Kava

Kava or kava kava Piper methysticum : Latin 'pepper' and Latinized Greek 'intoxicating' is a crop of the Pacific Islands. To a lesser extent, it is consumed in nations where it is exported as an herbal medicine. The root of the plant is used to produce a drink with sedative , anesthetic , and euphoriant properties. Its active ingredients are called kavalactones. Moderate consumption of kava in its traditional form, i. Kava is conspecific with Piper wichmannii, indicating Kava was domesticated from Piper wichmannii syn.

Kava: Inside the All-Natural High That’s Sweeping America

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety.

Hepatotoxicity can occur as an acute, severe form or a chronic, mild form. Inflammation appears to be involved in both forms and may result from activation of liver macrophages Kupffer cells , either directly or via kava metabolites.

Pharmacogenomics may influence the severity of this inflammatory response. Kava Piper methysticum Frost F. Traditionally, the rhizome of the plant is macerated with water or coconut milk to produce a beverage with relaxant and psychoactive properties [ 1 ].

In the 20th century, it became popular in the Western world as a herbal supplement for anxiety and insomnia. When these kavalactones are eluted from a sample of kava by HPLC and sorted by decreasing order of quantity, the chemical signature obtained distinguishes individual strains cultivars.

Such chemotyping has identified over variant strains of kava, but the chemical signature can vary between roots, rhizomes, and basal stems [ 3 ]. Whilst kava extracts are generally well tolerated, toxic doses were determined in vivo using animal studies and in vitro. Since the highest serum kavain concentration recorded in a human is Thus, PM is a potential cause of kava hepatotoxicity although it was not detected in any samples in a recent study using products available on the German market [ 13 ].

Flavokavain B is a cytotoxic component of kava root and is present in aqueous and organic extracts [ 14 ]. The highest yields are in chloroform extracts, followed by acetone then hexane fractions [ 15 ]. Hepatocellular toxicity results from mitogen-activated protein kinase MAPK signalling leading to oxidative stress and apoptosis [ 16 ]. Due to its location in the plant root, flavokavain B is likely to be present in both traditional and pharmaceutical preparations of kava. The chemical content of kava products and hence potential for adverse effects vary according to plant age, part used, cultivar, geographical location, and growth conditions.

In the Kava Act [ 17 ] the government of Vanuatu classified the different cultivars of kava as noble traditional social beverage with long history of safe use , medicinal used for specific therapeutic effects , two days can cause strong side effects such as nausea due to high levels of the kavalactone dihydromethysticin and banned for export , and wichmannii which also induce strong side effects and are banned from export [ 18 ].

Emphasis on the links between method of preparation and toxicity has declined recently. Meta-analyses of placebo-controlled studies showed a significant reduction in anxiety for patients receiving kava extract compared with patients receiving placebo [ 20 , 21 ]. Risk factors for adverse reactions include chronic, heavy use and concurrent use with other drugs, herbs, and dietary supplements [ 24 , 25 ].

Side effects of kava consumption include skin reactions and central nervous system effects. Kava dermopathy has been well documented among Pacific Islanders [ 26 ] and is a reversible condition characterised by dry scaly yellow skin covering the palms of the hands, soles of the feet, and back [ 27 ]. It is speculated to have a link to cholesterol metabolism and hepatotoxicity due to the presence of jaundice [ 28 ].

Short-term kava use can produce extrapyramidal side effects resulting in oral dyskinesia and serious exacerbations of parkinsonism-like symptoms, while heavy use may predispose individuals to seizures [ 27 ]. However, a double-blind placebo controlled trial showed kava has no effect on motor vehicle performance. In another study, no statistically significant difference between kava and placebo was present in participants performing tracking tasks [ 27 ]. The most serious adverse reaction associated with kava is hepatotoxicity.

Reports of kava hepatotoxicity first emerged in Germany in , and by the end of , the World Health Organisation had received 91 reports of adverse reactions relating to kava-only products. Fiftly-five of those reactions involved liver and biliary system disorders, including three cases of hepatic failure and two cases of hepatic comas [ 29 ]. The main metabolic pathways for kavalactones in humans and rats are hydroxylation of the C in the aromatic ring, breaking and hydroxylation of the lactone ring with subsequent dehydration, reduction of the 7,8-double bond, and demethylation of the 4-methoxyl group [ 30 — 32 ].

Products of kavain metabolism found in human serum and urine include p -hydroxykavain, p -hydroxy-5,6-dehydrokavain, p -hydroxy-7,8-dihydrokavain, 5,6-dehydrokavain, 6-phenylhexen-2,4-dione [ 33 ], and 6-phenylhexenone [ 34 ].

Human metabolites identified for other kavalactones include 11,dihydroxykavain- o- quinone for methysticin, 11,dihydroxy-7,8-dihydrokavain- o- quinone for 7,8-dihydromethysticin and desmethylyangonin either from demethylation of the methoxyl group of yangonin or hydroxylation at C of desmethoxyyangonin [ 30 , 35 ].

Reactive kava metabolites may potentially alkylate DNA or disrupt enzymatic and metabolic activity, inducing hepatotoxicity. Despite the evidence for liver damage and inflammation in animals and humans treated with kava, clinical cases of hepatotoxicity amongst indigenous users caused by traditional aqueous root extracts are limited to two cases in New Caledonia [ 37 ].

The dose of kavalactones in one patient was 18 grams per week for four to five weeks and was unknown in the other. Clinical surveillance in the Northern Territory, Australia over 20 years has not documented any cases of fulminant hepatic failure attributable to kava, despite doses estimated to be 10—50 times the recommended therapeutic doses.

Based on these observations, most hepatic effects of kava appear to be reversible or can be compensated for. Hence, pharmacogenomic effects may be involved in the most severe cases of toxicity. For example, the hydroxylation of the aromatic ring and demethylation of kavalactones is a function of CYP2D6 enzymes [ 30 ]. Four human phenotypes for CYP2D6 activity ultrarapid, efficient, intermediate, and poor are defined according to debrisoquine metabolism.

The two Europeans with kava-related hepatotoxicity were phenotyped as poor metabolisers according to CYP2D6 activity [ 38 ]. These individuals could experience adverse reactions following a burst of reactive kava metabolites. Acute kava hepatotoxicity involves inflammation. Histopathology results from a year-old man [ 40 ] and a year-old woman [ 38 ] displaying hepatic symptoms following use of kava supplements showed extensive, severe hepatocellular necrosis and infiltration with lymphocytes, eosinophils, and activated macrophages.

Experimental studies with kavain-perfused rat livers examined via electron microscopy displayed a disruption of hepatic vasculature with narrowing of blood vessels, constriction of sinusoidal blood vessels, and retraction of the endothelium compared to controls [ 41 ]. Liver macrophages Kupffer cells within the sinusoids of the kavain-perfused liver also appeared swollen with large cytoplasmic vacuoles and phagocytosed material.

Subclinical liver abnormalities occurred in clinical studies with chronic, indigenous, kava users. These enzymes return to normal after one to two months of abstinence [ 43 ]. There were no differences between the groups in ALT, bilirubin, albumin, or total protein. Unlike the German clinical trials for anxiety, kava consumption was not regulated in these studies, and the median duration of kava use was twelve years, with a range from one to eighteen years.

Similar results were observed in a predominantly Tongan population in Hawaii, which compared liver function tests between 31 healthy adult kava beverage drinkers and 31 healthy adult nonkava beverage drinkers [ 44 ]. Cholestasis can be due to either defective bile formation in hepatocytes or disruption to bile secretion and flow within bile ducts [ 45 ].

Mechanisms of noninflammatory cholestasis include inhibition of cellular proteins and transporters. Direct or indirect activation of Kupffer cells and their subsequent release of pro-inflammatory cytokines, growth factors, and reactive oxygen species is a cause of inflammatory cholestasis, which may involve hepatocytes or bile ducts [ 46 ].

Each of these mechanisms could be precipitated by kava extracts and are possible explanations for the cholestasis observed in chronic, indigenous, kava users. Hence, Kupffer cells could be involved in both acute and chronic kava hepatotoxicity. These cells are also implicated in the pathogenesis of many other liver conditions, including fibrosis, viral hepatitis, steatohepatitis, alcoholic liver disease, and activation or rejection of the liver during transplantation [ 47 , 48 ].

In animal studies, depletion of the Kupffer cell population is hepatoprotective during ischemia repurfusion injury [ 49 ], sepsis [ 50 , 51 ], radiotherapy [ 52 ], and diet-induced steatosis and insulin resistance [ 53 ]. Kupffer cell depletion experiments could be a valuable tool for determining their role in kava hepatotoxicity. Furthur studies could investigate the extent of kavalactone metabolism in humans and the proportions of urinary versus biliary excretion of kavalactones and their metabolites at different time points after ingestion.

Such studies would further define normal kavalactone metabolism, suggest target cytochrome P enzymes for pharmacokinetic herb-drug interactions with kavalactones, and aid the identification of toxic metabolite s and their contribution to kava hepatotoxicity. Similar animal studies could be conducted with the alkaloid Pipermethysticine and the chalcone Flavokavain B. CYP profiling of individuals involved in such studies could clarify pharmacogenomic differences in kava metabolism and could be performed either genotypically or phenotypically using substrates such as debrisoquine for CYP2D6 in humans [ 54 ].

This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We will be providing unlimited waivers of publication charges for accepted articles related to COVID Journal overview. Special Issues. Academic Editor: Charles P. Received 30 Nov Accepted 24 Jan Published 21 Mar Abstract Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia.

Introduction Kava Piper methysticum Frost F. Figure 1. Structures of the six main kavalactones 1—6 , Pipermethysticine 7 , and Flavokavain B 8. References P. Whitton, A. Lau, A. Salisbury, J. Whitehouse, and C. Fu, Q. Xia, L. Guo, H. Yu, and P. Teschke, J. Sarris, and V. Dinh, U. Simmen, K. Bueter, B. Bueter, K. Lundstrom, and W. Clayton, K. Yoshizawa, G. Kissling, L. Burka, P. Chan, and A. Zou, G.

Kava is a beverage or extract that is made from Piper methysticum, a plant native to the western Pacific islands. The name "kava" comes from the Polynesian. Kava Kava is an herbal remedy that's made from the roots of Piper methysticum -- a type of plant found in the islands of the Pacific Ocean.

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a chronic, mild form. Inflammation appears to be involved in both forms and may result from activation of liver macrophages Kupffer cells , either directly or via kava metabolites.

The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.

Read more about shipping and response delays due to Corona. Kava is the name given by Pacific islanders to both Piper methysticum, a shrub belonging to the pepper family Piperaceae, and the psychoactive beverage made from it. Kava also has a peppery taste.

Toxicokinetics of Kava

Kava kava is an herbal product sold over the counter for its calming effect. Individuals with liver damage or taking drugs that affect the liver should avoid using kava kava. Kava kava is an extract from the plant Piper methysticum that grows in several Pacific island chains. It is a member of the black pepper family and goes by some other names: kava, kava pepper, kava root, kawa kawa, Intoxicating pepper, ava pepper, and tonga. Kava kava has been used for thousands of years in Pacific cultures during rituals, social gatherings, and for medicinal purposes.

From Texas to Brooklyn, many Americans are turning to kava to deal with anxiety and stress. Tracy and Scott Pingel just had a baby. Life was tough enough in the late s, but add a newborn to the mix, and the stress levels went through the roof. So the couple decided to search for an all-natural remedy to relieve the anxiety they were feeling. While researching their options, the Pingels came across kava, a plant found throughout the Pacific islands that has been used as medicine and a ceremonial herb for centuries. That was more than eight years ago, and the couple still drinks kava pretty regularly. Although common in the South Pacific, consuming kava has only begun to surge in popularity in the United States. As drinking kava grows in popularity, so does the number of businesses catering to this new medicinal tea niche. What is kava?

Kava scientific name Piper methysticum is a tall shrub in the pepper family that grows in the Pacific islands.

Medically reviewed by Drugs. Kava has been used in alternative medicine as a possibly effective aid in treating anxiety. Other uses not proven with research have included cancer prevention, insomnia , depression , attention deficit disorder , preventing sedative withdrawal symptoms from medicines such as Valium , Xanax , or Tranzene , and other conditions. It is not certain whether kava is effective in treating any medical condition.

Kava is a depressant drug, which means it slows down the messages travelling between the brain and the body. Kava is made from the root or stump of the kava Piper methysticum shrub. Traditionally, Pacific Islanders crushed, chewed and ground the root and stump of the shrub, then soaked it in cold water to produce a drink for ceremonies and cultural practices. These rituals were said to strengthen ties among groups, reaffirm status and help people communicate with spirits. Many Pacific Islanders who have settled in Australia have continued drinking kava or using kava extracts. Kava was introduced to the communities in the north of Australia in the s as a substitute for alcohol, to reduce alcohol-related harms in the community. The kava drink is often used for sedative, hypnotic and muscle-relaxant effects, in much the same way that alcohol is used. Kava extract is used in some herbal preparations. They are sold as over-the-counter tablets and preparations to be used in the treatment of insomnia, stress and anxiety. There is no safe level of drug use. Use of any drug always carries some risk. Even medications can produce unwanted side effects. Manufactured products such as herbal remedies that contain kava extract have been linked to irreversible liver damage. Kava has been shown to cause liver damage when taken in an alcoholic or acetonic extract. For this reason water based extracts of Kava as a drink or tablet should not be consumed with alcohol, especially if there is a history of liver damage or disease.

Enter your email and we'll keep you on top of the latest nutrition research, supplement myths, and more. Kava is a herb that has traditionally been drunk as a hypnotic and anxiety reducer. It has been shown effective in reducing anxiety, sometimes at a potency similar to pharmaceuticals; may be a cognitive enhancer, but not completely safe. Our evidence-based analysis on kava features 68 unique references to scientific papers. Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists.