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Betel Nut

Scientific Name(s): Areca catechu L.
Common Name(s): Areca nut, Betel nut, Paan, Paan-gutkha pinlang, Pinang, Supari

Medically reviewed by Drugs.com. Last updated on Feb 8, 2019.

Clinical Overview

Use

Limited clinical applications exist, and long-term adverse reactions to betel quid chewing are well documented. A decrease in positive symptoms among men with schizophrenia was attributed to betel nut consumption.

Dosing

Limited clinical trials exist to guide dosage; limited clinical applications exist.

Contraindications

None well documented.

Pregnancy/Lactation

Documented adverse reactions, including teratogenic and fetotoxic effects. Avoid use.

Interactions

None well documented.

Adverse Reactions

Betel nut prevalence data strongly associates consumption with the incidence of metabolic syndrome.

Toxicology

Areca nut and the betel leaf have demonstrated mutagenic, carcinogenic, and genotoxic properties in in vitro and animal experiments. Prevalence studies show a dose- and duration-dependent association of betel quid chewing with precancerous oral submucous fibrosis and oral, pharyngeal, laryngeal, and esophageal cancer.

Scientific Family

  • Palmaceae (palms)

Botany

The areca tree is a tropical, feathery palm that grows to approximately 15 m in height and bears fruit year round. It is widely cultivated in tropical India, Bangladesh, Japan, Sri Lanka, south China, the East Indies, the Philippines, and parts of Africa. The nut is approximately 2.5 cm in length and may be used fresh, dried, or cured by boiling, baking, or roasting.1, 2 The quid is a mixture of areca nut, tobacco, and lime wrapped in the leaf of the betel vine (Piper betel L. Family: Piperaceae).

History

The chewing of betel nut quids dates to antiquity. In the 1st century AD, Sanskrit medical writings claimed that betel nut possessed 13 qualities found in the region of heaven. It is pungent, bitter, spicy, sweet, salty, and astringent. It expels wind, kills worms, removes phlegm, subdues bad odors, beautifies the mouth, induces purification, and is said to kindle passion.3

Because of its mild CNS-stimulating effects, betel nut is used in a manner similar to the western use of tobacco or caffeine.4 Arecoline is thought to be responsible for some of the claimed effects of betel quid chewing, such as alertness, increased stamina, a sense of well-being, euphoria, and salivation.5

Chewing the nut stimulates salivary flow, thereby aiding digestion. Betel nut also has been used as an appetite stimulant.2

Extracts of the nut have been used for the management of glaucoma in traditional medicine.6 Arecoline is a basic oily liquid that has been used in veterinary medicine as a cathartic (for horses) and a vermifuge.

Chemistry

The medicinal components are primarily associated with the nut and betel quid. The nuts contain at least 9 structurally related pyridine alkaloids, including arecoline, arecaidine, arecaine, arecolidine, guvacine, isoguvacine, guvacoline, and coniine. However, the most common is the parasympathetic stimulant alkaloid arecoline. The total alkaloid content can reach 0.45%.2, 4, 7, 8

The methyl esters of arecoline and guvacoline are hydrolyzed in the presence of alkali to the respective acids, arecaidine and guvacine. The hydrolysis is catalyzed by lime, which is added to the quid. Arecoline most likely is present in the nut as a salt of tannic acid, and the lime facilitates the release of the base from the salt.8

Components of the betel quid, most likely from P. betel and not betel nuts, contain about 1% of a volatile oil, chalbetol, chavicol, cadinene, allylpyrocatechol, and safrole.2, 9

Uses and Pharmacology

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

Dosing

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

Pregnancy / Lactation

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

Interactions

Information is lacking. Arecoline may antagonize the anticholinergic action of procyclidine, causing extrapyramidal symptoms.19 An experiment in rats showed inhibition of monoamine oxidase type A isolated from the brain.20

Adverse Reactions

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

Toxicology

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

References

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2. Arjungi KN. Areca nut: a review. Arzneimittelforschung. 1976;26(5):951-956.786304
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6. Morton JF. Major Medicinal Plants: Botany, Culture, and Uses. Springfield, IL: Charles C. Thomas Publishing Ltd; 1977.
7. Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985.
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9. Chen CL, Chi CW, Chang KW, Liu TY. Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history. Carcinogenesis. 1999;20(12):2331-2334.10590228
10. Sullivan RJ, Allen JS, Otto C, Tiobech J, Nero K. Effects of chewing betel nut ( Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia. Br J Psychiatry. 2000;177:174-178.11026959
11. Sullivan RJ, Andres S, Otto C, Miles W, Kydd R. The effects of an indigenous muscarinic drug, betel nut (Areca catechu), on the symptoms of schizophrenia: a longitudinal study in Palau, Micronesia. Am J Psychiatry. 2007;164(4):670-673.17403982
12. Inokuchi J, Okabe H, Yamauchi T, Nagamatsu A, Nonaka G, Nishioka I. Antihypertensive substance in seeds of Areca catechu L. Life Sci. 1986;38(15):1375-1382.3007909
13. Chung FM, Shieh TY, Yang YH, et al. The role of angiotensin-converting enzyme gene insertion/deletion polymorphism for blood pressure regulation in areca nut chewers. Transl Res. 2007;150(1):58-65.17585864
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18. López-Vilchez MA, Seidel V, Farré M, García-Algar O, Pichini S, Mur A. Areca-nut abuse and neonatal withdrawal syndrome. Pediatrics. 2006;117(1):e129-e131.
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21. Strickland SS. Anthropological perspectives on use of the areca nut. Addict Biol. 2002;7(1):85-97.11900627
22. Pickwell SM, Schimelpfening S, Palinkas LA. 'Betelmania'. Betel quid chewing by Cambodian women in the United States and its potential health effects. West J Med. 1994;160(4):326-330.8023480
23. Warnakulasuriya S. Areca nut use following migration and its consequences. Addict Biol. 2002;7(1):127-132.11900632
24. Winstock A. Areca nut-abuse liability, dependence and public health. Addict Biol. 2002;7(1):133-138.11900633
25. Gamble MV, Ahsan H, Liu X, et al. Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. Am J Clin Nutr. 2005;81(6):1372-1377.15941889
26. Yen AM, Chiu YH, Chen LS, et al. A population-based study of the association between betel-quid chewing and the metabolic syndrome in men. Am J Clin Nutr. 2006;83(5):1153-1160.16685060
27. Yen AM, Chiu YH, Chen LS, et al. A population-based study of the association between betel-quid chewing and the metabolic syndrome in men. Am J Clin Nutr. 2006;83(5):1153-1160.16685060
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29. Tung TH, Chiu YH, Chen LS, et al. A population-based study of the association between areca nut chewing and type 2 diabetes mellitus in men (Keelung Community-based Integrated Screening programme No. 2). Diabetologia. 2004;47(10):1776-1781.15517150
30. Guh JY, Chen HC, Tsai JF, Chuang LY. Betel-quid use is associated with heart disease in women. Am J Clin Nutr. 2007;85(5):1229-1235.17490957
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35. Kiyingi KS. Betel nut chewing and asthma. Lancet. 1992;340(8810):59-60.1351643
36. Ashby J, Styles JA, Boyland E. Betel nuts, arecaidine, and oral cancer. Lancet. 1979;1(8107):112.84123
37. Sundqvist K, Liu Y, Erhardt P, Nair J, Bartsch H, Grafström RC. Areca-nut toxicity in cultured human buccal epithelial cells. IARC Sci Publ. 1991;(105):281-285.1855866
38. Bhide SV, Shivapurkar NM, Gothoskar SV, Ranadive KJ. Carcinogenicity of betel quid ingredients: feeding mice with aqueous extract and the polyphenol fraction of betel nut. Br J Cancer. 1979;40(6):922-926.526433
39. Warnakulasuriya S, Trivedy C, Peters TJ. Areca nut use: an independent risk factor for oral cancer. BMJ. 2002;324(7341):799-800.11934759
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41. Eipe N. The chewing of betel quid and oral submucous fibrosis and anesthesia. Anesth Analg. 2005;100(4):1210-1213.15781548
42. Prabhu RV, Prabhu V, Chatra L, et al. Areca nut and its role in oral submucous fibrosis. J Clin Exp Dent. 2014;6(5):e569-75.25674328
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