Areca Nut Users Research Articles

Betel nut use and hyperglycemia

Betel nut chewing previously has not been common in North America, yet it is the fourth major source of addiction and abuse worldwide. Approximately 700 million individuals, or 10 % of the global population, chew beetle nut on regular basis. It is important for patient safety and improved quality to recognize its use in uncontrolled diabetes. Our case is of a 49 year-old Burmese female with PMH of DM2, HTN, and benign paroxysmal positional vertigo (BPPV) who presented with a complaint of dizziness. Patient denied alcohol or tobacco use, but reported a 20-year history of betel nut chewing (4-5 times/day). Physical exam showed oral mucosa was dry with poor dentition along with eroded enamel and gums. Point-of-care glucose was extremely elevated at 522 mg/dL with HbA1c of 10.8%. Dix-Hallpike maneuver was negative and CTA of the head and neck was unremarkable. Neurology was also consulted regarding her dizziness, and MRI head demonstrated no acute infarct or hemorrhage. Throughout admission, patient’s point of care glucose fluctuated between 91 and 316 (mg/dL), with several daily spikes. Her dizziness improved by day 2 of hospitalization. At the time of discharge, her glucose was controlled on 50 units of glargine at nighttime along with 8 units of insulin at meals. After a negative initial workup for occult causes of dizziness, it was concluded that her 20-year history of betel nut chewing contributed to dizziness and hyperglycemia. Multiple studies show high risk of diabetes, increased likelihood of coronary artery disease and all-cause mortality in betel nut users. Specifically, one study in Taiwan demonstrated increasing incidence ratios of type II diabetes with increasing age.

Risk of Betel Nut Chewing: Chemical and Toxicological Studies

Last few decades epidemiological reports warn that the development of oral submucous fibrosis − a precancerous state, is universal among betel nut or areca nut users. Betel nut contains arecoline and other microelements which are released into the buccal cavity during the process of areca nut chewing. The present effort was undertaken to find out the correlations between chemical ingredients, like arecoline, magnesium, iron and copper present in betel nut with toxicological incidences in experimental animals. Arecoline was estimated by HPLC (Perkin Elmer, USA) and other micronutrients like magnesium, iron and copper was assessed by AAS (Perkin Elmer, USA). Repeated dose 90-day sub-acute oral toxicity of betel nut water extract (BNE) at the dose of 0.5X10-2 ml/g/day and 1.0X10-2 ml/g/day was performed on Wistar rats as per the Organization for Economic Co-operation and Development (OECD) guidelines No. 408. The result indicates that betel nut contains Group 1 human carcinogen arecoline with significant high level of magnesium, iron and copper. Moreover, consumption of betel nut induces liver damage in rats by indicating significant enhancement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP). It may conclude that chemical ingredients presences in betel nut are harmful for health and it should be restricted.

Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline.

Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3′ UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.

A Study to Analyze Different Patterns of Quid Usage among Subjects with Oral Submucous Fibrosis in Mangalore Population.

Aim and Objectives. Oral submucous fibrosis (OSF) is a potentially malignant disorder associated with the usage of areca nut. Usage of processed forms of areca nut is popular among the youth and its carcinogenic effects are not well known. Due to large immigrant population, various patterns of areca nut usage are seen. The aim of this study is to assess the various quid chewing patterns and their association with severity of OSF. Materials and Methods. A cross-sectional study was carried out with 250 cases clinically and histologically diagnosed as having OSF lesion that were selected and subjected to a detailed habit history which was recorded through preformed questionnaire. The data obtained was statistically analyzed. Results. Among the 250 subjects, males were seen to be affected more than females within the age group of 26–35 years and were having clinical stage I OSF. A combination of processed areca nut and processed tobacco was used by the majority of the subjects with duration of 1 to 5 years, at a frequency of 3 to 5 quids per day. Conclusion. The present study confirms the association between oral submucous fibrosis and the quid containing processed areca nut and processed tobacco and also highlights the increasing youth population using the processed forms of areca nut.

Symptoms with betel nut and betel nut with tobacco among Micronesian youth

Betel nut has been stated to be addictive, but evidence is lacking. This study describes dependence symptoms among adolescents using betel alone or with tobacco. In the first study, participants were 151 9th graders in Saipan. In the second study, participants were 269 9th graders in Pohnpei and Yap. Participants completed a confidential questionnaire adapted from the U.S. National Survey of Drug Use and Health, which measured dependence symptoms. The 15 items were summed to form a scale, with a range of 0–15, where higher scores indicated greater endorsement of dependence symptoms. In the first study, 39.1% had used betel. More than two-thirds of all users (69.5%) used betel in the previous month: 87.8% also used tobacco with the betel. The mean (SD) dependence symptoms scale score among tobacco users was 8.2±4.0 versus 3.4±2.9 among those who used betel alone [t(7)=3.3, p=0.015]. In the second study, 38% from Pohnpei and 85% from Yap had used betel and most of the current users used it in the previous month (67% from Pohnpei, 91% from Yap). Among those who had used betel in the previous month, 90% from Pohnpei and 64% from Yap were using betel with tobacco. The dependence score was positively associated with frequency of tobacco use (e.g., mean (SD)=11.3 (±2.4) among most frequent users versus a mean (SD)=4.8 (±3.5) among the never users [F(3109)=28.8, p<0.001]). Betel nut users who also use tobacco may benefit from tobacco cessation strategies.

Effect of chewing betel nut (Areca catechu) on salivary cortisol measurement.

Cultural practices may compromise the accuracy of salivary hormone measurements and must be considered when designing human biology research protocols. This study aims to evaluate the acute effect of one common human practice-chewing betel nut-on the measurement of salivary cortisol levels under field conditions. Data were collected from 17 adult habitual betel nut users (males = 11; females = 6; mean age = 32.8 years) from a small rural community in Papua New Guinea. Saliva was collected in time series from each participant before and at 0, 15, 30, 45, 60, and 75 min after chewing betel nut. Samples were analyzed by radioimmunoassay and cortisol levels were compared across time using linear mixed effects modeling. Measured mean cortisol concentration fell nearly 40% immediately following betel nut use and remained significantly below baseline levels for the following 45 min (all P < 0.05). Cortisol concentrations measured at 60 min and 75 min were indistinguishable from baseline levels (all P > 0.16). Chewing betel nut is associated with a transient but significant reduction in measured levels of salivary cortisol. Future research must take this into account in populations where betel nut use is prevalent.

Impacts of autophagy-inducing ingredient of areca nut on tumor cells.

Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.

Evaluation of the Effect of Areca Nut Use During Pregnancy in the Commonwealth of the Northern Mariana Islands

INTRODUCTION: Betel quid chewing is very common among the native Pacific Islanders living in the Commonwealth of the Northern Mariana Islands and is the fourth most common habit in the world after tobacco, alcohol, and caffeine. Despite its widespread use, there are no studies regarding the effects of betel quid use during pregnancy in the Pacific Islanders living in the Commonwealth of the Northern Mariana Islands. The intent of this study was to assess whether there was a relationship between chewing areca nut and the incidence of preterm birth or meconium staining of amniotic fluid. METHODS: A retrospective chart review was conducted for all deliveries occurring in the territory during 2009. Residents with singleton pregnancies who self-identified during admission as areca nut chewers were selected as cases and compared with nonchewers after matching by age and ethnicity. RESULTS: Areca nut users had twice the odds of preterm birth compared with those who did not use areca nut and the odds of meconium staining of amniotic fluid were increased for areca nut users, although neither value was statistically significant. CONCLUSIONS: The effects of areca nut use during pregnancy remain largely unknown. Additional research with more accurate documentation and better quantification of intake is needed.

Betel nut chewing behaviour and its association with oral mucosal lesions and conditions in Ghaziabad, India.

To assess the practices and behaviour among Betel nut users in Ghaziabad and to detect the clinically associated oral mucosal lesions and conditions. A community-based survey was conducted in Ghaziabad among 332 betel nut users. Data on betel nut use was obtained through a self-administered questionnaire. Oral mucosal lesions and conditions were recorded using WHO criteria. Out of 332 betel nut users, 32.8% consumed Gutkha. 62.3% users used betel nut with tobacco. Most of the study population started chewing betel nut because of peer pressure and the habit started at the workplace or school. A majority found that there was no physical discomfort due to the habit. The significant oral diseases detected were oral leukoplakia in 11.7% and oral submucous fibrosis in 6.1% of individuals. The findings of the present study revealed that 74.7% of the participants were current chewers. 30.4% of all participants had oral mucosal lesions and conditions.

Androgenic Alopecia Is Associated with Less Dietary Soy, Higher Blood Vanadium and rs1160312 1 Polymorphism in Taiwanese Communities

BackgroundAlthough the genetic basis of androgenic alopecia has been clearly established, little is known about its non-genetic causes, such as environmental and lifestyle factors.ObjectiveThis study investigated blood and urine heavy metals concentrations, environmental exposure factors, personal behaviors, dietary intakes and the genotypes of related susceptibility genes in patients with androgenic alopecia (AGA).DesignAge, AGA level, residence area, work hours, sleep patterns, cigarette usage, alcohol consumption, betel nut usage, hair treatments, eating habits, body heavy metals concentrations and rs1998076, rs913063, rs1160312 and rs201571 SNP genotype data were collected from 354 men. Logistic regression analysis was performed to examine whether any of the factors displayed odds ratios (ORs) indicating association with moderate to severe AGA (≧IV). Subsequently, Hosmer-Lemeshow, Nagelkerke R2 and accuracy tests were conducted to help establish an optimal model.ResultsModerate to severe AGA was associated with the AA genotype of rs1160312 (22.50, 95% CI 3.99–126.83), blood vanadium concentration (0.02, 95% CI 0.01–0.04), and regular consumption of soy bean drinks (0.23, 95% CI 0.06–0.85), after adjustment for age. The results were corroborated by the Hosmer-Lemeshow test (P = 0.73), Nagelkerke R2 (0.59), accuracy test (0.816) and area under the curve (AUC; 0.90, 0.847–0.951) analysis.ConclusionsBlood vanadium and frequent soy bean drink consumption may provide protect effects against AGA. Accordingly, blood vanadium concentrations, the AA genotype of rs1160312 and frequent consumption of soy bean drinks are associated with AGA.

Betel Nut Usage Is a Major Risk Factor for Coronary Artery Disease

Aim:The objective of our study was to assess betel nut usage as one of the major risk factors associated with coronary artery disease.Methods:This case control study consisted of 300 controls and 300 cases. A structured questionnaire was administered to the participants to assess consumption of betel nut and confounding variables. A respondent was considered a regular consumer of betel nut if he/she consumed one or more pieces of betel nut every day for a period of greater than 6 months.Results:About 8 in 10 betel nut chewers developed coronary artery disease. After adjusting for diabetes and hypertension, the odds ratio analysis depicted 7.72 times greater likelihood for coronary artery disease in patients who chewed betel nut for more than 10 years.Conclusion:Our study concludes that betel nut chewing is a significant risk factor leading to the development of coronary artery disease.

Sweetened areca-nut chewing habit: A public health issue among school children of Indore, India

Chewing of the areca-nut usually starts early in life leading to a multitude of problems in adulthood. The areca-nut can be correlated with an increased incidence of cancer. Like tobacco, chewing the areca-nut also leads to oral and oro-pharyngeal cancers. The areca-nut is usually marketed in the form of a sweetened areca-nut (locally known as sweet supari) to target young children. A high proportion of school children use areca-nut daily in some form. This study was conducted to determine the prevalence of sweetened areca-nut use and assess the awareness of health risks among school students of Indore, India. Till date none of the studies have pointed out the prevalence of sweet-ened areca use. Population based studies on the habit of areca-nut chewing among children from the district of Indore, Central India have not been reported earlier in the studies. In our study we found 81% of the children used the sweetened form of the areca-nut. Fifty five percent of areca-nut users reported that they learnt the habit from their friends or siblings. The majority of the users (70.4%) were unaware of the harmful effects of areca-nut use, and only a few were aware that it may cause cancer or oral submucous fibrosis. Government school children are more involved in areca-nut chewing habit. Boys were more indulged than girls. Actively communicating the areca-nut’s health risks to the public, and creating strategies involving parents, teachers and local communities could be initiated to discourage areca-nut use. DOI: http://dx.doi.org/10.3329/seajph.v2i2.15959 South East Asia J Public Health | Jul-Dec 2012 | Vol 2 Issue 2 | 73-76

Areca nut chewing and metabolic syndrome: evidence of a harmful relationship.

BackgroundThere is some evidence which suggests that areca nut chewing has a relationship with metabolic syndrome. Areca nut chewing is continue to increase and so is the metabolic syndrome which is a major cause of cardiovascular mortality in developing countries. The aim of this study was to determine the relationship of raw areca nut and areca nut chewing with tobacco additives and metabolic syndrome.MethodsThis cross sectional study was conducted on population of Karachi, Pakistan. Simple random sampling was implied using the voter list as a sampling frame. A detailed questionnaire about the demographic details of all subjects was filled and an informed consent obtained for blood sampling. Logistic regression analyses were carried out to investigate the relationship between areca nut chewing and metabolic syndrome.ResultsOf the 1070 individuals, 192(17.9%) had metabolic syndrome with significantly higher (p-value <0.001) prevalence among females (26.3%) compared with males (11.4%). Eight individuals (11.1%) among non users had metabolic syndrome while significantly higher (p-value <0.001) proportion of both, raw areca nut users (n = 67, 29%) and areca users with tobacco additives (n = 45, 38.5%) had metabolic syndrome.The crude odds ratio for central obesity among raw areca nut users was 1.46 (95% CI 1.07-1.98) and among areca nut users with tobacco additives was 2.02 (95% CI 1.36-3.00), hypertension among raw areca nut users group was 1.31(0.96-1.78) and among areca nut users with tobacco additives group was 2.05 (95% CI 1.38-3.04). A significant positive association of raw areca nut chewing and metabolic syndrome was found among males (crude OR 2.74, 95% CI 1.52-4.95) and females (crude OR 3.80, 95% CI 2.32-6.20). Similarly, a significant positive association was found with regard to raw areca nut with tobacco additives chewing among males (crude OR 5.46, 95% CI 2.73-10.91) and females (crude OR 4.32, 95% CI 2.41-7.72). These associations remained significant adjustment for age, social class.ConclusionsThis study suggests a harmful relationship between areca nut chewing and metabolic syndrome. The deleterious effects were even stronger among areca nut chewer with tobacco additives. Further research with longitudinal data might help to understand the temporal relationship between areca nut chewing and metabolic syndrome.

Attentional biases for betel nut cues in heavy and light chewers.

The betel nut (Areca catecu) is regarded by the World Health Organization as the fourth most prevalent human carcinogen. Our study aims to investigate whether habitual chewers show bias in their attention toward betel nut usage. In the current study, heavy and light betel nut chewers were instructed to respond to a probe presented immediately after either one of a pair of areca-related picture and non-areca-matched picture. The presentation durations of these pictures were manipulated to investigate attentional biases under awareness threshold (17 ms), in initial orienting (200 ms), and maintenance of attention (2,000 ms). Faster response to the probe replacing the areca-related picture, in comparison with a matched picture, indicated attentional bias. The results showed that neither group showed subliminal attentional biases. Further, heavy chewers, but not light chewers, exhibited supraliminal biases toward betel nut cues in initial orienting of attention and maintained attention. Moreover, attentional bias scores at 2,000 ms were also shown to be positively associated with betel nut craving and dependence. Implications of the current findings are thoroughly discussed in the article.

Association between betel nut consumption and folate deficiency among pregnant women in rural Bangladesh

Background: Betel nut (BN) or areca nut (AN) chewing habits on its own or with other ingredients including chewing tobacco are highly prevalent in many South East Asian countries as well as among the migrants from these countries residing around the world. The major alkaloid arecoline in the BN has been found to carcinogenic and to be associated with a range of health risks, including negative effects on pregnancy outcomes. Pregnancy imposes stress on folate stores because of increased requirements for growth of maternal tissues, fetus, and placenta. Folate deficiency during pregnancy is a major public health concern as is associated with many adverse health outcomes including neural tube defects, low birth weight, preterm birth, and delayed maturation of the nervous system, growth retardation, and megaloblastic anemia. Objective: To investigate any association between BN consumption and folate status among pregnant women in rural Bangladesh. Materials and Methods: Data of 730 pregnant women aged 14-50 years from the Maternal and Infant Nutrition Intervention in Matlab (MINIMat) trial in Bangladesh were included in this study. Logistic regression analysis and analyses of covariance (ANCOVA) were used. Results were adjusted for potential confounders. Results and Interpretation: Two-third (63%) of the women consumed BN and 17% had folate deficiency. The women who consumed BN combined with chewing tobacco were 2.57 times more likely to have folate deficiency (OR = 2.57; 95% CI = 1.23-5.36; P = 0.012;) and the women who consumed BN 2-3 times/day were 2.51 times more likely to develop folate deficiency among users (OR = 2.51; 95% CI = 1.07-5.92; P = 0.035). Mean serum folate levels were significantly lower among BN users as compared to nonusers. Conclusion: The results suggest that betel nut consumption combined with chewing tobacco is associated with lower serum folate level and folate deficiency among pregnant women in rural Bangladesh. Strategies are needed for prevention and control of betel nut consumption in order to prevent adverse health outcomes.

Salivary ascorbic acid levels in betel quid chewers: A biochemical study

Background:Quid chewing practice has been a part of our tradition since centuries with little known evidence of oral cancer. However, recent trends show a rise in occurrence of oral cancer often associated with tobacco and arecanut usage. Ascorbic acid is an important salivary antioxidant. Betel leaf which is used in quid is known to contain ascorbic acid.Aim:The aim of our study was to assess the salivary levels of ascorbic acid in traditional quid chewers so as to determine whether the betel leaf has protective antioxidant action.Materials and Methods:Salivary ascorbic acid levels of 60 subjects were estimated using the Dinitrophenyl hydrazine method.Results:The results revealed that quid chewers who used betel leaf had higher salivary ascorbic acid content compared to nonbetel leaf quid chewers. This could possibly be due to the protective antioxidants in the betel leaf.

Oral lichenoid contact lesions induced by areca nut and betel quid chewing: a mini review

Betel quid (BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian-migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature.

Is areca innocent? The effect of areca (betel) nut chewing in a population of pregnant women on the Thai–Myanmar border

Eight manuscripts have specifically examined the effects of areca (betel) nut use in pregnant women, seven of which have documented adverse effects on birth weight, newborn neurological status, gender ratio and pregnancy outcomes such as anaemia and miscarriage following areca nut use during pregnancy. A retrospective cohort analysis of migrant and refugee pregnant women attending antenatal clinics along the Thai–Myanmar border (July 1997 to November 2006) was conducted to examine the adverse effects of areca nut use routinely recorded on enrolment. Of 7685 women, 2284 (29.7%) never used areca or smoked (cheroots), 2484 (32.3%) only used areca, 438 (5.7%) only smoked cheroots and 2479 (32.3%) used both areca and cheroots. Pieces of ripe areca nut in a leaf with lime, without tobacco, were used particularly among older multigravid women. Adverse pregnancy effects were not observed in areca nut users compared with non-users. Smoking, but not areca nut use, had a dose-related effect on miscarriage. Areca nut use in conjunction with smoking reduced the adverse effects of smoking on birth weight, further supporting a lack of effect of areca nut. Areca (betel) nut-related adverse pregnancy outcomes were not observed in this population, whereas smoking was clearly harmful. Differences from previous reports may result from the amount or types of areca nut, or quid content, consumed between countries. Smoking, but not areca nut, reduction is likely to improve pregnancy outcomes on the Thai–Myanmar border.

Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature.

Background:Head and neck squamous cell carcinoma (HNSCC) is an important public health problem in India. Several risk factors such as tobacco, human papilloma virus, alcohol, areca nut usage have been extensively studied as causative agents. Though Areca nut chewing is known cause of oral cancer, its association with hypopharynx cancer has not been previously reported. Since areca nut is mostly consumed along with tobacco, it is uncommon to find patients who consume the areca nut alone.Materials and Methods:This is a prospective case series of ten women who presented to us with HNSCC with history of chewing of areca nut alone for several years. We have excluded all those cases where areca nut was consumed along with tobacco in any form. The data were prospectively collected with regard to clinical parameters, duration and frequency of areca nut usage, the socio-economic status and education level.Results:All ten females had varying degree of submucous fibrosis and coexisting squamous cell carcinoma either in the oral cavity or hypopharynx. Submucous fibrosis was characterized by burning mouth, unhealthy oral mucosa, buried third molars, trismus, poor oral hygiene, etc. The disease presented in an advanced stage in majority of the cases. All patients were unaware of areca nut's deleterious effects.Conclusion:Areca nut chewing is an important risk factor for HNSCC in females. Despite plethora of information, little importance is given to areca nut control in cancer prevention campaigns in India.

Areca nut chewing and systemic inflammation: evidence of a common pathway for systemic diseases

BackgroundAreca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing increases the risk of systemic diseases remains elusive. We hypothesize that systemic inflammation may be elevated among areca nut users, which is linked with many systemic diseases. Therefore, this present study was conducted to examine the systemic inflammation among areca nut chewers and healthy controls.MethodsThis was an observational cross sectional study carried out on areca nut chewers and healthy individuals in Karachi, Pakistan. Participants were selected from a region of the city by invitation request sent from door to door. Information was collected regarding the socio-demographic profile and the pattern of use, and a blood sample was obtained to measure the level of C-reactive protein (CRP). We carried out multiple logistic regressions to investigate the association between socio-demographic profile, areca nut chewing and CRP levels.ResultsWe carried out final analysis on 1112 individuals of which 556 were areca nut chewers and 556 were the age, gender and area matched controls. Areca nut chewers had a significantly higher proportion of men (15.1%, n = 84) who had an elevated CRP (>10 mg/dl) as compared to controls (5.2%, n = 29). Multivariate analyses showed that areca nut chewers had significantly higher odds of an elevated CRP (OR = 3.23, 95% CI 2.08-5.02, p value <0.001) as compared to controls. Increase in amount of areca nut consumption had a significant dose–response relationship with systemic inflammation (p for trend <0.001). Further analysis revealed that areca nut chewers with tobacco additives were two times more likely to have an elevated CRP as compared to raw areca nut users. These associations remained unchanged after adjustments for age, BMI and years of full time education.ConclusionsAreca nut chewing has a significant association with systemic inflammation. Further work is required to confirm that systemic inflammation is the main pathway by which areca nut use increases the risk of systemic diseases.