By David Miller, BSc, ND
NHP Scientific Regulatory Associate
Kava (Piper methysticum; kava kava) has traditionally been used as an anxiolytic by western herbalists (Felter and Lloyd 1898) for over 100 years. It originates from the South Pacific, where it has been used for centuries (Ernst 2007).
Clinical evidence suggests that Kava is effective as an anxiolytic which helps to relieve nervousness (Pittler and Ernst, 2003; Sarris et al. 2007; Wheatley et al. 2001; Boerner et al. 2003; Cropley et al. 2002; Thompson et al. 2004). Furthermore Kava has also been found to be effective in supporting a healthy mood balance and enhancing short-term memory and cognitive performance (Thompson et al. 2004).
However, it is the safety of Kava that has come into question in the last 10 years.
In 2002 Health Canada issued a stop sale advising persons to not consume any products containing Kava (Boon & Wong 2003). However, until 2002 Kava was considered a relatively safe treatment for anxiety, with few side effects (Boon and Wong 2003). What happened?
In 2002 there were 25 case reports of serious toxic effects on the liver (cirrhosis, hepatitis, liver failure) from Germany, Switzerland, and the United States that were associated with the use of Kava. Upon hearing of these adverse events, Health Canada identified 4 possible cases of liver toxicity associated with Kava use (Health Canada 2002, cited in Boon and Wong 2003), leading to a stop-sale order in September of the same year (Health Canada 2002).
A traditionally used anxiolytic herb is suddenly a life-threatening hepatotoxin? Let’s make a balanced appraisal of the safety of Kava.
Sarris (2007) reported that although idiosyncratic health events have occurred, no serious adverse events were noted except for case reports of hepatotoxicity and theoretical potentiation of alcohol and benzodiazepines which were not found in clinical trials. Seventy-eight cases of hepatotoxicity have been documented to 2003, including 11 cases of hepatic failure leading to liver transplants and four deaths occurring. A more recent paper by Ernst (2007) states that only 14 of the approximately 100 cases of liver toxicity due to Kava were deemed to be ‘probable’, with some cases confused by concomitant drug and/or alcohol use or excessive doses(Ernst 2007). And you may have heard this in Embryology class; “the dose makes the poison”.
Important scrutiny is necessary before we presuppose that “Kava is toxic”. For example, what is the quality of case reports, the mechanism of toxicity, the source of the kava kava, the extraction method, and dose administered?
Case Reports: Firstly, how influential have Kava-related case reports been in the estimation of safety? It is possible that they have been too heavily weighted. According to the above by Ernst (2007), only 14% of case reports supported ‘probable’ causation. There were significant confounding variables such as multiple drug and alcohol ingestion. Also, what value is a case report? It has value, indeed, but its uncontrolled nature is not enough to positively prove causality and this form of safety evaluation is far from the gold standard.
Mechanism: An in vivo trial sought to evaluate the potential heptotoxicity of kava (Sorrentino et al., 2006). Wistar rats were fed 7.3 or 73 mg/kg body weight of ethanol kava extract for 3 and 6 months with no change in body weight, haematological or liver parameters or histological changes in the major organs. The mechanism, if one even exists, of kava kava toxicity has not been elucidated. In fact, the most likely explanation is “an immunologically mediated idiosyncratic reaction” (Schulze et al. 2003; Musch et al. 2006, cited in Ernst 2007). To date no adverse events have been documented in humans occurring from kava’s potential pharmacokinetic interaction with pharmaceutical medicines. Potential interaction of kava with benzodiazepines causing increased sedation has been posited (Singh, 2005; Stevinson et al., 2002), however, no clinical evidence currently supports this hypothesis (As reviewed by Sarris, 2007)
Source of Kava/Impurities: A report by Teschke (2011) indicates that liver toxicity and adverse reactions are associated with low quality kava, i.e. kava which has been contaminated with mold. This report emphasizes the importance of high quality products. Moreover, this report provides a valid explanation on why adverse reactions have not been experienced during clinical trials investigating the effects of high quality kava supplements.
Extraction method: There have been changes in the preparation of Kava extracts from how it was traditionally used by peoples of the South Pacific as a water extract (Ernst 2007). Felter and Lloyd describe a Fluid Extract that uses a 3:2 ratio of alcohol:water (Felter and Lloyd 1898). Preclinical studies indicate that water fractions of kava are less cytotoxic than organic solvent fractions (Jhoo et al. 2006; Sorrentino et al. 2006, cited in Ernst 2007), but modern commercial products use alcohol or acetone compounds (Ernst 2007). However, as stated above, adverse reactions have been absent in controlled clinical trials that have used high quality kava extracts.
It appears that the worst case scenario is an organic solvent-based preparation of an impure, moldy source of kava kava, administered at a high dose to a susceptible individual without the guidance of a qualified health professional.
However, to the practitioner who is searching for an effective intervention for anxiety, the efficacy of kava may outweigh the risks.
David Miller BSc, ND
Thanks to Ashleigh Hampton MSc, Manager Scientific Affairs at dicentra for her contribution to this composition.
dicentra provides regulatory and scientific solutions for accelerated business growth. We specialize in the areas of natural health products, dietary supplements, foods, cosmetics and OTCs. We can be reached at 1-866-647-3279 or at dicentra.com