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for the town in Mali see Kava, Mali
Young Piper methysticum
Young Piper methysticum
Scientific classification
Kingdom: Plantae
(unranked): Angiosperms
(unranked): Magnoliids
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: P. methysticum
Binomial name
Piper methysticum

Kava (Piper methysticum) (Piper Latin for "pepper", methysticum Greek for "intoxicating") is an ancient crop of the western Pacific. Other names for kava include ʻawa (Hawaiʻi), 'ava (Samoa), yaqona (Fiji), and sakau (Pohnpei). The word kava is used to refer both to the plant and the beverage produced from its roots. Kava is a tranquilizer primarily consumed to relax without disrupting mental clarity. Its active ingredients are called kavalactones. In some parts of the Western World, kava extract is marketed as herbal medicine against stress, insomnia, and anxiety. A Cochrane Collaboration systematic review of its evidence concluded that it was likely to be more effective than placebo at treating short-term social anxiety.[1] Safety concerns have been raised over liver toxicity, although research indicates that this may be largely due to the use of stems and leaves in supplements, which were not used indigenously.[2][3]


[edit] Preparation and consumption

Kava root drying in Lovoni village, Ovalau, Fiji

[edit] Traditional preparation

Kava is consumed in various ways throughout the Pacific Ocean cultures of Polynesia, Vanuatu, Melanesia and some parts of Micronesia and Australia. Traditionally it is prepared by either chewing, grinding or pounding the roots of the kava plant. Grinding is done by hand against a cone-shaped block of dead coral; the hand forms a mortar and the coral a pestle. The ground root/bark is combined with only a little water, as the fresh root releases moisture during grinding. Pounding is done in a large stone with a small log. The product is then added to cold water and consumed as quickly as possible.

The extract is an emulsion of kavalactone droplets in starch. The taste is slightly pungent, while the distinctive aroma depends on whether it was prepared from dry or fresh plant, and on the variety. The colour is grey to tan to opaque greenish.

Kava prepared as described above is much more potent than processed kava. Chewing produces the strongest effect because it produces the finest particles. Fresh, undried kava produces a stronger beverage than dry kava. The strength also depends on the species and techniques of cultivation. Many find mixing powdered kava with hot water makes the drink stronger. However the active ingredients of kava, such as Kavalactone, are ruined at 140 degrees F. Most tea steeps at 180 degrees F for at least a couple minutes which will reduce the potency of the kava.

In Vanuatu, a strong kava drink is normally followed by a hot meal or tea. The meal traditionally follows some time after the drink so that the psychoactives are absorbed into the bloodstream quicker. Traditionally no flavoring is added.

Fijians commonly share a drink called "grog", made by pounding sun-dried kava root into a fine powder and mixing it with cold water. Traditionally, grog is drunk from the shorn half-shell of a coconut, called a "bilo." Despite tasting very much like dirty water, grog is very popular in Fiji, especially among young men, and often brings people together for storytelling and socializing.[4]

Kava root being prepared for consumption in Asanvari village on Maewo Island, Vanuatu

[edit] Modern preparation

In modernized countries Kava beverage is usually made from Kava root powder. The root is dried and then finely ground into powder before being exported. Generally one tablespoon of powder is added per cup of water, but sometimes as much as a half a cup of powder (eight tablespoons) is added per cup of water to increase potency. The powder is then soaked in water for approximately 30 minutes to allow the water to completely soak through the powdered fibers. Lecithin is often added to aid in the process of emulsifying the kavalactones with water. The Kava powder, water, and lecithin are blended in a blender for several minutes then strained into a straining cloth. Nylon, cheesecloth, and silk screen are common materials for straining. The remaining liquid is squeezed from the pulp and the pulp is discarded. As an alternative to the blender method, with the powdered pulp enclosed within the straining material, the pulp is massaged for five to ten minutes in water, then the liquid is wrung out. The more pressure that is applied to the wet powdered pulp while wringing it out, the more kavalactones will be released from it[citation needed]. Finally the pulp resin is discarded and the beverage is enjoyed. Often coconut water, coconut milk, lemongrass, cocoa, sugar, or soy milk is added to improve flavor.

[edit] Pills

Pharmaceutical companies and herbal supplement companies extract kavalactones from the kava plant using solvents such as acetone and ethanol and produce pills standardized with between 30% and 90% kavalactones. Some kava herbal supplements have been accused of contributing to very rare but severe hepatotoxic reactions (see section on safety) such may have been due to the use of plant parts other than the root, such as stems or peelings that are known to have been exported to European manufacturers. A kava pill usually has anywhere from 60 mg to 150 mg of kavalactones. By comparison the typical bowl of traditionally prepared kava beverage has around 250 mg of kavalactones.

[edit] Herbal Medicine

Kava is chewed by some to relieve symptoms of throat pain, as Kava produces a "numbing" effect on the tongue and throat. The Kava is first chewed in the back of the mouth for 5 to 10 minutes while swallowing the saliva and kavalactones released from the process. The Kava produces an effect similar to that of a chloraseptic spray.

[edit] Pharmacology

Kava's active principal ingredients are the kavalactones, of which at least 15 have been identified and are all considered psychoactive. Only six of them produce noticeable effects, and their concentrations in kava plants vary. Different ratios can produce different effects. Kava has some abuse potential and some experts recommend cycling use over 1 to 3 months.[citation needed]

[edit] Pharmacodynamics

Effects of kavalactones include mild sedation, a slight numbing of the gums and mouth, and vivid dreams. Kava has been reported to improve cognitive performance and promote a cheerful mood. [5] Muscle relaxant, anaesthetic, anticonvulsive and anxiolytic effects are thought to result from direct interactions of kavalactones with voltage-gated ion channels. [6] Research currently suggests that kavalactones potentiate GABAA activity but do not alter levels of dopamine and serotonin in the CNS. [7] Heavy, long-term kava use does not cause any reduction of ability in saccade and cognitive tests but is associated with elevated liver enzymes. [8]

Desmethoxyyangonin, one of the six major kavalactones, is a reversible MAO-B inhibitor (Ki 280 nM)[9] and is able to increase dopamine levels in the nucleus accumbens. This finding might correspond to the slightly euphoric action of kava.[10]

Kavain, in both enantiomeric forms, inhibits the reuptake of noradrenalin at the transporter (NAT), but not of serotonin (SERT).[11] An elevated extracellular NA level in the brain may account for the reported enhancement of attention and focus.

[edit] Effects

50g package of Kava, Fiji

A moderately potent kava drink causes effects within 20–30 minutes that last for about two and a half hours, but can be felt for up to eight hours. Because of this, it is recommended to space out servings about fifteen minutes apart. Some report longer term effects up to two days after ingestion, including mental clarity, patience, and an ease of acceptance. The effects of kava are most often compared to alcohol, or a large dose of diazepam.[1]

The sensations, in order of appearance, are slight tongue and lip numbing (the lips and skin surrounding may appear unusually pale); mildly talkative and sociable behavior; clear thinking; calmness; relaxed muscles; and a sense of well-being. As with other drugs that affect the GABA receptors, there can also be paradoxical dysphoria. The numbing of the mouth is caused by the two kavalactones kavain and dihydrokavain which cause the contraction of the blood vessels in these areas acting as a local topical anesthetic. These anesthetics can also make one's stomach feel numb. Sometimes this feeling has been mistaken for nausea. Some report that caffeine, consumed in moderation in conjunction with kava can significantly increase mental alertness.

A potent drink results in a faster onset with a lack of stimulation; the user's eyes become sensitive to light, they soon become somnolent and then have deep, dreamless sleep within 30 minutes. Sleep is often restful and there are pronounced periods of sleepiness correlating to the amount and potency of kava consumed. Unlike with alcohol-induced sleep, after wakening the drinker does not experience any mental or physical after effects. However, this sleep has been reported as extremely restful and the user often wakes up more stimulated than he or she normally would (though excessive consumption of exceptionally potent brew has been known to cause pronounced sleepiness into the next day). Although heavy doses can cause deep dreamless sleep, it is reported that many people experience lighter sleep and rather vivid dreams after drinking moderate amounts of kava. [2]

After thousands of years of use by the Polynesians and decades of research in Europe and the U.S., the traditional use of kava root has never been found to have any addictive or permanent adverse effects. Users do not develop a tolerance. While small doses of kava have been shown to slightly improve memory and cognition, large amounts at one time have been shown to cause intoxication. In Utah, California, and Hawaii there have been cases where people were charged with driving under the influence of alcohol after drinking a significant amount of kava (eight cups or more) although some of them were acquitted due to the laws not being broad enough to cover kava consumption.

[edit] Kava culture

A sign showing a "Kava license area" at Yirrkala, in the Northern Territory of Australia

Kava is used for medicinal, religious, political, cultural and social purposes throughout the Pacific. These cultures have a great respect for the plant and place a high importance on it. Correspondingly, the paraphernalia surrounding the traditional kava ceremony are expertly crafted. Traditionally designed kava bowls[12] are bowls made from a single piece of wood, with multiple legs. More modern examples are also highly decorated, often carved and inlayed with mother of pearl and shell.

Kava is used primarily at social gatherings to increase amiability and to relax after work. It has great religious significance, being used to obtain inspiration. Among some fundamentalist Christian sects in the Western Pacific, the drink has been demonized and seen as a vice, and young members of these religions often reject its traditional use. However, among many mainline Christian denominations, i.e. the Roman Catholic, Methodist, and Anglican churches, kava drinking is encouraged where it replaces the greater danger of alcohol.

[edit] Botany and agronomy

There are several cultivars of kava, with varying concentrations of primary and secondary psychoactive substances. The largest number are grown in the Republic of Vanuatu, and so it is recognised as the "home" of kava. Kava was historically grown only in the Pacific islands of Hawaii, Federated States of Micronesia, Vanuatu, Fiji, the Samoas and Tonga. Some is grown in the Solomon Islands since World War II, but most is imported. Kava is a cash crop in Vanuatu and Fiji.

The kava shrub thrives in loose, well-drained soils where plenty of air reaches the roots. It grows naturally where rainfall is plentiful (over 2,000 mm/yr). Ideal growing conditions are 20 to 35 degrees Celsius (70 to 95 °F), and 70–100% relative humidity. Too much sunlight is harmful, especially in early growth, so kava is an understory crop.

Kava cannot reproduce sexually. Female flowers are especially rare and do not produce fruit even when hand-pollinated. Its propagation is entirely due to human efforts by the method of striking.

Traditionally, plants are harvested around 4 years of age, as older plants have higher concentrations of kavalactones. But in the past two decades farmers have been harvesting younger and younger plants, as young as 18 months. After reaching about 2 m height, plants grow a wider stalk and additional stalks, but not much taller. The roots can reach a depth of 60 cm.

[edit] Strains and origins

One of the most potent strains is called "Isa" in Papua New Guinea, and also called "Tuday" in Hawaii. In Vanuatu it is considered a type of "Tudei" kava, pronounced as "two-day" because it is said to have effects lasting two days due to its chemical profile being high in the kavalactone dihydromethysticin. The plant itself is a strong, very hardy, fast-growing variety with multiple light to dark green stems covered with raised dark spots.

In Vanuatu there are strict laws over the exportation of Kava. Only strains they deem as "noble" varieties that are not too weak or too potent are allowed to be exported. Only the most desirable strains for every day drinking are selected to be noble varieties in order to maintain quality control. In addition their laws mandate that exported kava must be at least five years old and farmed organically. Their most popular noble strains are "Borogu" from Pentecost Island. "Melomelo" from Ambae island, (called 'sese' in North Pentecost) and "Palarasul" kava from Espiritu Santo Island. In Vanuatu, Tudei (two-days) kava is reserved for special ceremonial occasions and exporting it is not allowed. "Palisi" is a popular Tudei variety.

In Hawaii there are many other strains of kava. Some of the most popular strains are the "Mahakea," "Mo'i," and "Nene" varieties. The Ali'i (kings) of old Hawaii coveted the special kava they called "Mo'i" that had a strong cerebral effect due to a predominant amount of the kavalactone kavain. This sacred variety was so important to them that no one but royalty could ever experience it, "lest they suffer an untimely death."

Other strains are found in Fiji, Tonga, and Samoa.

[edit] Composition

Fresh kava root contains on average 80% water. Dried root contains approximately 43% starch, 20% fibers, 15% kavalactones[13], 12% water, 3.2% sugars, 3.6% proteins, and 3.2% minerals. Kavalactone content is greatest in the roots and decreases higher up the plant. Relative concentrations of 15%, 10% and 5% have been observed in the root, stump, and basal stems, respectively.

The mature roots of the kava plant are harvested after a minimum of 4 years (at least five years ideally) for peak kavalactone content. Most kava plants produce around 50 kgs (110 lbs) of root when they are harvested. Kava root is classified into two categories: crown root (or chips) and lateral root. Crown roots are the large diameter pieces that look like big (1.5 inch to 5 inches diameter) wooden poker chips. Most kava plants consist of approximately 80% crown root upon harvesting. Lateral roots are smaller diameter roots that look more like a typical root. A mature kava plant is approximately 20% lateral roots. Kava lateral roots have the highest content of kavalactones in the kava plant. "Waka" grade kava is kava that is made of lateral roots only.

[edit] Basic research on anti-cancer potential

On 15 February 2006, the Fiji Times and Fiji Live reported that researchers at the University of Aberdeen in Scotland and the Laboratoire de Biologie Moleculaire du Cancer in Luxembourg had discovered that kava may treat ovarian cancer and leukemia. Kava compounds inhibited the activation of a nuclear factor that led to the growth of cancer cells. The Aberdeen University researchers published in the journal The South Pacific Journal of Natural Science that kava methanol extracts had been shown to kill leukemia and ovarian cancer cells in test tubes.[14] The kava compounds were shown to target only cancerous cells; no healthy cells were harmed. This may help explain why kava consumption is correlated with decreased incidence of cancer. [15]

Fiji Kava Council Chairman Ratu Josateki Nawalowalo welcomed the findings, saying that they would boost the kava industry. For his part, Agriculture Minister Ilaitia Tuisese called on the researchers to help persuade members of European Union to lift their ban on kava imports.

[edit] Side effects and safety

[edit] Skin rashes

Chronic and heavy use of kava for a period of three months or more has occasionally been reported to cause a scaly, yellow skin rash and an eye irritation that disappears after discontinuation of the herb. The rash resembles one brought on by a niacin (Vitamin B3) deficiency; however, a double-blind, placebo-controlled study showed no change in the rash after niacin supplementation.[citation needed] The 29 Tonga islanders who presented with the rash after heavy kava consumption--more than 900 g/week--were given either 100 mg of oral niacinamide or placebo. No statistically significant improvement was seen in the supplementing group, suggesting niacin deficiency may not cause the rash, which is more characteristic of an acquired ichthyosis. Until more is known, however, people taking kava regularly may also wish to take a multivitamin with at least 50 to 100 mg of niacin daily.

[edit] Liver damage incidents and regulation

In 2001 concerns were raised about the safety of commercial kava products. [16] There have been allegations of severe liver toxicity, including liver failure in some people who had used dietary supplements containing kava extract (but not in anyone who had drunk kava the traditional way). Out of the 50 people worldwide taking kava pills and extracts that have had some type of problem, almost all of them had been mixing them with alcohol and pills that could have effects on the liver.[16] The fact that different kava strains have slightly different chemical composition made testing for toxicity difficult as well.

The possibility of liver damage consequently prompted action of many regulatory agencies in European countries where the legal precautionary principle so mandated. In the UK, the Medicines for Human Use (Kava-kava) (Prohibition) Order 2002 prohibits the sale, supply or import of most derivative medicinal products. Kava is banned in Switzerland, France, Germany and The Netherlands[17]. The health agency of Canada issued a stop-sale order for kava in 2002. But legislation in 2004 made the legal status of kava uncertain. The United States CDC has released a report[18] expressing reservations about the use of kava and its possibly adverse side effects (specifically severe liver toxicity), as has the Food and Drug Administration (FDA).[19] The Australian Therapeutic Goods Administration has recommended that no more than 250 mg of kavalactones be taken in a 24 hour period.[20] According to the Medicines Control Agency in the U.K., there is no safe dose of kava, as there is no way to predict which individuals would have adverse reactions.[21]

[edit] Toxicology of pill from kava extracts with stems and leaves

Piperidine alkaloids from the kava plant

The legal intervention of several countries stimulated research, and hepatotoxic substances were found in the stems and leaves of the plant. Researchers from the University of Hawaii at Manoa found that an alkaloid called pipermethystine (formula 1), contained in stem peelings and leaves but not in the roots, had toxic effects on liver cells in vitro[22] and in vivo.[2] In rats fed with 10 mg/kg pipermethystine for two weeks, indications of hepatic toxicity were found. Comparable signs of toxicity were not detected with kava rhizome extracts (100 mg/kg, 2 weeks)[2], (73 mg/kg, 3 months).[3]

Flavokavain B, found in the plant's rhizome (large horizontal underground stem), may also contribute to toxic effects.[23] And, it is known that some of the kavapyrones block several subtypes of the enzyme cytochrome P450[24], which can result in adverse interactions with other drugs used concomitantly.

Hawaiian researchers learned from a trader in Fijian kava that European pharmaceutical companies eagerly bought up the stem and leaves peelings when demand for kava extract soared in Europe in 2000 and 2001. Before 2002, substantial amounts of aerial parts of the kava plant were being exported to North America and Europe and obviously used for the production of commercial pill extracts. For traditional use in the South Pacific, stem peelings and leaves are discarded, and only the rhizomes are used and extracted with water. This may explain why native populations that make heavy use of kava experience side effects that are mild, temporary, and confined to the skin, whereas industrialized countries that have newly adopted kava occasionally show severe, acute responses.

A medical conference in Fiji determined that the high concentrations of kava resins in pill form extracts alone could have been the culprit for the liver damage incidents[citation needed].

[edit] Toxicity of traditional kava beverage preparations

Kava has been consumed heavily as a beverage in the south Pacific for around 3000 years with mixed reports on liver problems[citation needed]. One study has reported that when kava preparations are made with the root of the plant no toxicity is found.[25] However, in two studies changes in liver function are noticed. The first claims that the effects are temporary and reversible when discontinuing kava use.[26] There is evidence of health concerns among heavy drinkers, including poor nutrition and a rise in liver enzymes typically associated with liver damage.[27] [28]

The plant also contains glutathione. In extracts its concentration varies depending on the lipophilicity of the applied solvent; the amount is higher in aqueous extracts. Glutathione in kava beverage preparations is able to provide a certain protection of liver cells.[29] However, kava extracts in pill form will not have the glutathione in it to help protect the liver.

[edit] Allergy

Literature suggests that <0.5% of people that take kava have an allergic reaction to it.[citation needed] Allergic reactions are usually mild and include itchy skin or itchy throat, and hives on the skin usually prevalent on the user's belly region. If someone has an allergy to any relative of the pepper family, such as black pepper, they have a higher chance of having a kava allergy.[citation needed]

[edit] See also

[edit] References

  1. ^ Pittler MH, Ernst E (2003). "Kava extract for treating anxiety". Cochrane database of systematic reviews (Online) (1): CD003383. doi:10.1002/14651858.CD003383. PMID 12535473. 
  2. ^ a b c Lim ST, Dragull K, Tang CS, Bittenbender HC, Efird JT, Nerurkar PV (May 2007). "Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats". Toxicol. Sci. 97 (1): 214–21. doi:10.1093/toxsci/kfm035. PMID 17329236. 
  3. ^ a b Sorrentino L, Capasso A, Schmidt M (September 2006). "Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats". Phytomedicine 13 (8): 542–9. doi:10.1016/j.phymed.2006.01.006. PMID 16904878. 
  4. ^ Kevin Cassell (2005). "Fiji: A Visitor's Guide". http://kevincassell.com/FIJIARTC/KEVIN.HTM. Retrieved on 2007-04-25. 
  5. ^ Thompson, R et al (2004). "Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava)". Hum Psychopharmacol. 19 (4): 243–250. doi:10.1002/hup.581. PMID 15181652. 
  6. ^ Cairney, S et al (2002). "The neurobehavioural effects of kava". Aust N Z J Psychiatry 36 (5): 657–652. doi:10.1046/j.1440-1614.2002.01027.x. PMID 12225450. 
  7. ^ Hunter, A (2006). "Kava (Piper methysticum) back in circulation". Australian Centre for Complementary Medicine 25 (7): 529. 
  8. ^ Cairney, S et al (2003). "Saccade and cognitive function in chronic kava users". Neuropsychopharmacology 28 (2): 389–396. doi:10.1038/sj.npp.1300052. PMID 12589393. 
  9. ^ Uebelhack R, Franke L, Schewe HJ (September 1998). "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)". Pharmacopsychiatry 31 (5): 187–92. PMID 9832350. 
  10. ^ Baum SS, Hill R, Rommelspacher H (October 1998). "Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats". Prog. Neuropsychopharmacol. Biol. Psychiatry 22 (7): 1105–20. PMID 9829291. http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(98)00062-1. 
  11. ^ Seitz U, Schüle A, Gleitz J (December 1997). "[3H]-monoamine uptake inhibition properties of kava pyrones". Planta Med. 63 (6): 548–9. PMID 9434608. 
  12. ^ Kava bowls in the collection of the Museum of New Zealand Te Papa Tongarewa
  13. ^ Naumov, P., Dragull, K., Yoshioka, M., Tang, C.-S., Ng, S. W. Structural Characterization of Genuine (—)-Pipermethystine, (—)-Epoxypipermethystine, (+)-Dihydromethysticin and Yangonin from the Kava Plant (Piper methysticum), Natural Product Communications(2008), 3(8) 1333—1336.
  14. ^ Tabudravu J N, Jaspars M (2005). "Anticancer activities of constituents of kava (Piper methysticum)" (PDF). http://www.publish.csiro.au/?act=view_file&file_id=SP05005.pdf. Retrieved on 2008-01-05. 
  15. ^ Steiner GG (November 2000). "The correlation between cancer incidence and kava consumption". Hawaii Med J 59 (11): 420–2. PMID 11149250. 
  16. ^ a b Blumenthal, Mark (2002). "Kava safety questioned due to case reports of liver toxicity". American Botanical Council (Austin, TX) (55): 26–32. http://content.herbalgram.org/new-chapter/herbalgram/articleview.asp?a=2147&p=Y. Retrieved on 2008-03-23. 
  17. ^ C.I.J.M. Ross-van Dorp (2003). "Besluit van 23 april 2003, houdende wijziging van het Warenwetbesluit Kruidenpreparaten (verbod op Kava kava in kruidenpreparaten)" (PDF). Sdu Uitgevers. Staatsblad van het Koninkrijk der Nederlanden. http://www.ipfsaph.org/cds_upload/kopool_data/FAOLEX_0/unknown_net60412.pdf. Retrieved on 2007-02-07. 
  18. ^ United States Centers for Disease Control and Prevention (2002). "Hepatic Toxicity Possibly Associated with Kava-Containing Products --- United States, Germany, and Switzerland, 1999—2002". Morbidity & Mortality Weekly Report 51(47): 1065–1067. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5147a1.htm. Retrieved on 2005-09-16. 
  19. ^ Center for Food Safety and Applied Nutrition (2002). Kava-Containing Dietary Supplements May Be Associated with Severe Liver Injury. United States Food and Drug Administration. http://www.cfsan.fda.gov/%7Edms/addskava.html. Retrieved on 2005-06-16. 
  20. ^ "Kava fact sheet". Therapeutic Goods Administration, Government of Australia. April 2005. http://www.tga.gov.au/cm/kavafs0504.htm. Retrieved on 2006-07-10.  (Download PDF 44KB)
  21. ^ "Kava: A supplement to avoid". Consumer Reports. March 2003. http://www.consumerreports.org/cro/health-fitness/drugs-supplements/kava-supplement-alert-303/overview/index.htm. Retrieved on 2006-07-17.  )
  22. ^ Pratibha V. Nerurkar et al. (2004): "In Vitro Toxicity of Kava Alkaloid, Pipermethystine, in HepG2 Cells Compared to Kavalactones", Toxicological Sciences 79, 106-111. Fulltext.
  23. ^ Jhoo JW, Freeman JP, Heinze TM, et al (April 2006). "In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)". J. Agric. Food Chem. 54 (8): 3157–62. doi:10.1021/jf051853j. PMID 16608246. 
  24. ^ a)Mathews JM, Etheridge AS, Valentine JL, et al (October 2005). "Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro". Drug Metab. Dispos. 33 (10): 1555–63. doi:10.1124/dmd.105.004317. PMID 16033948. http://dmd.aspetjournals.org/cgi/content/full/33/10/1555. 
    b)Mathews JM, Etheridge AS, Black SR (November 2002). "Inhibition of human cytochrome P450 activities by kava extract and kavalactones". Drug Metab. Dispos. 30 (11): 1153–7. PMID 12386118. http://dmd.aspetjournals.org/cgi/content/full/30/11/1153. 
  25. ^ "Kava Safety Facts" (PDF). KavaZen. March 2004. http://www.kavazen.com/pages/Facts%20on%20Kava%20Safety.pdf. Retrieved on 2007-09-05. )
  26. ^ Clough AR, Bailie RS, Currie B (2003). "Liver function test abnormalities in users of aqueous kava extracts". J. Toxicol. Clin. Toxicol. 41 (6): 821–9. PMID 14677792. 
  27. ^ Dr Joji Malani (2002). "Evaluation of the effects of Kava on the Liver" (pdf). http://www.spc.int/cis/documents/Kava%20article%20DrMalani.pdf. Retrieved on 2008-01-05. 
  28. ^ AC Brown (2007). "Traditional kava beverage consumption and liver function tests in a predominantly Tongan population in Hawaii" (html). http://md1.csa.com/partners/viewrecord.php?requester=gs&collection=ENV&recid=7500835&q=kava+beverage&uid=1126092&setcookie=yes. Retrieved on 2009-03-17. 
  29. ^ Whitton PA, Lau A, Salisbury A, Whitehouse J, Evans CS (October 2003). "Kava lactones and the kava-kava controversy". Phytochemistry 64 (3): 673–9. PMID 13679089. http://linkinghub.elsevier.com/retrieve/pii/S0031942203003819. 

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