Betel Nut

Generic name: Areca Catechu L.
Brand names: Areca Nut, Betel Nut, Paan, Paan-gutkha Pinlang, Pinang, Supari

Usage of Betel Nut

Limited clinical applications exist, and long-term adverse reactions to betel quid chewing are well documented.

Cardiovascular effects

Animal data

Betel nuts contain a tannin with angiotensin-converting enzyme inhibitory activity in vitro. The activity of this tannin was shown to be comparable with Captopril in an older experiment in rats.12

Clinical data

An acute cardiovascular response (hypertension and increased cardiac rate) to betel nut occurs in new chewers, but abates with chronic use.8, 13, 47 A review of this data and further study suggests this effect has a genetic dependency.13 A clinical application for this effect is unlikely considering the increased risk of cardiovascular disease associated with areca nut consumption.

CNS effects

Clinical data

Studies evaluating the effects of betel nut chewing suggest that a variety of the chemical compounds found in areca may exert activity. Arecoline demonstrates parasympathomimetic action on muscarinic and nicotinic receptors; arecaidine and guvacine act as gamma-aminobutyric acid uptake inhibitors, while phenolic compounds in the leaf stimulate the release of catecholamines.5 Electroencephalograph changes have been observed, with alpha and beta wave activity increased and theta decreased. Increases in plasma noradrenaline and adrenaline have been observed among betel nut chewers.5, 8 Topographic changes in EEG have been reported.47

In 65 patients with schizophrenia, a decrease in positive symptoms as measured by the Positive and Negative Syndrome Scale was observed among men who were high-consumption betel nut chewers (more than 7.5 whole betel nuts/day). No significant relationships existed between betel chewing and positive or negative symptoms among women.10, 11 The muscarinic cholinomimetic action of the alkaloids may be responsible for this effect, but a mechanism of action has not been determined.11

Betel Nut side effects

It is reported that between 10% and 25% of the world's population chews betel quid, and betel quid chewing is considered to be the world's 4th most common addiction.21, 22, 23, 24, 25, 26 Acute toxicity is considered rare, but may be clinically important.8, 27, 28

Metabolic syndrome

The consumption of betel nut has been associated with the development of obesity and hyperglycemia in mice, and with type 2 diabetes in humans.8, 26, 29

Large population-based prevalence studies have consistently shown an increased risk of cardiovascular disease among betel nut chewers.26, 30, 31, 32 Hypertriacylglycerol has shown the strongest statistical association with betel nut consumption, but hypertension and hyperglycemia are also important. Interference with vitamin D and homocysteine metabolism, factors associated with cardiovascular disease and metabolic syndrome, has also been demonstrated.25, 33 All-cause mortality has also been found to be higher among betel quid chewers.32 A gender bias has been demonstrated in some, but not all, studies; men are higher consumers and for longer periods of time.26, 30, 31

Other adverse reactions

An increased risk of peptic ulceration has been reported despite the use of betel quid chewing to aid digestion.8 Older case reports suggest a worsening of bronchoconstriction and reduced forced expiratory volume in the first second of expiration in asthmatics chewing betel nut.34, 35

Before taking Betel Nut

Avoid use. Documented adverse reactions, including teratogenic and fetotoxic effects.16 Arecoline has been found in the meconium and placenta, and case reports exist of neonatal withdrawal syndrome.17, 18

How to use Betel Nut

Limited clinical trials exist to guide dosage; limited clinical applications exist. A dose of arecoline 5 to 20 mg was used in a study of appetite suppression.14

Betel nut is widely available in East Asian grocery stores in the United States, and is commonly sold with tobacco as an additive. Other additives may include catechun tree extract, spices, and sweeteners.15 The quid generally is composed of a mixture of tobacco, powdered or sliced areca nut, and slaked lime (calcium hydroxide paste).2, 15 This mixture is wrapped in the leaf of the betel vine. Users may chew from 4 to 15 quids a day, with each quid being chewed for about 15 minutes.2

Warnings

Betel nut and the betel leaf have demonstrated mutagenic, carcinogenic, and genotoxic properties in vitro and in animal experiments.36, 37, 38, 46 Additionally, the betel nut is suggested to possess immunosuppressive activity.8, 39, 40 The addition of slaked lime to the quid facilitates the production of nitrosamines and reactive oxygen species, and nitrosamines from the betel nut have been shown to be mutagenic and carcinogenic.36, 40, 41, 42 Prevalence studies and other epidemiological data have shown a dose- and duration-dependent association of betel quid chewing with precancerous oral submucous fibrosis and oral, pharyngeal, laryngeal, and esophageal cancer.23, 39, 41, 42, 43, 44, 45, 48, 49 The combination of chewing betel quid (with or without tobacco) and smoking cigarettes has been shown to have an additive effect on risk of oral, oropharyngeal, and/or esophageal cancer.48, 49

Increases in serum aminotransferases have been noted in rats regularly fed betel nut8 and an increase in the incidence of cirrhosis and hepatocellular carcinoma has been described among chewers of betel quid40 (a mixture of betel leaf or fruit with other ingredients, such as areca palm nut and tobacco). Risk is increased in patients with chronic hepatitis B or C infection, a longer duration of chewing (ie, more than 20 years), and consuming more than 100,000 quids.40, 50, 51 This effect may be due in part to the high level of safrole content of the betel leaf, which has been implicated in liver carcinogenesis, and was measured in the saliva of betel quid chewers as well as in the hepatocellular tissue.4, 40

What other drugs will affect Betel Nut

Procyclidine: Betel nut may diminish the therapeutic effect of procyclidine. Monitor therapy.(19)

Tacrolimus (systemic): Betel nut may decrease the serum concentration of tacrolimus (systemic). Monitor therapy.(20, 52)

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