Herbal medicine toxicity: The role of adulterants, contaminants and pharmacokinetic interactions

Abstract

Complementary and alternative medicine (CAM) is a broad set of health care practices that are not part of a country's own medical traditions and are not integrated into the dominant health care system. CAM includes herb medicines, dietary supplements, acupuncture, diet, yoga, Tai chi, meditation, massage, Ayurvedic medicine, Traditional Chinese Medicine, naturopathy and homeopathy. Some have been used for centuries in many cultures and others are more recent innovations. CAM in all its forms is now becoming increasingly popular in Western society. For the purpose of this study, CAMs will be taken to mean only those CAM therapies which involve medications (eg. Herbals, Ayurvedic medicine, Traditional Chinese Medicine) rather than mind-body or physical therapies. Despite the popular belief that CAM is natural and therefore safe, CAMs are continually being linked to adverse reactions caused by adulterants, contaminants and heavy metals, as well as by interactions between pharmaceuticals, other xenobiotics and the phytochemicals in CAMs. During the 18th century and into the early part of the 20th century it was a very common practice in the United States of America and Australia to include drugs such as cocaine, opium or cannabis in tonics that were used to treat a broad spectrum of conditions and diseases. Mahomet Allum was a herbalist who worked in South Australia in the early part of last century, whose herbal therapies generated some controversy at the time. Chapter 1: “Evaluation of an early 20th century Afghan herbalist’s preparations” details the results of analyses of two of his preparations. With increased interest in natural medicines, health and wellness tourism has grown, as countries in South East Asia promote traditional medicine and sell their herbal products to tourists. Chapter 2 deals with this issue: “Potential forensic issues in overseas travellers exposed to local herbal products” Fourteen processed herbal preparations were randomly selected and purchased from a traditional herbal retailer in Yangon, Myanmar (Burma) and screened for contaminates and adulterants. Toxicological results showed that only one sample contained an adulterant, but that this was yohimbine, a prescription only substance in Australia, and one that it is illegal to import. x Parents are also now taking their children to see CAM practitioners as well as administering herbal products. Chapter 3 reviews this situation: “Potential adverse outcomes of herbal preparation use in childhood” highlighting that children may be more susceptible to harmful effects due to immature physiology and metabolic pathways as well as having different dosage requirements. Data from a collaborative project which screened 347 herbal products sold in Australia for the presence of adulterants of contaminants was used to randomly select 18 products to test in vitro in HepG2 (liver) and Caco2 (intestinal) cell lines. Chapter 4: “Complementary and alternative medicines in Australia: A hidden source of toxicity” demonstrates that toxicity occurs even in the absence of contaminants and adulterants. With increasing rates of obesity in Australia, CAM products claiming weight loss and anti-obesity effects have become popular in Western society despite a lack of scientific validation. Severe adverse reactions have been reported following the use of these products, including the need for organ transplantation. This background has been addressed in chapter 5: “Evidence for the efficacy and safety of herbal weight loss preparations.” Three CAM products advertised for weight loss that had caused adverse reactions shortly after consumption were investigated. The three products were added to HepG2 and Caco2 cells. All three supplements caused significant toxicity in both cell lines. Toxicological results showed that there were no contaminates or adulterants present. These results are summarized in chapter 6: “Hepatotoxicity associated with the use of herbal weight loss supplements.” Epigallocatechin gallate (EGCG) and Hydroxy citrate Acid (HCA) are two common ingredients found in CAMs targeting weight loss. Increasing concentrations (0-100μM) of the two phytochemicals were added to HepG2 and Caco2 cells individually and in the presence of each other to determine if any interactions were occurring. These results are reported in chapter 7: “Interactions between epigallocatechin-3-gallate (EGCG) and hydroxy citric acid potentiate EGCG hepatotoxicity.” xi These results demonstrate that despite the perceived perception of safety associated with CAMs, they have the possibility to interact with pharmaceuticals as well as with other herbal compounds. Whilst further work is required to investigate the mechanisms causing these adverse effects, the current work highlights the risk of using these preparations, and at-risk combinations that could be a significant public health concern.