REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Robert F. Schwabe and John W. Wiley, Section Editors Herbal Products and the Liver: A Review of Adverse Effects and Mechanisms Leonard B. Seeff, 1 Herbert L. Bonkovsky, 2 Victor J. Navarro, 3 and Guqi Wang 4 1 Einstein Healthcare Network, Philadelphia, Pennsylvania; 2 Liver Digestive & Metabolic Disorders Laboratory, Carolinas HealthCare System, Charlotte, North Carolina; 3 Jefferson Medical College, Einstein Healthcare Network, Philadelphia, Pennsylvania; and 4 Carolinas HealthCare System, Charlotte, North Carolina See commentary on page 480. Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses. Recently, their use in Western countries has grown signif- icantly, rivaling that of prescription medications. Currently, herbal products are used mainly for weight loss and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases. Many people believe that because they are natural, they must be effective and safe; however, these beliefs are erroneous. Few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary. Moreover, current highly effective antiviral drugs make efforts to treat hepatitis C with herbal prod- ucts redundant. Herbal products are no safer than con- ventional drugs and have caused liver injury severe enough to require transplantation or cause death. Furthermore, their efficacy, safety, and claims are not assessed by regu- latory agencies, and there is uncertainty about their re- ported and unreported contents. We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects. Keywords: Dietary Supplement Health and Education Act; Contamination and Adulteration; Herbal Therapie; sSilymarin. P harmacological agents emerged in the 19th century, when work in the textile and synthetic dye industry produced organic chemicals distilled from coal tar. 1 Before that, indigenous people treated illnesses with herbal prod- ucts; these practices date back more than 5000 years. 2 Supporting evidence comes from clay tablets by Sumerian people in Mesopotamia (Babylonia) as well as writings in a book from China titled Pen Tsao, describing >300 herbs for medical treatments that included ma huang containing ephedra. More than 3000 years ago, numerous herbs used in the Indian medical system called Ayurveda were listed in the Indian Materia Medica. Other early cultures that used herbal products as medicine included the ancient Greeks (Hippocrates was a herbalist), Romans, Egyptians, and Arabs, as well as native people of Africa, Australia, New Zealand, the South Pacific Islands, and the Americas. Inter- estingly, early European immigrants to the United States learned much about herbal medicines from Native Ameri- cans as part of their healing tradition. During the Middle Ages, monks preserved interest in medicinal herbs, aided by works compiled by Arab cultures. An Iranian physician, Ibn Sina, known as Avicenna, created The Canon of Medicine, an influential medical text based on herbal traditions. Interest in herbs grew during the Renaissance period, fueled by wealthy landowners who ob- tained spices from the East to flavor foods. In 1652, Nicholas Culpeper developed a systematic listing of all known herbs. In the early 18th century, because of confused nomenclature, the Swedish botanist Linnaeus catalogued all known plants, including medicinal plants, using Latin names. Sources and Production of Herbal Products Herbal products used for medicinal purposes comprise 3 broad categories. First are individual crude herbal products derived from plants (stems, roots, leaves, berries, seeds, flowers) and barks of trees, used over centuries and selected generally by traditional healers. Their chemical constituents are often unknown or not fully characterized and may vary widely depending on weather conditions, geographic location, and elevation where grown. Most are given as a single product, although some, such as traditional Chinese medicines (TCMs) or Japanese Kampo medicines, may include several herbal products bundled together, selected by experienced herbalists based on traditional values and long use. Herbal products are administered as infusions, decoctions, syrups, poultices, lotions, or Abbreviations used in this paper: ALT, alanine aminotransferase; CAM, complementary and alternative medicine; CHC, chronic hepatitis C; CYP, cytochrome P450; DILI, drug-induced liver injury; DILIN, Drug-Induced Liver Injury Network; EGCG, epigallocatechin gallate; FDA, Food and Drug Administration; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN, interferon; mRNA, messenger RNA; NAFLD, nonalcoholic fatty liver disease; SNMC, Stronger Neo-Minophagen C; TCM, traditional Chinese medicine. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.12.004 Gastroenterology 2015;148:517–532 REVIEWS AND PERSPECTIVES