Herbal remedies: adverse effects and drug interactions.
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A growing number of Americans are using herbal products for preventive and therapeutic purposes. The manufacturers of these products are not required to submit proof of safety and efficacy to the U.S. Food and Drug Administration before marketing. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents. St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants. Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death. Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin. Physicians must be alert for adverse effects and drug interactions associated with herbal remedies, and they should ask all patients about the use of these products. (+info)
The importance of pharmacological synergy in psychoactive herbal medicines.
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The therapeutic effects of many herbal medicines have been well established; however, definitive mechanisms of action remain to be elucidated for many psychoactive herbal medications. Although several mechanisms have been identified, they are often insufficient to account for the observed effects of the plant or its extracts. This review emphasizes that, in addition to searching for more potent mechanisms, one must consider the additive and supra-additive effects of a plant's multiple constituents. Synergy may occur through pharmacokinetic and/or pharmacodynamic interactions. Examples are given that illustrate synergistic actions in St. John's wort (Hypericum perforatum), kava kava (Piper methysticum), and valerian (Valeriana officinalis). (+info)
Densitometric analysis of kawain in kava-kava root extracts.
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A thin layer chromatographic-densitometric method for the identification and determination of kawain in a mixture of kavalactones obtained from a methanol extract of kava-kava roots (Piper methysticum) was developed. The main compounds present in the extract were separated with good results using silica gel F 254 coated TLC plates as the stationary phase and hexane-dioxane-butyl acetate-ammonia 25% (7:2:3:0.5 v/v/v/v) as the mobile phase. The qualitative identification and quantitative measurement of kawain were obtained by UV measurements at lambda=250 nm. The described method demonstrates very high sensitivity with the limit of detection established at 20 ng. 99.38% of the kawain was recovered and the concentration range showed a linearity from 0.0005% to 0.004%. Under these conditions, the percent of kawain in the presence of other kavalactones in the prepared extracts (I-VII), was determined. Similar results were obtained for all extracts, with the kawain content ranging from 1.01% to 1.16%. (+info)
Inhibition of human cytochrome P450 activities by kava extract and kavalactones.
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The herb kava has recently been associated with numerous drug interactions, but its interaction with cytochrome P450 (P450) enzymes has not been investigated. In the present work the inhibition of P450 enzymes by kava extract and individual kavalactones in human liver microsomes (HLMs) was investigated. Whole kava extract (normalized to 100 microM total kavalactones) caused concentration-dependent decreases in P450 activities, with significant inhibition of the activities of CYP1A2 (56% inhibition), 2C9 (92%), 2C19 (86%), 2D6 (73%), 3A4 (78%), and 4A9/11 (65%) following preincubation for 15 min with HLMs and NADPH; CYP2A6, 2C8, and 2E1 activities were unaffected. The activities of CYP2C9, 2C19, 2D6, and 3A4 were also measured after incubation of HLMs with the major kavalactones kawain (K), desmethoxyyangonin (DMY), methysticin (M), dihydromethysticin (DHM) (each at 10 microM), and NADPH. Whereas K did not inhibit these enzymes, there was significant inhibition of CYP2C9 by DMY (42%), M (58%), and DHM (69%); of 2C19 by DHM (76%); of 2D6 by M (44%); and of 3A4 by DMY (40%), M (27%), and DHM (54%). Consistent with their potency as inhibitors, the two major kavalactones bearing a methylenedioxyphenyl moiety (M and DHM) formed "455 nm" metabolic intermediate complexes after incubation with HLMs and NADPH, but K and DMY did not. These data indicate that kava has a high potential for causing drug interactions through inhibition of P450 enzymes responsible for the majority of the metabolism of pharmaceutical agents. (+info)
Hepatic toxicity possibly associated with kava-containing products--United States, Germany, and Switzerland, 1999-2002.
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Since 1999, health-care professionals in Germany, Switzerland, and the United States have reported the occurrence of severe hepatic toxicity possibly associated with the consumption of products containing kava (i.e., kava kava or Piper methysticum). A total of 11 patients who used kava products had liver failure and underwent subsequent liver transplantation. On March 25, 2002, in response to five such case reports (four in Europe and one in the United States), the Food and Drug Administration (FDA) issued a consumer advisory and subsequently completed an investigation already underway of a similar U.S. case. This report presents the investigation of the two U.S. cases of liver failure associated with kava-containing dietary supplement products and summarizes the European cases. FDA continues to advise consumers and health-care providers about the potential risk associated with the use of kava-containing products. (+info)
Saccade and cognitive function in chronic kava users.
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Kava is an extract from the Piper methysticum Forst. f. plant that has been consumed in the Pacific islands for millennia and more recently, among indigenous populations, in northern Australia and throughout the Western world as an herbal medicine. Through alterations on neuronal excitation, kava induces muscle relaxation, anasthesia, and has anxiolytic properties. There have been several isolated reports of psychotic syndromes, severe choreoathetosis and possible seizures following kava use. However, there is no conclusive evidence that kava interferes with normal cognitive processes. We tested a group of current, ex, and nonkava users among an indigenous population in northern Australia, using saccade and cognitive tests that have proven cross-cultural validity and are sensitive to subtle disruptions of the brain arising from substance abuse or neuropsychiatric illness. Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months. Current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, in addition, current kava users showed elevated liver enzymes. While there has recently been increasing concern about potentially fatal liver damage attributed to kava use, we have found no evidence of brain dysfunction in heavy and long-term kava users. (+info)
Case-control study of the association between kava use and pneumonia in eastern Arnhem and Aboriginal communities (Northern Territory, Australia).
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Pneumonia causes significant morbidity and mortality in Aboriginal populations in Australia's Northern Territory (NT). Kava, consumed in Arnhem Land since 1982, may be a risk factor for infectious disease including pneumonia. A case-control study (n = 115 cases; n = 415 controls) was conducted in 7001 Aboriginal people (4217 over 15 years). Odds ratios (OR) were calculated by conditional logistic regression with substance use and social factors as confounders. Pneumonia was not associated with kava use. Crude OR = 1.26 (0.74-2.14, P = 0.386), increased after controlling for confounders (OR = 1.98, 0.63-6.23, P = 0.237) but was not significant. Adjusted OR for pneumonia cases involving kava and alcohol users was 1.19 (0.39-3.62, P = 0.756). In communities with longer kava-using histories, adjusted OR was 2.19 (0.67-7.14, P = 0.187). There was no kava dose-response relationship. Crude ORs for associations between pneumonia and cannabis use (OR = 2.27, 1 18-4.37, P = 0.014) and alcohol use (OR = 1.95, 1.07-3.53, P = 0.026) were statistically significant and approached significance for petrol sniffing (OR = 1.98, 0.99-3.95, P = 0.056). (+info)
Sale of kava extract in some health food stores.
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January 2002, Health Canada issued an advisory, followed by a ban in August 2002, on the sale of herbal kava. One month after the advisory, 22 (67%) of 33 health food stores approached were selling kava. Two months after the ban, 17 (57%) of 30 stores continued to sell kava. These findings demonstrate that health food stores may need to be better informed about the sale of restricted natural health products. (+info)