Goldenseal

• How It Works

  Although goldenseal is popular for minor infections or as a tonic, there are no human data to back these claims.

  Goldenseal is a North American botanical with origins as a traditional remedy among Native Americans. It has historically been used for skin and eye irritations, and as a bitter tonic and to improve digestive function. It is also marketed as an antioxidant and is often combined with echinacea in supplements to support immune function.

  Two of its compounds, berberine and hydrastine, have been studied in the lab. In animal studies, goldenseal compounds appeared to kill bacteria and other microbes, and slow tumor growth. Anti-inflammatory, spasm-reducing, and muscle-contracting properties have also been observed. However, other animal studies suggest potential toxicity with long-term use and there are no human data to confirm supposed effects.

• Purported Uses
  • To treat infections
    Although goldenseal has been traditionally used for eye and skin ailments, human data are lacking. There is also no evidence for its use against the common cold. Laboratory data indicate that goldenseal compounds have antimicrobial properties, but also suggest potential sensitivity to sunlight with topical products that contain goldenseal.
  • To control muscle spasms
    Laboratory studies suggest goldenseal may relax muscle tissue, but human data are lacking.
  • To treat gastrointestinal disorders
    Laboratory studies show that a goldenseal extract causes relaxation of smooth muscle like that found in the gastrointestinal tract, but it is not known if goldenseal helps treat gastrointestinal disorders.
• Patient Warnings

  Avoid long-term use of this product due to potential toxicity issues raised in animal studies.

• Do Not Take If
  • You are taking drugs that are substrates of cytochrome P450 3A4 and 2D6 enzymes: Human studies suggest goldenseal may increase the risk of side effects of these drugs.
  • You are pregnant or nursing: Berberine in goldenseal may cause or worsen jaundice in newborns.
• Side Effects

  Case Reports

  • Photosensitivity: In a patient following use of a dietary supplement containing ginseng, goldenseal, bee pollen, and other ingredients. It is suggested that the combination rather than the individual herbs contributed to this side effect.
  • High salt concentrations in the blood: In a pre-teen with diabetic ketoacidosis (DKA) who took goldenseal for 2 weeks prior. This side effect did not occur again during a later episode of DKA when the individual was not taking goldenseal. Diuretic properties in goldenseal may have contributed.
• Special Point
  • The berberine content in goldenseal can vary widely.
  • Goldenseal is sometimes referred to as turmeric root, but should not be confused with turmeric (Curcuma longa).
• Scientific Name

  Hydrastis canadensis

• Clinical Summary

  Derived from the root of the plant, goldenseal is a North American botanical with origins as a traditional remedy among Native Americans. It has historically been used for skin and eye irritations, as a bitter tonic, and to improve digestive function. Purported properties have led to its use for a variety of ailments including the common cold, fever, infections, constipation, and muscle spasms. Goldenseal is also marketed as an antioxidant and is often combined with echinacea in supplements to support immune function.

  Studies on goldenseal and its compounds are limited. The primary active constituents are hydrastine and berberine. Among several herbs tested in vitro, goldenseal extract was the most active growth inhibitor of H. pylori ⁽¹⁾. Studies of berberine suggest that it has antimicrobial ⁽³⁾, cytotoxic, and apoptotic effects ^{(2) (4) (6)}. Other animal studies have suggested potential liver toxicity with goldenseal root, but this occurred at very high doses over long-term ingestion ⁽²⁶⁾. Laboratory studies demonstrating phototoxicity suggest this would be more likely from topical rather than supplement use ⁽²⁴⁾.

  Clinical studies are lacking and would be needed to determine safety and efficacy.

• Purported Uses
  • Digestive disorders
  • Spasms
  • Infections
• Mechanism of Action

  The active characteristics of goldenseal are attributed to the compounds hydrastine and berberine, in which most laboratory studies have been conducted. In human prostate and breast cancer cells, berberine induced cell cycle arrest ^(2) (4). At the same time, tumorigenicity in rodents from long-term high-dose ingestion of goldenseal root powder is partly attributed to the topoisomerase inhibition properties of berberine or its metabolite ⁽²⁶⁾, although the comparative doses are unlikely in humans. Still, DNA damage in liver cells via topoisomerase inhibition was attributed to berberine in goldenseal and was also observed with commercial goldenseal products, with the extent of DNA damage positively correlating with berberine content ⁽²⁷⁾.

• Contraindications

  Women who are pregnant or breastfeeding should avoid the use of goldenseal ^(28) (29).

• Adverse Reactions

  Case Reports

  • Hypernatremia: In a pre-teen with diabetic ketoacidosis who took goldenseal for 2 weeks prior. A subsequent episode of DKA while not taking goldenseal did not yield this effect. Diuretic properties in goldenseal may have contributed ⁽¹³⁾.
  • Photosensitivity: In a patient following use of a dietary supplement containing ginseng, goldenseal, bee pollen, and other ingredients ⁽²⁵⁾. It is posited that the combination rather than individual herbs contributed to this toxicity.
• Herb-Drug Interactions

  Cytochrome P450 substrates: In healthy volunteers, goldenseal inhibits CYP3A4 and CYP2D6 isoenzymes, and can affect the intracellular concentration of drugs metabolized by these enzymes ^{(11) (18) (30)}.

• Herb Lab Interactions
  • In vitro and animal studies suggest berberine may increase bilirubin levels due to displacement of bilirubin from albumin ⁽²¹⁾.
  • Goldenseal may cause a darkening in urine color in illicit drug testing ⁽²²⁾.
• References

  1. Cwikla C, Schmidt K, Matthias A, et al. Investigations into the antibacterial activities of phytotherapeutics against Heliobacter pylori and Campylobacter jejuni. Phytotherapy Research. 2010;24:649-656.

  2. Mantena SK, Sharma SD, Katiyar SK. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther. Feb 2006;5(2):296-308.

  3. Rabbani G, et al. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. J Infect Dis 1987;155:979-84.

  4. Kim JB, Yu JH, Ko E, et al. The alkaloid berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest. Phytomedicine. 2010 May;17(6):436-40.

  5. Werbach MR, et al. Botanical Influences on Illness: A Sourcebook of Clinical Research. Tarzana, California: Third Line Press; 1994.

  6. Zhang RX, et al. Laboratory studies of berberine use alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea to treat malignant brain tumors. Chin Med J 1990;103:658-65 PMID: 2122945

  7. Barnes J, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.

  8. Budzinski JW, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82.

  9. Chatterjee P,.Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos. 2003;31:1391-7.

  10. 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. Jan 2008;83(1):61-69.

  11. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77(5):415-26.

  12. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007;35(2):240-5.

  13. Bhowmick SK, Hundley OT, Rettig KR. Severe hypernatremia and hyperosmolality exacerbated by an herbal preparation in a patient with diabetic ketoacidosis. Clin Pediatr (Phila). Nov 2007;46(9):831-834.

  14. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal medicines. 2nd ed. Montvale (NJ): Medical Economics Company; 1998.

  15. Jantova S, Cipak L, Letasiova S. Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells. Toxicol In Vitro. Feb 2007;21(1):25-31.

  16. Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J. Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother Pharmacol. May 2008;61(6):1007-1018.

  17. Xu Z, Cao HY, Li Q. [Protective effects of berberine on spontaneous ventricular fibrillation in dogs after myocardial infarction]. Zhongguo Yao Li Xue Bao. Jul 1989;10(4):320-324.

  18. Gurley BJ, Swain A, Hubbard MA, et al. 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. Jul 2008;52(7):755-763.

  19. Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol. 2003;43:1283-8.

  20. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol. Sep 2005;61(8):567-572.

  21. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate. 1993;63(4):201-208.

  22. Mikkelsen SL, Ash KO. Adulterants causing false negatives in illicit drug testing. Clin Chem 1988; 34:2333-6.

  23. Abidi P, Chen W, Kraemer FB, Li H, Liu J. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms. J Lipid Res. 2006 Oct;47(10):2134-47.

  24. Chignell CF, Sik RH, Watson MA, Wielgus AR. Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.) 3: effect on human lens and retinal pigment epithelial cells. Photochem Photobiol. 2007 Jul-Aug;83(4):938-43.

  25. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol. 2003;41(6):865-7.

  26. Dunnick JK, Singh B, Nyska A, et al. Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle. Toxicol Pathol. 2011 Feb;39(2):398-409.

  27. Chen S, Wan L, Couch L, et al. Mechanism study of goldenseal-associated DNA damage. Toxicol Lett. Jul 31 2013;221(1):64-72.

  28. National Institutes of Health. Goldenseal. Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of Medicine (US); 2006.

  29. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. Mar 2002;109(3):227-235.

  30. Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): Drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med. Sep 2012;78(13):1490-1514.