Bottom Line: The risk of liver damage from using kava outweighs any benefits this herb might have for treating anxiety.
The active compounds in kava are called kavapyrones. In studies in animals and humans, kavapyrones provide pain relief and act as muscle relaxants and anticonvulsants. Kavapyrones might act the same way as the antidepressant drugs, monoamine oxidase inhibitors (MAOIs). Scientists are not sure whether kavapyrones change the levels of the hormones dopamine and serotonin in the brain. Kava is known to cause liver damage.
To treat anxiety and stress Several clinical trials support this use. A recent trial found kava is no more effective than placebo. However, the clear risk of liver damage from kava use outweighs any benefits.
To treat insomnia No scientific evidence supports this use.
Anxiety: A meta-analysis, which is a complete search of all articles that have been published on a topic, was performed for trials that used kava to treat anxiety. Out of seven trials, all found that kava works better than placebo in reducing anxiety, but five reported adverse effects to kava.
A clinical trial was performed studying the effects of kava in 40 women who were going through menopause and experiencing anxiety. For six months, the women took hormone replacement therapy with or without 100 mg/day of kava extract. Women taking kava reported lower anxiety after three and six months of taking the herb. However, the researchers did not report whether women had side effects from kava.
An Internet-based study with 391 participants found that kava is no more effective than a placebo for anxiety. Patients were recruited through e-mail or advertisements on web sites and assigned by chance to receive either kava, valerian, or a placebo for 4 weeks. At the end of the study, patients who received kava or valerian had similar improvements in anxiety symptoms as compared to the patients who received an inactive placebo. No severe adverse events were reported.
Kava may cause liver damage. The British, French, German, and Swiss governments have requested that kava be removed from the market. The Canadian government has warned consumers not to use kava-containing products.
Overdose or long-term use can cause low blood platelets and white blood cells, dry flaking skin (known as kava dermopathy), respiratory problems, and hearing impairment. Inform your doctor immediately if you have any of these symptoms.
Kava may impair your ability to drive or operate heavy machinery.
This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Liver damage (rare): Immediately inform your doctor if you have yellowish discoloration of the skin, eyes, fingernails or toenails, nausea, or vomiting.
Overdose or long-term use can cause low blood platelets and white blood cells, dry flaking skin (known as kava dermopathy), respiratory problems, and hearing impairment.
Inform your doctor immediately if you have any of these symptoms.
Derived from the rhizome, or root, of the plant, kava is from the Pacific Rim and Hawaiian Islands. It is used for anxiety, stress, and insomnia. The kavapyrones, thought responsible for activity, produce skeletal muscle relaxation, non-narcotic anesthesia, and local anesthetic effects. Some clinical trials suggest that kava is more effective than placebo in reducing anxiety (1)(2) while others reported no effects (3). Kava has been suggested as an alternative to benzodiazepines, but this has not been confirmed by clinical trials. Common adverse effects include headache, restlessness, tiredness, stomach complaints, visual disturbances, tremor, and a hangover effect (2). Chronic administration can result in dermopathy, thrombocytopenia, leukopenia, and hepatotoxicity (4), which appear to be reversible following discontinuation. Additive effects may occur when combined with benzodiazepines, barbiturates, and alcohol (5). Patients should be warned that kava may reduce reaction time and affect driving ability (6). Kava inhibits CYP2E1 (7), CYP1A2 (8), and CYP2D6 (9) and therefore may interact with substances metabolized by these enzymes. Although available data suggest kava to have short-term benefits for anxiety (10), the Canadian, French, and British governments have warned consumers not to consume kava-containing products due to concerns of hepatotoxicity (11). The U.S. Food and Drug Administration is asking all physicians to report any cases of hepatotoxicity possibly linked to the consumption of kava.
Kavapyrones are centrally-acting skeletal muscle relaxants, anticonvulsants, and peripherally-acting local anesthetics. They induce anesthesia via non-narcotic pathways. Animal studies suggest interaction with GABA-A receptors and inhibition of monoamine oxidase B (MAO-B). There are conflicting data concerning whether kavapyrones increase or have no effect on CNS levels of dopamine and serotonin (14). Possible mechanisms for hepatotoxicity are thought to be: inhibition of cytochrome P450, reduction in liver glutathione content, or inhibition of cyclooxygenase (COX) activity (4)(15). In vitro and in vivo studies suggest that kavapyrone- and pipermethystine-containing extracts induce mitochondrial dysfunction, oxidative stress, and apoptosis of Hep2G cells (16)(17).
Absorption: The kavapyrones, kawain and dihydrokawain, were well absorbed following oral administration in mice. Plasma levels of 2 micrograms/ml were detected 30 minutes after initial oral dose of 100 mg/kg kava extract (standardized to 70% kavapyrones). It should be noted that extraction and preparation of dosage form could affect bioavailability. Distribution: Dihydrokawain, kawain, desmethoxyyangonin, and yangonin have been shown to cross the blood-brain barrier in mice. (18) Elimination: Plasma half-life of kavapyrones range from 90 minutes to several hours. (19)
Benzodiazepines: Kava may enhance sedation when administered concurrently. Kava indirectly increases the affinity of GABA receptor binding sites (in vitro) (24). Alcohol: Kava may enhance the hypnotic and sedative effect of alcohol. Avoid concomitant administration. Barbiturates: Theoretically, kava may have an additive effect on sedation and muscle-relaxant activity; however, this has only been demonstrated in animals. Sedatives: Theoretically, kava may have an additive effect with any centrally-acting medication that can potentially cause sedation. (5) Kava can inhibit CYP2E1 (7), CYP1A2 (8), and CYP2D6 (9) and may therefore interact with substances metabolized by these enzymes.
Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. A systematic analysis of all randomized, double-blind, placebo-controlled trials using preparations of kava for the treatment of anxiety. Seven trials were found that met criteria, all of which used Hamilton Rating Scale for Anxiety (HAM-A) scores as an outcome. All trials showed significant advantage of kava as compared to placebo in the reduction of anxiety of HAM-A scores (95% confidence interval 3.54-15.83 points). Five of seven trials reported adverse events including stomach complaints, restlessness, drowsiness, tremor, headache, and tiredness. Although no trial was flawless, with problems ranging from inadequate power analysis to poor randomization, the weighted mean difference of the meta-analysis favored kava when compared to placebo.
De Leo V, et al. Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Maturitas 2001;39:185-8. A prospective, randomized evaluation of 40 women experiencing anxiety associated with physiological or surgically induced menopause. Patients had anxiety scores greater than 19 based on the Hamilton Anxiety Scale (HAM-A). Patients were randomized to standard hormone treatment either with or without kava extract 100 mg/day (55% kavain). Treatments were continued for 6 months with HAM-A scores measured at 3-month intervals. There were no dropouts during the study. Patients receiving combined therapy (hormones plus kava) demonstrated significantly lower HAM-A scores indicating lower anxiety. No adverse effects were reported. The author concludes that kava extract is effective in managing anxiety associated with menopause, but does not report adverse effects that occurred during treatment or following discontinuation.
Jacobs B, et al. An Internet-Based Randomized, Placebo-Controlled Trial of Kava and Valerian for Anxiety and Insomnia. Medicine 2005 Jul;84(4):197-207. An Internet-based double-blind study found that kava is no more effective than an placebo for anxiety. 391 patients were recruited through e-mail or advertisements on web sites. The participants were randomly assigned to 1 of 3 treatment groups that were given capsules containing either kava, valerian, or a placebo for 4 weeks. At the end of the study, patients who received kava or valerian had similar improvements in anxiety symptoms and in sleep as compared to the placebo group. Kava group and the placebo group reported similar adverse events with no report on hepatotoxicity.
Brown AC, et al. Traditional kava beverage consumption and liver function tests in a predominantly Tongan population in Hawaii. Clin Toxicol (Phila). Jun-Aug 2007;45(5):549-556. To determine if chronic kava beverage consumption may result in hepatotoxicity, liver functional analysis was carried out in 31 healthy, adult kava drinkers and 31 healthy, adult non-kava drinkers. Liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT) as well as total bilirubin, direct bilirubin, indirect bilirubin, and albumin were determined. Individuals regularly consuming kava beverage were more likely to have elevated GGT levels. Further studies are required to determine if GGT levels can be reduced upon abstaining from kava drinking. In addition, determining whether elevated GGT levels mediate kava-induced hepatotoxicity is necessary.
