Herbal assault: liver toxicity of herbal and dietary supplements

Abstract

The worldwide market for herbal and dietary supplements is booming. Even actress Gwyneth Paltrow's lifestyle company Goop has got in on the action, pedalling quirkily named supplements like “Balls in the air” and “The mother load”, targeted at those working at an “intense pace” and expectant mothers, respectively. These supplements promise to revitalise, replenish, and reinvigorate, in part via proprietary blends of herbal extracts. But the health benefits of such products are largely unsubstantiated by scientific data, and they are increasingly associated with harmful side-effects, including liver toxicity. The number of people who use herbal and dietary supplements is not entirely clear, but the popularity of these products is undeniable. Surveys suggest that roughly 20% of Europeans and half of all Americans use these products. In one national survey, more than three-quarters of patients with, and survivors of, cancer in the USA reported using dietary supplements; boosting the immune system and helping to prevent cancer were among the most cited reasons for use. In the USA alone, sales of supplements were nearly US$37 billion in 2014, up from only $7 billion in 1994. In Australia, spending on complementary medicines increased by more than 100% between 1996 and 2004. The lure of herbal and dietary supplements is not difficult to understand. They promise seemingly boundless health benefits—among them improved health, weight loss, decreased stress, increased energy, and relief from depression—and they are freely available for purchase, relatively inexpensive, and do not require a prescription. Indeed, the widespread absence of regulation of these products—which are widely considered food additives rather than medicines—means that hard data and clinical trials are not required to support claims of general health benefits. The natural origin of many of these products also gives many people a false sense of security regarding safety. Indeed, the assumption that herbal supplements are innocuous might explain why many patients do not disclose their use to their physicians, meaning that related side-effects are frequently misattributed. Even when patients disclose supplement use to their doctors, they often do not know exactly what they are taking—few of these products contain single ingredients and many are proprietary mixtures sold under commercial names. Even more worryingly is the finding that these products can be spiked with pharmaceuticals not disclosed on labels, or contain toxic substances like arsenic and DDT, as reported in a review from Australia. That herbal and dietary supplements are associated with health risks—including potentially dangerous interactions with prescription drugs and other herbal compounds—is not new. But reports of liver toxicity attributed to these products have increased in recent years. In 2013–14, 20% of cases of drug-induced liver injury (DILI) in the USA were blamed on supplement use, compared with 7% in 2004–05. In a Spanish DILI registry, 13% of cases were attributed to herbal and dietary supplements in 2010–13, and reports from Singapore and South Korea estimate this proportion at a staggering 70% or greater. New evidence is also emerging that the type of liver injury caused by herbal and dietary supplements might be particularly dangerous. In a report from the Spanish DILI registry, most cases of herbal and dietary supplement-induced liver injury reported between 1994 and 2016 had a hepatocellular pattern with very high alanine aminotransferase values—features associated with increased risk of severe outcomes. Indeed, a greater proportion of patients with liver injury attributed to supplement use died or required liver transplantation compared with cases attributed to anabolic steroid use or conventional medications. In a prospective registry study from the USA, higher transplantation rates and lower survival—but no difference in type of liver injury—were reported among patients with liver injury caused by so-called complementary and alternative medications compared with that of patients with prescription drug-related liver injury. With mounting evidence of the health risks associated with herbal and dietary supplements, it is clear that increased awareness and education—among both physicians and patients—is essential. Patients should also adopt a full disclosure approach when communicating with their doctors. But beyond improvements in awareness and communication, it is time to call for more rigorous scrutiny and increased quality control of herbal and dietary supplements, along with more honest reporting of ingredients. When it comes to health claims, these products should no longer be free of the burden of proof. For the European survey see PLoS One 2014; 9: e92265For the USA survey see JAMA Int Med 2013; 173: 355–61For the review from Australia see Med J Aust 2017; 206: 86–90For the Spanish DILI registry report see Clin Gastroenterol Hepatol 2018; published online Jan 4. DOI:10.1016/j.cgh.2017.12.051For the prospective USA registry study see Am J Gastroenterol 2016; 111: 958–65 For the European survey see PLoS One 2014; 9: e92265 For the USA survey see JAMA Int Med 2013; 173: 355–61 For the review from Australia see Med J Aust 2017; 206: 86–90 For the Spanish DILI registry report see Clin Gastroenterol Hepatol 2018; published online Jan 4. DOI:10.1016/j.cgh.2017.12.051 For the prospective USA registry study see Am J Gastroenterol 2016; 111: 958–65 Dietary supplements: improving education is not enoughWorldwide demand for dietary supplements skyrocketed at the beginning of the COVID-19 pandemic; some countries reported sales increases of more than 50% in March, 2020, compared with the same period the previous year, and the market continues to grow . Concerns about vaccine safety and hopes of boosting immune function against COVID-19 propelled people to turn to dietary supplements , despite insufficient data to support recommendations for this purpose. In response to concerns about public health and safety, the US Food and Drug Administration (FDA) launched Supplement Your Knowledge on June 2 , 2022, an education initiative aimed at helping people make informed decisions about taking dietary supplements. Full-Text PDF