription medicine.
Warfarin: goldenseal has not been tested against warfarin in people, and human studies have not found goldenseal to inhibit CYP2C9. Because warfarin has a narrow safety margin, do not add goldenseal without telling the clinician who manages the INR.
Metformin: goldenseal lowers metformin absorption. In 16 healthy adults it cut metformin exposure by about 23 percent, and in adults with type 2 diabetes exposure fell about 20 percent at metformin doses of 500 to 750 mg per day and less at higher doses, with the effect across all doses falling inside the no-effect range. Renal clearance and half-life were unchanged. The direction is less drug, not more, so glucose control could drift rather than overshoot. Tell your prescriber if you take both.
Digoxin and other transporter substrates: goldenseal at about 3 g per day for 14 days did not meaningfully change digoxin pharmacokinetics in a controlled human study, so goldenseal is not a strong P-glycoprotein inhibitor and the enzyme effects above should not be assumed to extend to drugs handled mainly by transporters. Goldenseal is not a substitute for an antibiotic and should not be used to self-treat an infection.

Frequently asked questions about Goldenseal (Hydrastis canadensis)

What is goldenseal used for?

Goldenseal is a North American woodland herb whose root is sold for colds, sinus complaints and digestive upset, often combined with echinacea. It contains berberine, which is antimicrobial in laboratory tests. None of those uses has been tested in a clinical trial of goldenseal.

Does goldenseal help with colds and infections?

There is no controlled trial of goldenseal for colds or infections. The use is traditional, and the echinacea pairing is a marketing convention rather than a tested combination.

How much goldenseal should I take?

No trial has established an effective dose, so label amounts rest on tradition rather than evidence; typical products give 500 to 1,000 mg of root, taken short-term. Because wild goldenseal is listed on CITES Appendix II as a species at risk from trade, choose cultivated, sustainably sourced root.

Is goldenseal safe?

Short courses are usually tolerated, but goldenseal has one of the better documented herbal drug interactions: it inhibits the CYP3A4 and CYP2D6 enzymes that clear a large share of prescription drugs, by about 40 percent in controlled human studies, which can push the levels of those drugs up. It also lowers the absorption of metformin. Avoid it in pregnancy and breastfeeding and in newborns. If you take any prescription medicine, ask a pharmacist or prescriber before using it.

What is Goldenseal?

Goldenseal is a North American woodland plant whose root and rhizome contain berberine — the same isoquinoline alkaloid found in berberis, barberry, and Chinese goldthread. No published clinical trial has tested goldenseal itself for infection, immune function, digestion or blood sugar.

What is the recommended dosage of Goldenseal?

The clinically studied dose is No efficacy trial has established a dose. Human studies gave about 3 g/day of a standardized goldenseal root supplement for 14 to 28 days, and those measured drug metabolism, not a health outcome. Always follow the product label and check with a healthcare provider for personal advice.

Is Goldenseal safe, and does it have side effects?

For most healthy adults, Goldenseal is well tolerated at studied doses. Reported effects can include: GI effects (nausea, vomiting, diarrhea) at high doses. In the US National Toxicology Program two-year feeding studies, goldenseal root powder caused liver tumours in rats of both sexes and in male mice, with liver cell enlargement in every exposed group of rats; it was not mutage… It may also interact with some medications. Goldenseal is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Goldenseal interact with any medications?

Possible interactions include: Drug metabolism, and this is goldenseal's biggest practical risk. In controlled studies in healthy adults, 14 to 28 days of standardized goldenseal inhibited CYP3A4/5 and CYP2D6 activity by about 40 percent and raised exposure to the test drug midazolam by 43 to 62 percent. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Goldenseal?

NutraSmarts rates the evidence for Goldenseal as Preliminary (1 out of 5). It is backed by 2 clinical trials and 8 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(8 citations)

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

  1. Gurley BJ, Swain A, Barone GW, Williams DK, Breen P, Yates CR, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metabolism and Disposition. 2007;35(2):240-5.PubMedUsed to support: A controlled study in 20 healthy adults. Fourteen days of a standardized goldenseal supplement at 3,210 mg per day did not meaningfully change the pharmacokinetics of digoxin, a P-glycoprotein substrate, apart from a 14 percent rise in peak concentration, while the positive control drugs rifampin and clarithromycin changed digoxin exposure substantially. The authors concluded that goldenseal is not a potent modulator of P-glycoprotein in the body.
  2. Ding J, Yan Z, Peng L, Li J, Yang F, Zheng D Inhibitory effects of berberine on fungal growth, biofilm formation, virulence, and drug resistance as an antifungal drug and adjuvant with prospects for future applications. World Journal of Microbiology & Biotechnology. 2024;41(1):5. doi: 10.1007/s11274-024-04223-4.PubMedUsed to support: A review of berberine, one of goldenseal's alkaloids, covering laboratory and animal work on its activity against fungal growth, biofilm formation, virulence and drug resistance, and its possible use as an antifungal drug or adjuvant. The authors state that robust in vivo and clinical studies are scarce, so berberine's antifungal efficacy and safety are not established. No people were studied and goldenseal itself was not tested.
  3. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes Clinical Pharmacology and Therapeutics. 2005;77(5):415-26.PubMedUsed to support: Twelve healthy volunteers took goldenseal for 28 days. Goldenseal inhibited CYP2D6 and CYP3A4/5 activity by roughly 40 percent, while black cohosh, kava and valerian did not, leading the authors to warn that serious adverse interactions may result from taking goldenseal with drugs cleared by those two enzymes. This study measured drug metabolism, not any health outcome.
  4. Gurley BJ, Swain A, Hubbard MA, Hartsfield F, Thaden J, Williams DK, Gentry WB, Tong Y Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo Clinical Pharmacology and Therapeutics. 2008;83(1):61-9.PubMedUsed to support: Sixteen healthy volunteers took goldenseal for 14 days. Exposure to the CYP3A probe drug midazolam rose from 108 to 175 nanogram-hours per millilitre, an increase of about 60 percent, and its half-life rose from 2.0 to 3.2 hours. Kava had no such effect. This confirms goldenseal slows the clearance of CYP3A substrate drugs; it did not test goldenseal for any health benefit.
  5. Nguyen JT, Arian CM, Tanna RS, Cherel MG, Layton ME, White JR, Thummel KE, Paine MF 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 Clinical and Translational Science. 2025;18(2):e70120. doi: 10.1111/cts.70120.PubMedUsed to support: An open-label crossover study in adults with type 2 diabetes taking 500 to 2,550 mg of metformin daily. Goldenseal reduced metformin exposure by about 20 percent at metformin doses of 500 to 750 mg, 14 percent at 1,000 to 1,500 mg, and not at all at the highest doses, without changing renal clearance or half-life. The authors advise cautioning patients about adding goldenseal to metformin because of the risk of unwanted changes in blood sugar control.
  6. Mandal SK, Maji AK, Mishra SK, Ishfaq PM, Devkota HP, Silva AS, Das N Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues Pharmacological Research. 2020;160:105085.PubMedUsed to support: A critical review of the goldenseal literature. It finds that the reported antimicrobial, anti-inflammatory, glucose-lowering and lipid effects come from extracts and isolated alkaloids rather than from trials of goldenseal in people, notes reports of neurotoxic, hepatotoxic and phototoxic activity of goldenseal extract and its alkaloids, and concludes that large randomized double-blind clinical studies still need to be conducted before goldenseal's clinical efficacy can be judged.
  7. National Toxicology Program Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis canadensis) in F344/N rats and B6C3F1 mice (feed studies) National Toxicology Program Technical Report Series. 2010;(562):1-188.PubMedUsed to support: A two-year feeding study of goldenseal root powder in rats and mice. It found clear evidence of carcinogenic activity in male and female rats, based on increased liver adenomas and, in males, adenoma or carcinoma combined, and some evidence in male mice. Liver cell enlargement occurred in every exposed group of rats. Goldenseal root powder was not mutagenic in bacterial or micronucleus assays. These were dietary doses far above a human supplement serving and the study was in animals, not people, but the liver was the affected organ at every exposure tested.
  8. Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae The Journal of Infectious Diseases. 1987;155(5):979-84.PubMedUsed to support: A randomized controlled trial in 165 adults in Bangladesh with acute infectious diarrhea. A single 400 mg dose of isolated berberine sulfate reduced stool volumes in the E. coli group and stopped diarrhea by 24 hours in 42 percent of patients versus 20 percent of controls. In cholera the effect was slight, and 1,200 mg of berberine plus tetracycline gave no reduction in stool output over tetracycline alone. The trial tested purified berberine sulfate, not goldenseal, at a dose roughly ten to forty times the berberine content of a standard goldenseal capsule.