Kava - Its Resurgence, Quality Control, Anxiolytic Activity, and Hepatotoxic Risk, a Natural Medicine with Future Promise and Challenges

Abstract

Consumed as a daily beverage by South Pacific islanders for centuries, traditional kava is prepared as an aqueous extract of the roots of Piper methysticum. Other than its traditional use, kava had previously been employed clinically to treat mild to moderate anxiety and was widely available as a dietary supplement for such use. Reports of rare hepatotoxicity linked to use of unspecified kava products led to its removal from the European market. Subsequently, in 2002, the US FDA issued a warning regarding potential hepatotoxicity and although kava was not banned, safety and liability concerns led most manufacturers to abandon commercialization of kava as a dietary supplement. Surprisingly, kava is experiencing a dramatic resurgence in popularity globally and increased human exposure is evident and inevitable. Our team conducted an analysis of kava exportation from Vanuatu, Fiji, and Tonga. Between 2009 and 2011 kava exports from these countries increased each year and were noted to be 727, 804 and 1089 tons respectively, a significant portion being to the USA, demonstrating large and increasing popularity among certain populations. Although it is commonly believed that kava use is associated with liver injury, a cause and effect relationship as well as mechanism of action for such injury remains ill defined. Furthermore, it is unknown which components of kava may be responsible for injury and whether or not the extraction process and resulting chemical characteristics may have played a role in previously reported adverse events. Considering that human use is continuing and increasing, there may or may not be a significant emerging public health issue. Therefore, renewed interest in researching potential cause and effect relationships between kava use, its clinical utility and liver injury is warranted. Kava's anxiolytic activity is attributed to kavalactone-based chemicals yet there have been no animal or human studies to confirm the anxiolytic component(s). From a safety perspective, many factors influence the composition of kava products, and various hypotheses have been proposed for its hepatotoxic risk but again none has validated a cause and effect relationship or mechanism of action. Pending the outcome of more definitive toxicity investigations, additional studies to validate the active components and mechanism of action for its anxiolytic effects are also warranted and may lead to successful reintroduction of safer commercial forms of kava with substantial potential for beneficial clinical use. Our team proposes new approaches to study this issue and will present suggested appropriate models for further investigation.