By year's end, the kava industry had collapsed. At least 68 suspected cases of kava-linked liver toxicity had been reported, including nine liver failures that resulted in six liver transplants and three deaths. Countries in Europe, Asia, and North America had banned the sale of all kava products. In the U.S., where the Federal Drug Administration issued warnings but did not institute a ban, supplement sales plummeted.

Kava growers, users, and researchers were perplexed. Pacific Islanders have used kava for at least two thousand years without apparent liver damage. Is the plant harmful or benign? UHM researchers think it may be both.

In an article soon to be published in the journal Phytochemistry, Prof. C.S. Tang (MBBE), his doctoral student Klaus Dragull, and Mr. Wesley Yoshida (Dept. of Chemistry) characterize several chemical compounds present in aboveground portions of the kava plant but absent from the underground tissues used by kava drinkers. The UH scientists hypothesize that these compounds, called alkaloids, may be responsible for the liver toxicity observed in some users of kava supplements.

Kava (Piper methysticum G. Forster) is a shrub that belongs to the same botanical family as black pepper. It is cultivated throughout the Pacific Islands, where its roots and underground stump tissues are pulverized and extracted with water to make a tongue-numbing, earth-flavored beverage that is consumed in ceremonies and at social functions. The water-based kava drink contains kavalactones, pharmacologically active compounds that relax muscles, ease nervous tension, and promote sleep. Outside the Pacific Islands, kava users typically consume the plant in capsules or tablets. Pharmaceutical companies extract the root powder with solvents to enrich the kavalactone content of these products and for standardization purposes.

Prof. Tang began research on kava in July 1999. He focused on questions of toxicity after the kava market crashed. A Fijian trader told him that in 2000 and 2001, a period during which the supply of kava roots was insufficient to meet demand, European pharmaceutical companies had purchased kava stem peelings (bark), considered a waste product by traditional kava users. This practice may have been widespread. By 1998, the first year in which reports proposed a link between kava and liver toxicity in German and Swiss supplement consumers, dried bark constituted 82% of U.S. kava imports. This bark probably included stem peelings in addition to stump tissues.

Stem peelings are rich in kavalactones, but contain other compounds as well. Twenty years before issues of kava toxicity emerged, kava stems and leaves were reported to contain the alkaloid pipermethystine. While investigating the chemicals present in leaves and peelings from the aboveground stem, Tang and Dragull discovered a problem with the analytical method commonly used on kava. The high-performance liquid chromatography (HPLC) assay for kavalactone concentration was unable to distinguish between pipermethystine and a kavalactone, yangonin. This analytical insensitivity didn't affect results when roots were assayed, since roots contain no pipermethystine. However, if stem peelings were extracted and concentrated to generate kava capsules, pharmaceutical companies relying on HPLC could confuse the contaminant pipermethystine for the desirable product yangonin.

Liver cell studies conducted by Prof. Pratibha Nerurkar (MBBE) suggest that alkaloid contamination may play a key role in the liver toxicity associated with kava. Pipermethystine has a strong negative effect on liver cell cultures. Kavalactones, on the other hand, have not been found to damage cultured liver cells. Profs. Tang and Nerurkar plan to investigate these toxicity issues further using rats as an animal model.

Prof. Tang and Mr. Dragull determined that gas chromatography is able to distinguish yangonin from pipermethystine, and confirmed the presence of pipermethystine in stem peelings. In addition, they and Mr. Yoshida purified and characterized two previously unknown kava alkaloids. Awaine, named after the Hawaiian word for kava, was found in varying concentrations in the unopened leaves of all eleven cultivars tested. An epoxy alkaloid similar to pipermethystine was present in stem peelings and leaves of the Isa cultivar. The ability of pipermethystine to form a relatively stable epoxide may be associated with its apparent toxicity to liver cells.

The UH researchers did not detect the three alkaloids in commercial kava root powders, and Prof. Tang believes that traditional kava beverage is not harmful. However, he recommends that consumers avoid kava products that may contain aerial tissues, including capsules, tablets, and kava leaf tea. He hopes that these research findings, if confirmed, will help resuscitate the industry by leading to the repeal of national bans on products made from kava roots and stumps.

Other CTAHR projects also focus on kava. Prof. Amy Brown (HNFAS) and collaborators in the Dept. of Anthropology and the John A. Burns School of Medicine's Dept. of Complementary and Alternative Medicine are screening blood samples from kava drinkers and non-drinkers to assess whether consumption of traditional kava beverage is associated with altered liver function and whether ethnicity plays any role in the liver function of kava users. Dr. H.C. Bittenbender (TPSS), Prof. Tang, and Dr. Mel Jackson (Hawaii Agriculture Research Center) are evaluating a rapid, inexpensive method to assay kavalactone concentration and determine how it is affected by cultivar, light intensity, fertilization, pruning, plant part, and age. Dr. Scot Nelson (PEPS) has studied disease and pest problems associated with kava production in Hawai'i. CTAHR is working to help an ancient crop find a safe and secure future.

CTAHR-PIO thanks C.S. Tang, Klaus Dragull, and H.C. Bittenbender for providing background material and images.

Additional information about kava can be found at: http://www.ctahr.hawaii.edu/fb