North American woodland plant with centuries of traditional use as a mucosal antiseptic, but no clinical evidence of efficacy for any indication. Most significant medically for potent CYP enzyme inhibition — goldenseal can substantially increase or decrease blood levels of dozens of pharmaceuticals.
Traditions: Cherokee, Iroquois, Crow, Eclectic medicine
Root decoctions for mouth sores, sore throats, and conjunctivitis — the origin of the folk name 'eye root.' Root applied topically as antiseptic wound dressing. Yellow rhizome used as dye for baskets and clothing ('Indian dye').
Bitter digestive tonic for liver support and nausea; topical preparations for skin infections and eye washes. Yellow rhizome dye documented across multiple nations.
Elevated to one of their primary botanical medicines. Felter & Lloyd's King's American Dispensatory (1898) describes it as specific for 'catarrhal states of all mucous surfaces' — respiratory, GI, urinary, ophthalmic. Listed in the US Pharmacopeia 1831–1936. Explicitly noted that pregnancy was a contraindication due to uterotonic effects.
No RCTs have ever tested goldenseal for any therapeutic indication. Every human clinical trial has measured pharmacokinetic endpoints — specifically, how much goldenseal disrupts pharmaceutical drug metabolism. What is well-documented: 40–62% inhibition of CYP3A4 and 40–50% inhibition of CYP2D6, making this one of the most clinically significant supplement-drug interaction risks. NCCIH conclusion: 'not enough evidence to determine whether goldenseal is useful for any health condition.'
16 healthy adults; midazolam AUC increased 62% after 14 days supplementation. CYP clearance decreased from 1.26 to 0.81 L/h/kg.
16 healthy adults; 43% midazolam AUC increase; inhibition is primarily intestinal CYP3A (not hepatic); metformin exposure reduced 23% (GMR 0.77)
54 healthy adults; ~50% CYP2D6 inhibition; strongest effect among 6 herbs tested. Only goldenseal produced measurable CYP2D6 inhibition (all other herbs near baseline).
2-year rodent feeding study: 'clear evidence of carcinogenic activity' in male and female rats; hepatocellular adenoma and carcinoma. Berberine identified as topoisomerase II inhibitor causing DNA double-strand breaks in human liver cells.
Most common contemporary form. Choose 'goldenseal root,' not 'goldenseal herb' — root products average 4× higher alkaloid content. Standardized products should specify ≥2.0% hydrastine and ≥2.5% berberine.
Taste: Intensely bitter, astringent, sharp. The Eclectics considered the bitterness the 'tonic signature.' Hard to mask.
1:10 in 60–70% ethanol (traditional Eclectic ratio). Quality tinctures contain ~4,000–5,000 μg/mL per alkaloid. Should stain intensely yellow-orange — if the liquid looks tan or clear, quality is suspect.
Traditional preparation. Deep canary yellow. Used both internally (short-term) and as topical wound wash.
Traditional antiseptic application. Carries less systemic risk than internal use. Do not use homemade preparations as eye washes — contamination risk; safer alternatives exist.
Goldenseal is one of the best-selling herbs in North America, positioned as an immune support supplement. The actual clinical evidence tells a different story — and the story it does tell is worth understanding.
What the human trials actually show:
No RCT has ever tested goldenseal for a therapeutic outcome — not respiratory infections, not UTIs, not digestive complaints, not wound healing. Every published human clinical trial has tested one question: how does goldenseal affect the enzymes that metabolize pharmaceutical drugs?
The answer is: substantially.
NCCIH’s current assessment: “Not enough evidence to determine whether goldenseal is useful for any health condition.”
What preclinical evidence suggests:
The antimicrobial activity is real in laboratory settings. Berberine shows activity against common pathogens in vitro, and whole-plant extracts appear more potent than isolated berberine — consistent with synergistic flavonoid mechanisms. The traditional antimicrobial model is pharmacologically plausible. But “plausible in a lab dish” and “effective in a human trial” are different claims, and no one has run that trial.
A serious safety signal:
A 2-year National Toxicology Program feeding study found “clear evidence of carcinogenic activity” — the strongest NTP classification — in both male and female rats, producing hepatocellular adenoma and carcinoma [4]. An FDA/NCTR follow-up identified the mechanism: berberine inhibits topoisomerase II, causing DNA double-strand breaks detectable in human liver cells at doses achievable from commercial goldenseal products [5]. Human cancer risk hasn’t been formally established, but this changes the calculus for long-term use.
Goldenseal has one of the more coherent traditional records among North American plants — not because it’s been clinically validated, but because its uses show internal consistency across independent traditions over centuries.
Native American origins: The names tell the history. “Eye root” comes from Cherokee use of root preparations for conjunctivitis. “Yellow root” and “Indian dye” come from the intensely yellow rhizome used as dye for baskets and clothing. Pre-contact and 19th-century ethnobotanical records document root decoctions for mouth sores and sore throats, topical wound dressings, digestive tonics (Iroquois, Crow), and eye washes. The coherent theme: inflamed or infected mucous membranes, treated short-term.
Eclectic medicine (1850–1930): American Eclectic physicians built one of the most detailed materia medica records for any native herb. Felter & Lloyd’s King’s American Dispensatory (1898) describes goldenseal as the specific remedy for “catarrhal states of all mucous surfaces” — respiratory, GI, urinary, ophthalmic. It was listed in the US Pharmacopeia from 1831 to 1936.
The Eclectics also documented what we now recognize as a major contraindication: goldenseal stimulates uterine contractions. This was explicitly noted as a caution against use in pregnancy — the same uterotonic activity we now understand is mediated by hydrastine and berberine.
What traditional use tells us: The historical pattern is short-term, acute use for mucosal infections — not indefinite daily supplementation for “immune support.” That shift is a modern commercial invention with no traditional precedent and no clinical evidence behind it.
Given the absence of efficacy evidence and real drug interaction risk, the most defensible approach follows the traditional model: short-term, acute use for people taking no pharmaceutical medications.
Before anything else, check your medications. Goldenseal inhibits CYP3A4 by 40–62% [1][2] — which metabolizes roughly 50% of all pharmaceuticals — and CYP2D6 by 40–50% [3]. If you take any of the following, goldenseal carries meaningful interaction risk:
Oral use (7–14 days maximum):
| Form | Dose | What to look for |
|---|---|---|
| Dried root capsule | 500mg–1g, 2–3× daily | ”Goldenseal root” (not “herb”); ≥2.0% hydrastine and ≥2.5% berberine |
| Tincture (1:10) | 2–4mL, 3× daily | Should stain intensely yellow-orange; if tan or clear, poor quality |
| Root decoction | 1–2 tsp root, simmered 15–20 min | Traditional preparation; useful for short-term acute use |
Topical use (wound wash, dilute decoction for skin) carries fewer systemic risks and has the strongest traditional support. Do not use homemade preparations as eye washes — contamination risk makes this unsafe despite historical precedent.
Before starting:
During use (keep it short):
Stopping: CYP inhibition has an irreversible component. Even after stopping goldenseal, enzyme activity takes 2–4 weeks to fully recover. Plan accordingly if starting new medications.
Potentially appropriate:
Not appropriate:
Drug test masking: Goldenseal does not mask THC or other drug metabolites in urine testing. This belief originates from a 1900 novel (John Uri Lloyd’s Stringtown on the Pike) and has been tested and disproven. Using goldenseal specifically to pass a drug test has no pharmacological rationale.
Goldenseal has one of the most unmistakable signatures of any American herb. The rhizome is a vivid canary yellow — deep enough to stain skin and clothing immediately. This color is berberine, the same alkaloid that makes turmeric yellow and Oregon grape root yellow. A quality tincture should stain your tongue and fingers orange-yellow on contact. If your preparation looks tan or is tasteless, something has gone wrong: poor-quality root, adulteration (Oregon grape and barberry are common substitutes), or expired product.
The taste is intensely bitter and astringent — sharp in a way that’s distinct from most bitters. The Eclectic physicians associated this intensity with its mucous membrane action. Capsules avoid it entirely. There’s no good way to mask it in a decoction.
The quality problem in goldenseal is worse than most herbs. A 2003 survey of 20 commercial products found 41% failed proposed USP alkaloid standards — and some products contained zero detectable hydrastine [6].
What to verify:
Common adulterants: Oregon grape root (Mahonia aquifolium), barberry bark, goldthread (Coptis), and celandine all contain berberine and look similar. They can pass basic color/taste tests but have different alkaloid ratios and pharmacological profiles. HPLC testing distinguishes them.
Sustainability: Wild goldenseal is listed on CITES Appendix II and classified as “at-risk” by United Plant Savers. Its native range has been severely depleted by overharvesting. Cultivated goldenseal is the ecologically appropriate choice — ask suppliers about sourcing.
Goldenseal’s traditional uses are coherent and internally consistent: a short-term mucosal antiseptic for acute conditions, used by multiple independent American traditions over centuries. The pharmacological plausibility is real — antimicrobial activity in vitro, whole-plant synergy that isolated berberine lacks.
What doesn’t hold up: the modern use case. There is no clinical trial showing goldenseal treats infections, supports immune function, or improves any outcome a person might care about.
What is well-documented: goldenseal is one of the most significant supplement-drug interaction risks available without a prescription. The CYP inhibition is reproducible, substantial (40–62%), and persistent for weeks after stopping. The carcinogenicity signal from the NTP rodent study is among the strongest a dietary supplement has produced.
Short-term topical or acute oral use in people taking no medications: reasonable risk profile if you source quality product and stay within 7–14 days.
Daily supplementation as an “immune herb”: no evidence, meaningful risks, no traditional precedent for this pattern. The gap between goldenseal’s commercial reputation and its evidence base is one of the widest in American herbalism.
Duration: If used at all: short-term only (7–14 days maximum for acute conditions). No basis for indefinite daily supplementation — no efficacy evidence, and ongoing CYP inhibition affects pharmaceutical medications.
What to notice:
Before starting, list all medications including OTC drugs and other supplements. The CYP interaction is not subtle — a 40–62% increase in benzodiazepine or statin blood levels is clinically meaningful. The inhibition has an irreversible component; effects persist 2–4 weeks after stopping. Topical use (wounds, skin) carries far less systemic risk than oral use and follows the best-supported traditional pattern.
Generally considered: caution
Contraindications:
Pregnancy/Nursing: Absolutely contraindicated in pregnancy and breastfeeding. Berberine is uterotonic, may stimulate uterine contractions, crosses the placenta, and causes kernicterus risk in neonates via bilirubin displacement from albumin.
CYP inhibition occurs at commercially available doses after ~14 days of use — not just at high experimental doses. Recovery requires new enzyme protein synthesis (~2 weeks after stopping) due to irreversible mechanism-based inhibition. Discontinue at least 2–4 weeks before surgery or procedures requiring CYP-metabolized anesthetics. Drug test masking: goldenseal does not mask THC, cocaine, or other drug metabolites in urine. This myth originates from a 1900 novel (Lloyd's Stringtown on the Pike) and has been definitively disproven.