Systemic and Neuropsychiatric Implications of Betel Quid and Areca Nut Use: A Multidisciplinary Review of Carcinogenesis and Mental Health Outcomes

Abstract

Background: Betel quid (BQ) and areca nut (AN) chewing are ancient cultural practices prevalent across the Asia-Pacific region. While the carcinogenic potential of BQ is well-documented by the IARC, emerging research suggests a complex profile of systemic toxicity and profound neuropsychiatric effects. This review aims to synthesize current findings regarding the association between BQ use, systemic malignancies, and mental health disorders.

Methods: A multidisciplinary review was conducted analyzing epidemiological, genomic, and behavioral studies. The scope includes cancer risks beyond the oral cavity, genomic instability mechanisms, and psychiatric correlations ranging from dependence to psychosis.

Results: BQ use is strongly associated with Oral Potentially Malignant Disorders (OPMD) and Oral Squamous Cell Carcinoma (OSCC), alongside significant risks for esophageal, stomach, and breast cancers. Molecular studies indicate that AN induces chromosomal instability and alters mitotic checkpoint genes. Neuropsychiatrically, BQ use is linked to DSM-5 Use Disorders, schizophrenia, and common mental disorders. Mechanistic data reveals that arecoline affects Monoamine Oxidase A (MAO-A) activity and Brain-Derived Neurotrophic Factor (BDNF) signaling, creating a complex interplay of nociceptive and anxiodepressive responses.

Conclusion: The health impact of BQ extends far beyond oral hygiene. It represents a dual public health burden, driving systemic carcinogenesis and contributing to psychiatric morbidity. Effective health policy must address the neurobiological addiction mechanisms to mitigate cancer risks effectively.

Keywords:

Betel quid, Areca nut, Oral cancer, Neuropsychiatry

References

Adel M, Liao CT, Lee LY, et al. Incidence and Outcomes of Patients With Oral Cavity Squamous Cell Carcinoma and Fourth Primary Tumors: A Long-term Follow-up Study in a Betel Quid Chewing Endemic Area. Medicine. 2016 Mar;95(12):e2950.

Burton-Bradley BG. Papua and New Guinea transcultural psychiatry: some implications of betel chewing. The Medical journal of Australia. 1966 Oct 15;2(16):744-6.

Chandra PS, Carey MP, Carey KB, Jairam KR. Prevalence and correlates of areca nut use among psychiatric patients in India. Drug and alcohol dependence. 2003 2003/04/01/;69(3):311-6.

Chen PH, Tu HP, Wang SJ, et al. Monoamine oxidase A variants are associated with heavy betel quid use. Addiction biology. 2012 Jul;17(4):786-97.

Chen QY, Zhang Y, Ma Y, Zhuo M. Inhibition of cortical synaptic transmission, behavioral nociceptive, and anxiodepressive-like responses by arecoline in adult mice. Molecular brain. 2024 Jun 17;17(1):39.

Chen SH, Lee JM, Liu HH, Wang HC, Ye CY. The cross-effects of cigarette and betel nut consumption in Taiwan: have tax increases made a difference? Health policy and planning. 2011 May;26(3):266-73.

Garg A, Chaturvedi P, Gupta PC. A review of the systemic adverse effects of areca nut or betel nut. Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology. 2014 Jan;35(1):3-9.

IARC. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC monographs on the evaluation of carcinogenic risks to humans. 2004;85:1-334.

Kaushal M, Mishra AK, Sharma J, et al. Genomic alterations in breast cancer patients in betel quid and non betel quid chewers. PloS one. 2012;7(8):e43789.

Kurkalang S, Banerjee A, Ghoshal N, Dkhar H, Chatterjee A. Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut. BMC cancer. 2013 Jun 28;13:315.

Lee C-H, Ko AM-S, Yang FM, et al. Association of DSM-5 Betel-Quid Use Disorder With Oral Potentially Malignant Disorder in 6 Betel-Quid Endemic Asian Populations. JAMA Psychiatry. 2018;75(3):261-9.

Li S, Li Z, Chen J, et al. Brief psychotic disorder related to areca nut use: a case report. Frontiers in psychiatry. 2024;15:1360493.

Lin TY, Chang HC, Hsu KH. Areca nut chewing is associated with common mental disorders: a population-based study. Social psychiatry and psychiatric epidemiology. 2018 Apr;53(4):393-401.

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. The British journal of psychiatry : the journal of mental science. 2000 Aug;177:174-8.

Wu MT, Lee YC, Chen CJ, et al. Risk of betel chewing for oesophageal cancer in Taiwan. British journal of cancer. 2001 Sep 1;85(5):658-60.

Yao C, Zhang Y, Sun X, et al. Areca catechu L. ameliorates chronic unpredictable mild stress-induced depression behavior in rats by the promotion of the BDNF signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023 Aug;164:114459.