Goldenseal
Also called Hydrastis canadensis, orangeroot, yellow root.
No graded human outcome yet Botanical Last checked
The short answer
From 12 sourcesGoldenseal is a North American root containing berberine and hydrastine. No rigorous human trial shows it helps any health condition, according to NIH. Its best-documented effect is on drug handling: goldenseal blocked CYP3A and CYP2D6 in volunteers and lowered metformin levels in healthy adults. Pregnancy, breastfeeding and infants are no-go groups.
Key facts
- Human efficacy trials
- None rigorous for any health condition, per NIH (NCCIH, 2025)1
- CYP enzymes
- About 40% inhibition of CYP3A4/5 and CYP2D6 after 28 days in 12 volunteers; about 50% CYP2D6 inhibition in a 16-person study23
- Midazolam (CYP3A probe)
- Blood levels (AUC) rose 40–60% with goldenseal, after a single 3 g dose or 1 g three times daily for 6 days75
- Metformin
- Exposure fell 23% in 16 healthy adults; in people with type 2 diabetes the overall change (7%) was within the no-effect range56
- Animal cancer data
- A 2-year US NTP feeding study found liver tumours in rats and male mice8
- Liver (LiverTox)
- No goldenseal chapter; berberine, its main alkaloid, has likelihood score E (unlikely cause of clinically apparent liver injury)12
What it is
Goldenseal is a North American root sold for colds and digestion; its alkaloids include berberine and hydrastine.
How it works
ProposedLab work shows that the goldenseal alkaloids berberine and (−)-β-hydrastine are time-dependent inhibitors of CYP3A in intestinal and liver microsomes, with hydrastine the stronger inhibitor; modelling suggests goldenseal mainly blocks gut CYP3A. Claimed antimicrobial and cholesterol-lowering actions come from cell and animal studies, not human trials of goldenseal.79
Forms, side by side
2 forms named in our sources. The rest show what our data holds, and say plainly where it holds nothing yet.
Goldenseal forms compared
2 forms| 2 forms | Root or rhizome powder | Extract standardized to berberine |
|---|---|---|
| Absorption in people | NIH notes that very little berberine may be absorbed when goldenseal is taken by mouth.1 | No head-to-head human data comparing extract and root powder.5 |
| GI tolerance | About 3 g/day for short periods was used in small studies without serious harmful effects; longer-term safety is uncertain.1 | Adverse events are not described in the abstracts of the cited interaction studies.56 |
| Studied for | Drug-interaction studies only (about 3 g/day) | Drug-interaction studies (CYP3A, transporters, metformin) |
- Goldenseal root or rhizome powder
- Absorption in people
- NIH notes that very little berberine may be absorbed when goldenseal is taken by mouth.1
- GI tolerance
- About 3 g/day for short periods was used in small studies without serious harmful effects; longer-term safety is uncertain.1
- Studied for
- Drug-interaction studies only (about 3 g/day)
- Extract standardized to berberine
- Absorption in people
- No head-to-head human data comparing extract and root powder.5
- Studied for
- Drug-interaction studies (CYP3A, transporters, metformin)
What the human research says
Human trials only, one row per outcome. The form line shows what each trial actually tested. Grades follow our evidence-grading policy.
No human trials met our inclusion bar yet. See how we grade evidence.
What the numbers add up to
Each point is worked out from the data and the sources numbered on this page, with the arithmetic shown under it. It adds no new data and is not medical advice.
A page about interactions, not benefits
Metformin effect shrinks at higher doses
In type 2 diabetes the metformin drop was about 20% at 500–750 mg, 14% at 1,000–1,500 mg and 0% at 2,000–2,550 mg, and average HbA1c did not rise during the study.6
Studied doses
Doses used in research, shown against the official limits. They describe the studies, not a recommendation for you.
Studied doses in research, not advice. These are amounts used in research, not personal advice. Your clinician or pharmacist can say what fits you.
Doses studied in human trials
Doses studied in human trials ranged from about 3 g/day of goldenseal (3,210 mg/day for 14 days, or 1 g three times daily for 6 days), and every one of those studies measured drug handling, not health benefits. A 28-day study did not state its dose in the abstract, and no efficacy trial has set a dose.1472
Interactions and safety
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
What Goldenseal meets
5 cited rowsMedicines 5
Supplements and foods 0
No supplement rows in our sources.
- Measured in a human study
Choose a medicine or supplement above to read its cited rows here.
Also cited:
Digoxin (P-glycoprotein substrate)
PK studyMeasured in a human study
Digoxin (P-glycoprotein substrate): 3,210 mg/day of goldenseal for 14 days did not significantly change digoxin exposure, apart from a 14% higher peak level.
Source 4, Drug Metab Dispos (2007)
Drugs cleared by CYP2D6
PK studyMeasured in a human study
Drugs cleared by CYP2D6, for example debrisoquine (the probe drug); many antidepressants, beta-blockers and codeine-type opioids are CYP2D6 substrates (inferred): About 40–50% inhibition of CYP2D6 activity (debrisoquine test) after 14–28 days of goldenseal; the authors warn of possible adverse interactions with CYP2D6 substrates.
Source 2, Clin Pharmacol Ther (2005); Source 3, Mol Nutr Food Res (2008)
Drugs cleared by CYP3A
PK studyMeasured in a human study
Drugs cleared by CYP3A, for example midazolam (the probe drug); many statins, calcium-channel blockers, immunosuppressants and some antiretrovirals use the same enzyme (inferred): Goldenseal raised midazolam exposure (AUC) by about 40–60% in healthy adults, mainly by blocking gut CYP3A; a 28-day study found about 40% lower CYP3A4/5 activity.
Source 7, J Pharmacol Exp Ther (2023); Source 5, Clin Pharmacol Ther (2021); Source 2, Clin Pharmacol Ther (2005)
Metformin
PK studyMeasured in a human study
Metformin: In 16 healthy adults, goldenseal cut metformin exposure by 23% (AUC ratio 0.77), which NIH says could hinder glucose control. In adults with type 2 diabetes, the drop was about 20% at low metformin doses and about 0% at high doses, with no clinically meaningful change overall.
Source 5, Clin Pharmacol Ther (2021); Source 6, Clin Transl Sci (2025); Source 1, National Center for Complementary and Integrative Health (NCCIH) (2025)
Rosuvastatin and furosemide (transporter probe drugs)
PK studyMeasured in a human study
Rosuvastatin and furosemide (transporter probe drugs): In the same 16-person probe-cocktail study that lowered metformin, goldenseal had no effect on rosuvastatin (BCRP and OATP1B1/3) or furosemide (OAT1/3) pharmacokinetics.
Source 5, Clin Pharmacol Ther (2021)
Interactions
5 agents| Agent | What the source says | Evidence |
|---|---|---|
| Medicines5 | ||
| Drugs cleared by CYP3Ae.g. midazolam (the probe drug); many statins, calcium-channel blockers, immunosuppressants and some antiretrovirals use the same enzyme (inferred) | Goldenseal raised midazolam exposure (AUC) by about 40–60% in healthy adults, mainly by blocking gut CYP3A; a 28-day study found about 40% lower CYP3A4/5 activity.752 | PK study |
| Drugs cleared by CYP2D6e.g. debrisoquine (the probe drug); many antidepressants, beta-blockers and codeine-type opioids are CYP2D6 substrates (inferred) | About 40–50% inhibition of CYP2D6 activity (debrisoquine test) after 14–28 days of goldenseal; the authors warn of possible adverse interactions with CYP2D6 substrates.23 | PK study |
| Metformin | In 16 healthy adults, goldenseal cut metformin exposure by 23% (AUC ratio 0.77), which NIH says could hinder glucose control. In adults with type 2 diabetes, the drop was about 20% at low metformin doses and about 0% at high doses, with no clinically meaningful change overall.561 | PK study |
| Digoxin (P-glycoprotein substrate) | 3,210 mg/day of goldenseal for 14 days did not significantly change digoxin exposure, apart from a 14% higher peak level.4 | PK study |
| Rosuvastatin and furosemide (transporter probe drugs) | In the same 16-person probe-cocktail study that lowered metformin, goldenseal had no effect on rosuvastatin (BCRP and OATP1B1/3) or furosemide (OAT1/3) pharmacokinetics.5 | PK study |
Check with what you take
Kept on this device onlyAdd what you take. We list every interaction our evidence profiles cite between Goldenseal and your picks, and between your picks.
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Add a supplement or medicine you take to check it against Goldenseal.
Starting from one medicine? The interaction checker rates how serious each pair is, on a curated list of 19 entries for 11 medicines. This cabinet has no severity rating: it lists every interaction row our supplement pages cite.
Who should be careful
5 groups- Pregnancy and breastfeeding
- NIH says women who are pregnant or breastfeeding should not use goldenseal. LactMed found no data on goldenseal in breast milk; because berberine can displace bilirubin from blood proteins, a concern for newborns, most sources it reviewed recommend avoiding newborn exposure through breastfeeding or otherwise.111
- Infants
- NIH says goldenseal should not be given to infants; its berberine can be harmful to newborns.1
- People on prescription medicines
- Goldenseal changes how the body handles several drugs, including midazolam and metformin; NIH advises talking with a clinician before use.157
Safety first
4 notesThe interaction data are stronger than any benefit data.
- Drug interactions
- Goldenseal is a clinical CYP3A and CYP2D6 inhibitor in volunteers, and it lowered metformin levels in healthy adults.2357
- Animal carcinogenicity
- The US National Toxicology Program reported clear evidence of liver tumours in male and female rats and some evidence in male mice fed goldenseal root powder for 2 years.8
- Skin reaction
- A 32-year-old woman had a sun-triggered rash while using a supplement containing ginseng, goldenseal and bee pollen; it is unclear which ingredient was responsible.10
- Legal status
- US: sold as a dietary supplement; NIH notes the FDA does not approve supplements before sale. Wild goldenseal has been overharvested.1
How the body handles goldenseal
3 notesGut effects explain most of what has been measured.
- Where it acts
- Midazolam AUC and peak level rose 40–60% while its half-life rose by 23% or less, which points to inhibition of CYP3A in the gut wall.7
- Metformin absorption
- Goldenseal lowered metformin exposure without changing its half-life or kidney clearance, suggesting it reduced absorption in the gut.56
- Berberine uptake
- Very little berberine may reach the blood when goldenseal is swallowed.1
How to read the label
What to check on the Supplement Facts panel.
How to read the label
3 checksGoldenseal is not berberine
Berberine studies may not apply to goldenseal, because little berberine may be absorbed from goldenseal taken by mouth.1
Check the plant
NIH reports that some goldenseal products contained other herbs or ingredients not on the label, in addition to or instead of goldenseal.1
Frequently asked questions
Short answers to common questions; the numbers link to the sources below.
Common questions
7 answersDoes goldenseal work for colds?
NIH says no rigorous human studies have tested goldenseal for any health condition, including colds.1
Do goldenseal products always contain goldenseal?
Not always. NIH reports that some products contained other herbs or ingredients not on the label, in addition to or instead of goldenseal.1
Is long-term goldenseal use safe?
Does goldenseal interact with medications?
Is goldenseal safe in pregnancy?
NIH says goldenseal should not be used during pregnancy or breastfeeding or given to infants.1
Is goldenseal the same as berberine?
No. Berberine is one alkaloid in goldenseal, and little of it may be absorbed from goldenseal by mouth, so berberine trials may not apply.1
Can goldenseal help pass a urine drug test?
No good evidence. LactMed notes goldenseal has been used to try to mask illicit drugs in urine, but it appears ineffective with modern laboratory methods.11
Sources
12 sources: trial abstracts, NIH fact sheets and reference databases. Numbers in the text link here.
Sources cited on this page
12 sources- 1GoldensealFact sheet National Center for Complementary and Integrative Health (NCCIH), 2025 · nccih.nih.gov
- 2In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.PK study Clin Pharmacol Ther, 2005 · PMID 15900287
- 3Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea.PK study Mol Nutr Food Res, 2008 · PMID 18214849
- 4Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.PK study Drug Metab Dispos, 2007 · PMID 17079360
- 5Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.PK study Clin Pharmacol Ther, 2021 · PMID 33174626
- 6The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose-Dependent: A Three-Arm Crossover Study in Adults With Type 2 Diabetes.PK study Clin Transl Sci, 2025 · PMID 39943692
- 7An 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.PK study J Pharmacol Exp Ther, 2023 · PMID 37541764
- 8Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1 mice (feed studies).Animal study Natl Toxicol Program Tech Rep Ser, 2010 · PMID 21372858
- 9Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues.Review Pharmacol Res, 2020 · PMID 32683037
- 10Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen.Observational J Toxicol Clin Toxicol, 2003 · PMID 14677798
- 11GoldensealDatabase LactMed (NCBI Bookshelf), 2025 · ncbi.nlm.nih.gov
- 12BerberineDatabase LiverTox (NCBI Bookshelf), 2020 · ncbi.nlm.nih.gov
What changed
Every dated change to this page: what changed, who made it and why.
Change log
3 entries| Date | Change | Who and why |
|---|---|---|
| who should avoid, key facts, interactions, FAQ, questions, related | Added LactMed (no milk data; berberine and newborn bilirubin concern; urine drug-test masking appears ineffective) and LiverTox (no goldenseal chapter; berberine likelihood score E) with a liver note, the no-effect rosuvastatin and furosemide results from the 2021 probe-cocktail study, an FAQ on drug tests, page questions and goal-hub links. Evidence search (PubMed goldenseal or Hydrastis canadensis human studies, through October 2026) found no efficacy trial in people, so the evidence table stays empty; NCCIH (re-read 2026-10-21) still says no rigorous studies have been done. No new drug-interaction study since the 2025 metformin crossover. | Writer: Kymata Health EditorialTrigger: A–Z audit against docs/supplements/AUDIT-STANDARD.md |
| all | Adversarial review pass: every evidence row, key fact, interaction, safety note and FAQ re-read against its PubMed abstract or source page, and every number machine-checked against the cited source text. Retraction, expression-of-concern and withdrawn checks on all PMIDs: none flagged. Fixes: studied-dose text now separates the 14-day and 6-day doses from the 28-day study with no stated dose; extract tolerability reworded (abstracts do not describe adverse events); an unsupported urine-test FAQ replaced with the NIH label-accuracy finding. | Writer: Kymata Health EditorialTrigger: review |
| all | Initial editorial evidence review (first draft). Every PMID checked against NCBI E-utilities esummary (titles and years taken from the record) and the abstract read for each cited row. Studied doses are reported as research doses, not dosing advice. | Writer: Kymata Health EditorialTrigger: new page |
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