- Author: Fermin Barrueto, Jr, MD, FAAEM, FACEP; Chief Editor: Asim Tarabar, MD more...
Although most plant exposures are unintentional, many adults ingest herbal products for self-treatment of illness and for health maintenance; indeed, the sale of herbal preparations has developed into a billion-dollar industry. What constitutes an herbal product is generally ill-defined and, though the term implies a leafy plant, herbal products may contain nonherb plant materials, animal products, and/or mineral products.
While many herbal products are innocuous or possess minimal toxicity, some contain toxic ingredients that may not be identified on the label. These unidentified ingredients may be unintentionally included in the product (eg, misidentification of a toxic plant as a desired nontoxic plant or contamination with pesticide residues or heavy metals) or adulterants introduced for increased effect (eg, addition of a pharmaceutical agent to an herbal preparation).
Dietary supplements, including herbal products, are regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994 as a food product. This Act does not require these products to be effective or safe prior to marketing.
The US Food and Drug Administration (FDA) has little control over the marketing of herbal products, but may prohibit sales of herbal products containing pharmaceutical agents. The FDA also may prohibit sale of an herbal product proven to have serious or unreasonable risk under conditions of use on the label or as commonly consumed. However, prohibition of an herbal product generally does not occur until after marketing and extensive distribution to the public. The burden of proof lies with the FDA and consumer reporting.
Case reports and studies have documented that herbal products may contain ingredients, sometimes toxic, not listed on the label. In addition, the quantities of ingredients listed on the label can vary greatly, hindering definition of toxic ingredients and unsafe products for public consumption.
This article discusses several plants and plant products commonly used to improve health or to treat illness as herbs and herbal products. Herbs and herbal products in this article are discussed because of their reported toxicity and increased use in the general patient population. Many herbal products continue to be available to the public with either ill-defined or unknown toxicity.
Herbal products are generally heterogeneous, may produce multiple effects, and may affect multiple organ systems, including the nervous, cardiovascular, gastrointestinal (GI), hepatic, renal, and hematologic systems. The following section discusses specific toxic plants, categorized by the system most severely affected.
Central nervous system
Several herbal products can produce anticholinergic symptoms. Atropa belladonna contaminated burdock root tea in the 1970s and 1980s, resulting in anticholinergic toxicity. Datura metel L fastuosa mistakenly has been used in place of Campsis and Paulownia species, producing anticholinergic poisoning.
Plants with anticholinergic activity include Datura stramonium (jimson weed), A belladonna (deadly nightshade), and Hyoscyamus niger (henbane). In the 1970s, ginseng contaminated with Mandragora officinarum (scopolamine-containing mandrake) produced anticholinergic toxicity.
Kava-kava (Piper methysticum) is an herbal preparation that may be brewed into a beverage and is especially popular among natives of the South Pacific islands. Methysticine and kawain (a local anesthetic) are its main constituents; however, primary effects of kava-kava are anxiolytic, myorelaxant, and sedation. This herbal preparation has also been associated with hepatotoxicity.
St. John's wort (Hypericum perforatum) is a weak monoamine oxidase inhibitor (MAOI) and serotonin agonist. Concern has been raised regarding initiation of hyperadrenergic MAOI reactions by mixing adrenergic preparations, such as ephedra and ephedrine-containing preparations, with St. John's wort; however, no cases of serotonin syndrome or MAOI crisis have been linked to the use of St. John's wort. When taken in conjunction with other prescription medications, St. John's wort may decrease their systemic bioavailability.
Podophyllum emodi and Podophyllum peltatum (mandrake and mayapple, respectively) contaminated herbal preparations (eg, Gentiana and clematis) in the 1980s and 1990s. Podophyllin causes metaphase arrest at the cellular level and altered mental status, peripheral motor and sensory neuropathy, gastroenteritis, and multisystem organ failure.
Lobelia inflata and Nicotiana products can cause nicotine toxicity with hypertension, fasciculations, and CNS excitation. Severe cases may progress to neuromuscular paralysis. Older versions of smoking-deterrent tablets contained Lobelia.
Strychnos nux-vomica (strychnine) has been found in imported herbal patent medicines and can cause abdominal distress. Although frequently formulated in homeopathic doses, toxic amounts of strychnine cause profound metabolic acidosis, rhabdomyolysis, and generalized "spinal seizures" in fully alert patients.
Cardiac glycosides and other cardioactive steroid contaminants may cause toxicity. Digitalis lanata was mistaken for plantain and caused severe cardiotoxicity (eg, complete heart block) in 1997 when consumed as an internal cleansing product.
Ephedra and ephedrine-containing products (eg, Ma Huang) may produce cardiac stimulation, hypertension, peripheral vasoconstriction, chest pain, myocardial infarctions, and intracerebral hemorrhage. Ma Huang (ephedra) may produce hypersensitivity myocarditis (case report) and vasculitis.
A sufficient public outcry and data collected on adverse effects enabled the FDA to ban ephedra products for use in weight loss. However, ephedra is available for sale as an asthma preparation and should still be considered for abuse. It is still promoted in body-building circles.
Aconitum species (ie, monkshood or wolfsbane) contain aconitine; Veratrum species contain Veratrum alkaloids. These toxins open sodium channels in cardiac myocytes, resulting in conduction blockade, bradycardia, ventricular dysrhythmias (especially bidirectional tachycardia), and refractory cardiovascular collapse. Aconitine-containing Chinese herbal medicine compounds have been used to treat chronic pain syndromes and unfortunately have also been associated with deaths in Asia and Australia.
Cinchona bark ingestion can cause quinine toxicity.
Hepatic toxicity with Budd-Chiari syndrome has been reported with pyrrolizidine alkaloids, which are metabolized to alkylating agents that produce hepatic veno-occlusive disease, hepatomegaly, and cirrhosis. Toxicity can affect the fetus as well. Plants that contain these substances include Heliotropium (heliotrope), Senecio (gordolobo), Crotalaria, and Symphytum (comfrey). Senecio and Crotalaria have been used in Jamaica to make bush tea.
Mentha pulegium (ie, pennyroyal oil, "squaw" mint) teas have been mistaken for other mint teas and have been used intentionally as abortifacients. These teas contain the hepatotoxin pulegone, which causes hepatocellular necrosis. Pulegone toxicity can result in multisystem organ failure.
Germander (Teucrium chamaedrys) can cause centrilobular necrosis. In France, germander was marketed as a slimming agent in the 1990s; fatalities were reported.
Chaparral (ie, creosote bush, greasewood, hediondillo) can produce periportal injury, inflammatory changes, scarring, cholangitis, and cholestasis.
Jin Bu Huan is a Chinese herbal preparation with a long history of use as a sedative, analgesic and decongestant. The compositions of Jin Bu Huan may vary, but can include Lycopodium serratum, Panax, Pseudo ginseng, Polygala chinensis and Stephania. Some preparations have caused fatal hepatic injury. Other preparations have caused severe bradycardia.
A survey of worldwide cases of liver injury associated with herbal traditional Chinese medicine established causality for 28 different herbs or herbal mixtures: Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao.
Sho-saiko-to (a mixture of 7 herbs) is a Chinese preparation that is widely used as a prescription medicine in Japan, principally for treatment of hepatitis. Nevertheless, it has been associated with toxic hepatitis.
Artemisinin, which is found in the leaves of Artemisia annua, is a component of therapies for malaria that generally are considered safe, effective, and well tolerated. In addition, herbal supplements containing artemisinin are marketed for general health maintenance and for treatment of parasitic infections and cancers. A case of hepatitis associated with ingestion of an herbal supplement containing artemisinin has been reported, however.
Dai-saiko-to is a traditional Japanese herbal medicine. A case of autoimmune hepatitis becoming clinically apparent in a patient using dai-saiko-to has reported.
Kombucha tea is a symbiotic mixture of yeast and bacteria brewed into tea. Case reports describe a syndrome characterized by hepatotoxicity, pulmonary edema, and disseminated intravascular coagulation (DIC) after ingestion.
Case reports of hepatotoxicity from kava-kava led to bans and regulations of its use in several countries. However, a comprehensive review estimated that the incidence rate of hepatotoxicity from kava-kava is one in 60-125 million users. In 2014, a German court overturned that country's ban on kava-kava, stating that risk from kava exposure had not been clearly demonstrated and did not appear unusually high.
Ginkgo biloba has been reported to increase bleeding times and may have contributed to intracranial hemorrhages. Yohimbine use has been associated with agranulocytosis (probably an idiosyncratic response) and priapism. Dysosma pleianthum (ie, bajiaolian) contains podophyllotoxin and causes thrombocytopenia and leukocytosis.
Jui, a Chinese herbal medication, has been associated with thrombocytopenia. A reaction may be triggered by repeat exposure because of sensitization from previous exposure or exposures. Jui contains Sinomeni caulis et rhizoma, Glycyrrhizae radix, Aralia elata, Glechomae herba, and Taxus cuspidata.
L-tryptophan has been contaminated with a by-product and associated with 38 deaths. Numerous chronic pulmonary effects are known collectively as eosinophilia-myalgia syndrome. Elevated eosinophil levels are characteristic of the syndrome.
Adverse effects of herbal preparations may also include the following:
Aristolochia species (eg, birthwort, heartwort, fangji) can cause interstitial renal fibrosis due to aristolochic acid, a known nephrotoxin 
Licorice root may cause profound renal potassium loss (see Licorice Poisoning)
Echinacea and chamomile tea can cause anaphylaxis
Royal jelly and yohimbine can cause allergic reactions
Shiitake mushrooms can cause severe dermatitis
Garlic, chamomile tea, and capsicum may produce contact dermatitis
Contamination and adulteration
Some herbal products contain high concentrations of heavy metals, such as lead, mercury, and arsenic (also found in kelp). Use of ayurvedic medications should arouse suspicion of lead contamination.) Chinese herbal medications have been an incredible source of contamination, with one study showing that, out of 247 traditional Chinese medicines investigated, a proportion were contaminated with arsenic (5-15%), lead (5%), and mercury (approximately 65%).
In a study of 6,712 women aged 20 years or older, those using herbal supplements had lead levels that were 10% higher than nonusers. Blood lead levels were 24% higher in women using ayurvedic or traditional Chinese medicine herbs; 23% higher in those using St. John's wort, and 21% higher in those using kava, valerian, black cohosh, bee pollen, or nettle.
Some herbal preparations have been found to be adulterated with undeclared ingredients. For example, the prostate cancer remedy PC-SPES was withdrawn from the market in 2002 after samples were found to contain warfarin, diethylstilbestrol, and indomethacin. Other drugs that have been found in herbal preparations include the following:
Adulteration with mefenamic acid and cadmium has resulted in acute renal failure. Adulteration with dipyrone and phenylbutazone has resulted in agranulocytosis.
Adverse effects from herbal preparations can be categorized by type. One schema divides reactions into the following 4 types:
Type A - Pharmacologically predictable, dose dependent, and preventable by dose reduction
Type B - Idiosyncratic, pharmacologically unpredictable, toxicity not correlated with dose, often immunologically mediated, often serious and potentially fatal
Type C - Developed over long-term therapy, well-described, and may be anticipated
Type D - Delayed effects (eg, carcinogenicity, teratogenicity)
Another schema divides reactions as follows:
Adverse effects related to desired pharmacologic actions
United States statistics
According to a rural Mississippi study, almost three fourths of respondents had used plant-derived remedies during the preceding year. Another study found that one third of US citizens have used herbal medicines. The National Center for Health Statistics reports that in 2007-2012, almost 4 out of 10 adults and over 1 in 10 children aged 4–17 years had used complementary and alternative medicine (CAM) therapy in the previous 12 months and that nonvitamin, nonmineral dietary supplements were the most commonly used, comprising approximately 18% of CAM therapies in adults and approximately 5% in children.[13, 14]
Some ethnic groups are more likely to utilize herbal preparations. One survey in a New York urban hospital showed overall herbal use to be 21%, with highest use (36%) reported among the Asian population.
The World Health Organization (WHO) estimated that herbal and other plant-derived remedies are the most frequently used therapies worldwide. WHO estimated that in 2003, the global market for herbal medicines stood at over US $60 billion annually. WHO estimated that in Africa, up to 80% of the population used traditional medicine, including herbal preparations, for primary health care, and that in China, traditional herbal preparations accounted for 30-50% of all medicinal consumption.
Traditional Chinese herbal medications have been an ever-increasing source of contamination, either intentional or unintentional. Due to lack of transparency of reporting, however, the risk to the general population has been difficult to assess.
Slifman NR, Obermeyer WR, Aloi BK, Musser SM, Correll WA Jr, Cichowicz SM, et al. Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med. 1998 Sep 17. 339(12):806-11. [Medline].
National Institutes of Health. Jin Bu Huan (Lycopodium serratum). LiverTox. United States National Library of Medicine. Available at http://livertox.nih.gov/JinBuHuan.htm. Accessed: February 11, 2016.
Teschke R, Zhang L, Long H, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, et al. Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases. Ann Hepatol. 2015 Jan-Feb. 14 (1):7-19. [Medline].
Centers for Disease Control and Prevention. Hepatitis temporally associated with an herbal supplement containing artemisinin - Washington, 2008. MMWR Morb Mortal Wkly Rep. 2009 Aug 14. 58(31):854-6. [Medline].
Kamiyama T, Nouchi T, Kojima S, Murata N, Ikeda T, Sato C. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol. 1997 Apr. 92(4):703-4. [Medline].
Baker JD. Tradition and toxicity: evidential cultures in the kava safety debate. Soc Stud Sci. 2011 Jun. 41 (3):361-84. [Medline].
Showman AF, Baker JD, Linares C, Naeole CK, Borris R, Johnston E, et al. Contemporary Pacific and Western perspectives on `awa (Piper methysticum) toxicology. Fitoterapia. 2015 Jan. 100:56-67. [Medline].
Kuchta K, Schmidt M, Nahrstedt A. German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics. Planta Med. 2015 Dec. 81 (18):1647-53. [Medline].
Fox S. Chinese Herb Remains Health Threat Despite Widespread Bans. Medscape Medical News, March 18, 2013. Available at http://www.medscape.com/viewarticle/780947. Accessed: February 11, 2016.
Buettner C, Mukamal KJ, Gardiner P, Davis RB, Phillips RS, Mittleman MA. Herbal supplement use and blood lead levels of United States adults. J Gen Intern Med. 2009 Nov. 24(11):1175-82. [Medline]. [Full Text].
White J. PC-SPES--a lesson for future dietary supplement research. J Natl Cancer Inst. 2002 Sep 4. 94(17):1261-3. [Medline].
Centers for Disease Control and Prevention. Self-treatment with herbal and other plant-derived remedies--rural Mississippi, 1993. MMWR Morb Mortal Wkly Rep. 1995 Mar 24. 44(11):204-7. [Medline].
Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl Health Stat Report. 2015 Feb 10. 1-16. [Medline]. [Full Text].
Black LI, Clarke TC, Barnes PM, Stussman BJ, Nahin RL. Use of complementary health approaches among children aged 4-17 years in the United States: National Health Interview Survey, 2007-2012. Natl Health Stat Report. 2015 Feb 10. 1-19. [Medline]. [Full Text].
Hung OL, Shih RD, Chiang WK, Nelson LS, Hoffman RS, Goldfrank LR. Herbal preparation use among urban emergency department patients. Acad Emerg Med. 1997 Mar. 4(3):209-13. [Medline].
World Health Organization. Traditional Medicine. Available at http://www.who.int/mediacentre/factsheets/2003/fs134/en/. May 2003; Accessed: February 11, 2016.
Haslan H, Suhaimi FH, Das S. Herbal Supplements and Hepatotoxicity: A Short Review. Nat Prod Commun. 2015 Oct. 10 (10):1779-84. [Medline].