“EXPLORING THE CONTROVERSIAL LINK BETWEEN ARTIFICIAL SWEETENERS AND CANCER RISK: A NARRATIVE REVIEW”

Main Article Content

Dr. Hafsa Niazi
Dr. Nadia Nahal
Dr. Huzaira Zainab
Dr. Tehniat Bashir
Dr. Syed Hassnain Zafar Bukhari
Dr. Aousaf Ahmed

Keywords

Aspartame, carcinogen, genotoxicity, artificial sweetener, intake, safe use

Abstract

Aspartame is a widely consumed non-sugar sweetening agent used in more than ninety different countries. It is a methoxycarbonyl of apeptidyl of aspartic acid and phenylalanine. It is many times more saccharine than sugar but has very less calories therefore it is widely used in diet or zero-sugar food products. When metabolized in our body it is broken down into diketopiperazine, aspartyl phenylalanine, and phenylalanine. It is a frequently used and studied synthetic sweetening agent. However, there is a controversy related to its possible carcinogenic effect. Some studies have shown it to have some genotoxic and carcinogenic effects. But others have shown no genotoxic or carcinogenic effects of aspartame when ingested. The possible carcinogenic effect of aspartame is controversial for a long time. As aspartame is widely used in daily use dietary products, finding out whether it is safe for human consumption is extremely important. This literature review/study’s sole objective is to know about aspartame’s possible carcinogenic roles. The search engine used to find articles related to the possible carcinogenic effects of aspartame is PubMed. The keywords used for searching the articles are; aspartame, carcinogenesis, metabolism of aspartame in humans, aspartame as a carcinogen, genotoxicity, genotoxicity induced by aspartame, and artificial sweeteners. The articles are further filtered by the timeline (articles from 2013 – 2023 only). Articles from only the past 10 years are included, which consist of systemic reviews, meta-analyses, research articles, and literature reviews. 27 articles are studied.

Abstract 216 | PDF Downloads 64

References

1. Haighton L, Roberts A, Walters B, Lynch B. Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria. Vol. 103, Regulatory Toxicology and Pharmacology. Academic Press Inc.; 2019. p. 332–44.
2. Vasconcelos MA, Orsolin PC, Silva-Oliveira RG, Nepomuceno JC, Spanó MA. Assessment of the carcinogenic potential of high intense-sweeteners through the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster. Food and Chemical Toxicology. 2017 Mar 1;101:1–7.
3. Chung YS, Lee M. Genotoxicity assessment of erythritol by using short-term assay. Toxicol Res. 2013;29(4):249–55.
4. Food and Drug Administration and others. Aspartame: Commissioner’s final decision. Fed Regist. 1981;46:38285–308.
5. Yılmaz S, Uçar A. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not? Vol. 66, Cytotechnology. Kluwer Academic Publishers; 2014. p. 875–81.
6. Yılmaz S, Uçar A. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not? Vol. 66, Cytotechnology. Kluwer Academic Publishers; 2014. p. 875–81.
7. Czarnecka K, Pilarz A, Rogut A, Maj P, Szymańska J, Olejnik Ł, et al. Aspartame—true or false? Narrative review of safety analysis of general use in products. Vol. 13, Nutrients. MDPI AG; 2021.
8. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernández-López JA, et al. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci. 1998 Jun;63(5):337–49.
9. Choudhary AK, Lee YY. The debate over neurotransmitter interaction in aspartame usage. Journal of Clinical Neuroscience. 2018 Oct;56:7–15.
10. Bandyopadhyay A, Ghoshal S, Mukherjee A. Genotoxicity Testing of Low-Calorie Sweeteners: Aspartame, Acesulfame-K, and Saccharin. Drug ChemToxicol. 2008 Jan 3;31(4):447–57.
11. Lea IA, Chappell GA, Wikoff DS. Overall lack of genotoxic activity among five common low- and no-calorie sweeteners: A contemporary review of the collective evidence. Vols. 868–869, Mutation Research - Genetic Toxicology and Environmental Mutagenesis. Elsevier B.V.; 2021.
12. Landrigan PJ, Straif K. Aspartame and cancer – new evidence for causation. Vol. 20, Environmental Health: A Global Access Science Source. BioMed Central Ltd; 2021.
13. pmc_4781641.
14. Kavet R, Nauss KM. The Toxicity of Inhaled Methanol Vapors.
15. Davoli E, Cappellini L, Airoldi L, Fanelli R. SERUM METHANOL CONCENTRATIONS IN RATS AND IN MEN AFTER A SINGLE DOSE OF ASPARTAME. Vol. 24, Fd Chem. Toxic. 1986.
16. Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. American Journal of Clinical Nutrition. 2012 Dec 1;96(6):1419–28.
17. Pandurangan M, Enkhtaivan G, Mistry B, Chandrasekaran M, Noorzai R, Kim DH. Investigation of role of aspartame on apoptosis process in HeLa cells. Saudi J Biol Sci. 2016 Jul 1;23(4):503–6.
18. KATALIN GOMBOS1 TVZOÉPJPZVGNATGM and IE. The Effect of Aspartame Administration on Oncogene and Suppressor Gene Expressions. 2007 Jan;21(1):89–92.
19. Soffritti M, Belpoggi F, DegliEsposti D, Lambertini L, Tibaldi E, Rigano A. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect. 2006 Mar;114(3):379–85.
20. Alkafafy MES, Ibrahim ZS, Ahmed MM, El-Shazly SA. Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach. Int J ImmunopatholPharmacol. 2015 Jan 1;28(2):247–55.
21. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan;66(1):7–30.
22. Bosetti C, Gallus S, Talamini R, Montella M, Franceschi S, Negri E, et al. Artificial sweeteners and the risk of gastric, pancreatic, and endometrial cancers in Italy. Cancer Epidemiology Biomarkers and Prevention. 2009 Aug;18(8):2235–8.
23. McCullough ML, Teras LR, Shah R, Diver WR, Gaudet MM, Gapstur SM. Artificially and sugar-sweetened carbonated beverage consumption is not associated with risk of lymphoid neoplasms in older men and women. Journal of Nutrition. 2014;144(12):2041–9.
24. Okasha E. Effect of long term-administration of aspartame on the ultrastructure of sciatic nerve. J MicroscUltrastruct. 2016;4(4):175.
25. Czarnecka K, Pilarz A, Rogut A, Maj P, Szymańska J, Olejnik Ł, et al. Aspartame—true or false? Narrative review of safety analysis of general use in products. Vol. 13, Nutrients. MDPI AG; 2021.
26. Rencüzoǧullari E, Tüylü BA, Topaktaş M, Ila HB, Kayraldiz A, Arslan M, et al. Genotoxicity of aspartame. Drug ChemToxicol. 2004;27(3):257–68.
27. Demir E, Turna F, Aksakal S, Kaya B, Marcos R. Genotoxicity of different sweeteners in Drosophila. Fresenius Environ Bull. 2014 Jul;23:3426–32.
28. Kirkland D, Gatehouse D. “Aspartame: A review of genotoxicity data.” Vol. 84, Food and Chemical Toxicology. Elsevier Ltd; 2015. p. 161–8.
29. Marinovich M, Galli CL, Bosetti C, Gallus S, La Vecchia C. Aspartame, low-calorie sweeteners and disease: Regulatory safety and epidemiological issues. Vol. 60, Food and Chemical Toxicology. 2013. p. 109–15.
30. Soffritti M, Padovani M, Tibaldi E, Falcioni L, Manservisi F, Belpoggi F. The Carcinogenic Effects of Aspartame: The Urgent Need for Regulatory Re-Evaluation.
31. Horio Y, Sun Y, Liu C, Saito T, Kurasaki M. Aspartame-induced apoptosis in PC12 cells. Environ ToxicolPharmacol. 2014 Jan;37(1):158–65.
32. Borghoff SJ, Cohen SS, Jiang X, Lea IA, Klaren WD, Chappell GA, et al. Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame. Vol. 172, Food and Chemical Toxicology. Elsevier Ltd; 2023.