OVERVIEW

Introduction

Areca nut, commonly known as betel nut, is the fruit of the Areca palm (Areca catechu), which is found in tropical areas of the Pacific, south Asia and eastern Africa. The major use of areca nut is as a recreational stimulant typically chewed wrapped in betel leaves (Piper betle), powdered with calcium hydroxide (slaked lime), and flavored with mint, clove or tobacco. Areca nut has also been used as an extract in traditional medicine as a cathartic or as treatment of intestinal parasites. Areca nut has not been linked to cases of clinically apparent acute liver injury, but epidemiologic studies from Asia have found a strong link between habitual betel nut chewing and oral cancer, and it may also increase the risk of cirrhosis and hepatocellular carcinoma.

Background

Areca nut is not a nut but rather the seed containing fruit of the areca palm (Areca catechu), which is found in tropical areas of the Pacific, South Asia and Western Africa, where it is frequently cultivated. Chewing areca nut for its recreational stimulant effect is the most common use of the herb which is also called betel nut chewing for the betel leaves (Piper betle) in which the areca nut is wrapped. Chewing areca nut releases a central nervous system stimulant that causes a heightened awareness, increased stamina, euphoria and feeling of well-being. Betel nut chewing is the fourth most common form of substance abuse (after caffeine, alcohol, and nicotine) and is practiced by 10% of the world’s population. The active components of areca nut are thought to be the arecal alkaloids, including arecoline, arecaidine, guvacine and guvacolin which have cholinergic (predominantly muscarinic) and other psychoactive properties. Other ingredients include tannins, such as arecatannin and gallic acid, oil gum, and lignin. Habitual betel nut chewing is associated with serious long term health risks including cancer, heart disease and cirrhosis.

In India and China, areca nut extracts have also been used in traditional medicine as treatment of parasitic diseases and to improve digestion, diarrhea, abdominal distension, dyspepsia and jaundice. The only widely accepted medicinal use of Areca catechu at present is in veterinary medicine where it is used as a cathartic and treatment for tapeworm in horses, cattle and dogs. Areca nut is considered unsafe for human consumption by the U.S. Food and Drug Administration (FDA), and it is not approved for any medical condition. Nevertheless, arena nut is available over-the-counter in the United States and in Europe, typically in Asian markets in forms that can be used in chewing. Areca catechu nut chewing is most common in India, Pakistan, southeast Asia, Micronesia, and western Africa. In these areas, areca catechu nut use disorders are common and are the focus of government and public health efforts to decrease its use. Adverse events associated with use of Areca catechu extracts have not been well defined, but chewing betel nut is associated with palpitations, arrhythmias, hypotension, chest pain, dyspnea, tachypnea, acute myocardial infarction, chronic kidney disease, and nephrolithiasis. Importantly, areca nut has carcinogenic potential in vitro and in vivo, and long term, habitual betel nut chewing has been linked to oral and esophageal cancer. In addition, cross sectional population based and cohort studies have suggested that betel nut chewing is also a risk factor for cirrhosis and hepatocellular carcinoma.

Hepatotoxicity

There have been few studies on the clinical effects and adverse effects of betel nut chewing or of extracts of the areca nut. However, there have been no reports of acute liver injury and marked serum aminotransferase elevations attributed to betel nut chewing or of use of areca nut extracts. On the other hand, several cross sectional epidemiologic studies have linked regular betel nut chewing with a higher prevalence of hepatic cirrhosis and hepatocellular carcinoma. The excess risk of cirrhosis and liver cancer from areca nut use is independent and apparently synergistic with hepatitis B and C virus infection and nonalcoholic fatty liver disease.

Likelihood score for Areca catechu extract use: E (unlikely cause of clinically apparent acute liver injury).

Likelihood score for Areca catechu nut chewing: C (probable cause of increased risk of cirrhosis and hepatocellular carcinoma with habitual use).

Mechanism of Injury

Areca nut has multiple components that might promote carcinogenesis, but the major candidate is the psychoactive areca alkaloids, including arecoline, arecaidine, guavacoline, and guavacine.

Outcome and Management

Acute hepatotoxicity from areca nut has not been described. Habitual use of areca nut chewing should be discouraged, particularly in persons with underlying chronic liver disease, chronic alcohol abuse or fatty liver.

Drug Class: Herbal and Dietary Supplements

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Areca catechu – Generic

DRUG CLASS

Herbal and Dietary Supplements

CHEMICAL FORMULA AND STRUCTURE

While areca catechu nut has multiple components, its major alkaloid is arecoline which is believed to be the active component responsible for its central nervous system stimulation.

ANNOTATED BIBLIOGRAPHY

References updated: 22 March 2023

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