Via, e-mail,, Skip, Bittenbender,, Mon, 4/7/2003, 8:52, AMAloha, 'Awa, leaders,, UH, and, international, kava, colleagues, ,Below, is, the, article, that, appears, in, the, Honolulu, Advertiser, Monday, 4/7/03,, it, is, followed, by, a, background, statement, about, UH's, work, on, kava., This, begins, Hawaii's, attempt, to, restore, kava's, reputation.Skip...........Monday,, April, 7,, 2003Advertiser, Big, Island, BureauBy, Kevin, Dayton, <mailto:kdayton@honoluluadvertiser.com><http://www.honoluluadvertiser.com>UH, scientists, may, have, solved, kava, mysteryHILO,, Hawai'i, ?, A, team, of, University, of, Hawai'i, scientists, may, have, solved, the, mystery, of, why, some, Europeans, who, used, products, containing, kava, extract, suffered, severe, liver, damage,, prompting, a, number, of, nations, to, ban, sales, of, the, herbal, supplement.The, culprit, may, be, a, compound, found, in, the, stem, peelings, and, leaves, of, the, kava, plant, known, in, Hawai'i, as, 'awa, but, not, in, the, roots, that, are, used, to, make, the, traditional, kava, drink, consumed, by, Pacific, Islanders.Just, to, be, safe,, people, should, avoid, tea, or, anything, else, made, from, the, leaves, or, stems, of, the, plant,, according, to, C.S., Tang,, professor, of, molecular, biosciences, and, biosystems, engineering, at, UH-Manoa.Bans, in, Singapore,, Germany,, Canada,, the, United, Kingdom, and, elsewhere, wiped, out, pharmaceutical, sales, of, kava, and, virtually, destroyed, it, as, an, export, crop, in, Hawai'i., While, kava, supplements, are, not, banned, in, the, United, States,, the, Food, and, Drug, Administration, issued, an, advisory, in, March, 2002, warning, of, the, potential, risk, of, severe, liver, injury, from, dietary, supplements, containing, kava.The, health, alarms, left, farmers, in, Hamakua, and, elsewhere, with, crops, that, were, hardly, worth, harvesting.Experts, were, unable, to, explain, how, a, plant, used, in, island, cultures, for, 2,000, years, could, suddenly, be, so, toxic,, causing, liver, damage, that, was, fatal, in, some, cases.Now, researchers, led, by, Tang, believe, they, may, have, found, the, key:, , Peelings, from, the, stem, bark, of, kava, plants, apparently, were, used, to, create, the, extract, for, the, herbal, supplements,, and, may, be, to, blame, for, liver, failure, and, liver-related, injuries, that, included, hepatitis, and, cirrhosis.Traditional, kava, drinkers, discard, the, peelings,, but, Tang, and, his, team, learned, from, a, trader, in, Fijian, kava, that, European, pharmaceutical, companies, eagerly, bought, up, the, peelings, when, demand, for, kava, extract, soared, in, Europe, in, 2000, and, 2001."Peelings, are, traditionally, avoided, by, the, kava, drinkers, with, good, reason,", Tang, said., "If, you, don't, respect, the, traditional, use, or, people, who, learn, by, experience,, if, you, don't, respect, that,, you, might, get, yourself, in, trouble."Supplements, containing, kava, are, promoted, as, remedies, for, sleeplessness, and, menopausal, symptoms.Drinking, kava, has, not, been, associated, with, liver, damage.In, Europe,, where, most, of, the, health, problems, occurred,, kava, extract, is, used, in, capsule, form,, and, the, cases, of, liver, damage, apparently, involved, people, who, took, the, capsules,, the, scientists, reported.In, a, research, paper, accepted, for, publication, in, the, scientific, journal, Phytochemistry,, researchers, Klaus, Dragull,, W.Y., Yoshida, and, Tang, report, they, found, an, alkaloid, called, pipermethystine, in, tests, of, stem, peelings, and, kava, leaves.Pipermethystine, also, was, present, in, lower, concentrations, in, the, bark, of, the, stump, but, was, not, found, in, the, root, itself., The, root, is, what, is, used, to, make, the, traditional, drink.Preliminary, tests, by, researcher, Pratibha, Nerurkar, show, pipermethystine, has, a, "strong, negative, effect", on, liver, cell, cultures., If, peelings, containing, the, alkaloid, were, used, to, make, kava, capsules, ?, and, the, scientists, suspect, they, were, ?, that, could, explain, the, liver, damage, in, some, of, the, people, who, took, the, capsules.The, peelings, were, available, during, the, kava, boom, because, kava, drinkers, in, the, Pacific, didn't, want, them,, and, the, stem, peelings, contain, high, levels, of, kavalactones,, the, ingredient, in, kava, that, provides, its, calming, effects.The, Fijian, kava, dealer, reported, the, peelings, had, emerged, as, a, very, important, trading, item, because, "it's, cheap, and, it's, a, waste, product, by, the, kava, drinkers,, therefore, the, pharmaceutical, companies,, they, love, it, and, it, became, part, of, the, trade,", Tang, said.The, UH, researchers, also, learned, that, the, analysis, method, used, by, some, companies, to, test, plant, products, could, not, detect, the, difference, between, the, alkaloids, and, kavalactones,, "and, therefore, they, mistakenly, thought, there's, no, problem,, that, it's, similar, stuff,", Tang, said."I'm, fairly, optimistic, that, we, are, on, the, right, track,, because, everything, seems, to, be, falling, into, the, picture, because, of, the, use, of, peelings,", Tang, said., "But, like, any, scientist,, I, would, say, that, nothing, is, final, until, our, results, are, accepted, by, the, regulatory, agencies."If, the, researchers, are, right,, kava, could, again, emerge, as, a, viable, export, crop., But, that, could, take, quite, awhile.At, its, peak, in, 2001,, the, state, Department, of, Agriculture, estimates, there, were, 65, farms, in, Hawai'i, growing, kava,, but, growers, agreed, that, has, dropped, off, dramatically.Matthew, Archibald,, vice, president, of, operations, for, Agrinom,, an, agricultural, company, in, Hakalau, on, the, Big, Island,, said, the, UH, research, is, an, important, step, in, resuscitating, the, kava, industry, worldwide,, but, that, it, could, take, years, and, millions, of, dollars, to, rebuild, the, European, market.In, August, 2001,, Agrinom, was, shipping, 50,000, pounds, of, dried, kava, a, month,, grossing, $300,000., That, operation, collapsed, two, months, later, when, the, German, government, banned, sales."The, damage, has, been, done,", he, said., "For, example,, we're, not, going, to, get, into, Germany, for, a, very,, very, long, time., There, would, have, to, be, some, major, development, for, us, to, be, able, to, get, back, in, there., But, if, someone, could, open, up, China,, for, example,, where, they're, more, accepting, of, herbal, medicines, in, general,, that, could, be, a, possibility.".......................3/28/03UH, working, to, save, Hawaii's, Kava, IndustryCS, Tang,, K., Dragull,, Pratibha, Nerurkar,, Molecular, Biosciences, and, Biosystems, EngineeringandHC, Bittenbender,, Tropical, Plant, and, Soil, SciencesCollege, of, Tropical, Agriculture, and, Human, ResourcesUniversity, of, Hawaii, at, ManoaWhen, the, future, of, Hawaii's, kava, ('awa, in, Hawaiian,, Piper, methysticum, in, Latin), industry, was, threatened, by, bans, in, Europe, due, to, reports, of, liver, problems,, UH's, College, of, Tropical, Agriculture, and, Human, Resources, set, to, work, to, understand, the, accusations, and, solve, the, problem., In, 2000, Hawaii, farmers, received, $120,000, for, the, kava, crop,, in, 2001, sales, quadrupled, to, $585,000, , these, were, mostly, to, dietary, supplement, manufacturers., But, later, that, year, market, demand, from, these, manufactures, crashed., Today, kava, sales, are, dry,, powdered, root, to, individuals, and, dry, and, fresh, root, and, stump, sales, to, a, handful, , kava, cafes, around, the, state, where, customers, drink, kava.A, new, era, for, kava, began, in, the, islands, of, the, Pacific, when, the, US, Congress, passed, the, Dietary, Supplement, Health, and, Education, Act, of, 1994., This, act, led, to, the, mainstream, retailing, of, herbal, products, called, dietary, supplements, or, nutraceuticals., Kava's, traditional, use, was, ceremonial, as, well, as, practical., People, have, been, drinking, the, water-based, beverage, prepared, from, the, root, and, underground, stump, for, at, least, two, thousand, years., The, beverage, relaxes, the, muscles,, calms, the, , mind,, and, promotes, sleep., In, Europe, kava, capsules, made, of, concentrated, extracts, of, kavalactones, (the, active, ingredients, in, kava), were, prescribed, for, treating, anxiety, and, insomnia.Demand, for, kava, had, been, increasing, in, Europe,, and, after, 1994, the, US, market, expanded, rapidly., Suddenly, the, international, demand, exceeded, production, and, kava, prices, rose, in, Fiji,, Vanuatu,, Samoa,, Tonga, and, Hawaii., Farmers, and, middle, men, in, these, countries, scrambled, to, plant, more, acreage, and, to, produce, the, most, pounds, of, kava, 'product', per, acre, as, possible.The, first, report, of, liver, problems, thought, to, be, associated, with, kava, , was, 1998, in, Germany, and, Switzerland., These, liver, problems, were, associated, with, the, consumption, of, capsules, and, tablets, containing, a, concentrated, extract, of, the, known, active, ingredients, called, kavalactones, and, other, compounds, from, kava., No, similar, problems, have, been, reported, from, drinking, the, water-based, beverage, made, from, the, underground, parts, of, the, kava, plant-, the, roots, and, the, underground, stump, also, called, a, rootstock., Capsules, made, from, extracts, have, been, used, for, many, years, in, Germany,, and, only, the, capsules, made, from, concentrated, extracts, are, apparently, associated, with, liver-damage, incidents.Traditionally, some, cultures, remove, and, discard, the, bark, of, the, stump, (called, peelings), to, lighten, the, color, of, the, powder, and, subsequent, beverage., Kava, beverage, in, Fiji, and, elsewhere, in, the, Pacific, is, made, from, the, roots, and, underground, stump, (peeled, or, unpeeled)., Kava, peelings, are, sold, as, a, lower, value, product., Fiji, a, major, exporter, of, kava, parts, to, Europe, and, the, US,, sells, to, processors, Kasa, (dried, stems), and, civicivi, (dried, peelings, of, the, bark, of, the, stump)., Concentrated, extracts, made, from, roots, and, peelings, containing, the, kavalactones, and, other, compounds, dissolved, by, non-water, solvents-, like, ethanol, and, acetone, are, produced, by, the, European, and, US, processors.The, demand, and, price, for, kava, rapidly, increased, in, the, mid, and, late, 1990's., By, 1998, Port, Import/Export, Reporting, Service, (US), reported, 186,000, pounds, of, dried, kava, peelings, (bark, of, stump, and, stems), was, the, major, (82%), kava, import, into, US,, far, greater, than, roots., It, is, very, likely, that, stem, peelings, (bark), were, being, sold, to, kavalactone, extractors, in, Europe, and, US, as, demand, outstrip, supply, of, this, plant, that, takes, 3-5, years, to, reach, maturity, on, most, farms.Six, kavalactones, are, the, active, ingredients, found, throughout, the, kava, plant, that, are, responsible, for, its, calming, effects., Other, compounds, of, lower, water, solubility, than, the, kavalactones, are, found, in, parts, of, the, kava, plant;, one, of, these, is, the, predominant, kava, alkaloid,, pipermethystine., Pipermethystine, is, found, in, fairly, high, levels, in, leaves, and, bark, (peelings), of, stems, and, at, lesser, concentration, in, the, bark, of, stump, (rootstock), but, not, in, the, roots.In, March, 2003, the, paper, by, Klaus, Dragull,, WY, Yoshida,, and, CS, Tang, entitled, 'Piperidine, alkaloids, from, Piper, methysticum', was, accepted, for, publication, in, the, journal, Phytochemistry., Dr., Tang's, research, was, funded, , by, the, USDA, TSTAR, (Tropical, and, Subtropical, Agriculture, Research), program, reports, the, isolation,, identification, and, quantification, of, three, kava, alkaloids, in, the, above, ground, parts, of, kava, plants., Dr, Tang's, lab, analyzed, 11, varieties, from, Hawaii,, Pohnpei,, and, Papua, New, Guinea., These, alkaloids, are, not, found, in, roots, and, stumps, of, kava, and, one, of, them,, pipermethystine,, previously, reported, from, Fijian-grown, kava, is, present, in, the, stem, bark, (peelings), and, leaves, of, all, the, varieties, of, kava, examined., Moi, and, Hiwa, stem, peelings, had, the, highest, concentration, of, Hawaii, varieties, tested, but, less, than, half, to, a, third, that, found, in, Isa,, a, variety, from, Papua, New, Guinea., Standard, kavalactone, analysis, is, done, using, HPLC, which, cannot, detect, pipermethystine, because, the, alkaloid, appears, as, yangonin,, one, of, the, six, major, kavalactones., Dr., Tang's, student, Mr., Dragull, used, a, gas, chromatograph, to, quantify, these, alkaloids, and, discovered, this, problem, with, the, HPLC, method.Preliminary, tests, on, human, liver, cell, cultures, by, a, new, CTAHR, scientist, Dr., Pratibha, Nerurkar, working, with, Dr., Tang, found, kavalactones, are, well, tolerated., However, the, alkaloid, pipermethystine, has, a, strong, negative, effect, on, liver, cell, cultures., Even, at, low, concentrations, pipermethystine, is, much, more, toxic, than, any, kavalactone, tested.Dr., Tang's, team, now, has, a, working, hypothesis, to, explain, the, kava, liver, controversy., During, the, height, of, the, kava, boom, in, the, late, 1990's, European, and, US, nutraceutical, companies, scrabbled, to, buy, kava, to, extract, kavalactones, for, the, new, and, rapidly, growing, market, for, kavalactone-fortified, kava, capsules., Manufacturers, purchased, peelings, of, the, stump, and, later, probably, peelings, of, stems, were, sold, to, them, as, well., The, peelings, contain, kavalactones, and, were, available, as, a, favored, merchandise, since, peelings, are, not, used, to, prepare, the, traditional, kava, beverage., Because, this, alkaloid, assays, identical, to, yangonin, in, the, standard, kavalactone, analysis,, companies, extracting, the, kavalactones, to, make, capsules, might, not, know, the, alkaloid, was, present., Peelings, containing, the, alkaloid, pipermethystine, were, extracted, and, used, to, make, kava, capsules.Drs., Tang, and, Nerurkar, have, another, TSTAR, grant, pending, to, evaluate, their, findings, on, rats,, this, might, take, several, years., The, CTAHR/UH, team, believes, it, has, found, the, cause, for, the, crisis, that, the, threatened, the, reputation, of, the, Pacific, Islands, oldest, beverage.Several, other, projects, at, CTAHR, focus, on, kava, to, support, the, resurgence, of, this, ancient, crop, in, Hawaii., CTAHR's, Dr., Amy, Brown, working, with, others, in, the, college, and, in, the, John, A., Burns, School, of, Medicine, ,, will, screen, the, liver, function, via, blood, tests, of, kava, drinkers, and, non-drinkers, in, Hawaii., This, project, will, determine, if, there, is, any, association, between, the, consumption, of, traditional, kava, beverage, and, alterations, in, liver, function, tests., , It, will, also, explore, the, role, if, any, of, ethnicity, on, the, liver, function, tests, of, kava, users., Drs., HC, Bittenbender,, Tang,, and, Mel, Jackson, have, a, TSTAR, grant, to, evaluate, a, rapid,, inexpensive, method, to, determine, kavalactone, concentration, in, kava, and, the, effects, of, variety,, light, intensity,, fertilization,, pruning,, plant, part, and, age, on, the, kavalactone, concentration., Dr., Scot, Nelson, has, investigated, and, clarified, the, disease, and, pest, problems, of, kava, production, in, Hawaii., CTAHR's, new, kava, focus, is, working, with, industry, to, educate, the, public, about, kava, and, to, develop, a, ready-to-use,, traditional, kava, drink, product.--, H.C., 'Skip', Bittenbender, ,, Ph.D.Extension, Specialist, for, Coffee,, Kava,, and, Cacaoaddress:Department, of, Tropical, Plant, and, Soil, Science, CTAHR, (College, of, Tropical, Agriculture, and, Human, Resources)University, of, Hawaii, at, Manoa3190, Maile, WayHonolulu,, HI, 96822-2279telephone, :, 808-956-6043fax:, 808-956-3894http://www.ctahr.hawaii.edu/ctahr2001">
UH explanation for the kava-liver controversy
yee Via e-mail, Skip Bittenbender, Mon 4/7/2003 8:52 AM Aloha 'Awa leaders, UH and international kava colleagues , Below is the article that appears in the Honolulu Advertiser Monday 4/7/03, it is followed by a background statement about UH's work on kava. This begins Hawaii's attempt to restore kava's reputation. Skip ........... Monday, April 7, 2003 Advertiser Big Island Bureau By Kevin Dayton <mailto:kdayton@honoluluadvertiser.com><http://www.honoluluadvertiser.com> UH scientists may have solved kava mystery HILO, Hawai'i ? A team of University of Hawai'i scientists may have solved the mystery of why some Europeans who used products containing kava extract suffered severe liver damage, prompting a number of nations to ban sales of the herbal supplement. The culprit may be a compound found in the stem peelings and leaves of the kava plant known in Hawai'i as 'awa but not in the roots that are used to make the traditional kava drink consumed by Pacific Islanders. Just to be safe, people should avoid tea or anything else made from the leaves or stems of the plant, according to C.S. Tang, professor of molecular biosciences and biosystems engineering at UH-Manoa. Bans in Singapore, Germany, Canada, the United Kingdom and elsewhere wiped out pharmaceutical sales of kava and virtually destroyed it as an export crop in Hawai'i. While kava supplements are not banned in the United States, the Food and Drug Administration issued an advisory in March 2002 warning of the potential risk of severe liver injury from dietary supplements containing kava. The health alarms left farmers in Hamakua and elsewhere with crops that were hardly worth harvesting. Experts were unable to explain how a plant used in island cultures for 2,000 years could suddenly be so toxic, causing liver damage that was fatal in some cases. Now researchers led by Tang believe they may have found the key: Peelings from the stem bark of kava plants apparently were used to create the extract for the herbal supplements, and may be to blame for liver failure and liver-related injuries that included hepatitis and cirrhosis. Traditional kava drinkers discard the peelings, but Tang and his team learned from a trader in Fijian kava that European pharmaceutical companies eagerly bought up the peelings when demand for kava extract soared in Europe in 2000 and 2001. "Peelings are traditionally avoided by the kava drinkers with good reason," Tang said. "If you don't respect the traditional use or people who learn by experience, if you don't respect that, you might get yourself in trouble." Supplements containing kava are promoted as remedies for sleeplessness and menopausal symptoms. Drinking kava has not been associated with liver damage. In Europe, where most of the health problems occurred, kava extract is used in capsule form, and the cases of liver damage apparently involved people who took the capsules, the scientists reported. In a research paper accepted for publication in the scientific journal Phytochemistry, researchers Klaus Dragull, W.Y. Yoshida and Tang report they found an alkaloid called pipermethystine in tests of stem peelings and kava leaves. Pipermethystine also was present in lower concentrations in the bark of the stump but was not found in the root itself. The root is what is used to make the traditional drink. Preliminary tests by researcher Pratibha Nerurkar show pipermethystine has a "strong negative effect" on liver cell cultures. If peelings containing the alkaloid were used to make kava capsules ? and the scientists suspect they were ? that could explain the liver damage in some of the people who took the capsules. The peelings were available during the kava boom because kava drinkers in the Pacific didn't want them, and the stem peelings contain high levels of kavalactones, the ingredient in kava that provides its calming effects. The Fijian kava dealer reported the peelings had emerged as a very important trading item because "it's cheap and it's a waste product by the kava drinkers, therefore the pharmaceutical companies, they love it and it became part of the trade," Tang said. The UH researchers also learned that the analysis method used by some companies to test plant products could not detect the difference between the alkaloids and kavalactones, "and therefore they mistakenly thought there's no problem, that it's similar stuff," Tang said. "I'm fairly optimistic that we are on the right track, because everything seems to be falling into the picture because of the use of peelings," Tang said. "But like any scientist, I would say that nothing is final until our results are accepted by the regulatory agencies." If the researchers are right, kava could again emerge as a viable export crop. But that could take quite awhile. At its peak in 2001, the state Department of Agriculture estimates there were 65 farms in Hawai'i growing kava, but growers agreed that has dropped off dramatically. Matthew Archibald, vice president of operations for Agrinom, an agricultural company in Hakalau on the Big Island, said the UH research is an important step in resuscitating the kava industry worldwide, but that it could take years and millions of dollars to rebuild the European market. In August 2001, Agrinom was shipping 50,000 pounds of dried kava a month, grossing $300,000. That operation collapsed two months later when the German government banned sales. "The damage has been done," he said. "For example, we're not going to get into Germany for a very, very long time. There would have to be some major development for us to be able to get back in there. But if someone could open up China, for example, where they're more accepting of herbal medicines in general, that could be a possibility." ....................... 3/28/03 UH working to save Hawaii's Kava Industry CS Tang, K. Dragull, Pratibha Nerurkar, Molecular Biosciences and Biosystems Engineering and HC Bittenbender, Tropical Plant and Soil Sciences College of Tropical Agriculture and Human Resources University of Hawaii at Manoa When the future of Hawaii's kava ('awa in Hawaiian, Piper methysticum in Latin) industry was threatened by bans in Europe due to reports of liver problems, UH's College of Tropical Agriculture and Human Resources set to work to understand the accusations and solve the problem. In 2000 Hawaii farmers received $120,000 for the kava crop, in 2001 sales quadrupled to $585,000 these were mostly to dietary supplement manufacturers. But later that year market demand from these manufactures crashed. Today kava sales are dry, powdered root to individuals and dry and fresh root and stump sales to a handful kava cafes around the state where customers drink kava. A new era for kava began in the islands of the Pacific when the US Congress passed the Dietary Supplement Health and Education Act of 1994. This act led to the mainstream retailing of herbal products called dietary supplements or nutraceuticals. Kava's traditional use was ceremonial as well as practical. People have been drinking the water-based beverage prepared from the root and underground stump for at least two thousand years. The beverage relaxes the muscles, calms the mind, and promotes sleep. In Europe kava capsules made of concentrated extracts of kavalactones (the active ingredients in kava) were prescribed for treating anxiety and insomnia. Demand for kava had been increasing in Europe, and after 1994 the US market expanded rapidly. Suddenly the international demand exceeded production and kava prices rose in Fiji, Vanuatu, Samoa, Tonga and Hawaii. Farmers and middle men in these countries scrambled to plant more acreage and to produce the most pounds of kava 'product' per acre as possible. The first report of liver problems thought to be associated with kava was 1998 in Germany and Switzerland. These liver problems were associated with the consumption of capsules and tablets containing a concentrated extract of the known active ingredients called kavalactones and other compounds from kava. No similar problems have been reported from drinking the water-based beverage made from the underground parts of the kava plant- the roots and the underground stump also called a rootstock. Capsules made from extracts have been used for many years in Germany, and only the capsules made from concentrated extracts are apparently associated with liver-damage incidents. Traditionally some cultures remove and discard the bark of the stump (called peelings) to lighten the color of the powder and subsequent beverage. Kava beverage in Fiji and elsewhere in the Pacific is made from the roots and underground stump (peeled or unpeeled). Kava peelings are sold as a lower value product. Fiji a major exporter of kava parts to Europe and the US, sells to processors Kasa (dried stems) and civicivi (dried peelings of the bark of the stump). Concentrated extracts made from roots and peelings containing the kavalactones and other compounds dissolved by non-water solvents- like ethanol and acetone are produced by the European and US processors. The demand and price for kava rapidly increased in the mid and late 1990's. By 1998 Port Import/Export Reporting Service (US) reported 186,000 pounds of dried kava peelings (bark of stump and stems) was the major (82%) kava import into US, far greater than roots. It is very likely that stem peelings (bark) were being sold to kavalactone extractors in Europe and US as demand outstrip supply of this plant that takes 3-5 years to reach maturity on most farms. Six kavalactones are the active ingredients found throughout the kava plant that are responsible for its calming effects. Other compounds of lower water solubility than the kavalactones are found in parts of the kava plant; one of these is the predominant kava alkaloid, pipermethystine. Pipermethystine is found in fairly high levels in leaves and bark (peelings) of stems and at lesser concentration in the bark of stump (rootstock) but not in the roots. In March 2003 the paper by Klaus Dragull, WY Yoshida, and CS Tang entitled 'Piperidine alkaloids from Piper methysticum' was accepted for publication in the journal Phytochemistry. Dr. Tang's research was funded by the USDA TSTAR (Tropical and Subtropical Agriculture Research) program reports the isolation, identification and quantification of three kava alkaloids in the above ground parts of kava plants. Dr Tang's lab analyzed 11 varieties from Hawaii, Pohnpei, and Papua New Guinea. These alkaloids are not found in roots and stumps of kava and one of them, pipermethystine, previously reported from Fijian-grown kava is present in the stem bark (peelings) and leaves of all the varieties of kava examined. Moi and Hiwa stem peelings had the highest concentration of Hawaii varieties tested but less than half to a third that found in Isa, a variety from Papua New Guinea. Standard kavalactone analysis is done using HPLC which cannot detect pipermethystine because the alkaloid appears as yangonin, one of the six major kavalactones. Dr. Tang's student Mr. Dragull used a gas chromatograph to quantify these alkaloids and discovered this problem with the HPLC method. Preliminary tests on human liver cell cultures by a new CTAHR scientist Dr. Pratibha Nerurkar working with Dr. Tang found kavalactones are well tolerated. However the alkaloid pipermethystine has a strong negative effect on liver cell cultures. Even at low concentrations pipermethystine is much more toxic than any kavalactone tested. Dr. Tang's team now has a working hypothesis to explain the kava liver controversy. During the height of the kava boom in the late 1990's European and US nutraceutical companies scrabbled to buy kava to extract kavalactones for the new and rapidly growing market for kavalactone-fortified kava capsules. Manufacturers purchased peelings of the stump and later probably peelings of stems were sold to them as well. The peelings contain kavalactones and were available as a favored merchandise since peelings are not used to prepare the traditional kava beverage. Because this alkaloid assays identical to yangonin in the standard kavalactone analysis, companies extracting the kavalactones to make capsules might not know the alkaloid was present. Peelings containing the alkaloid pipermethystine were extracted and used to make kava capsules. Drs. Tang and Nerurkar have another TSTAR grant pending to evaluate their findings on rats, this might take several years. The CTAHR/UH team believes it has found the cause for the crisis that the threatened the reputation of the Pacific Islands oldest beverage. Several other projects at CTAHR focus on kava to support the resurgence of this ancient crop in Hawaii. CTAHR's Dr. Amy Brown working with others in the college and in the John A. Burns School of Medicine , will screen the liver function via blood tests of kava drinkers and non-drinkers in Hawaii. This project will determine if there is any association between the consumption of traditional kava beverage and alterations in liver function tests. It will also explore the role if any of ethnicity on the liver function tests of kava users. Drs. HC Bittenbender, Tang, and Mel Jackson have a TSTAR grant to evaluate a rapid, inexpensive method to determine kavalactone concentration in kava and the effects of variety, light intensity, fertilization, pruning, plant part and age on the kavalactone concentration. Dr. Scot Nelson has investigated and clarified the disease and pest problems of kava production in Hawaii. CTAHR's new kava focus is working with industry to educate the public about kava and to develop a ready-to-use, traditional kava drink product. -- H.C. 'Skip' Bittenbender , Ph.D. Extension Specialist for Coffee, Kava, and Cacao address: Department of Tropical Plant and Soil Science CTAHR (College of Tropical Agriculture and Human Resources) University of Hawaii at Manoa 3190 Maile Way Honolulu, HI 96822-2279 telephone : 808-956-6043 fax: 808-956-3894 http://www.ctahr.hawaii.edu/ctahr2001
yee Have the capsules in question been tested for pipermethystine? Seems like a logical next step. --Stuart [via email, Mon 4/7/2003 9:47 AM] The research methodology, which apparently unmasks the pipermethystine from yangonin, seems useful. Some questions/comments, some maybe rhetorical =) 1. Stuart's question can be pivotal to the "working hypothesis." What if those capsules in question (samples from the victims) contain "little" or no amount of the alkaloid? Can we find that any constituent part of kava is still to blame for the controversy? 2. Questions of extent. What concentrations of that alkaloid pose a danger? How should it affect industry practice, e.g., to what extent should precise parts of plant material be discarded from harvest? To what extent is the alkaloid present in the traditional parts - stump, lateral roots - that will be expressed in water-based preparations? 3. Proof might take forever if at all. Should we work with hypotheses - presuming probabilities - that we should urge the FDA to do "something" say regulate, ban, or be patient about kava?... 4. The negative taint of kava still remains. And I don't suggest that we get political about it by saying traditional is the only way. There is quite a bit of wisdom to traditional practices, and I do think it's still important to support the science from as many aspects as scientists can find. Mahalo, Jonathan
yee [via email, C.S. Tang, Mon 4/7/2003 12:50 PM] Dear Jonathen and Staurt: Thank you both for the interesting questions and comments. We've not placed analyzing the capsules a high priority at this point even though it appears to be a logical next step. The reason is multiple: First of all, there could be batch to batch differences of products even from the same source. We simply don't know which capsules to work on. Secondly, the stability under various storage conditions of the alkaloid in question has not been well characterized. If it is unstable, it may change to compound(s) either less or more toxic. Assuming we found the alkaloid at low level, what does it mean? It would mean very little in terms of toxicity and would confuse the picture in my judgment. Thirdly, we believe the publication in "Phytochemistry" will lead to other research efforts to also examine our hypothesis, rather than focusing on the possible negative effects of kavalactones. I would not be surprised if the research arms of the pharmaceutical industry and regulatory agencies will look into the problems of the alkaloid in kava products. With the support of CTAHR, our laboratory will use our resource wisely and continue to focus on the basic science to facilitate solving the kava crisis. Aloha! CS Tang
yee [via email, K. Dragull, Fri 4/11/2003 8:24 AM] > Aloha Klaus, > > The photo's been removed. I forgot about that link as it's not in the > menu. Mahalo! > > Congradulations on your findings. It was important enough to translate > and publicizes Hawai'i. =) Wouldn't have been possible without your plant collection and help!!! > > Unless they have a really good CEO or manager I think it would > take more > time for the pharmaceuticals to respond. > > Mahalo, > Jonathan > ) > )Aloha Jonathan: > ) > )the German yahoo internet news took the time to translate the > honolulu > )advertiser article and comment on it. > ) > )http://de.news.yahoo.com/030408/295/3dyfm.html > ) > )Since they can just copy anything from the internet, would you > mind to > )remove the very last picture in your photoalbum for cosmetic > reasons? > ):) > ) > )http://www.hawaiiankavacenter.com/photoalbum.html > ) > )In the other pics I don't look quite as funny and it's very good > )photography, by the way. Thanks for putting them on your site. > ) > )About the alkaloid, it is a possibility that regulatory agencies > could > )come up with a reasonable limit for pipermethystine and its > )breakdown- products, in case our hypothesis is proved to be correct. > ) > )Thanks, > ) > )Klaus
yee [via email, H.C. Bittenbender, Mon 4/7/2003 1:26 PM] Aloha Jonathan, CS may have answers for you from my position I see the answers to your questions are in the future. More below: >The research methodology, which apparently unmasks the pipermethystine >from yangonin, seems useful. Some questions/comments, some maybe >rhetorical =) > >1. Stuart's question can be pivotal to the "working hypothesis." What >if those capsules in question (samples from the victims) contain >"little" or no amount of the alkaloid? Must be evaluated but problem may be a breakdown product of the alkaloid. >Can we find that any constituent part of >kava is still to blame for the controversy? Not clear but stem peelings and the alkaloid are a constitutent part of kava. > >2. Questions of extent. What concentrations of that alkaloid pose a >danger? Unknown yet. >How should it affect industry practice, e.g., to what extent should >precise parts of plant material be discarded from harvest? Stems and leaves should not be used for consumption purposes. > To >what extent is the alkaloid present in the traditional parts - stump, >lateral roots - that will be expressed in water-based preparations? Apparently only trace amounts in the bark of the stump none found in roots or stump interior. > >3. Proof might take forever if at all. Should we work with hypotheses - >presuming probabilities - that we should urge the FDA to do "something" >say regulate, ban, or be patient about kava?... Industry should sell stump and root only is a start. If processors doubt the quality evaluate for the alkaloid. Skip
hkobayashi
quote:
Originally posted by yee
[via email, H.C. Bittenbender, Mon 4/7/2003 1:26 PM] Industry should sell stump and root only is a start. If processors doubt the quality evaluate for the alkaloid.
An article has been published on line in the journal Phytochemistry. It does mention that some of kavapyrones are toxic ("Two 7,8-epoxydized kavalactones have been isolated from kava roots and have recently been linked to hepatotoxicity of kava")(Dragull, et al., 2003). So checking only alkaloids may not be sufficient. I think I may have mentioned somewhere, and there is a review article on European cases. The article raises interesting questions (acetone vs. methanol extraction, etc.) but they did not think of a possibility hepatotoxicity of kava alkaloid(s). Hideka
hcbitt Mr Klaus Dragull is Dr CS Tang's Ph.D. student and my colleague in the UH kava community. My comments about aklaloids were reviewed by Dr. Tang and Mr Dragull. I am guilty of confusing the situation. Pipermethystine is the alkaloid of concern because Mr Dragull found it in the above ground stem bark and/or leaves of all varieties, albeit some had higher levels than others. Skip H.C "Skip" Bittenbender
hkobayashi
quote:
Originally posted by hcbitt
Mr Klaus Dragull is Dr CS Tang's Ph.D. student and my colleague in the UH kava community. My comments about aklaloids were reviewed by Dr. Tang and Mr Dragull. I am guilty of confusing the situation. Pipermethystine is the alkaloid of concern because Mr Dragull found it in the above ground stem bark and/or leaves of all varieties, albeit some had higher levels than others. Skip H.C "Skip" Bittenbender
I wasn't confused, but now I am a little confused. According to the article, hepatotoxicity of kava may be partly due to piperidine alkaloids found in kava tissue. Surely, pipermethystine was one, but they found several more including novel ones such as awain. I was a little confused by the article since it cited Dr. Ono's presentation at the Awa meeting last year. This is rather unusual thing to "cite" for a scientific publication. Anyway, the artcile did mention epoxidized kavapyrones were hepatotoxic by citing Dr. Ono's statment. This means some of kavapyrones may be in fact hepatotoxic and kava also contains piperidine alkaloids that are hepatotoxic. No? Hideka
yee via e-mail, from Skip Bittenbender, Fri, 09 May 2003 14:40:12 -1000 Aloha Gary, Thank you for your comments. It is unfortunate the press in Vanuatu got the story wrong , I'll rely on Dr. Lebot to straighten out the issue there. We are in contact with scientists in Fiji as well. A paper will be submitted soon comparing the effect of the alkaloid pipermethystine with kavalactones on liver cells, in vitro. We feel strongly it is our duty as scientists in a land grant institution to share our knowledge with the public. Specifically that consumption of above ground plant parts is potentially dangerous. Peelings have been heavily used by the industry, often without informing the consumers that peelings and not roots or stumps were processed. Kava consumed as an aqueous extract of roots and stumps is not the same as non aqueous extracts from peelings, though both have kavalactones. The research article in Phytochemistry is intended to provide novel scientific and technical information to the research community. We hope that our findings will lead to increased activities in searching for an answer to the controversy. You may wish read about the most recent kava-liver AER story in Australia, there are three items on kava on this page http://www.mja.com.au/public/issues/178_09_050503/contents_050503.html, Skip cc. Vincent Lebot, CS Tang, Dennis McKenna, Michael McGuffin, Mark Blumenthal, Joerg Gruenwald, Hawaii 'Awa Industry leaders Skip: Thanks for providing the article. Unfortunately, Dr. Tang's paper has caused much confusion throughout the Pacific - particularly in Vanuatu, where local tabloids are printing highly erroneous information [e.g. that kava is a "potential killer" that affects the LUNGS, that kava is banned in U.S., etc.]. Having now read Tang's entire paper, I feel that it was irresponsible for him to give the media the impression that he and his people might have found the 'smoking gun' when it has not been proven in the first place that kava is toxic. As such, he is lending undue credibility to that 'working hypothesis'. Unfortunately, most countries that banned kava did not pursue any scientific investigations of their own and simply followed France's lead - particularly when the media created such hysteria. Health Canada, for example, blatantly stated that they were banning kava because they didn't have enough evidence that it is safe - not that they had any evidence of it being dangerous. Then there are the matters of unsubstantiated AER's on kava being miniscule compared to proven liver damage from prescription pharmaceuticals and OTC's [such as Tylenol] and almost all AER's having been discounted after further investigation [e.g. even the FDA says that there are but two AER's warranting further investigation]. I should also point out that none of the kava products cited in European or U.S. AER's would have been made from the varieties of kava that Tang tested. Due to their high cost and limited availability, Hawaiian kavas have been used almost exclusively for 'tinctures' [not for producing the concentrated hydro-alcohol, super-critical or acetone extracts that are then used for tablets, capsules, etc.]. Ponhnpei certainly does not produce commercial quantities of kava and I am not aware that any European or U.S. extract manufacturers have even used anything from there. As for PNG 'kavas', they are not purchased by European or U.S. manufacturers because they are relatively ineffective and are commonly mixed with or completely consist of Piper wichmannii. Kavas - even peelings from Fiji - exported for commercial processes are all sun dried - not air-dried in the dark and/or oven-dried (per Tang's procedures). This is important because we know that drying procedures do dramatically affect the chemical composition of kava. For Tang's work to even be close to credible, he would have to test the actual herbal products implicated in the AER's to see if they contain pipermethystine and go on from there - provided, that is, that he can also establish that kava is actually liver toxic. I have other problems with Tang's paper that I will leave to a more appropriate time, but it does appear to me that Tang is bending to commercial pressures and/or is so anxious to get credit for having a paper published that he has ignored proper scientific protocols. In any case, please do keep me posted. Regards, Gary -- H.C. 'Skip' Bittenbender , Ph.D. Extension Specialist for Coffee, Kava, and Cacao address: Department of Tropical Plant and Soil Science CTAHR (College of Tropical Agriculture and Human Resources) University of Hawaii at Manoa 3190 Maile Way Honolulu, HI 96822-2279 telephone : 808-956-6043 fax: 808-956-3894 http://www.ctahr.hawaii.edu/ctahr2001
yee via e-mail, from Ed Johnston, Sat 5/10/2003 8:27 AM Gary: If the Vanuatu papers are reporting what you say regarding kava and the lungs and kava as a "potential killer" or that kava is banned in the US, then they are reporting wrong information and certainly not information that has anything to do with UH, CTAHR research. Can you send me a copy of any of those "local tabloids"? You have it wrong if you think that Dr. Tang is in any way being "irresponsible" to suspect that a smoking gun may have been found. The UH researchers have said time and time again that that they are only "…fairly optimistic that we are on the right track…But like any scientist, I would say that nothing is final until our results are accepted by the regulatory agencies." To discover the alkaloid and NOT report it would be irresponsible. This is in keeping with the cultivars studied as well-- if they have the alkaloid in the stem peelings then it is likely other cultivars do as well (in the peelings). The similarity in the contents of kava is elementary when you understand its origin. But, as has already been said, more study is necessary to come to final conclusions.--Ed Johnston
yee via e-mail, from Gary Friedman, Sat 5/10/2003 6:11 PM Skip: Being that you've chosen to copy my e-mail to you on to several others, I will respond in kind. If the true intent of the research article is to "provide novel scientific and technical information to the research community", then why all the play to the public media? Also, one of the Vanuatu newspaper publishers is claiming that everything they've printed - two highly erroneous articles to date - came directly to them from Dr. Tang. Gary
hkobayashi
quote:
Originally posted by yee
via e-mail, from Gary Friedman, Sat 5/10/2003 6:11 PM If the true intent of the research article is to "provide novel scientific and technical information to the research community", then why all the play to the public media?
Scientists are often accused of residing high up in the ivory tower, so it is important to attempt disseminating information to the public.
quote:
Also, one of the Vanuatu newspaper publishers is claiming that everything they've printed - two highly erroneous articles to date - came directly to them from Dr. Tang.
You may want to post the aricles here somehow so that we can verify the claim. Hideka
yee At Hideka's prompting, I asked Mr. Friedman about the erroneous article on Wed 5/28/03. He responded to me today. It's yours to figure out or comment whether it leaves a true impression. Mahalo, Jonathan. Via e-mail, Gary Friedman, Thu 5/29/2003 5:26 PM. The first erroneous Vanuatu newspaper article on kava - entitled "Kava identified as potential killer" - was published on April 26, 2003. It was faxed to me, so I don't have it in a computer file. Here is the equally erroneous follow-up article that appeared in the next issue of the Port Vila Presse. Gary Friedman, Chairman American Herbal Products Association Kava Committee Stems and branches of kava are poisonous: Mr Lebo by Anne-Marie Sarisets Due to confusion last week about an article on the front page of Presse issue N0.123 "Kava identified as potential killer" Mr Vincent Lebo has further explained the exact part of kava that was described as a potential killer. In the past five years, various companies in the western countries started to buy kava from the Pacific to make medicine out of it for "stress" But later they found out that some people had incurred lung problems after taking the medicine that was made out of kava, and it is believed to have cause death to some. The authorities in many countries have stopped the use of kava products. Some of those countries are Australia, Canada, Switzerland, England (UK) and United States of America, USA. This has caused the kava market to drop in the Pacific. In an interview with Hilaire Bule of Radio Vanuatu, Mr Lebo who was attached to the Department of Agriculture in Vanuatu, explained that the skin of the branch contains a poisonous element called "Piper Methysticum", an alcohol, related to chemical molecules that can affect the body. The poison, identified after testing was found that it can cause liver problems in human beings. Mr Lebo indicated that in regards to the result of the test, it was believed that maybe the poison was one of the reasons why Germany banned kava. Also reports from Germany also indicate that kava can cause liver problems. "In Vanuatu, it is very surprising that people consumed kava a thousand years ago, there's no record from the hospital that stated that people died from kava" said Mr Lebo. Maybe the only thing that many people face in Vanuatu is that it causes rough, white and dry skin. He said, this information has given us a message that kava is only good when it was well prepared such as people in the island always do (they only use roots). "Maybe if people aren't doing a proper job of peeling off the skin of the roots, it could also be the problem" said Mr Lebo. "One problem with the kava bars today I noticed, was many times people do not peel properly and sometimes grind their kava with the skin on which can become a problem in the future if they are not careful about it" he said. He emphasized that the food and roots are good because they are underground and do not have any contact with the light instead of everything that is above the ground, that's what the scientist believe to cause problem. When asked if there is control measures taken when kava reaches the main wharf in Port-Vila or Luganville, Mr Lebo said that as of this time they don't have any proper control as yet and many plants came with the branches still attached. "Because kava is not controlled at the wharf, it is very important that the kava bars or nakamals must make sure that they do not sell the branch or skin because its poisonous. "There is no authorities present at the wharf, only the Department of Quarantine who make some control at the International Airport, but in the future they will have good control over kava that is exported to New Caledonia" said Lebo. The Kava bill that was passed by the parliament previously, states clearly that skin and branch of kava are not to be sold because the skin is a stem product. It is now becoming law and therefore if anyone does not abide by it, he/she has broken the law at once. He emphasized that Vanuatu has to make sure that kava is still safe before exporting to other countries such as New Caledonia to avoid any future problems, especially in the kava market in a country where many families are depending on it for their income. "We must consider the important information and people in the kava bar must take their job seriously and make sure that they do not put us into trouble in the future, because if we are not careful we will have the same problem " said Mr Lebo. Mr Tang stated that the findings show that products that were made out of the branch of kava are really different from those made out of the roots and tests have even been carried out to find out if it can affect the lungs. "But we must not forget that the branch can also be made a good business" said Tang. He goes further in saying that today scientists are still continuing to carry out studies to extract kava to find out the exact cause of the potential killer and their study will be based mainly on stems and branches. Mr Lebo concluded that Vanuatu is on the list with other Pacific countries to take part in a meeting about kava in June in Germany. He said "Germany will have to justify the problem I face with kava causing lung problems". Remember "Prevention is Better than Cure"
hkobayashi
quote:
Originally posted by yee
At Hideka's prompting, I asked Mr. Friedman about the erroneous article on Wed 5/28/03. He responded to me today. It's yours to figure out or comment whether it leaves a true impression. Mahalo, Jonathan.
I scanned through, and it does not seem the author of the article has a clear understanding of the problem(s). I tend not to trust much of what I read in newspaper articles, etc. After all, this appeared in one of "local tabloids", right? Misquotation and misinterpretation can happen very easily, especially if the issue is complicated. I am not defending Dr. Tang et al., but they seems very clear about potential health hazard caused by consumption of kava. The Phytochemistry paper I read did not address any issue regarding "lung" problems. Hideka
yee Via e-mail, Wed 7/30/2003 3:45 PM Hi Jonathon... You've been so kind in patiently answering a neophyte's questions...I'm wondering if you could handle one more..I'm trying to follow the discussion concerning the hypothesis on why kava may have caused liver damage.am I understanding correctly when I read that it's better to use kava with the skin removed? I know you sell a skinless mo'i....do you feel it's a safer product? Thanks very much, Al
yee Al, This is an interesting question. The kava harvest here comprises stump and root, not stem or leaves. Albeit the stump has part of its surface above ground, its proportion of skin or peelings in the mix is small. Moreover, in the traditional drink, no solvents like used by those pharmaceutical companies are used. As such I feel, based on traditional, water-based, beverages that the mo'i and skinless mo'i are comparatively free of this concern. I drink Hawaiian kavas - stump and root - mostly with skin on, and occasionally with the skin off. I have posted your question for one of our scientists at the University of Hawai'i, et al for a review and comment. Mahalo, Jonathan Manager, Hawaiian Kava Center, LLC