Goldenseal and the Common Cold: Is There Any Evidence?
By David Kiefer, MD
Goldenseal, or hydrastis canadensis, is a popular cold remedy and immune system stimulant, and combination products with Echinacea sp. for this purpose remain a common part of any herbal medicine or dietary supplement shelf at pharmacies and health food stores. In 2000, goldenseal ranked 12th in sales in the natural food trade in the United States,1 and in 1999, an eight-month estimate of echinacea/goldenseal product sales was $44.6 million. This was only about 90% of the total market.2 Such popularity was also enough to earn echinacea/goldenseal products fifth place in herb market sales in 1998.1 A review for this newsletter in 1998 helped readers sort fact from fiction about this botanical remedy, pointing out the lack of clinical research, and some of the possible side effects associated with using this plant.3 More research has been done in recent years to help guide physicians and consumers in the correct use of goldenseal.
History and Traditional Use
Goldenseal is native to North America and was used historically by the Cherokee Indians to treat skin ailments and as an eye wash.4 Goldenseal also was used traditionally to treat tonsillitis, gastritis, diarrhea, and cystitis; as an oxytocic; and to induce abortions.5 Early settlers in the United States picked up on the use of goldenseal as a medicine, and it became a popular cure for a variety of gastrointestinal and genitourinary complaints, as well as being an effective bitter tonic.4 At present, H. canadensis most often is used for gastrointestinal infections, and to treat mucous membrane problems of the respiratory or gastrointestinal systems.6
In recent years, there has been the rumor that H. canadensis in tea form will mask the presence of illicit substances (i.e., opiates, marijuana) in the urine, allowing people to pass drug tests. Scientific investigations into these claims have found no corroborating evidence to substantiate them.4,7
Botany and Pharmacology
H. canadensis is a small perennial forest plant of the family Ranunculaceae (Buttercup family). There are numerous isoquinoline alkaloids in the roots and rhizomes (horizontal-growing structures just below the soil’s surface) of H. canadensis that are thought responsible for some of its observed physiological effects.8 The major isoquinoline alkaloids are berberine (which give the herb its characteristic yellow color), beta-hydrastine, canadine, and canadaline.9 There is some debate about whether these alkaloids are absorbed following oral administration in humans,4 though it appears that adequate absorption does occur in some animal models.6
Mechanism of Action
The existing research relating to H. canadensis is a combination of experiments done using extracts of the crude herb as well as those concentrating on the isoquinoline alkaloid berberine. In vitro studies indicate that berberine has antibacterial and antifungal effects against a variety of microorganisms, including many of the common gastrointestinal pathogens.1,6 Berberine and two flavonoids found in extracts of the powdered rhizomes of H. canadensis displayed antimicrobial properties against the common oral bacteria Streptococcus mutans and Fusobacterium mucleatum;10 another in vitro analysis found berberine and beta-hydrastine to be active against Helicobacter pylori, though the mechanism of this latter finding is still unknown.11
Another study used a 70% alcoholic extract of the rhizomes and roots of H. canadensis and tested its bacteriocidal and bacteriostatic activities.9 The alkaloid hydrastine did not demonstrate antimicrobial activity against any of the strains tested, whereas berberine was active against the gram-positive and gram-negative bacteria tested, except for Pseudomonas aeruginosa. Canadine and canadaline were both active against P. aeruginosa and most of the other bacteria with specific nuances; canadine did not work against Escherichia coli, and canadaline was more effective than berberine against gram-positive bacteria.
One animal study demonstrated that goldenseal caused an increase in the acute primary IgM antibody response to a specific antigen after H. canadensis root extract was added to drinking water; there was no change in IgG antibody production.12 Other animal experiments have shown that berberine also may improve symptoms of diarrhea, decrease intestinal secretion, affect cardiac function, and support in vitro findings of antimicrobial effects.1,6
Clinical Studies
There are no clinical studies investigating the use of H. canadensis in the treatment or prevention of the common cold. There have been trials of varying methodological quality on the use of berberine (not the crude herb goldenseal) in humans to treat diarrhea, cholera, giardia, liver cirrhosis, trachoma, cutaneous leishmaniasis, and diabetes.5,6 One researcher pointed out that it is problematic to extrapolate studies on berberine to the use of extracts of whole H. Canadensis because it is difficult to consume enough hydrastis to achieve the amounts of berberine necessary for therapeutic effects.5
Dosages and Forms
The roots and rhizomes of H. canadensis are the plant parts used medicinally. There is a wide variety of recommended dosages for products made from H. canadensis. One recent study used 1.53-3.0 g per day of dried rhizomes in divided doses as their standard;13 this was based on one textbook,14 and agrees with other reputable sources stating the dosage range as being 500-1,000 mg three times a day.4,15 Tinctures and extracts often are dosed at 2.0-4.0 mL of 1:10 tincture in 60% ethanol three times a day, or 0.3-1.0 mL of 1:1 liquid extract in 60% ethanol three times a day.15
A recent study examined the stated content on the labels of 10 commonly used herbal medicines,13 and compared the content listed to the recommended dosage amounts in a popular textbook.14 For the goldenseal part of the study, the range of strengths listed varied by a factor of 20, and only 36% of the products surveyed were consistent with the textbook’s standard in both ingredients and dosage. The results of this study illustrate but one of the challenges to consumers and physicians in interpreting the correct dosage regimen of herbal medicines available in the U.S. market, and reinforces the importance of carefully reading labels and comparing the listed contents with reputable sources.
A further confounding factor is the fact that goldenseal products may be adulterated by less expensive, more easily obtainable plants such as Oregon grape (Berberis aquifolium or Berberis nervosa).3,5 Though Oregon grape also contains berberine, this herb has a different phytochemical profile and may have different physiological functions as compared to pure goldenseal products.
The U.S Pharmacopeial Convention (USP) represents an effort at the standardization and quality control of herbal products, and their recommendation is that goldenseal root should contain no less than 2.5% berberine and 2.0% hydrastine calculated on a dried basis.16
Conservation
H. canadensis is listed under Appendix II of CITES, or the Convention in Trade in Endangered Species.17,18 This designation requires permits from the U.S.Fish and Wildlife Service for any exports of goldenseal roots or rhizomes. Furthermore, H. canadensis currently is listed as "At Risk" by the United Plant Savers, a non-profit education corporation whose "¼ mission is to protect native medicinal plants of the United States and Canada and their native habitat while ensuring an abundant renewable supply of medicinal plants for generations to come."19 A plant is "At Risk" if it is a medicinal plant in active commerce, its population is dwindling within its current range, and it is rare or sensitive. Due to concerns about the threatened status of wild populations of H. canadensis, most herbal medicine experts recommend only using products made from cultivated goldenseal, or switching to other more abundant berberine-containing plants such as barberry (Berberis vulgaris).6
Adverse Effects, Contraindications, and Drug Interactions
H. canadensis may cause a toxic reaction in humans, inducing symptoms such as nausea, vomiting, elevated blood pressure, convulsions, and respiratory failure after ingesting unspecified "large" doses.7 Others note that diarrhea and vasoconstriction may result from high doses and prolonged use.20 Isolated berberine in humans may cause cardiac damage, dyspnea, and hypotension in large doses; such toxic doses may occur with 500 mg or more of berberine, and one estimate of the LD50 for goldenseal is 27.5 mg/kg.15 Animal studies have shown respiratory and cardiac depression, and stimulation of the gastrointestinal system in large doses, and the opposite effect in lower doses.15 For these reasons, goldenseal is not recommended for people with hypertension, cardiovascular disease, or respiratory problems. Interestingly, however, recent data suggest a potential benefit of berberine for people with congestive heart failure.21
Topical preparations of goldenseal or other berberine-containing plants may react with ultraviolet light to create free radical oxygen compounds and skin and eye irritation in humans; the researchers discovering this effect note that this may also be the mechanism of action for the antimicrobial effect of topical goldenseal preparations.22
It is recommended that berberine-containing plants (such as goldenseal) be avoided in pregnancy due to possible uterine stimulant effects, and the fact that berberine can displace bilirubin from serum albumin, which may lead to neonatal jaundice.4,23 Other contra-indications mentioned in the literature include kidney disease (goldenseal alkaloids may accumulate), acute gastric inflammation (goldenseal induces acid production), and high blood pressure.23
In vitro studies have shown that the berberine alkaloids present in goldenseal may potentiate the activity of certain medications, including penicillin, chloromycetin, pentobarbital, and isoproterenol.22 It is possible that these herb-drug interactions are mediated through the cytochrome P450 (CP450) enzyme system; researchers have demonstrated that a 70% ethanol extract of goldenseal tea is capable of inhibiting several isoforms of the CP450 system,24 a finding consistent with a past study documenting the inhibitory effects of herbal extracts, tinctures, and pure plant compounds on the CP450 3A4 system.25
Berberine has been shown to up-regulate the multi-drug resistant transporter (pgp-170) in two in vitro models.26,27 This is the same gene product that can cause Paclitaxel, or taxol, to be less effective as an anticancer agent. It would be prudent to recommend to patients taking taxol or other drugs affected by this transporter system to be wary of ingesting berberine-containing plants.
Conclusion
Goldenseal (H. canadensis) is a plant native to North America with both present and past uses of its roots and rhizomes as a medicine. There are interesting in vitro studies documenting efficacy as an antimicrobial; however, most of the research was conducted using the isolated alkaloid berberine, the primary alkaloid in goldenseal. There are no clinical studies relevant to its uses as a common cold remedy, and there are a significant number of adverse effects in humans and animals, as well as drug interactions.
Recommendation
Goldenseal is a good example of an herbal medicine whose popular uses as a cold remedy and immune system booster do not coincide with most of the published scientific literature. There are interesting in vitro and animal studies, primarily done on goldenseal’s main alkaloid berberine, that demonstrate a range of effects, including as an antimicrobial and antidiarrheal agent. However, it is unknown how well berberine research results can translate to the use of crude, whole plant extracts of goldenseal. Furthermore, the issues of poor absorption from oral administration, numerous documented side effects and possible drug interactions, a lack of human clinical research for efficacy in treating or preventing the common cold, and goldenseal’s threatened status in the wild, make an effective case for not recommending this plant in most, if not all, clinical scenarios until more evidence accumulates in the literature to guide clinicians in its proper and appropriate use.
Dr. Kiefer recently completed a fellowship at the Program in Integrative Medicine, College of Medicine, University of Arizona, Tucson.
References
1. Blumenthal M. The ABC Clinical Guide to Herbs. Austin, TX: American Botanical Council; 2003.
2. Blumenthal M. Herb market levels after five years of boom. HerbalGram 1999;47:64-65.
3. O’Mathúna DP. Goldenseal: The golden cure for common colds? Altern Med Alert 1998;2:90-93.
4. Foster S, Tyler VE. Tyler’s Honest Herbal: A Sensible Guide To The Use Of Herbs And Related Remedies. 4th ed. London: Haworth Press; 1999.
5. Mahady GB, Chadwick LR. Goldenseal (Hydrastis canadensis): Is there enough scientific evidence to support safety and efficacy. Nutr Clin Care 2001;4:243-249.
6. Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh, England: Churchill Livingstone; 2000.
7. Johnson LP. Pocket Guide to Herbal Remedies. Malden, MA: Blackwell Publishing; 2002.
8. Edwards DJ. Draper EJ. Variations in alkaloid content of herbal products containing goldenseal. J Am Pharm Assoc 2003;43:419-423.
9. Scazzocchio F, et al. Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids. Planta Med 2001;67:561-564.
10. Hwang BY, et al. Antimicrobial constituents from goldenseal (the rhizomes of Hydrastis canadensis) against selected oral pathogens. Planta Med 2003;69:623-627.
11. Mahady GB, et al. In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis. Phytother Res 2003;17:217-221.
12. Rehman J, et al. Increased production of antigen- specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunol Lett 1999; 68:391-395.
13. Garrard J, et al. Variations in product choices of frequently purchased herbs: Caveat emptor. Arch Intern Med 2003;163:2290-2295.
14. Fetrow CW, Avila JR. Professional’s Handbook of Complementary and Alternative Medicines. 2nd ed. Springhouse, PA: Springhouse Corp; 2001.
15. McGuffin M, et al, eds. American Herbal Products Association Botanical Safety Handbook. Boca Raton, FL: CRC Press; 1997.
16. Goldenseal. The United States Pharmacopeia. 27th rev. Rockville, MD: United States Pharmacopeial Convention, Inc.; 2004.
17. Bannerman JE. Goldenseal in world trade: Pressures and potentials. HerbalGram 1997;41:51-52.
18. Concannon JA, DeMeo TE. Endangered Species Bulletin 1997;22:10-12.
19. United Plant Savers. Available at: www.plantsavers.org. Accessed Feb. 15, 2004.
20. Mar C, Bent S. An evidence-based review of the 10 most commonly used herbs. West J Med 1999;171: 168-171.
21. Zeng XH, et al. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2003;92:173-176.
22. Inbaraj JJ, et al. Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.) 1. Berberine. Chem Res Toxicol 2001;14:1529-1534.
23. Brinker F. Herb Contraindication and Drug Interactions. 3rd ed. Sandy, OR: Eclectic Medical Publications; 2001.
24. Foster BC, et al. In vitro inhibition of human cyto-chrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10: 334-342.
25. Budzinski JW, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7: 273-282.
26. Lin HL, et al. Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br J Cancer 1999;81:416-422.
27. Lin HL, et al. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer 1999;85:1937-1942.
Kiefer D. Goldenseal and the common cold: Is there any evidence? Altern Med Alert 2004;7(5):55-58.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.