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Hepatotoxicity due to herbal medications and dietary supplements

Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Complementary and alternative medical (CAM) therapies are a diverse group of practices that includes the use of herbal and dietary supplements (HDS) (table 1) [1]. Between 1997 and 2002, overall CAM therapy use remained relative stable [1]. By contrast, the use of HDS increased by 50 percent, from 23 million adult users to over 38 million adult users [1]. The use of CAM therapies in the United States and worldwide has continued to increase dramatically [2]. At least 55.2 million adults (23.5 percent) and 4.1 million children (7.1 percent) reported the use of CAM therapies, depending upon how they were defined, with out-of-pocket costs in 2012 exceeding $30.2 billion [3-5]. The most commonly used CAM therapies were herbal and dietary supplements, with $12.8 billion of all out-of-pocket costs for the purchase of nonvitamin, nonmineral natural products [5,6]. The most common reason for their use is for health improvement and health maintenance [7]. Women and Alaska Natives/American Indians were more likely to use CAM therapies, with greater use in persons younger than 65 years of age and in those with a higher annual household income [1,3,5,8,9].

Use of herbal preparations can be traced back as far as ancient Egypt, China, India, and Sumeria, and formulations have been expanded upon over the centuries [10,11]. Many patients consider "natural" herbal remedies to be completely free of unwanted side effects [12-14]. This is concerning since many herbal products have biological activity that can lead to severe toxicity or that interact with each other or with prescription medications. Fewer than 40 percent of patients disclose to their clinician that they are using these products [1,3,15].


Over 1000 medications and herbal products have been implicated in the development of drug-induced liver injury, and the list continues to grow [16,17]. A searchable database of drugs, herbal medications, and dietary supplements associated with hepatotoxicity has been developed by the National Institutes of Health [18].


In 1962, the Kefauver-Harris Drug Amendment required that all over-the-counter and prescription products show proof of safety and efficacy [19]. Complementary and alternative medicines (CAMS) were assigned to the food supplement category and had a lower threshold of required evidence for safety [19]. An attempt by the US Food and Drug Administration (FDA) in the early 1990s to develop more strict regulations was met with significant opposition by supplement manufacturers, lobbyists, and consumers.

The Dietary Supplement Health and Education Act (DSHEA) of 1994 was an amendment to the US Federal Food, Drug, and Cosmetic Act (FD&C) [20]. The DSHEA defined dietary supplements as products that are taken by mouth that contain an ingredient (vitamin, mineral, amino acids, enzyme, organ tissues, glandular, metabolites, and herb or botanicals) intended to supplement the diet [10,20-22]. These products may be in the form of tablets, capsules, soft gels, gel caps, liquids, teas, or powders. The DSHEA named the United States Pharmacopeia–National Formulary (USP–NF) as its official reference for herbal preparations [20]. The United States Pharmacopeia is an official public standards-setting authority for all prescription and over-the-counter medicines and other healthcare products manufactured or sold in the United States [23]. The USP also sets standards for food ingredients and dietary supplements.


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