Goldenseal (Hydrastis canadensis), also called orangeroot or yellow puccoon, is a perennial herb in the buttercup family Ranunculaceae, native to southeastern Canada and the eastern United States. It may be distinguished by its thick, yellow knotted rootstock. The stem is purplish and hairy above ground and yellow below ground where it connects to the yellow rhizome. Goldenseal reproduces both clonally through the rhizome  and sexually, with clonal division more frequent than asexual reproduction. It takes between 4 and 5 years for a plant to reach sexual maturity, i.e. the point at which it produces flowers. Plants in the first stage, when the seed erupts and cotyledons emerge, can remain in this state one or more years. The second vegetative stage occurs during years two and three (and sometimes longer) and is characterized by the development of a single leaf and absence of a well developed stem. Finally, the third stage is reproductive, at which point flowering and fruiting occurs. This last stage takes between 4 and 5 years to develop.
It is known due to its use in traditional medicine and although there is only anecdotal evidence that it could have some therapeutic benefit it can be harmful, potentially causing death.
According to the American Cancer Society, "evidence does not support claims that goldenseal is effective in treating cancer or other diseases. Goldenseal can have toxic side effects, and high doses can cause death."
At the time of the European colonization of the Americas, goldenseal was in extensive use among certain Native American tribes of North America, both as a medicine and as a coloring material. Benjamin Smith Barton, in his first edition of Collections for an Essay Toward a Materia Medica of the United States (1798), refers to the Cherokee use of goldenseal as a cancer treatment. Later, he calls attention to its properties as a bitter tonic, and as a local wash for ophthalmia. It became a favorite of the Eclectics from the time of Constantine Raffinesque in the 1830s. Tribes also used goldenseal for digestive issues, as an eyewash, as a diuretic and as a bitter.
In the early 20th century, it was used as a yellow dye, astringent, and insect repellent.
Constituents and modern pharmacology
Goldenseal contains the isoquinoline alkaloids hydrastine, berberine, berberastine, hydrastinine, tetrahydroberberastine, canadine and canalidine. A related compound, 8-oxotetrahydrothalifendine, was identified in one study. The United States Pharmacopoeia requires goldenseal sold as a supplement to have hydrastine concentrations of at least 2% and berberine concentrations of at least 2.5%. The requirements in Europe are that hydrastine concentrations be at least 2.5% and that berberine concentrations at least 3%. The hydrastine concentrations of goldenseal plants range between 1.5% and 5%, while the berberine concentrations are usually between 0.5% and 4.5%. Goldenseal is harvested for its rhizomes because the concentrations of hydrastine and berberine in the shoots do not meet these requirements. Berberine and hydrastine act as quaternary bases and are poorly soluble in water but freely soluble in alcohol. The herb seems to have synergistic antibacterial activity over berberine in vitro, possibly as a result of efflux pump inhibitory activity.
Side effects of goldenseal may include "digestive complaints, nervousness, depression, constipation, rapid heartbeat, diarrhea, stomach cramps and pain, mouth ulcers, nausea, seizures, vomiting, and central nervous system depression. High doses may cause breathing problems, paralysis, and even death. Long-term use may lead to vitamin B deficiency, hallucinations, and delirium." In addition, goldenseal may cause brain damage to newborn babies if given directly or if taken by breastfeeding or pregnant mothers, and may affect blood pressure unpredictably because it contains several compounds that have opposite effects on blood pressure.
Taking goldenseal over a long period of time can reduce absorption of B vitamins, and it is cautioned to avoid goldenseal during pregnancy and lactation, with gastrointestinal inflammation and with pro-inflammatory disorders. A 2011 study found rats fed goldenseal constantly for two years had a greater tendency to develop tumors.
Goldenseal has been found to have inhibited cytochrome P450 CYP2D6, CYP3A4 and CYP3A5 activity by approximately 40%, a statistically and clinically significant reduction. CYP2D6 is a known metabolizer of many commonly used pharmaceuticals, such as antidepressants (including all SSRIs except for fluvoxamine), neuroleptics and codeine. Combining goldenseal with such medications should be done with caution and under the supervision of a doctor as it can lead to serious, perhaps fatal, toxicity. Those with a genetic deficiency in these enzymes are at particular risk.
Goldenseal became popular in the mid-nineteenth century. By 1905, the herb was much less plentiful because of overharvesting and habitat destruction. Wild goldenseal is listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), which by definition means harvest from public land is prohibited and may require a permit to export, although trade of the plants is not deemed to be detrimental to the wildlife population and is otherwise unregulated. The U.S. Fish and Wildlife Service recommends that diggers and harvesters track sales and harvests and prove legality of all harvests.
Canada, as well as 17 of the 27 U.S. states where goldenseal grows natively, have declared it as threatened, vulnerable or uncommon. More than 60 million goldenseal plants are picked each year without being replaced. Although goldenseal's geographical range is wide, it is found in small quantities in these habitats. The core of the herb's range is in the Ohio River Valley, but its population there has decreased by almost half. The process of mountain top removal mining has recently put the wild goldenseal population at major risk from loss of habitat.
Research on harvest effects
Research completed by Albrecht and McCarthy shows that when goldenseal is harvested in the fall season, it has a faster population recovery than with midsummer harvests. However, a study by Douglas et al. showed that goldenseal has the highest concentrations of hydrastine and berberine in the early summer. Their research also showed that three to five years of growth will yield the highest concentration of alkaloids in the plant.
Two experiments done by Sinclair and Catling on the effects of soil turnover, fertilization and transplanting of goldenseal show that disturbances actually benefit the growth of goldenseal. The results from the first growing season of the experiment showed that soil turnover and fertilization combined show the greatest increase in plant biomass, while the results after two growing seasons showed that this group also yielded the highest proportion of flowering plants, fruit production and seed production. Both experiments also showed that soil disturbances benefit the growth of goldenseal.
As of 1998, only 2.4% of goldenseal plant material originated from a cultivated source rather than wild harvest, although that number was projected to rise by 15–30% over the next several years. In response to conservation concerns, research has expanded regarding the propagation success of wild plant material for commercial yield. Because goldenseal grows in patches of interconnected ramets reproducing asexually through clonal propagation, transplanting rhizome propagules into cultivated settings is possible. Seed propagation is also feasible and has advantages such as lower cost and greater genetic variability, but is considered difficult and unpredictable.
Goldenseal may be commercially cultivated through agroforestry in natural settings mirroring the plant's ecological environment, or on farms with artificial shade canopies. Another propagation method of goldenseal utilizes a controlled environment such as a greenhouse growing lab where the plant's environmental needs such as light, water and temperature are artificially simulated. Crop selection and biotechnology experimentation may be employed to increase yield and pharmacological potency. Controlled environments can greatly reduce the amount of time required to grow goldenseal to its desired harvestable state. While forest-cultivated plants double in mass every three to fiveyears, plants can double in mass every 15 weeks in growth chambers and triple in growth when in a course soil medium. Subculturing can take place every 30 days to mass-propagate the plant.
Another option is cultivating goldenseal in new regions. An experiment conducted by Douglas et al. grew goldenseal over a six-year period in a warm, temperate environment in New Zealand. The yields were 74% higher in the sixth year of growth compared to the fourth year of growth, which is when goldenseal is normally harvested. The overall growth of the allochthonous goldenseal was comparable to that found in the United States, and the hydrastine and berberine concentrations were within the American and European standards. Cultivating goldenseal in a New Zealand environment that is similar to its home range is an option to maintain its population.
- Oliver, L. (2016). "Hydrastis canadensis". The IUCN Red List of Threatened Species. IUCN. 208. e.T44340011A44340071. doi:10.2305/IUCN.UK.2017-2.RLTS.T44340011A44340071.en.
- "Hydrastis canadensis". Germplasm Resources Information Network (GRIN). Agricultural Research Service (ARS), United States Department of Agriculture (USDA). Retrieved 2017-12-12.
- Christensen, Deanna; Gorchov, David (2010). "Population dynamics of goldenseal (Hydrastis canadensis) in the core of its historical range". Plant Ecology. 210 (2): 195–211. doi:10.1007/s11258-010-9749-2.
- Goldenseal, American Cancer Society.
- Barton, Benjamin. "Benjamin Smith Barton MD – Collections for an Essay Towards a Materia Medica of the United States (p. 8)". Nlm.nih.gov. Retrieved 2017-02-20.
- Mahady, Gail; Chadwick, Lucas (2001). "Goldenseal (Hydrastis canadensis): Is there enough scientific evidence to support safety and efficacy?". Nutrition in Clinical Care. 4 (5): 243–249. doi:10.1046/j.1523-5408.2001.00004.x.
- Niering, William A.; Olmstead, Nancy C. (1985) . The Audubon Society Field Guide to North American Wildflowers, Eastern Region. Knopf. p. 737. ISBN 0-394-50432-1.
- Weber HA, Zart MK, Hodges AE, et al. (December 2003). "Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers". Journal of Agricultural and Food Chemistry. 51 (25): 7352–8. doi:10.1021/jf034339r. PMID 14640583.
- Gentry EJ, Jampani HB, Keshavarz-Shokri A, et al. (October 1998). "Antitubercular natural products: berberine from the roots of commercial Hydrastis canadensis powder. Isolation of inactive 8-oxotetrahydrothalifendine, canadine, beta-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and −2". Journal of Natural Products. 61 (10): 1187–93. doi:10.1021/np9701889. PMID 9784149.
- Douglas, JA; Follett, JM; Waller, JE; Sansom, CE (2010). "Seasonal variation of biomass and bioactive alkaloid content of goldenseal, Hydrastis canadensis". Fitoterapia. 81 (7): 925–928. doi:10.1016/j.fitote.2010.06.006. PMID 20550958.
- Ettefagh K.A., Burns J.T., Junio H.A., Kaatz G.W., Cech N.B., "Goldenseal (Hydrastis canadensis L.) Extracts Synergistically Enhance the Antibacterial Activity of Berberine via Efflux Pump Inhibition", Planta Medica 2010
- Goldenseal, WebMD.
- "Drugs and Lactation Database (LactMed)". Drugs and Lactation Database (LactMed). 2006. PMID 30000926.
- Dunnick JK, "Investigating the Potential for Toxicity from Long-Term Use of the Herbal Products, Goldenseal and Milk Thistle." Toxicol Pathol. 2011 Feb 7;
- Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A (2005). "In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes". Clin. Pharmacol. Ther. 77 (5): 415–26. doi:10.1016/j.clpt.2005.01.009. PMC 1894911. PMID 15900287.
- "Interaktion mellan läkemedel - FASS Vårdpersonal". Fass.se. Retrieved 16 March 2019.
- Zackrisson, A.L.; Holmgren, P.; Gladh, A.B.; Ahlner, J.; Lindblom, B. (October 2004). "Fatal intoxication cases: cytochrome P 450 2D6 and 2C19 genotype distributions". European Journal of Clinical Pharmacology. Springer-Verlag. 60 (8): 547–552. doi:10.1007/s00228-004-0800-x. ISSN 1432-1041. PMID 15349706.
- Foster Steven and Tyler Varro E. (1999): Tyler's Honest Herbal: A sensible guide to the use of herbs and related remedies. Binghamton, NY, The Haworth Herbal Press
- Robbins, C.S., 2000. Comparative analysis of management regimes and medicinal plant trade monitoring mechanisms for American ginseng and goldenseal. Conservation Biology, 14(5), pp.1422–1434.
- "United Plant Savers, Goldenseal". Unitedplantsavers.org.
- Dworkin, Norine (1999). "Where Have All the Flowers Gone? – herbal supplements threaten some herb species". Vegetarian Times.
- Mulligan, Margaret; Gorchov, David (2004). "Population loss of goldenseal, Hydrastis canadensis L. (Ranunculaceae) in Ohio". Journal of the Torrey Botanical Society. 131 (4): 305–310. doi:10.2307/4126936. JSTOR 4126936.
- Dean Myles Saving Wild Ginseng, Goldenseal, and other Native Plants from Mountain Top Removal. HerbalGram. 2007;73:50 © American Botanical Council
- Bergner, Paul. The Healing Powers of Echinacea, Goldenseal and Other Immune System Herbs. Prima 1997 ISBN 978-0-7615-0809-0
- Albrecht, M.A. and McCarthy, B.C., 2006. Comparative analysis of goldenseal (Hydrastis canadensis L.) population re-growth following human harvest: implications for conservation. The American midland naturalist, 156(2), pp.229–236.
- Sinclair, Adrianne; Catling, Paul (2003). "Restoration of Hydrastis canadensis by transplanting with disturbance simulation: results of one growing season". Restoration Ecology. 11 (2): 217–222. doi:10.1046/j.1526-100x.2003.00183.x.
- Sinclair, Adrianne; Catling, Paul (2004). "Restoration of Hydrastis canadensis: experimental test of a disturbance hypothesis after two growing seasons". Restoration Ecology. 12 (2): 184–189. doi:10.1111/j.1061-2971.2004.00297.x.
- Predny, M.L. and Chamberlain, J.L., 2005. Goldenseal (Hydrastis canadensis): an annotated bibliography. Gen. Tech. Rep. SRS-88. Asheville, NC: US Department of Agriculture, Forest Service, Southern Research Station. 67 p., 88.
- Van der Voort, M.E., Bailey, B., Samuel, D.E. and McGRAW, J.B., 2003. Recovery of populations of goldenseal (Hydrastis canadensis L.) and American ginseng (Panax quinquefolius L.) following harvest. The American Midland Naturalist, 149(2), pp.282–292.
- Davis, Jeanine M. (1999). "Forest Production of Goldenseal". Agroforestry Notes (USDA-NAC). 15.
- Burkhart, E.P. and Jacobson, M.G., 2009. Transitioning from wild collection to forest cultivation of indigenous medicinal forest plants in eastern North America is constrained by lack of profitability. Agroforestry systems, 76(2), pp.437–453.
- Canter, P.H., Thomas, H. and Ernst, E., 2005. Bringing medicinal plants into cultivation: opportunities and challenges for biotechnology. TRENDS in Biotechnology, 23(4), pp.180–185.
- Adelberg, J., Salido, A., Kelly, R.M. and Beavers, R., 2016. Rapid Growth of High Quality Goldenseal Plants in Controlled Environment Growth Chambers. In Medicinal and Aromatic Crops: Production, Phytochemistry, and Utilization(pp. 65–74). American Chemical Society.
- Bedir, E., Lata, H., Schaneberg, B., Khan, I.A. and Moraes, R.M., 2003. Micropropagation of Hydrastis canadensis: Goldenseal a North American endangered species. Planta medica, 69(01), pp.86–88.
- Douglas, JA; Follett, JM; Waller, JE; Sansom, CE (2013). "Root and rhizome production of goldenseal (Hydrastis canadensis L.) under cultivated conditions in New Zealand". New Zealand Journal of Crop & Horticultural Science. 41: 32–40. doi:10.1080/01140671.2012.743467.
- Blanchan, Neltje (2005). Wild Flowers Worth Knowing. Project Gutenberg Literary Archive Foundation. ISBN 0-665-98934-2.
- John Uri Lloyd (1908). Hydrastis canadensis. Lloyd Library, Cincinnati. PDF
- W. Scott Persons and Jeanine M. Davis (2005) Growing & Marketing Ginseng, Goldenseal & Other Woodland Medicinals Bright Mountain Books. ISBN 978-0-914875-42-0
- Richo Cech. (2002) Growing At-Risk Medicinal Herbs, Cultivation, Conservation and Ecology ISBN 978-0-9700312-1-1