Systemic Health Effects of Areca Nuts with Particular Emphasis on Carcinogenesis – A Review

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Review Paper 01/01/2021
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Systemic Health Effects of Areca Nuts with Particular Emphasis on Carcinogenesis – A Review

Maryam Khan, Saba Shamim
Int. J. Biosci.18( 1), 113-127, January 2021.
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Abstract

Areca (betel) nut (Areca catechu) is regarded as one of the most addictive masticatory substances in the world, with approximately 600 million users globally. Extensively grown and found in India, China and Indonesia; areca nut is also native to many other countries of the South and Southeast Asia. Its usage and beneficial effects have been reviewed since centuries. The systemic effects associated with areca nut usage have been in the limelight for many years. This review provides a narrative insight to assess and collate published data that reports the harmful effects of areca nut. An electronic search amassed literature from the NCBI and Google Scholar databases with the help of keywords. Various studies on the correlation of areca nut and its effect on the oral health, metabolism and the incidence of cancer were selected. Its usage is reported to be associated with cancers of the oral cavity, esophagus, pharynx, liver and has been declared a human group 1 carcinogen by the International Agency for Research on Cancer (IARC). It is also associated with the incidence of cardiovascular disease and chronic kidney disease. Hence, there is a dire need to identify the role of areca nut as a causative agent of cancer and several other health disorders. Clinical evidence has indicated and proved that the use of areca nut causes several types of head and neck cancers, as to effects on intracellular levels of GSH, and on tumor suppressing gene P53 are quite evident clinical evidence has indicated and proved that the use of areca nut causes several types of head and neck cancers, as to effects on intracellular levels of GSH, and on tumor suppressing gene P53 are quite evident.

VIEWS 40

Arjungi KN. 1976. Areca nut: a review. Arzneimittelforschung 26(5), 951-956.

Bagchi M, Balmoori J, Bagchi D, Stohs SJ, Chakrabarti J, Das DK. 2002. Role of reactive oxygen species in the development of cytotoxicity with various forms of chewing tobacco and pan masala. Toxicology 179(3), 247-255. http://dx.doi.org/10.1016/S0300-483X(02)00357-8

Bhat SJS, Blank MD, Balster RL, Nichter M, Nichter M. 2010. Areca nut dependence among chewers in a South Indian community who do not also use tobacco. Addiction 105(7), 1303-1310. http://dx.doi.org/10.1111/j.1360-0443.2010.02952.x

Bhat SK, Sarpangala M, Ashwin D. 2017. Antilipidemic activity of arecanut, Areca catechu L.: A valuable herbal medicine. International Journal of Herbal Medicine 5(1), 35-38.

Chang YC, Tsai CH, Lai YL, Yu CC, Chi WY, Li JJ, Chang WW. 2014. Arecoline-induced my fibroblast trans differentiation from human buccal mucosal fibroblasts is mediated by ZEB1. Journal of Cellular and Molecular Medicine 18(4), 698-708. http://dx.doi.org/10.1111/jcmm.12219

Chatterjee A, Deb S. 1999. Genotoxic effect of arecoline given either by the peritoneal or oral route in murine bone marrow cells and the influence of N-acetylcysteine. Cancer Letters 139(1), 23-31. http://dx.doi.org/10.1016/S0304-3835(98)00364-4

Chen CH, Lu HI, Wang YM, Chen YH, Lo CM, Huang WT, Li SH. 2017. Areca nut is associated with younger age of diagnosis, poor chemoradiotherapy response, and shorter overall survival in esophageal squamous cell carcinoma. PLoS One 12(2), e0172752. http://dx.doi.org/10.1371/journal.pone.0172752

Chen CL, Chi CW, Liu TY. 2002. Hydroxl radical formation and oxidative DNA damage induced by areca quid in vivo. Journal of Toxicology and Environmental Health Part A 65(3-4), 327-336. http://dx.doi.org/10.1080/15287390252800909

Chen WY, Lee CY, Lin PY, Hsieh CE, Ko CJ, Lin KH, Lin CC, Ming YZ, Chen YL. 2017. Betel nut chewing is associated with reduced tacrolimus concentration in Taiwanese liver transplant recipients. Transplantation Proceedings 49(2), 326-329. http://dx.doi.org/10.1016/j.transproceed.2016.11.037

Chin CT, Lee KW. 1970. The effects of betel-nut chewing on the buccal mucosa of 296 Indians and Malays in West Malaysia. A clinical study. British Journal of Cancer 24(3), 427-432.

Chung CS, Lee YC, Wang CP, Ko JY, Wang WL, Wu MS, Wang HP. 2010. Secondary   prevention of esophageal squamous cell carcinoma in areas where smoking, alcohol, and betel quid chewing are prevalent. Journal of the Formosan Medical Association 109(6), 408-421. http://dx.doi.org/10.1016/S0929-6646(10)60072-1

Dave BJ, Trivedi AH, Adhvaryu SG. 1992. In vitro genotoxic effects of areca nut extract and arecoline. Journal of Cancer Research and Clinical Oncology 118(4), 283-288. https://dx.doi.org/10.1007/BF01208617

Deb S, Chatterjee A. 1998. Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced chromosomal damage and sister chromatid exchange in mouse bone marrow cells in vivo. Mutagenesis 13(3), 243-248. https://dx.doi.org/10.1093/mutage/13.3.243

Esposito K, Giugliano D. 2011. Obesity, the metabolic syndrome, and sexual dysfunction in men. Clinical Pharmacology and Therapeutics  90(1), 169-173. http://dx.doi.org/10.1038/clpt.2011.91

 Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. 1994. Impotence and its medical and psychosocial correlates: Results of the Massachusetts male aging study. Journal of Urology 151(1), 54-61. http://dx.doi.org/10.1016/s0022-5347(17)34871-1

Franke AA, Lai JF, Kawamoto CT, Pokhrel P, Herzog TA. 2014. University of Hawai’i Cancer Center connection: Areca (betel) nut consumption: An underappreciated cause of cancer. Hawaii J Med Public Health 73(12), 400-403.

Gupta PC, Warnakulasuriya S. 2002. Global epidemiology of areca nut usage. Addiction Biology 7(1), 77-83. http://dx.doi.org/10.1080/13556210020091437

Gupta S, Sm M, Jawanda MK, Bharti A. 2014. Quantification of plasma fibrinogen degradation products in areca nut chewers with and without oral submucous fibrosis. Journal of Clinical and Diagnostic Research 8(11), ZC27-ZC30. http://dx.doi.org/10.7860/JCDR/2014/9854.5123

Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, Paulino YC. 2017. Betel nut chewing, oral premalignant lesions, and the oral microbiome. PloS One 12(2), e0172196.  http://dx.doi.org/10.1371/journal.pone.0172196

Hosein M, Mohiuddin S, Fatima N. 2015. Association between grading of oral submucous fibrosis with frequency and consumption of areca nut and its derivatives in a wide age group: A multi-centric cross sectional study from Karachi, Pakistan. Journal of Cancer Prevention 20(3), 216-222. http://dx.doi.org/10.15430/JCP.2015.20.3.216

Hu JJ, Dubin N, Kurland D, Ma BL, Roush GC. 1995. The effects of hydrogen peroxide on DNA repair activities. Mutation Research 336(2), 193-201. http://dx.doi.org/10.1016/0921-8777(94)00054-a

Huang TC, Wu WT, Chen YC, Yang FM, Tsai WC, Lee CH. 2020. Betel-quid chewing, heart failure, and premature ventricular contractions in patients with cardiopulmonary symptoms. International Journal of Environmental Research and Public Health 17(20), 7472. http://dx.doi.org/10.3390/ijerph17207472

Huang YJ, Jiann BP. 2017. Association of areca nut chewing with risk of erectile dysfunction. Sexual Medicine 5(3), e163-e168. http://dx.doi.org/10.1016/j.esxm.2017.05.002

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. 2004. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. Monographs on the evaluation of carcinogenic risks. 85 IARC, Lyon, France 85, 1-334.

Illeperuma RP, Kim DK, Park YJ, Son HK, Kim JY, Kim J, Lee DY, Kim KY, Jung DW, Tilakaratne WM, Kim J. 2015. Areca nut exposure increases secretion of tumor-promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes. International Journal of Cancer 137(11), 2545-2557. http://dx.doi.org/10.1002/ijc.29636

Jaiswal P, Kumar P, Singh VK, Singh DK. 2011. Areca catechu L.: A valuable herbal medicine against different health problems. Research Journal of Medicinal Plant 5(2), 145-152. http://dx.doi.org/doi:10.3923/rjmp.2011.145.152

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. 2011. Global cancer statistics. CA: A Cancer Journal for Clinicians 61(2), 69-90. http://dx.doi.org/10.3322/caac.20107

Jeng JH, Hahn LJ, Lin BR, Hsieh CC, Chan CP, Chang MC. 1999. Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes. Journal of Oral Pathology and Medicine 28(2), 64-71. https://doi.org/10.1111/j.1600-0714.1999.tb01998.x

Karim MT, Inam S, Ashraf T, Shah N, Adil SO, Shafique K. 2018. Areca nut chewing and the risk of re-hospitalization and mortality among patients with acute coronary syndrome in Pakistan. Journal of Preventive Medicine and Public Health 51(2), 71-82. http://dx.doi.org/10.3961/jpmph.17.189

Khan I, Kumar N, Pant I, Narra S, Kondaiah P. 2012. Activation of TGF-β pathway by areca nut constituents: A possible cause of oral submucous fibrosis. PLoS One 7(12), e51806. http://dx.doi.org/10.1371/journal.pone.0051806

Khan I, Pant I, Narra S, Radhesh R, Ranganathan K, Rao SG, Kondaiah P. 2015. Epithelial atrophy in oral submucous fibrosis is mediated by copper (II) and arecoline of areca nut. Journal of Cellular and Molecular Medicine 19(10), 2397-2412. http://dx.doi.org/10.1111/jcmm.12622

Khan MS, Bawany FI, Ahmed MU, Hussain M, Khan A, Lashari MN. 2013. Betel nut usage is a major risk factor for coronary artery disease. Global Journal of Health Science 6(2), 189-195. http://dx.doi.org/10.5539/gjhs.v6n2p189

Khandelwal A, Khandelwal V, Saha MK, Khandelwal S, Prasad S, Saha SG. 2012. Prevalence of areca nut chewing in the middle school-going children of Indore, India. Contemporary Clinical Dentistry 3(2), 155-157. http://dx.doi.org/10.4103/0976-237X.96817

Krishnamurthy KH. 2008. Medicinal uses of arecanut and coconut. Pragun Publishers, New Delhi, in association with Arecanut Research and Development Foundation®, Varanashi Towers, Mission Street, Mangalore, Karnataka, India, p 61.

Kumpawat K, Deb S, Ray S, Chatterjee A. 2003. Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Mutation Research 538(1-2), 1-12. http://dx.doi.org/10.1016/s1383-5718(03)00048-2

Lee J, Gunawardhana ND, Jang S, Choi YH, Illeperuma RP, Kim A, Su H, Hong YA, Kim JH, Kim J, Jung DW, Cha IH, Bak EJ, Cha JH. 2016. Effect of areca nut on Helicobacter pylori-induced gastric diseases in mice. Journal of Microbiology and Biotechnology 26(10), 1817-1823. http://dx.doi.org/10.4014/jmb.1606.06043

Liaquat N, Jaffar AM, Haroon MZ, Khan MB, Habib H. 2016. Knowledge and perception of areca/smokeless tobacco users about oral cancer. Journal of Ayub Medical College Abbottabad 28(1), 164-167.

Lin CF, Shiau TJ, Ko YC, Chen PH, Wang JD. 2008. Prevalence and determinants of biochemical dysfunction of the liver in Atayal Aboriginal community of Taiwan: Is betel nut chewing a risk factor? BMC Gastroenterology 8(1), 13. http://dx.doi.org/10.1186/1471-230X-8-13

Lin CY, Young YH. 2017. Effect of betel nut chewing on the otolithic reflex system. Clinical Neurophysiology 128(1), 138-146. http://dx.doi.org/10.1016/j.clinph.2016.09.016

Lin MY, Chen MC, Wu IC, Wu DC, Cheng YJ, Wu CC, Chai CY, Lee JM, Wu MT. 2011. Areca users in combination with tobacco and alcohol use are associated with younger age of diagnosed esophageal cancer in Taiwanese men. PLoS One 6(10), e25347. http://dx.doi.org/10.1371/journal.pone.0025347

Lin WY, Pi-Sunyer FX, Liu CS, Li TC, Li CI, Huang CY, Lin CC. 2009. Betel nut chewing is strongly associated with general and central obesity in Chinese male middle-aged adults. Obesity (Silver Spring) 17(6), 1247-1254. http://dx.doi.org/10.1038/oby.2009.38

Ling HY, Wang G, Zhang W, Li X, Zhou SH, Hu B. 2012. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating K (ATP) channels. Acta Pharmacologica Sinica 33(8), 1023-1029. http://dx.doi.org/10.1038/aps.2012.63

Mathew P, Austin RD, Varghese SS, Manojkumar AD. 2015. Effect of copper-based fungicide (bordeaux mixture) spray on the total copper content of areca nut: Implications in increasing prevalence of oral submucous fibrosis. Journal of International Society of Preventive and Community Dentistry 5(4), 283-289. http://dx.doi.org/10.4103/2231-0762.161755

Mathew P, Austin RD, Varghese SS, Manojkumar. 2014. Estimation and comparison of copper content in raw areca nuts and commercial areca nut products: Implications in increasing prevalence of oral submucous fibrosis (OSMF). Journal of Clinical and Diagnostic Reserach 8(1), 247-249. http://dx.doi.org/10.7860/JCDR/2014/8042.3932

McClintock TR, Parvez F, Wu F, Wang W, Islam T, Ahmed A, Shaheen I, Sarwar G, Demmer RT, Desvarieux M, Ahsan H, Chen Y. 2014. Association between betel quid chewing and carotid intima-media thickness in rural Bangladesh. International Journal of Epidemiology 43(4), 1174-1182. http://dx.doi.org/10.1093/ije/dyu009

Mirza SS, Shafique K, Vart P, Arain MI. 2011. Areca nut chewing and dependency syndrome: is the dependence comparable to smoking? A cross sectional study. Substance, Abuse, Treatment, Prevention and Policy 6, 23. http://dx.doi.org/doi:10.1186/1747-597X-6-23

Murphy KL, Herzog TA. 2015. Sociocultural factors that affect chewing behaviors among betel nut chewers and ex-chewers on Guam. Hawaii Journal of Medicine & Public Health 74(12), 406-411.

Muttagi SS, Chaturvedi P, Gaikwad R, Singh B, Pawar P. 2012. Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature. Indian Journal of Medical and Paediatric Oncology 33(1), 32-35. http://dx.doi.org/10.4103/0971-5851.96966

Nevels RM, Gontkovsky ST, Williams BE. 2016. Paroxetine-The antidepressant from Hell? Probably not, but caution required. Psychopharmacology Bulletin 46(1), 77-104.

Oakley E, Demaine L, Warnakulasuriya S. 2005. Areca (betel) nut chewing habit among high-school children in the Commonwealth of the Northern Mariana Islands (Micronesia). Bulletin of the World Health Organization 83(9), 656-660. http://dx.doi.org//S0042-96862005000900010

Panigrahi GB, Rao AR. 1982. Chromosome-breaking ability of arecoline, a major betel-nut alkaloid, in mouse bone-marrow cells in vivo. Mutation Research Letters 103(2), 197-204. https://dx.doi.org/10.1016/0165-7992(82)90029-X

Paulino YC, Novotny R, Miller MJ, Murphy SP. 2011. Areca (Betel) Nut chewing practices in Micronesian populations. Hawaii Journal of Public Health 3(1), 19-29.

Peng W, Liu YJ, Wu N, Sun T, He XY, Gao YX, Wu CJ. 2015. Areca catechu L. (Arecaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Journal of Ethnopharmacology 164, 340-356. http://dx.doi.org/10.1016/j.jep.2015.02.010

Pero RW, Anderson MW, Doyle GA, Anna CH, Romagna F, Markowitz M, Bryngelsson C. 1990. Oxidative stress induces DNA damage and inhibits the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene in human peripheral mononuclear leukocytes. Cancer Research 50(15), 4619-4625.

Rahmatullah M, Mukti IJ, Haque AKMF, Mollik MAH, Parvin K, Jahan R, Chowdhury MH, Rahman T. 2009. An ethnobotanical survey and pharmacological evaluation of medicinal plants used by the Garo Tribal community living in Netrakona district, Bangladesh. Advances Natural and Applied Sciences 3(3), 402-418.

Rajalalitha P, Vali S. 2005. Molecular pathogenesis of oral submucous fibrosis – A collagen metabolic disorder. Journal of Oral Pathology and Medicine 34(6), 321-328. http://dx.doi.org/10.1111/j.1600-0714.2005.00325.x

Ray J, Ganguly M, Rao BHS, Mukherjee S, Mahato B, Chaudhuri K. 2013. Clinico-epidemiological profile of oral potentially malignant and malignant conditions among areca nut, tobacco and alcohol users in Eastern India: A hospital based study. Journal of Oral Maxillofacial Pathology 17(1), 45-50. http://dx.doi.org/10.4103/0973-029X.110720

Rehman A, Ali S, Lone MA, Atif M, Hassona Y, Prime SS, Pitiyage GN, James ELN, Parkinson EK. 2016. Areca nut alkaloids induce irreparable DNA damage and senescence in fibroblasts and may create a favourable environment for tumour progression. Journal of Oral Pathology and Medicine 45(5), 365-372. http://dx.doi.org/10.1111/jop.12370

Sazwi NN, Nalina T, Rahim ZHA. 2013. Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria gambir and betel quid with and without calcium hydroxide. BMC Complementary  and Alternative Medicine 13(351), 1-12. http://dx.doi.org/10.1186/1472-6882-13-351

Shafique K, Mirza SS, Vart P, Memon AR, Arain MI, Tareen MF, Haq ZU. 2012. Areca nut chewing and systemic inflammation: Evidence of a common pathway for systemic diseases. J Inflammation (London) 9(1), 22. http://dx.doi.org/10.1186/1476-9255-9-22

Shah G, Chaturvedi P, Vaishampayan S. 2012. Areca nut as an emerging etiology of oral cancers in India. Indian Journal of Medical and Paediatric Oncology 33(2), 71-79. http://dx.doi.org/10.4103/0971-5851.99726

Shamim S, Khan M. 2017. Phytochemical screening by high performance liquid chromatography (HPLC) and antimicrobial activity of different solvent fractions of areca nuts against Bacillus subtilis biofilm. International Research Journal of Pharmacy 8(10), 29-37. http://dx.doi.org/10.7897/2230-8407.0810178

Shan LM, Zhang JC, Zhao YL, Cui WY, Wang H. 2004. Molecular mechanisms for arecoline against atherosclerosis. Chinese Pharmacological Bulletin 20(2), 146-149.

Shirname LP, Menon MM, Bhide SV. 1984. Mutagenicity of betel quid and its ingredients using mammalian test systems. Carcinogenesis 5(4), 501-503. http://dx.doi.org/10.1093/carcin/5.4.501

Shivashankar S, Dhanaraj S, Mathew AG, Srinivasa Murthy S, Vyasamurthy MN, Govindarajan VS. 1969. Physical and chemical characteristics of processed arecanuts. Journal of Food Science and Technology 6(2), 113-116.

Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafström RC. 1989. Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Research 49(19), 5294-5298.

Trivedy C, Baldwin D, Warnakulasuriya S, Johnson N, Peters T. 1997. Copper content in Areca catechu (betel nut) products and oral submucous fibrosis. Lancet (London, England) 349(9063), 1447. http://dx.doi.org/10.1016/S0140-6736(97)24020-1

Trivedy C, Meghji S, Warnakulasuriya KA, Johnson NW, Harris M. 2001. Copper stimulates human oral fibroblasts in vitro: A role in the pathogenesis of oral submucous fibrosis. Journal of Oral Pathology and Medicine 30(8), 465-470. http://dx.doi.org/10.1034/j.16000714.2001.030008465.x

Trivedy C, Warnakulasuriya KA, Hazarey VK, Tavassoli M, Sommer P, Johnson NW. 1999. The upregulation of lysyl oxidase in oral submucous fibrosis and squamous cell carcinoma. Journal of Oral Pathology and Medicine 28(6), 246-251. http://dx.doi.org/10.1111/j.16000714.1999.tb02033.x

Tsai WC, Wu MT, Wang GJ, Lee KT, Lee CH, Lu YH, Yen HW, Chu CS, Chen YT, Lin TH, Su HM, Hsu PC, Cheng KH, Duh TH, Ko YC, Sheu SH, Lai WT. 2012. Chewing areca nut increases the risk of coronary artery disease in Taiwanese men: A case-control study. BMC Public Health 12, 162. http://dx.doi.org/10.1186/1471-2458-12-162

Wade WG. 2013. The oral microbiome in health and disease. Pharmacological Research 69(1), 137-143. http://dx.doi.org/10.1016/j.phrs.2012.11.006.

Wang M, Yu SY, Lv Z, Yao Y. 2018. Betel nut chewing and the risk of chronic kidney disease: Evidence from a meta-analysis. International Urology and Nephrology 50(6), 1097-1104. http://dx.doi.org/10.1007/s11255-018-1819-8

Williams S, Malik A, Chowdhury S, Chauhan S. 2002. Sociocultural aspects of areca nut use. Addiction Biology 7(1), 147-154. http://dx.doi.org/10.1080/135562101200100147

Wu IC, Wu CC, Lu CY, Hsu WH, Wu MC, Lee JY, Chou SH, Lee JM, Chou YP, Wu DC, Wu MT. 2013. Substance use (alcohol, areca nut and cigarette) is associated with poor prognosis of esophageal squamous cell carcinoma. PLoS One 8(2), e55834. http://dx.doi.org/10.1371/journal.pone.0055834

Xiong X, Hou A, Yi S, Guo Y, Zhao Z, Wu Z, Cheng H, Li K, Li Z, Ren Y, Wang Y. 2018. Analysis of oral microrganism diversity in healthy individuals before and after chewing areca nuts using PCR-denatured gradient gel electrophoresis. Animal Nutrition 4(3), 294-299. http://dx.doi.org/10.1016/j.aninu.2018.07.001

Yamada T, Hara K, Kadowaki T. 2013. Chewing betel quid and the risk of metabolic disease, cardiovascular disease, and all-cause mortality: A meta-analysis. PLoS One 8(8), e70679. http://dx.doi.org/10.1371/journal.pone.0070679

Yongxiu D, Dongye S, Xinchun J, Qiuhua M, Yanan C, Pu X. 2016. Epidemiological investigation of chewing fresh or dried betel nut and oral mucosal disease. Hua Xi Kou Qiang Yi Xue Za Zhi 34(4), 391-394. http://dx.doi.org/10.7518/hxkq.2016.04.014