Betel nut

Betel nut/Drug Interactions:

  • AlcoholAlcohol: Theoretically, concomitant chronic use of betel and alcohol may lead to an increased risk of oral cancer.
  • Angiotensin II receptor antagonist (A2R blockers)Angiotensin II receptor antagonist (A2R blockers): Areca II-5-C, a fraction isolated from betel nut (Areca catechu L.), showed angiotensin converting enzyme inhibitory activity in vitro (116). Use with ACE inhibitors may result in additive effects.
  • AntibioticsAntibiotics: De Miranda et al. investigated the growth of salivary and oral microorganisms exposed to extracts of betel or to the saliva after chewing betel nut (117). The extract of baked or boiled nuts (10%) inhibited the growth of S. aureus, F. nucleatum, and S. salivarius, but not C. albicans.
  • AnticholinergicsAnticholinergics: Anticholinergic effects may be reduced when used in combination with betel nut, due to the cholinergic properties of the betel constituent arecoline (59). The skin temperature-elevating effects of betel in humans has been found to be completely inhibited by atropine (49). However, anecdotal reports have noted that atropine may enhance the CNS stimulatory effects of the arecoline constituent of betel.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The dichloromethane fraction of betel nut has been shown to inhibit monoamine oxidase in a rat model (118), and therefore may potentiate the effects of monoamine oxidase inhibitors.
  • Antidiabetic agentsAntidiabetic agents: The arecoline fraction from betel nuts has been found to reduce blood sugar in diabetic rabbits (41). Use of betel may have additive effects with hypoglycemic agents. Data from a population-based cross-sectional survey and a multiple-disease-screening program that tested for hyperglycemia, type 2 diabetes, and risk factors related to type 2 diabetes demonstrated that the habit of chewing areca nut independently contributes to the risk of both hyperglycemia and type 2 diabetes in Taiwanese men (47).
  • AntihypertensivesAntihypertensives: Patients chewing betel nuts have reported acute chest pain, ventricular arrhythmias, tachycardia, palpitations, and hemodynamic instability (hypotension/hypertension) (27; 28; 29; 30; 31; 32), which may be attributed to the cholinergic betel nut constituent arecoline (33).
  • Anti-inflammatory agentsAnti-inflammatory agents: Arecoline, in high concentrations, had an inhibitory effect on neutrophil functions (119). Betel nut extracts stimulate the production of prostaglandin E2 and induce COX-2 mRNA in human gingival keratinocytes in vitro, providing a potential explanation for the oral inflammation seen in betel nut users. However, cytotoxicity appears to occur independently from prostaglandin alterations (120).
  • Antilipemic agentsAntilipemic agents: Betel nut extracts lowered concentrations of cholesterol and triglycerides significantly in rats fed a diet containing cholesteryl oleate (121). Use of betel with hyperlipidemic agents may result in additive effects.
  • Antineoplastic agentsAntineoplastic agents: Based on a case report, chewing areca nuts concurrent with anthracycline chemotherapy may induce grade IV mucositis in oral, genital, and anal mucosa (38).
  • Antipsychotic agentsAntipsychotic agents: Extrapyramidal symptoms (EPS), such as tremor and stiffness, have been reported in patients who chewed betel while receiving anti-psychotic drugs (59; 60).
  • Beta blockersBeta blockers: The betel nut constituent arecoline possesses cholinergic properties and may cause bradycardia. Concomitant use with beta blockers, calcium channel blockers, digoxin, or other agents that reduce heart rate may increase the risk of bradycardia. In a human study, the skin temperature-elevating effects of betel were found to be partially inhibited by the beta adrenergic antagonist propranolol (49), which is of unclear clinical significance.
  • Calcium channel blockersCalcium channel blockers: The betel nut constituent arecoline possesses cholinergic properties and may cause bradycardia. Concomitant use with beta blockers, calcium channel blockers, digoxin, or other agents that reduce heart rate may increase the risk of bradycardia. In a human study, the skin temperature-elevating effects of betel were found to be partially inhibited by the beta adrenergic antagonist propranolol (49), which is of unclear clinical significance.
  • Cardiac glycosidesCardiac glycosides: The betel nut constituent arecoline possesses cholinergic properties and may cause bradycardia. Concomitant use with beta blockers, calcium channel blockers, digoxin, or other agents that reduce heart rate may increase the risk of bradycardia. In a human study, the skin temperature-elevating effects of betel were found to be partially inhibited by the beta adrenergic antagonist propranolol (49), which is of unclear clinical significance.
  • Cardiovascular agentsCardiovascular agents: Based on in vitro study, arecoline from areca nuts may cause endothelial cells to relax, and at high doses may inhibit endothelial cell growth (122).
  • Cholinergic agonistsCholinergic agonists: Cholinergic toxicity (salivation, lacrimation, urinary incontinence, sweating, diarrhea, emesis, facial flushing, and fever) may be seen with the use of betel (53; 54), and has been attributed to the cholinergic properties of the betel constituent arecoline (59). Betel may lead to additive effects when used with other cholinergic agents. Acetylcholinesterase (AChE) inhibitory effects have been observed in animals (123).
  • CNS stimulantsCNS stimulants: Constituents of betel have been shown to possess psychoactive and euphoric effects (62). Theoretically, betel use may result in additive effects with other CNS stimulants.
  • Glaucoma agentsGlaucoma agents: Anecdotal reports have noted that betel may either increase or decrease effects of antiglaucoma medications. Review of the scientific literature reveals no reliable human data in this area.
  • Hypertensive drugsHypertensive drugs: Patients chewing betel nuts have reported acute chest pain, ventricular arrhythmias, tachycardia, palpitations, and hemodynamic instability (hypotension/hypertension) (27; 28; 29; 30; 31; 32), which may be attributed to the cholinergic betel nut constituent arecoline (33).
  • ImmunosupressantsImmunosupressants: Based on in vitro study, components of areca nut inhibit cellular immune activity (124; 125; 126).
  • PhenothiazinesPhenothiazines: Extrapyramidal symptoms (EPS), such as tremor and stiffness, may result when used concomitantly with betel nut (59; 60).
  • Muscarinic antagonistsMuscarinic antagonists: Based on a clinical study in outpatients with diagnoses of schizophrenia or schizoaffective disorder, chewing betel nut may reduce symptoms of schizophrenia (127).
  • Thyroid hormonesThyroid hormones: Betel nut has exhibited both stimulatory and inhibitory effects on thyroid function in male mice (48), and may have unpredictable effects on serum levels of thyroid hormones.

    • Betel nut/Herb/Supplement Interactions:

  • AntibacterialsAntibacterials: De Miranda et al. investigated the growth of salivary and oral microorganisms exposed to extracts of betel or to the saliva after chewing betel nut (117). The extract of baked or boiled nuts (10%) inhibited the growth of S. aureus, F. nucleatum, and S. salivarius, but not C. albicans.
  • Anticholinergic herbsAnticholinergic herbs: Cholinergic toxicity (salivation, lacrimation, urinary incontinence, sweating, diarrhea, emesis, facial flushing, and fever) may be seen with the use of betel (53; 54), and has been attributed to the cholinergic properties of the betel constituent arecoline (59). Betel may reduce the effects of agents with possible anticholinergic properties, such as belladonna, henbane (Hyoscyamus niger), hyoscyamine, and Swertia japonica Makino (Gentianaceae).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The dichloromethane fraction of betel nut has been shown to inhibit monoamine oxidase in a rat model (118), and therefore may potentiate the effects of monoamine oxidase inhibitors.
  • Anti inflammatory herbsAnti inflammatory herbs: Arecoline, in high concentrations, had an inhibitory effect on neutrophil functions (119). Betel nut extracts stimulate the production of prostaglandin E2 and induce COX-2 mRNA in human gingival keratinocytes in vitro, providing a potential explanation for the oral inflammation seen in betel nut users. However, cytotoxicity appears to occur independently from prostaglandin alterations (120).
  • AntilipemicsAntilipemics: Betel nut extracts lowered concentrations of cholesterol and triglycerides significantly in rats fed a diet containing cholesteryl oleate (121). Use of betel with hyperlipidemic agents may result in additive effects.
  • AntineoplasticsAntineoplastics: Based on a case report, chewing areca nuts concurrent with anthracycline chemotherapy may induce grade IV mucositis in oral, genital, and anal mucosa (38).
  • AntipsychoticsAntipsychotics: Extrapyramidal symptoms (EPS), such as tremor and stiffness, have been reported in patients who chewed betel while receiving anti-psychotic drugs (59; 60).
  • Cardiac glycoside herbsCardiac glycoside herbs: The betel nut constituent arecoline possesses cholinergic properties and may cause bradycardia. Concomitant use with cardiac glycoside herbs, or other agents that reduce heart rate, may increase the risk of bradycardia.
  • Cardioactive herbsCardioactive herbs: Based on in vitro study, arecoline from areca nuts may cause endothelial cells to relax, and at high doses may inhibit endothelial cell growth (122).
  • Cholinergic herbsCholinergic herbs: Cholinergic toxicity (salivation, lacrimation, urinary incontinence, sweating, diarrhea, emesis, facial flushing and fever) may be seen with the use of betel (53; 54), and has been attributed to the cholinergic properties of the betel constituent arecoline (59). Betel may lead to additive effects when used with other agents with cholinergic properties, such as American hellebore (Veratrum viride), jaborandi (Pilocarpus jaborandi), lobelia (Lobelia inflata), pulsatilla (Anemone pulsatilla [LINN.]), and snakeroot (Rauwolfia serpentina). Acetylcholinesterase (AChE) inhibitory effects have been observed in animals (123).
  • HypertensivesHypertensives: Patients chewing betel nuts have reported acute chest pain, ventricular arrhythmias, tachycardia, palpitations, and hemodynamic instability (hypotension/hypertension) (27; 28; 29; 30; 31; 32), which may be attributed to the cholinergic betel nut constituent arecoline (33).
  • HypoglycemicsHypoglycemics: The arecoline fraction from betel nuts has been found to reduce blood sugar in diabetic rabbits (41). Use of betel may have additive effects with hypoglycemic agents. Data from a population-based cross-sectional survey and a multiple-disease-screening program that tested for hyperglycemia, type 2 diabetes, and risk factors related to type 2 diabetes demonstrated that the habit of chewing areca nut independently contributes to the risk of both hyperglycemia and type 2 diabetes in Taiwanese men (47).
  • HypotensivesHypotensives: Patients chewing betel nuts have reported acute chest pain, ventricular arrhythmias, tachycardia, palpitations, and hemodynamic instability (hypotension/hypertension) (27; 28; 29; 30; 31; 32), which may be attributed to the cholinergic betel nut constituent arecoline (33).
  • ImmunosupressantsImmunosupressants: Based on in vitro study, components of areca nut inhibit cellular immune activity (124; 125; 126).
  • Muscarinic antagonistsMuscarinic antagonists: Based on a clinical study in outpatients with diagnoses of schizophrenia or schizoaffective disorder, chewing betel nut may reduce symptoms of schizophrenia (127).
  • StimulantsStimulants: Constituents of betel have been shown to possess psychoactive and euphoric effects (62). Theoretically, betel use may result in additive effects with other CNS stimulants, such as caffeine, guarana, or ephedra (ma huang).
  • Thiamine (vitamin B1)Thiamine (vitamin B1): Betel has been reported to possess anti-thiamine effects (52), and theoretically may precipitate neurologic damage including Wernicke-Korsakoff syndrome. Wernicke's encephalopathy is characterized by confusion, ataxia, nystagmus, and opthalmoplegia (weakness of the lateral rectus muscle and conjugate gaze palsies), while Korsakoff's psychosis involves confusion and amnesia.
  • Thyroid agentsThyroid agents: Betel nut has exhibited both stimulatory and inhibitory effects on thyroid function in male mice (48), and may have unpredictable effects on serum levels of thyroid hormones.
  • Vitamin DVitamin D: Based on human study, chewing betel nut may aggravate the effects of vitamin D deficiency (110).

    • Betel nut/Food Interactions:

  • Insufficient available evidence.

    • Betel nut/Lab Interactions:

  • CopperCopper: Based on human study, patients who chew betel nuts may have increased copper level in oral mucosal tissue (128; 129).
  • Fecal occult blood test/stool guaiacFecal occult blood test/stool guaiac: Anecdotal reports have noted that chewing areca nuts can stain feces red, and may interfere with fecal lab tests.
  • GlucoseGlucose: The arecoline fraction from betel nuts has been found to reduce blood sugar in diabetic rabbits (41). Systematic study in humans is lacking.
  • Serum calcitrolSerum calcitrol: Betel chewing also increases 25(OH)D-24-hydroxylaseexpression and decreases serum calcitriol, which indicates betel chewing may aggravate the effects of vitamin-D deficiency (110).
  • SGOT and SGPTSGOT and SGPT: Based on animal study, arecoline may up regulate hepatotoxic marker enzymes (SGOT and SGPT) in serum (10).
  • Thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3)Thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3): Betel nut has exhibited both stimulatory and inhibitory effects on thyroid function in male mice (48), and may have unpredictable effects on serum levels of thyroid hormones.
  • Total cholesterol, triglyceridesTotal cholesterol, triglycerides: Betel nut extracts lowered concentrations of cholesterol and triglycerides significantly in rats fed a diet containing cholesteryl oleate (121). Systematic study in humans is lacking.
  • Urinary albuminUrinary albumin: In type 2 diabetic patients, betel nut chewing is independently associated with urinary albumin excretion rate (130).