Introduction
Kava, derived from the Piper methysticum plant, has a rich history of use in Pacific Island cultures. Traditionally consumed for its relaxant and medicinal properties, kava has gained popularity worldwide as a herbal remedy and recreational drink. Recent studies suggest potential anti-inflammatory and anticancer effects, adding to its well-documented neurological benefits. However, concerns about rare hepatotoxicity have also emerged, highlighting the need for quality control and further research. This review provides an overview of kava use, its chemical composition, mechanisms of action, therapeutic potential, and associated challenges.
Historical Background and Traditional Use
Kava beverages, prepared from the root of Piper methysticum, have been consumed for centuries in Pacific Island cultures. Kava, also known as kava kava, ‘Awa, or ‘awa, is a perennial shrub belonging to the pepper family, Piperaceae. The word “kava” in the local language and culture means “bitter”. Native to Oceania, kava holds significant cultural and historical importance, having been grown in Micronesia, Polynesia, and Melanesia for its relaxant and medicinal effects. It is used as a pain reliever, muscle relaxant, and remedy for anxiety, nervousness, and insomnia. Kava has been domesticated in these regions for thousands of years and is cultivated by propagation from stem cuttings, with over one hundred different chemotypes and cultivars.
In Pacific cultures, kava is considered sacred and served during significant events such as welcoming guests, celebrating childbirth, marriages, and funerals. Traditional kava use extends beyond important occasions, with many local residents drinking a cup before meals. Kava acts as an inebriating beverage, inducing physiological and psychological relaxation, making it an essential part of Pacific Island societies, particularly in Vanuatu, Fiji, Tonga, and Samoa.
Traditional kava is typically prepared from the root of the plant (fresh or dry), although some regions use peelings or stems. The dried root is ground into a powder, mixed with ambient temperature water or coconut milk, and filtered through a cloth into a suspension. The estimated doses of traditional kava use vary substantially across regions, ranging from 750 to 8000 mg kavalactones/day.
Kava as a Herbal Drug and Social Drink
In addition to its traditional use, kava has been used as a herbal drug for the treatment of anxiety, with kavalactones identified as the responsible ingredients. Clinical trials have shown kava to be efficacious within the daily dose range of 20-300 mg kavalactones, particularly for mild and moderate anxiety.
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Due to the potential limitations of traditional preparations, such as low yield and high cost, non-traditional forms of kava have been developed. One common method for anxiolytic kava is ethanol or acetone extraction, with the solvent-free extract packaged into tablets and capsules. However, due to the potential risk of hepatotoxicity from these products, Germany banned kava’s clinical anxiolytic use in 2002.
Kava is also consumed as a social drink. The history of kava bars originated in New Caledonia, where young people sought a place to meet and relax without alcohol. Kava bars later expanded to Hawaii and have sprung up in the Pacific and in some Western nations. In the United States, the number of kava bars increased by approximately 30% from 2012 to 2017.
Chemical Composition of Kava
The chemical components of kava with substantial reported biological activities are the kavalactones and flavokavains. Most biological studies of kava have focused on the six major kavalactones, which can account for up to 20-50% of the dry weight of the kava root and 96% of organic/lipid extracts. The relative concentrations of these six compounds are critical to the quality of kava. Flavokavains A, B, and C are minor constituents, though they are generated through similar biosynthetic pathways as kavalactones.
Cultivar Types
One main factor contributing to kava product variation is the cultivar type. There are over 150 different cultivars, with different regions having unique cultivars and chemotypes. These cultivars have varying levels of kavalactones and flavokavains. In Vanuatu, kava cultivars are categorized into four groups: noble, medicinal, two-day (also known as tuidei), and wichmannii. Only noble kava cultivars are permitted for export due to the varying effects produced in the user. Noble cultivars produce a more desirable and safer experience, with relatively high kavain content enhancing the anxiolytic properties. Dihydromethysticin and dihydrokavain-forward cultivars produce more overpowering and unpredictable effects, such as nausea and headaches that can last multiple days.
Plant Parts
Kava can be prepared from different parts of the plant-the roots, the rhizomes, and sometimes the stem peelings, but not the leaves.
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Solvent for Extraction
Another major contributing factor to the different chemical compositions of kava products is the solvent used for extraction. The solvent for traditional kava preparations is water. Since the introduction of kava consumption to Western society, other solvents have been used to optimize the kavalactone extraction yield, often resulting in higher concentrations of these active compounds, but also other potentially less desirable flavokavains and alkaloids. For instance, the abundance of flavokavains A and B in ethanolic kava preparations has been reported to be significantly higher than in traditional aqueous kava preparations. Acetone is considered the best solvent for the extraction of kavalactone compounds, followed by ethanol and water.
Other factors that contribute to variations in kava composition include the age of the plant, storage conditions, climate, soil, and potential adulterations.
Need for Kava Product Standardization
Due to the variables that can lead to different pharmacology and safety profiles, there is a crucial need for kava product standardization. The most common analytical method for kava characterization continues to be HPLC-based analysis, widely applied in industry and academia to fingerprint different cultivars and to inform the actual kava dosage of the analyte product. The current method for kava product standardization is the sum of the six major kavalactones. However, this standardization has limitations as it does not categorize the flavokavain content and other ingredients, which may introduce new pharmacology or toxicity. Additionally, the six major kavalactones could have different and sometimes unique pharmacological properties, making total kavalactone standardization insufficient.
Kava and Inflammation
Inflammation plays important roles in the pathology of a wide variety of diseases, ranging from cancer to neurological disorders. Studies into kava and inflammation have been partly stimulated by its analgesic effects, as anti-inflammatory drugs are widely used for pain relief. Historically, kava has been used for the treatment of urinary tract infections and immune-related disorders, such as asthma.
Some of the first robust demonstrations of kava’s anti-inflammatory potential in a laboratory setting dated back to a study published in 1965. This study reported that natural kavalactones, particularly kavain, showed significant inhibitory effects on edema induced by either formalin, serotonin, carrageenan, or dextran on rat paws, as well as on UV light-induced inflammation of the rat skin.
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Specific Kavalactones and Their Effects
Kavain, dihydrokavain, methysticin, and dihydromethysticin were investigated in the context of TNF-α production in human acute monocytic leukemia cells, as well as for their response to lipopolysaccharide (LPS)-induced lethality in lab animals. All of these kavalactones were able to suppress LPS-induced TNF-α production, with kavain being the most potent. Kavain also protected C57 mice from lethal doses of LPS. In a model of Alzheimer’s disease, methysticin significantly reduced the secretion of TNF-α and IL-17A and improved the symptoms of the disease. Methysticin was shown to activate the Nrf2 pathway in the mouse hippocampus and cortex, inducing an antioxidant response to maintain cellular redox homeostasis. This was consistent with results from another study, which showed that methysticin, kavain, and yangonin activated the Nrf2 pathway in neuronal PC-12 and astroglial C6 cells. The effect of yangonin on estrogen-induced hepatic cholestasis, an inflammatory disease of the liver, was explored in C57BL/6 mice. Yangonin treatment reduced es…
Kava and Weight Loss: Examining the Evidence
While kava is primarily known for its calming and anti-inflammatory properties, its potential role in weight loss has also garnered some attention. However, it's important to note that direct research on kava and weight loss is limited, and the existing evidence is largely indirect.
Potential Mechanisms
Several mechanisms could potentially link kava consumption to weight management:
- Stress Reduction: Kava's anxiolytic effects may indirectly influence weight management. Chronic stress can lead to increased cortisol levels, which are associated with increased appetite, cravings for unhealthy foods, and abdominal fat storage. By reducing stress and anxiety, kava may help individuals better manage their eating habits and prevent weight gain.
- Improved Sleep: Kava has been traditionally used to promote relaxation and improve sleep quality. Adequate sleep is crucial for maintaining a healthy metabolism and regulating hormones that control appetite and satiety. By improving sleep, kava may indirectly support weight management efforts.
- Anti-inflammatory Effects: Chronic inflammation is linked to obesity and metabolic disorders. Kava's anti-inflammatory properties may help reduce inflammation, potentially improving metabolic function and supporting weight loss.
Lack of Direct Evidence
Despite these potential mechanisms, it's crucial to emphasize that there is currently no direct scientific evidence to support the claim that kava promotes weight loss. Most studies have focused on kava's effects on anxiety, sleep, and inflammation, without specifically examining its impact on body weight or metabolism.
Considerations
It's also important to consider that kava consumption can have side effects, including potential liver toxicity. Therefore, it's essential to consult with a healthcare professional before using kava for any purpose, including weight management.
Kava and Liver Toxicity
Rare hepatotoxicity has been associated with the use of certain kava preparations. The FDA continues to advise consumers and health-care providers about the potential risk associated with the use of kava-containing products. Cases of liver failure associated with kava-containing dietary supplement products have been reported.
Several cases highlight the potential risks:
- Case 1: A patient taking a kava-containing supplement developed jaundice and hepatitis, with a liver biopsy demonstrating subfulminant hepatic necrosis.
- Case 2: A patient using two kava-containing products experienced decreased appetite, weight loss, and fatigue, leading to hospitalization with acute hepatitis.
Similar cases have been reported in Europe, with patients requiring liver transplants after using kava-containing products. The duration of kava use ranged from 8 weeks to 12 months, with doses ranging from 60 mg to 240 mg per day. Symptoms varied, including influenza-like symptoms and jaundice, with each patient's condition progressing to fulminant hepatic failure.
Additional caution by persons who have pre-existing liver disease or are at risk for liver disease might be warranted. Health-care providers should consider questioning patients with evidence of hepatic injury about the use of dietary supplements and herbal products.