Betel Nut Chewing Research Articles

Guideline for the Diagnosis and Clinical Management of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive and potentially malignant oral mucosal disease. Patients often have a habit of chewing betel nuts. Areca catechu has been listed as a Class 1 carcinogen by the International Agency for Research on Cancer (IARC), and its main active component, arecoline, is classified as a Group 2B carcinogen by the IARC. The World Health Organization (WHO) categorises OSF as an oral potentially malignant disorder (OPMD). The present guideline describes the risk factors, clinical symptoms and clinical signs of OSF. Clinical staging, auxiliary examination methods, basis for diagnosis and differential diagnosis and the need to improve bad lifestyle habits are proposed and addressed, and local treatment drugs, therapies, dosage and course of treatment, possible adverse reactions, and oral treatment drugs, dosage and course of treatment are proposed. The guideline also addresses the indications for surgical treatment, alternative non-drug treatment methods, selection of treatment plans for different clinical stages, criteria for efficacy evaluation, and preventive measures.

Guvacoline in betel nuts directly binds to and inhibits AChE activity, lowering ACh levels released by neurons

This paper investigates guvacoline, a compound found in betel nut, and its activity on acetylcholine level. Betel nuts are the chewable seeds of plant used in Chinese traditional medicine. It is commonly used all over southern Asia and the east African seaboard, being the fourth most commonly used drug in the world. It is known for being carcinogenic for throat cancer. Immediate symptoms of betel nut chewing indicate activation of the parasympathetic system, in which acetylcholine and acetylcholinesterase is involved. This paper predicts that guvacoline, found in areca nuts, increases free acetylcholine levels released from neurons by allosterically binding to acetylcholinesterase inhibiting it.

Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Progress of EGFR targeted therapy for oral cancer

Because of some uncertain factors such as eating habits and smoking, oral cancer has become one of the serious diseases of the oral and maxillofacial region. Especially in some Chinese cities where betel nut chewing is customary, the incidence of oral cancer has been high. Today, the main treatment methods are still traditional surgical excision, radiation and chemotherapy. However, with the development of medical technology, gene-targeted therapy has become the most important research object. Gene targeting technology is mainly targets the treatment of cancer organ cells, reducing the damage of traditional treatment methods on other areas without lesions. At present, the epidermal cytokine EGFR has been the most studied, and some research results have been put into clinical application. However, in terms of targeted therapy, the development of technology is still incomplete and immature. This article mainly discusses the pathogenic mechanism of EGFR in oral cancer, the synergistic effect of EGFR and other factors on the development of oral cancer, and the research results of EGFR-targeted therapy and combination therapy for oral cancer. The significance of this study is that based on these discussions, it provides reference opinions for treatment that can achieve a good prognosis for oral cancer patients and alleviate the pain of oral cancer patients, and evaluate the current development status of clinical application of EGFR targeted therapy for oral cancer. At present, the targeted therapy technology of oral cancer is still immature. In the future, the role of other factors in the development of oral cancer can be studied, and the influence of the combination of targeted therapy and other therapeutic methods on the treatment results of oral cancer can be studied.

Areca nut cultivators from Tamil Nadu: Is the nut their friend or foe – A questionnaire study

Objective: The present study was done to evaluate the awareness of people involved in cultivation of areca nut from Tamil Nadu on various oral and systemic health effects of chewing areca nut. Material and Methods: A cross-sectional study was conducted among areca nut cultivators from various districts of Tamil Nadu. People involved in the cultivation of areca nut were included in the study. 500 individuals participated in the study. They were instructed to complete a pre-tested questionnaire with 25 questions. Results: 58% of the participants were males and 42% were females. Dryness of the mouth from decreased production of saliva due to areca chewing was known to 57% of the study participants. 39% of the participants were aware of addiction. Oral cancer from areca nut chewing in various forms with/without tobacco was also known to 51% of them. 86% of them were prepared to quit the habit and 92% of them admitted that government has banned the sale of commercial pan masala products. Conclusion: The study evaluated the awareness of oral and systemic effects of chewing areca nut among people involved in cultivation of areca nut from rural parts of Tamil Nadu. Appropriate regulatory measures are critical for educating people from a variety of occupational and socioeconomic backgrounds in both rural and urban areas.

Submucosal Hematoma of Esophagus Induced by Chewing Betel Nut

Submucosal Hematoma of Esophagus Induced by Chewing Betel Nut

Fluoride as a potential contributory factor in pathogenesis of oral submucous fibrosis: A novel hypothesis

Oral submucous fibrosis (OSMF) is a chronic premalignant condition of the oral cavity characterized by progressive submucosal fibrosis and high malignant transformation risk. Areca nut chewing is an established aetiological factor, but OSMF's sporadic incidence in nut users indicates other contributing cofactors. This paper propose a novel hypothesis on the potential role of fluoride exposure in OSMF pathogenesis. Evidence in the literature demonstrates fluoride readily accumulates in oral tissues upon topical exposure and can elicit oxidative stress, chronic inflammation, collagen changes, and muscle degeneration through various mechanisms. We hypothesize chronic topical fluoride exposure from gutkha, areca nut or other smokeless tobacco products, along with other aetiologic factors, may induce an aberrant microenvironment in the oral mucosa, initiating and propagating submucosal fibrosis. Resultant repetitive injury coupled with fluoride's interference in collagen metabolism and wound healing may culminate in OSMF pathogenesis. We further speculate that chronic ingestion of dietary fluoride especially from drinking water and food may predispose individuals to OSMF when it interacts synergistically with direct contact of gutkha or other smokeless products. In addition, it is also speculated that the cellular effects of fluoride in a dose-dependent manner, could contribute to dysplastic changes and malignant transformation in severe OSMF cases. Further research should systematically investigate fluoride levels in OSMF cohorts and correlate with disease severity and malignant transformation rates. Confirming the aetiopathologic role of fluoride as a promoting factor would highlight public health efforts to limit its topical exposure from oral habits and diet to combat this oral potentially malignant disorder.

Evaluation of fluoride levels in areca nut, tobacco, and commercial smokeless tobacco products: a pilot study

Oral submucous fibrosis (OSMF) is a premalignant condition associated with chewing areca nut and tobacco products. We observed increased fluoride levels in some OSMF-endemic regions,and the observation suggested that fluoride exposure may contribute to its pathogenesis. This study aimed to assess the fluoride content of various smokeless tobacco items as a potential influencing source. Fluoride concentration was analysed in commercial areca nut products, including gutkha, pan masala, and raw areca nut, along with tobacco, slaked lime, and catechu samples from Karnataka, India. Fluoride was measured using alkali fusion and the ion selective electrode method. All products showed high fluoride, with catechu having the highest mean concentration at 51.20 mg/kg, followed by tobacco, gutkha, pan masala, processed areca nut, and raw areca nut. Fluoride was also elevated in soil, but not in water. The findings demonstrate substantial fluoride levels in popular types of smokeless tobacco, and highlight an overlooked source of exposure among consumers of gutkha, pan masala and similar oral tobacco-products. The fluoride content warrants an investigation of potential links with the occurrence and severity of OSMF.

Do the American guideline-based leisure time physical activity levels for civilians benefit the mental health of military personnel?

This study aimed to clarify the association of American guideline-based leisure time physical activity (PA) level with mental health in 4,080 military personnel in Taiwan. The moderate intensity PA level was assessed according to the total running time per week (wk) reported in a self-administered questionnaire over the previous 6 months and was categorized into PA level <150, 150-299, and ≥300 min/wk. Mental stress was assessed by the Brief Symptom Rating Scale (BSRS)-5 for which ≥15 points were classified as great mental stress. Suicide ideation (SI) was graded as 1 for mild, 2 for moderate, and 3 or 4 for severe. Multivariable logistic regression analysis was employed to determine the association between PA and mental health while adjusting for demographics, smoking, alcohol intake, betel nut chewing, and obesity. As compared to participants with a PA level of <150 min/wk., those with PA levels 150-299 min/wk. and ≥ 300 min/wk. had a lower possibility of SI ≥1 [odds ratios (ORs) and 95% confidence intervals (CIs): 0.58 (0.40-0.83) and 0.23 (0.14-0.36), respectively] and SI ≥1 and/or BSRS-5 ≥ 15 [ORs: 0.55 (0.39-0.79) and 0.21 (0.13-0.34), respectively]. The possibilities were more significantly lower for SI ≥2 [ORs: 0.37 (0.20-0.68) and 0.10 (0.04-0.26), respectively] and SI ≥2 and/or BSRS-5 ≥ 15 [ORs: 0.35 (0.20-0.62) and 0.10 (0.04-0.25), respectively]. Our findings indicate that participating in moderate-intensity leisure time PA level for ≥150 min/wk. may have a positive effect on mental health among military personnel. The impact appears to be even more significant when engaging in a higher PA level of ≥300 min/wk.

Integrated metabolomics and network pharmacology to reveal the mechanism of areca nut addiction.

As a chewing hobby, areca nut (Areca catechu L.) has become the most common psychoactive substance in the world, besides tobacco, alcohol and caffeinated beverages. Moreover, as a first-class carcinogen designated by International Agency for Research on Cancer, long-term chewing areca nut can result in oral mucosal diseases and even oral cancer. To clarify the potential mechanism of areca nut addiction, an integrated strategy of metabolomics and network pharmacology was adopted in this study. Network pharmacology study indicated that all the key targets related to areca nut addiction could be regulated by arecoline and pointed out the importance of G-protein coupled receptor signalling pathway. Analysis results of mice plasma metabolome and faeces metabolome intervened by arecoline suggested that the component may affect the dopamine system and 5-HT system by regulating phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and intestinal flora structure. Moreover, the potential importance of bile acids in formation of addictive behaviour of chewing areca nut was investigated by integrative analysis of the relationships between metabolites and intestinal flora. The study can provide scientific basis for the addiction intervention and treatment of areca nut chewers.

Oral Health Beliefs, Perceptions and Utilisation of Oral Health Care Services among the Indigenous People (Orang Asli) in Pahang, Malaysia: A Qualitative Study

Introduction: Orang Asli refers to the indigenous people of Peninsular Malaysia, representing 0.6% of the Malaysian population. Vast inequality was observed regarding oral health beliefs, behaviour, and utilisation of oral health services between the Orang Asli and non-Orang Asli. The aim of the study was to explore the oral health beliefs, perceptions, and oral health service utilization behaviour among Orang Asli in the district of Bera, Pahang, Malaysia. Methods: Orang Asli’s oral health beliefs and perceptions of oral healthcare service were ascertained through four FGDs. Nineteen participants from Bera’s semi-urban and rural Orang Asli communities were convened. Emerging themes from the qualitative data were analyzed using thematic analysis. Results: Orang Asli believed that oral health is essential for an individual’s function and aesthetics. They are also aware that inadequate oral hygiene care will result in tooth decay and gum disease. Most of the Orang Asli that chewed betel nuts believed that limestone paste could cause oral cancer. The main barriers to Orang Asli accessing oral healthcare services were time constraints and distance to the nearby clinic. Conclusion: The Orang Asli believed oral health care is essential in ensuring a healthy oral condition. Despite their generational belief towards traditional healers and medication, Orang Asli in Bera had a perceived positive acceptance towards oral healthcare services.

Assessing the burden of HPV-related head and neck cancers in mainland China: protocol of a nationwide, multisite, cross-sectional study

BackgroundPersistent human papillomavirus (HPV) infection is a known cause of a subset of head and neck cancers (HNCs). In the last two decades, the proportion of HNCs attributable to HPV...

Inhibition of Oral Fibrinogenesis Through Transforming Growth Factor-Beta/SMAD2/3 Signalling Inhibition Using Mangosteen Pericarp Extract.

Background Chewing areca nuts can result in an oral disorder known as oral submucous fibrosis (OSF), which has the potential to be cancerous. Although it is only beginning to spread to European and the North American continents, it is highly prevalent in Southeast Asia. The probability of malignant transformation from OSF is raised by chewing tobacco use. In the current research, our objective was to assess the potential anti-fibrosis effects and the ability to prevent malignant transformation through the application of mangosteen pericarp extract. Methodology The Ethical Approval-IHEC/SDC/OMED-2101/23/085 from the institution was obtained to conduct this ex vivo study. The cytotoxicity effect of mangosteen pericarp extract on both normal and fibrotic buccal mucosal fibroblasts originating from OSF tissues was tested. Cell proliferationand cell migration by scratch wound healing assay was examined. Dual staining was done to determine the mode of cell death. Additionally, real-time PCR was utilized to measure the expression of TGF-β/Smad2/3 signalling, α-SMA, and type I collagen gene expression. Results Mangosteen extract exerted higher cytotoxicity of fibrotic buccal mucosal fibroblasts compared to normal cells. Furthermore, mangosteen-receiving cells exhibited downregulation in the expression of the TGF-β/Smad2 pathway, as well as reduced expression of α-SMA and type I collagen. Conclusion Findings from this study suggest that mangosteen could serve as a promising agent for averting the progression of oral fibrogenesis and halting the malignancy of the oral epithelium in patients with OSF.

Lifestyle and Diet as Risk Factors for Urinary Stone Formation: A Study in a Taiwanese Population.

Background and Objectives: Urinary tract stones have long been a common ailment afflicting the population, with a high incidence and a wide distribution across different age groups. Effectively preventing the occurrence of urinary tract stones is of paramount importance. The primary aim of this study is to investigate the correlations between individual characteristics, water consumption habits, dietary habits, exercise habits, and the occurrence of urinary tract stones in a Taiwanese population. Materials and Methods: This study is cross-sectional research conducted over one month in 2022. One hundred eligible urinary stone cases were recruited through physician screening at outpatient clinics, and an additional one hundred samples from surgical outpatients without urinary tract stones were included as the control group. A questionnaire survey was employed to gather information on demographic variables, dietary habits, water consumption, and exercise habits of the cases. Descriptive statistics, chi-square tests, and logistic regression were used to explore the impact of relevant factors on urinary stone formation. Results: The analysis results revealed that among the demographic variables, males exhibited a higher risk of contracting urinary tract stones than females, and the majority of cases fell within the 40- to 49-year-old age group. Unhealthy lifestyle habits such as smoking and betel nut chewing also demonstrated a higher susceptibility to urinary tract stones. A logistic regression analysis showed that individuals who engaged in physical activity more than three times per week and those with inadequate water intakes had a higher risk of developing urinary tract stones. Conclusions: There is a close relationship between lifestyle and urinary tract stones. It is recommended that individuals continue to hydrate adequately during exercise.

Epidemiological and clinical characteristics of esophageal carcinoma: An experience from tertiary care hospital of Karachi, Pakistan.

To describe current trends and characteristics of esophageal cancer (EC) over the past ten years largest tertiary care hospital of Karachi, Pakistan. This single center retrospective study was conducted at the Department of Gastroenterology and Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan, between the period of ten years from 1st January 2010 to 31st December 2019. Patient data including epidemiological characteristics such as age, gender, education, residence, occupation, addictions, comorbidities, symptoms, location of EC, laboratory parameters and histopathological type were recorded. All patients with missing histological and radiological findings were excluded. The mean age of all patients was 49.26±14.24 years and among them majority were females 566 (56.1%). Almost, 834 (82.7%) patients had SQC and 175 (17.3%) presented with ADS. Most common presenting symptom was dysphagia in both groups 327 (32.4%) followed by vomiting (22.8%) and weight loss 196 (19.4%). The Esophagogastroduodenoscopy (EGD) findings showed the distal esophagus involvement in most of the patients (36.3%) in both groups. CT scan findings showed that the lower region was the most involved region in 367 (36.4%) patients, followed by middle and upper in 227 (22.5%) and 156 (15.5%) patients respectively. The thickening of mass on CT- scan was circumferential in most of the patients (42.7%) in both groups. According to our findings, SQC is more prevalent than ADC. Female predominance especially at younger age was most common as compared to past studies. No significant association between a single risk factor has been found in our study however smoking and betel nut chewing were found as known putative risk factors.

Relationship between mood disorders and substance involvement and the shared genetic liabilities: A population-based study in Taiwan

BackgroundThis study explored the phenotypic association of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BPD), with a range of substance involvement, including lifetime experience and age at initiation of tobacco, alcohol, and betel nut use. Additionally, we elucidated polygenic risk score (PRS) association. MethodsIn total, 132,615 community participants were recruited from the Taiwan Biobank. Genome-wide genotyping data were available for 106,806 unrelated individuals, and the PRS for MDD and BPD was calculated. The significance of mood disorders and PRSs associated with substance involvement were evaluated using a linear/logistic regression model with adjustment for potential confounders. Sex differences were assessed. ResultsMDD and BPD were associated with regular alcohol consumption, drinking cessation, tobacco smoking, smoking cessation, betel nut chewing, and earlier onset of drinking. BPD was associated with an earlier onset of smoking. MDD PRS was associated with regular alcohol use (odds ratio [OR] per standard deviation increase in PRS = 1.03, p = 0.018), alcohol cessation (OR = 1.05, p = 0.03), regular tobacco use (OR = 1.08, p < 0.0001), and betel nut chewing (OR = 1.06, p < 0.0001), whereas BPD PRS was not associated with substance use. Phenotypic association strengths between MDD/BPD and regular drinking/smoking and the polygenic association between MDD PRS and regular smoking were larger in females than in males. LimitationsRetrospective self-reported MDD/BPD diagnoses and substance involvement. ConclusionsMood disorders were associated with a range of substance involvement. Shared genetic architecture contributed to the co-occurrence of MDD and substance involvement. These findings may help design prevention and cessation strategies for substance use.

Oral Submucous Fibrosis: A Review of the Current Concepts in Management.

Oral submucous fibrosis (OSMF) is a precancerous disorder of the submucosa that causes inflammation and progressive fibrosis, leading to pronounced stiffness and trismus. Chewing betel nuts is a significant risk factor for OSMF in India. Arecoline from betel nuts and copper, which causes fibroblast dysfunction and the development of fibrotic bands, are the main components of betel quid. OSMF is distinguished by fibrosis in the submucosal region, which affects the majority of the oral cavity and results in advanced lockjaw due to rigidity in the lips, pharynx, cheeks, and upper third of the oesophageal canal, which progresses to dysphagia. The prevalence of OSMF is rising, particularly among younger generations, as more commercially available areca nut products like gutka (chewing tobacco) and others are being introduced. The severity of OSMF develops as the practice continues and is permanent. It also persists even after chewing has been stopped. The hallmark of oral submucous fibrosis (OSF) is abnormal collagen deposition. It is a precancerous condition and progresses to malignant tumours. Symptoms include ulcers, xerostomia, submucous fibrosis, burning sensation, and a reduction in mouth opening. Each of these drastically reduces the patient's quality of life. In the past, many treatment modalities have been tried but none of them has resulted in a cure for the disease. The primary focus of the treatment is to reduce the signs and symptoms so that the patient can have a better quality of life. Along with principles, conservative, medical, and surgical management issues have also been covered.

Areca nut – A gift by nature but a sweet poison for oral environment: A comprehensive review

Abstract Background: Nature provides us with a diversity of plants and fruits. These organic plants and the products they produce might have some therapeutic potential that can be applied to the treatment of specific bacterial and pathological disorders of the body. Yet, some of these ingredients may have harmful effects on tissue and health if they are abused. In Hindu culture, areca nuts (ANs) are widely used for food, Ayurvedic medicine, and social and religious purposes. Nonetheless, frequent use may cause some changes to the oral environment. Aim: The purpose of this review is to provide an overview of how AN addiction affects the oral environment and dental health. Materials and methods: Electronic research of the published English literature was performed in PubMed/Medline, Science Direct, Web of Science, Embase, Google Scholar, and Scopus databases, from 2001 to 2023 using mesh keywords such as (areca nut or betel nut) and (oral tissues or oral cavity or oral environment). A manual search of all the related journals was also performed. We also checked the reference lists of the relevant articles. Conclusions: Although the AN plays a positive function in dental and digestive health, excessive ingestion can have negative effects on the environment and oral tissues. The globe is now aware of using this sweetener with caution because of the increased prevalence and incidence of numerous oral illnesses induced by this habit for the last few years, especially in school-age youngsters. It has been discovered that this behavior is linked to even the precancerous diseases and lesions that lead to mouth cancer. Hence, it is essential to persuade them to stop chewing ANs to avoid further difficulties.

Evaluation of Iron Deficiency in OSMF patients: A Cross-sectional Study

Oral submucous fibrosis is a type of chronic oral pathological ailment, which is having insidious onset. It possesses high rate of malignant transformation, which gets accentuated by pernicious oral habits like chewing of areca nut in betel. OSMF predisposes to marked hematological abnormalities, leading to anemia and reduction in levels of serum iron and proteins. The aim of this study was to measure the hemoglobin, serum iron and protein levels among OSMF patients and also to compare these parameters with healthy controls.In the hospital-based study, among 100 study subjects, 45 OSMF patients were selected as cases, whereas 55 apparently healthy individuals were chosen as controls. The hemoglobin, serum iron and protein levels were estimated using hematological and biochemical autoanalyzers. Significantly lower levels of hemoglobin, serum iron, and protein levels were observed in OSMF patients in comparison with apparently healthy subjects.Findings of this study focus on the necessity and rationale of assessing hemoglobin, serum iron and protein amongst OSMF patients. These biochemical assessments in the precancerous condition of OSMF may help in early diagnosis and prognosis. Besides that, iron therapy should be initiated at the earliest with the initial diagnosis, which can be helpful to check further deterioration of the aforesaid premalignant condition. Further extensive studies are required for fine delineation of hematological alterations in OSMF patients.

Dental Health Utilization in Palau: Feasibility of an Oral Cancer Screening Program.

Cancer is the second leading cause of death in the Western Pacific region. The prevalent tradition of chewing betel nut in Palau, an island nation in this region, is a risk factor in the development of oral cancer. Oral cancer is the fifth most common cancer in Palau, and the prognosis can be improved with early detection facilitated by visual inspection of the oral cavity by dentists. The purpose of this study is to assess the feasibility of oral cancer screening using existing dental health infrastructure in Palau. A mixed methods approach was used to explore topics related to the use of dental care resources in Palau. Primary outcome measures were collected using an electronic survey with closed- and open-ended questions addressing dental health utilization as well as barriers and facilitators to accessing dental care. Secondary measures assessed knowledge, attitudes, and beliefs about betel nut use and oral cancer. Open-ended survey questions were analyzed and coded to develop themes based in grounded theory. Two hundred twenty-three surveys were completed. The mean age was 42.7 years, 80% identified as female, and most (94.3%) report having seen a dentist in Palau. Dental care is seen as important (mean score 82.3/100), and 57.9% reported it was easy to access a dentist. Themes regarding facilitators include multilevel resources and transportation. Themes regarding barriers include cost and availability of dentists/appointments. Approximately half of the respondents were current users of betel nut. Our results suggest facilitators are in place to promote seeking and obtaining dental care; however, existing infrastructure may not support an oral cancer screening program. These data provide important areas to address that can improve access and support the implementation of oral cancer screening through existing dental care in the future.