Medically reviewed by Drugs.com. Last updated on Jan 4, 2018.
Scientific Name(s): Hydrastis canadensis L.
Common Name(s): Eyebalm, Eyeroot, Goldenroot, Goldenseal, Ground raspberry, Indian turmeric, Jaundice root, Orangeroot, Radix Hydrastis, Sceau d'or, Yellow puccoon, Yellowroot
Traditional uses of goldenseal are not validated by clinical studies, although it may be of use in diabetes, dyslipidemia, cardiovascular conditions, and cancer.
Clinical evidence is lacking; few well-controlled clinical trials are available to guide dosage for goldenseal root extract.
Recommended dosages vary considerably, from 250 mg to 1 g 3 times daily. Some product labeling suggests higher dosages.
Traditional dosages include 0.5 to 1 g dried rhizomes 3 times daily, and 0.3 to 1 mL 1:1 liquid extract in 60% ethanol 3 times daily.
None well defined.
Avoid use; activity as a uterine stimulant has been documented. Safety in lactation has not been established.
Goldenseal may affect the cytochrome CYP-450 (CYP450) system. The clinical importance of this interaction has not been established.
Information from clinical studies is lacking, but adverse reactions with common doses are rare. Very high doses of goldenseal may occasionally induce nausea, anxiety, depression, seizures, or paralysis.
Toxicological concerns have been reported, with some evidence of carcinogenicity in rodents.
- Ranunculaceae (buttercup)
Goldenseal is a perennial herb found in the rich woods of the Ohio River Valley and other locations in the northeastern United States. The single, green-white flower, which has no petals, appears in the spring on a hairy stem above a basal leaf and two palmate, wrinkled leaves. The flower develops into a red-seeded berry. The plant grows from horizontal, bright yellow rhizomes, which have a twisted, knotty appearance.1, 2
Native Americans of the Cherokee, Catawba, Iroquois, and Kickapoo tribes used goldenseal root as an insect repellent, diuretic, stimulant, and wash for sore or inflamed eyes. It was used to treat arrow wounds and ulcers, as well as to produce yellow dye. Early settlers learned of these uses from Native Americans, and the root found its way into most 19th century pharmacopeias. The Eclectic medical movement was particularly enthusiastic in its adoption of goldenseal to treat gonorrhea and urinary tract infections. The widespread harvesting of goldenseal in the 19th century, coupled with loss of habitat, resulted in the depletion of wild populations. In 1997, goldenseal was listed under Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora treaty, which controls exports of the root to other countries. The final listing included roots or live plants, but excluded finished products. As an alternative to wild harvesting, goldenseal is cultivated in the Skagit Valley of Washington state and is being promoted as a cash crop in New York, North Carolina, and Canada. The popular notion that goldenseal can be used to affect the outcome of urinalysis for illicit drugs evolved from the novel Stringtown on the Pike by pharmacist John Uri Lloyd. In the book, goldenseal bitters are mistaken for strychnine in a simple alkaloid test by an expert witness in a murder trial.3, 4, 5, 6, 7 Testing in a small group of healthy volunteers suggests that less sensitive drug assays (threshold higher than 100 ng/mL for morphine) may yield false negative results.
The isoquinoline alkaloids hydrastine (4%), berberine (up to 6%), canadine, and palmatine are present in goldenseal root and are viewed as its principle bioactive components.6, 8 Considerable variation in alkaloid content has been noted among various commercial products, with some not meeting United States Pharmacopeial standards for berberine and hydrastine.6, 9, 10 Some preparations contain alkaloids associated with other herbal substances.9, 11 Other minor alkaloids, such as canadaline and canadinic acid,12, 13 have been isolated. Quinic acid esters were elucidated.14 Traces of calcium, magnesium, potassium, and zinc have been described.15 Quantitation of the alkaloids has been accomplished in a variety of ways, including spectrophotometry, thin-layer chromatography, ion-pair dye colorimetry, high-performance liquid chromatography, capillary electrophoresis, and capillary electrophoresis-mass spectrometry. 2, 7, 10, 11, 16, 17
Uses and Pharmacology
Despite the widespread use of goldenseal, controlled clinical trials are lacking and studies tend to focus on the constituent berberine. The alkaloids are poorly absorbed when taken orally; in vitro and animal studies must be interpreted carefully.17
Goldenseal alkaloids showed modest antimicrobial activity in vitro against Staphylococcus aureus, Klebsiella and Candida species, and Mycobacterium tuberculosis in older studies.18, 19, 20 More recent studies have focused on activity versus Helicobacter pylori,21 methicillin-resistant S. aureus,22 and influenza A virus.23
Older, limited clinical studies evaluated berberine in treating diarrhea due to E. coli and cholera,24, 25 and for use against microbes such as Giardia and Trichomonas.2 Goldenseal has traditionally been used for eye ailments.26 Berberine has been evaluated against sulfacetamide in ocular trachoma infections with comparable effects; however, a phototoxic reaction between berberine alkaloid and ultraviolet A (UVA) light leading to decreased lens epithelial cell viability has been described.26, 27
Induction of apoptosis and cell cycle arrest, inhibition of glucose uptake, and tumor promotion have been shown in vitro by both goldenseal and berberine extracts.28, 29, 30, 31 In mice, an ethanolic extract of goldenseal showed some protective activity against induced hepatocarcinoma (lower incidence and slower growth of tumors).32 In a 2-year toxicity study of goldenseal root powder, it was shown to decrease the incidence of mammary gland tumor rates in female rats, possibly because of resulting weight loss.33, 34
Research reveals no clinical data regarding the use of goldenseal in cancer. Berberine alone has been evaluated as an adjunct to prevent adverse effects of radiation.35
Experiments have shown goldenseal and berberine to affect the cardiovascular system, though the mechanisms remain poorly understood. Positive inotropic, negative chronotropic, vasodilatory, and hypotensive effects have been described.36, 37 In a 2-year toxicity study of goldenseal root powder, the incidence of cardiomyopathy was decreased in male and female rats; however, cardiovascular effects were not the focus of the study.33, 34 Inhibitory activity of goldenseal alkaloids on isolated rabbit aorta stimulated by epinephrine has been evaluated; a weak synergistic effect was found for berberine, canadine, and canadaline, but not for hydrastine.38 Similar studies have been conducted on ileum, trachea, and prostate preparations.39, 40, 41
There is a case report of reversible hypernatremia in a child due to the sodium-sparing diuretic effect of goldenseal.37 In a clinical study (N = 130), patients with acute coronary syndrome following percutaneous coronary intervention who received berberine as adjunctive therapy showed improvements in inflammatory indices.42 Study assessments did not include outcome measures.
When administered to mice with induced diabetes, berberine lowered the elevated fasting blood glucose level. Whether this action is via modulation of CYP450 expression or by some other mechanism is unestablished.43
Berberine exerted a hypoglycemic action in a small trial of patients with type 2 diabetes.44 In women with metabolic-associated polycystic ovary syndrome, berberine administered over 3 months decreased fasting blood glucose levels.45 Findings from a larger, multicenter clinical trial evaluating this effect have yet to be published.46
Goldenseal decreased low-density lipoprotein in hyperlipidemic rats.47, 48
Berberine alone improved the lipid profile in dyslipidemia in several clinical trials among participants with various conditions, including familial hyperchosterolemia, obesity, and diabetes.44, 49, 50, 51 Clinical trials evaluating goldenseal root powder in dyslipidemia are lacking.
Goldenseal administered to rats protected against acetaminophen-induced hepatotoxicity, possibly via modulation of the cytochrome P450 system.52 In a 2-year toxicity study of goldenseal root powder, it was shown to decrease chronic lung and nasal inflammation.33, 34
Studies evaluating berberine alone have described immunostimulation and antioxidant activity.53, 54, 55 Berberine as a gel has been used orally to treat minor recurrent aphthous stomatitis.56
Although hydrastine is closely related to the convulsant isoquinoline alkaloid bicuculline, it had no activity in a gamma-aminobutyric acid–receptor binding assay at high concentrations.57
Further effects for berberine alone have been described in studies using barberry (see Barberry monograph).
Clinical evidence is lacking; few well-controlled clinical trials are available to guide dosage for goldenseal root extract. Recommended dosages vary considerably, from 250 mg to 1 g 3 times daily. Some product labeling suggests higher dosages.47
Berberine alone has been used at 300 to 500 mg 3 times daily in clinical studies.42, 50
Traditional dosages include 0.5 to 1 g dried rhizomes 3 times daily, and 0.3 to 1 mL 1:1 liquid extract in 60% ethanol 3 times daily.2 Ten to 30 drops of the extract 2 to 4 times a day has been recommended for influenza.58
Pregnancy / Lactation
Avoid use; activity as a uterine stimulant has been documented.2, 59, 60, 61 Safety in lactation has not been established.2 Berberine has been reported to displace bilirubin in rat experiments62 and should not be used in infants with jaundice.
Antihypertensives: Herbs (Hypotensive Properties) may enhance the hypotensive effect of Antihypertensives. Monitor therapy.63, 64
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Monitor therapy.65, 66, 67, 68
Cyclosporine: CYP3A4 inhibitors may increase cyclosporine blood concentrations. Avoid combination.69
Herbs (Hypotensive Properties): May enhance the adverse/toxic effect of other Herbs (Hypotensive Properties). Excessive blood pressure lowering may manifest. Monitor therapy.63, 64
Losartan: CYP2C9 inhibitors may decrease metabolism of losartan to its active metabolite. Avoid combination.70
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Consider therapy modification.71
Midazolam: CYP3A4 inhibitors may increase serum concentrations of midazolam. Avoid combination.70, 72
Oseltamivir: In vitro data suggests that oseltamivir’s conversion to the active carboxylate metabolite may be hindered by goldenseal.81
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination.73, 74, 75, 76
Information from clinical studies is lacking, but adverse reactions with common doses are rare. Very high doses of goldenseal may rarely induce nausea, anxiety, depression, seizures, or paralysis.2
Caution is warranted in patients with cardiovascular conditions because of the actions of the constituent alkaloids. A large, retrospective evaluation of patient data related to blood pressure and herbal product use found a significantly higher mean systolic blood pressure, but not diastolic blood pressure, in users of goldenseal compared with non-users.80 There is a case report of photosensitivity with the use of a combination product containing ginseng, goldenseal, and bee pollen.77
Findings from a 2-year toxicity study of goldenseal root powder in male and female mice and rats have been published.33, 34 Evidence of carcinogenic activity of the root powder exists, based on an increased incidence of hepatocellular adenoma and carcinoma in both male and female rats, and some evidence in male, but not female, mice after 2 years exposure to goldenseal. An increased incidence of non-neoplastic hepatic lesions has also been demonstrated in rodents.33, 34 DNA damage has been suggested to be due, at least in part, to inhibition of topoisomerases.78
Goldenseal root powder did not show mutagenicity in S. typhimurium or E. coli strains;33, 34 however, berberine showed mutagenicity in yeast cells and the Ames test.2, 61
A phototoxic reaction between berberine alkaloid and UVA light has been described.26, 27
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