Kava, aqueous extracts from the roots of Piper methysticum, is traditionally served as a beverage for South Pacific islanders. Epidemiologic evidence has also linked kava to a very low incidence of certain cancers in several South Pacific countries, proposed to be related to the presence of compounds called kavalactones. Organic extracts also have a long history of traditional use for anxiety.
However, kava has often made headlines for the wrong reasons, with reports of potential liver toxicity associated with various commercially available kava-containing dietary supplements being reported for over 10 years. As a result of this, many regulatory bodies around the world have restricted the product, or issued official recommendations to avoid use. The US FDA recommends consumers consult a physician before using kava-containing supplements.
Evidence of carcinogenic activity due to kava in rodents was reported by the National Toxicology Program (NTP) in 2011, available here.
Such reports, which have been questioned and challenged by some in the herbal community and beyond, have essentially kept an entire plant out of commerce, said Dr Rick Kingston, President, Regulatory and Scientific Affairs, SafetyCall International and Clinical Professor of Pharmacy, University of Minnesota.
Not all kava products are equal
Researchers from the University of Minnesota have now identified the naturally occurring components of kava that appear responsible for all the cancer-preventative benefits. The team also found that daily consumption of the kava-derived product prevented the formation of 99% of tumors in a mouse model that is routinely used in predicting lung cancer behavior in humans.
Some mice developed no tumors at all, according to findings published in Cancer Prevention Research. DNA damage resulting from tobacco carcinogens was also significantly reduced by way of prevention.
In addition, by carefully selecting only the cancer-preventative compounds, the research team was also able to avoid liver damage.
“This research is truly unprecedented in its potential impact,” said Dr Kingston. “A 99% cancer prevention efficacy is unheard of with this very sensitive research model and paves the way for future clinical trials to assess human applications.
“We should look at kava as an example that we shouldn’t rely on NTP to kill a very promising product.”
Dr Kingston added that, by identifying the kava components likely responsible for rare cases of liver toxicity associated with kava dietary supplements, the findings should allow development of supplement preparations devoid of the compounds that can be used for both anti-anxiety and wellness applications in the supplement arena.
“Kava could be a good or bad product depending on how you prepare it,” said Chengguo (Chris) Xing, PhD, an associate professor of medicinal chemistry at the University of Minnesota College of Pharmacy, and co-author on the new paper.
“We have data to strongly support that, when formulated correctly, kava can produce significant benefits,” Dr Xing told us. “Kava is one the best cases to demonstrate the importance of high QA/QC standards. We need to make the industry understand that many products are called kava, but they are not the same stuff.”
‘This kava study emphasizes what good science coupled with quality botanicals can produce’
Commenting independently on the research, Mark Blumenthal, founder and executive director of the American Botanical Council (ABC), said: “This is highly interesting research and suggests a potential new use for certain preparations made from kava root and rhizome. Of course, the preliminary results must be confirmed in human clinical trials.
“ABC does not usually cover animal research in its scientific reporting, preferring human clinical trials. However, in this case ABC believes that the potential implications for human health and the herb kava are significant enough, as suggested by this particular animal research, to warrant attention by ABC.”
Prof. Bill Gurley, PhD, from the College of Pharmacy of the University of Arkansas for Medical Sciences in Little Rock, reviewed the study and commented to ABC: “…the findings are both compelling and certainly merit further research in order to translate them into the clinic. The findings are a breath of fresh air for kava, in particular, and botanical supplements, in general.
“Recently supplements have suffered quite a bit of negative publicity — some of it deserved, some not — but the kava study from the University of Minnesota emphasizes what good science coupled with quality botanicals can produce."
Development and commercialization
The kava preparation is the subject of a patent application from the team at the University of Minnesota. Dr Xing said that, while industrial scale-up and commercialization are still ahead, the team estimates that the preparation is going to be very cost effective for supplements.
“We are currently planning to pursue clinical trials with a number of patent-pending dietary supplement kava formulations,” added Dr Xing. “In the meantime, I would be hesitant to recommend that consumers start using currently available kava-containing dietary supplements in hopes of receiving cancer prevention benefits. Although occasional use of current kava-containing supplements likely has a low risk of liver injury, these products are not well suited for chronic and daily administration.”
In addition to developing safer kava formulations for the dietary supplement market, the team is also pursuing development of kava-derived drugs that may aid in both the prevention and treatment of various cancers including tobacco smoke-induced lung cancer.
QC and effectiveness
Quality control issues have previously been cited for kava, with a 2011 review by Rolf Teschke, MD in the American Herbal Products Association (AHPA) Report, stating that kava-related adverse events were, “most probably a consequence of poor-quality raw kava material employed in the manufacture of a few kava extracts.
“To minimize hepatotoxic risks due to kava use, efforts have to be undertaken to improve kava quality standards and to establish strict regulations for kava cultivators, farmers, harvesters, manufacturers, and physicians treating patients for anxiety, tension, and restlessness,” concluded Dr Teschke.
The anti-anxiety effects of the botanical were supported by a review in the prestigious Cochrane Database of Systematic Reviews (2006, issue 3), which included 12 relevant randomized clinical trials. Seven of these suggest that kava could have a favorable effect on anxiety, when ranked using the Hamilton Anxiety Scale.
“These data imply that, compared with the placebo, kava extract might be an effective symptomatic treatment for anxiety, although, at present, the size of the effect seems to be small,” wrote authors Dr M H Pittler and Professor Edzard Ernst of the University of Exeter, UK.
Source: Cancer Prevention Research
January 2014, Volume 7, Pages 86-96, doi: 10.1158/1940-6207.CAPR-13-0301
“Kava Blocks 4-(Methylnitrosamino)-1-(3-pyridyl)-1-Butanone–Induced Lung Tumorigenesis in Association with Reducing O6-methylguanine DNA Adduct in A/J Mice”
Authors: P. Leitzman, S.C. Narayanapillai, S. Balbo, B. Zhou, P. Upadhyaya, A.A. Shaik, M.G. O'Sullivan, S.S. Hecht, J. Lu, C. Xing