Evaluation of the effects of Kava on the Liver (original) (raw)
Kava as a Clinical Nutrient: Promises and Challenges
Nutrients, 2020
Kava beverages are typically prepared from the root of Piper methysticum. They have been consumed among Pacific Islanders for centuries. Kava extract preparations were once used as herbal drugs to treat anxiety in Europe. Kava is also marketed as a dietary supplement in the U.S. and is gaining popularity as a recreational drink in Western countries. Recent studies suggest that kava and its key phytochemicals have anti-inflammatory and anticancer effects, in addition to the well-documented neurological benefits. While its beneficial effects are widely recognized, rare hepatotoxicity had been associated with use of certain kava preparations, but there are no validations nor consistent mechanisms. Major challenges lie in the diversity of kava products and the lack of standardization, which has produced an unmet need for quality initiatives. This review aims to provide the scientific community and consumers, as well as regulatory agencies, with a broad overview on kava use and its relat...
Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava
Food and Chemical Toxicology, 2011
Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125-to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1 g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment-related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.
Liver transplantation and the use of KAVA: Case report
Phytomedicine, 2019
Background: Self-medication and the belief that herbal products are free of health risks are common in Brazil. The kava (Piper methysticum), known for its anxiolytic action, has a widespread popular use. Hepatotoxicity of kava is reported, including cases of liver transplantation and death. The kava had its use prohibited or restricted in countries like Germany, France, among others. Toxicity may be related to overdosage; however, factors such as botanical characteristics of the plant, the harvesting, storage, and production process may be associated with the development of hepatotoxic substances, such as triggering idiosyncratic reactions. Hypothesis: In this case, there is a suspicion that the toxicide is intrinsic to the drug; however, the possibility of adulterants and contaminants must be ruled out. Study design: This study reports the case of a patient who, after using the herbal kava for 52 days, evolved into acute liver failure and liver transplantation. Methods: The data were collected directly with the patient and compared with their clinical records. Causality was determined through the RUCAM algorithm. In addition, a phytochemical analysis of the drug used was performed. Results: According to the patient's report, there is no evidence of overdosage. Results from RUCAM algorithm infer causality between liver damage and the use of kava. The analysis chemical constituents did not find any possible contaminants and major changes in the active compounds. Seven months after transplantation, the patient is well and continues to be followed up by a medical team. Conclusion: Our investigation indicates that there was kava-induced hepatotoxicity at standard dosages. In Brazil, self-medication by herbal medicines is frequent and many patients and health professionals do not know the risks associated with their use. Diagnosing and notifying cases in which plants and herbal medicine induce liver damage is of paramount importance to increase the knowledge about DILI and to prevent or treat similar cases quickly.
Is kava alcohol?: The myths and the facts.
This paper addresses the misconception that kava is an alcoholic substance. After a brief introduction as to what prompted the writing of this, I follow by discussing kava‟s cultural importance to Pacific peoples, and then compare kava „intoxication‟ with alcohol intoxication. The paper concludes with a discussion of the historical influences that have promoted some of the misconceptions surrounding kava. Ultimately the paper demonstrates that kava and alcohol are entirely different kinds of beverages with different effects, and that lingering misconceptions can be seen as a „colonial hangover‟.
Altered mental status and ataxia secondary to acute Kava ingestion
The Journal of Emergency Medicine, 2005
Kava has traditionally been used for a variety of purposes in the tropical islands of Polynesia but is becoming more frequently available in the United States health supplement market due to its calming effects in patients with anxiety. The side effect profile is poorly known but has recently gained the attention of the Food and Drug Administration (FDA). Although hepatitis and liver failure have been described with chronic ingestion, the effects of acute overdose are poorly described. We present a case of acute Kava overdose resulting in altered mental status and ataxia similar to that seen with ethanol intoxication.
Kava beverage observational study
Purpose. To determine the effects of traditionally prepared kava beverages on the liver function tests of regular kava beverage consumers in a population of Tongan and non-Tongan residents of Hawaii (Oahu). Methods. The liver function tests of 31 healthy adult kava drinkers were compared against a control group of 31 healthy adult non-kava drinkers. Subjects were recruited from the general population, a kava bar, and Tongan kava drinking circles. The liver function profile included AST, ALT, ALP, GGT, and bilirubin (total and direct). Other tests included total protein, albumin, and screens for viral hepatitis and hemochromatosis when indicated. Results. Chronic kava beverage consumption was associated with elevation of GGT in 65% of the kava drinkers versus 26% in the controls (P=.005). ALP was elevated in 23% of kava drinkers versus 3% in the controls (P = .053). Conclusion. Heavy kava beverage consumption was associated with significantly elevated GGT levels.
Acute hepatitis induced by kava kava
Clinical Toxicology, 2003
Background. Herbal preparations are available widely and regarded generally by the public as harmless remedies for a variety of medical ailments. We report a case of acute hepatitis associated with the use of kava kava, derived from the root of the pepper plant, Piper methysticum. It is used in the United States as an antianxiety and sedative agent. Case report. A previously healthy 14-year-old female was admitted to the hospital with hepatic failure. Initial therapy, including plasmapheresis, was unsuccessful and she deteriorated. She ultimately required a liver transplant and now remains well. The liver biopsy showed hepatocellular necrosis consistent with chemical hepatitis. A work-up for alternative causes of liver failure was negative. The patient gave a history of taking a kava kava -containing product for four months. The use of kava kava and liver failure, is supported by kava kava use, a negative work-up for alternative causes of liver failure, and histological changes in the liver. Conclusions. Health care professionals need to be aware of the possibility of kava kavainduced hepatotoxicity. The toxicity of these alternative remedies emphasizes the importance of surveillance programs and quality control in the manufacture of these products. Clinicians must remain aware of the toxic potential of herbal products and always inquire about their intake in cases of unexplained liver injury.
Kava and balance: The effects of traditionally influenced kava consumption on human physiology
2020
I have attended and formed my image of a faikava or kalapu (Tecun, 2017). I understand that kava ceremonies are more formal and ritualised elsewhere in Oceania and that cultures drink kava in different ways. However, for a university student with little knowledge of kava culture, this was how naturalistic kava consumption can be defined, at least in the casual setting in which I have drunk kava.
Kava - The unfolding story: Report on a work-in-progress
The Journal of Alternative and Complementary Medicine
This paper, originated as a submission (now updated) to the U.K. Medicines Control Agency and Committee of Safety of Medicines (CSM) on January 11, 2002, in response to a report circulated by the German Federal Institute for Drugs and Medical Products (German initials are BfArM), a compilation of which is summarized in Appendix 2. This agency issued notification in late November 2001 of some thirty adverse events associated with the use of concentrated standardized preparations of kava (Piper methysticum, Forst. f.) reported from Germany and Switzerland. An analysis of the summary of the BfArM case reports (see Appendix 2) shows that these contain duplications among the cases cited. The original submission that was sent to the CSM January 2002 has been updated to the version published here. This new version was completed in April 2002. As a result of the alert from BfArM, the evaluation of kava's safety is now occurring on a worldwide basis and, being that this a matter of consi...
A Systematic Review of the Safety of Kava Extract in the Treatment of Anxiety
Drug Safety, 2002
This paper systematically reviews the clinical evidence relating to the safety of extracts of the herbal anxiolytic kava (Piper methysticum). Literature searches were conducted in four electronic databases and the reference lists of all papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting schemes of the WHO and national drug safety bodies and ten manufacturers of kava preparations were contacted. Data from short-term post-marketing surveillance studies and clinical trials suggest that adverse events are, in general, rare, mild and reversible. However, published case reports indicate that serious adverse events are possible including dermatological reactions, neurological complications and, of greatest concern, liver damage. Spontaneous reporting schemes also suggest that the most common adverse events are mild, but that serious ones occur. Controlled trials suggest that kava extracts do not impair cognitive performance and vigilance or potentiate the
Hepatitis induced by Kava (Piper methysticum rhizoma)
Journal of Hepatology, 2003
Background/Aims: Botanical drugs are widely used and often contain highly active compounds. Kava root (Piper methysticum rhizoma), used frequently in Europe as a remedy against anxiety, contains kavapyrones with sedative effects. Seven case reports suggested the development of hepatitis after the intake of Kava. Methods: We analyzed 29 novel cases of hepatitis along with Kava ingestion which occurred between 1990 and 2002 in addition to the seven already published case reports using a clinical diagnostic scale established for adverse hepatic drug reactions. Results: Hepatic necrosis or cholestatic hepatitis were noticed with both alcoholic and acetonic Kava extracts. The majority of the 29 patients and the additional seven published reports were women (27 females, nine males). Both the cumulative dose and the latency to when the hepatotoxic reaction emerged were highly variable. Nine patients developed fulminant liver failure, of which eight patients underwent liver transplantation. Three patients died, two following unsuccessful liver transplantation and one without. In all other patients, a complete recovery was noticed after the withdrawal of Kava. Pathophysiologically, both immunoallergic and idiosyncratic factors may be responsible. Conclusions: The present report emphasizes the potentially severe hepatotoxicity of Kava which has recently led to the retraction of Kava-containing drugs by the pharmacovigilance authorities in Germany.
Phytomedicine, 2004
popular herbal product in terms of global sales (Blumenthal, 2001). The kava lactones are considered to be the major psychoactive components of kava. Approximately 17 have been characterized and six-kavain, methysticin, dihydrokavain, dihydromethysticin, yangonin, and desmethoxyyangonin, (chemical structures shown in Fig. 1)-are considered to be the most important pharmacologically. Earlier studies in one of our laboratories (GH) revealed that five kava lactones-kavain, methysticin, dihydrokavain, dihydromethysticin, and desmethoxyyangonin-inhibited at least one recombinant human CYP450 enzymes at a concentration less than 10 µM
Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat
International Journal of Molecular Sciences, 2016
The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by "the 3Ks", while trying to clarify the numerous aspects that still need to be addressed.
De-mythologizing and re-branding of kava as the new 'world drug' of choice
Journal of Drug Science, Policy and Law, 5, 1-13., 2019
What seemed impossible 50 years ago is today becoming a reality as 'soft drugs' such as cannabis are being decriminalized and accepted for their calming effects as well as their legitimate medicinal properties. Several countries have now made the possession of cannabis legal, with others considering this, while the coffee shops in the Netherlands have been supplying cannabis in different forms for many years. It is now the turn of kava to be re-evaluated, to see whether there are properties in this plant that might be readily substituted for more conventional and harmful drugs, for instance tobacco and alcohol. However, as highlighted by Norton and Ruze (1994), kava like cannabis, has an enduring reputation that still makes it difficult for many to accept. Kava has been mythologized as an illicit alcohol, highly addictive, and causing physical harm. When examining the history of kava use in traditional contexts and considering the evidence now available, it is possible to demythologize this characterization. Looking at the potential benefits, it is time to re-brand kava, not only on the grounds as a relaxant, but in possessing life enhancing medicinal properties and as an alternative to alcohol, understanding that will be beneficial to policy makers, doctors and pharmacists.
Kava: Weighing the negatives against the positives
Kava, in both its plant and drink form, is Pasifika's 'cultural keystone species' and a potent icon of identity with some of its medicinal efficacy recognised by Western pharmacology and research. However, for every positive concerning kava there appears to be a counterpoint: kava is being 'abused'; kava causes liver damage; kava encourages men to stay away from home for lengthy periods negatively impacting the family; kava turns it's drinkers into Zombies incapable of functioning, etc. This presentation will address these claims while also seeking reasons as to what motivates kava criticism. (Presentation limit: 15 minutes).