Abstract

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 related research. We first provide a historical background for its different uses and then discuss the current state of the research, including its chemical composition, possible mechanisms of action, and its therapeutic potential in treating inflammatory and neurological conditions, as well as cancer. We then discuss the challenges associated with kava use and research, focusing on the need for the detailed characterization of kava components and associated risks such as its reported hepatotoxicity. Lastly, given its growing popularity in clinical and recreational use, we emphasize the urgent need for quality control and quality assurance of kava products, pharmacokinetics, absorption, distribution, metabolism, excretion, and foundational pharmacology. These are essential in order to inform research into the molecular targets, cellular mechanisms, and creative use of early stage human clinical trials for designer kava modalities to inform and guide the design and execution of future randomized placebo controlled trials to maximize kava’s clinical efficacy and to minimize its risks.

Highlights

  • IntroductionKava, kava kava, kava, ‘Awa, ‘Awa,or or‘awa,‘awa,isisa atype typeofof perennial shrub that belongs toKava, known as kava perennial shrub that belongs to the the pepper family, known as Piperaceae methysticum its botanical name, which derives pepper family, known as Piperaceae [1]. [1].PiperPiper methysticum is itsisbotanical name, which derives from from the Latin “methysticum”.In the local language and culture,the theword word“kava”“kava” is is used to the Latin language and culture, to denote denote somethingKava is is native native to toOceania, Oceania,with withimportant importantcultural culturaland andhistorical historicalsignificance. significance.something “bitter”

  • One main factor contributing to kava product variation is the cultivar type

  • This study reported that natural kavalactones, 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 [50]

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Summary

Introduction

Known as kava perennial shrub that belongs to the the pepper family, known as Piperaceae methysticum its botanical name, which derives pepper family, known as Piperaceae [1]. [1]. Kava is cultivated by Female kava are scarce and pollination fruit pollination is not productive. It has over one hundred different chemotypes and cultivars. A ofof lactones areare abundant andand present almost exclusively in kava, named kavalactones. Asetset lactones abundant present almost exclusively in kava, named kavalactones. The preparations have been used to distinguish different kava kava cultivars. The mechanisms and responsible ingredients for these functions require further exploration and validation. This review, focuses on kava’s chemical composition and and diversity, its anti-inflammatory potential, its neurological its anti-cancer properties, and, diversity, its anti-inflammatory potential, its neurological effects,effects, its anti-cancer properties, and, issues relating to its safety.

Different Forms of Kava
Kava Diversity
Cultivars
Biosynthetic
Plant Parts
Extraction Solvents
Different
Regulation of the Inflammatory Responses by Kava and Its Components
Effects of Kava Components on Inflammation
Improving the Anti-Inflammatory Effects via Chemical Modifications
Neurological Functions of Kava and Their Mechanisms
Clinical Evidence of Kava’s Neuropharmacological Effects
Kava and Cancer
Lung Cancer
Other Cancers
Anticancer Activities of Kava and Its Components
Flavokavain A
Flavokavain B
Kavalactones
Safety of Kava and Its Hepatotoxic Risk
Kava Safety in Lab Animals
Safety Data of Traditional Kava
Safety of Kava as an Herbal Anxiolytic Drug
Safety of Kava in Recent Clinical Trials
Safety Issues of Kava with No or Limited Knowledge of Composition
Safety of Individual Kava Compounds
Findings
Conclusions and Future Directions
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