A Study of Artificial Sweeteners and Thyroid Cancer Risk

Navdeep Singh

Sandeep Lubana

Saurabh Arora

Issac Sachmechi

Background

In recent decades, data from certain observational studies have stirred controversy over artificial sweeteners by linking them with certain malignancies. As the incidences of artificial sweetener consumption and thyroid cancer are both increasing, our study aimed to determine any possible association between them.

Methods

This retrospective observational study enrolled 50 patients (group 1) with proven diagnosis of well-differentiated thyroid cancer (WDTC) and 50 control subjects (group 2) diagnosed as having benign thyroid nodule by fine-needle aspiration. The survey questionnaire included the total amount and duration of intake of artificial sweeteners.

Results

Increased consumption of artificial sweeteners was noted in group 1 as compared to group 2, which was statistically significant (76% vs. 24%, P < 0.01). This study suggested that the use of an average of four packets (4 g) per day of artificial sweetener for an average duration of 5 years is associated with WDTC.

Conclusions

Our study emphasizes the significance of artificial sweetener consumption as a potential risk factor for WDTC and increase in public awareness regarding this association if other studies in future report similar findings.

^{Department of Internal Medicine, North Shore University Hospital, Manhasset, NY 11030, USA}

^{Department of Hematology/Oncology, State University of New York (SUNY) Downstate Medical School, 450 Clarkson Ave., Brooklyn, NY 11203, USA}

^{Department of Endocrinology, Dayanand Medical College and Hospital, Tagore Nagar, Ludhiana, Punjab 141001, India}

^{Department of Endocrinology, Icahn School of Medicine at Mount Sinai/Queens Hospital Center, 82-68 164th St., Jamaica, NY 11432, USA}

^{Corresponding Author: Navdeep Singh, Department of Internal Medicine, North Shore University Hospital, 300 Community Dr., Manhasset, NY 11030, USA. Email:}moc.liamg@hgnisdemi

Received 2020 Jun 8; Accepted 2020 Jun 17.

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Methods

Results

Conclusions

Keywords: Artificial sweeteners, Well-differentiated thyroid cancer, Benign thyroid nodule

Abstract

Acknowledgments

We appreciate the support of the Kozuki Foundation for Sports.

Acknowledgments

References

1. Bright GLow-calorie sweeteners - from molecules to mass markets. World Rev Nutr Diet. 1999;85:3–9. doi: 10.1159/000059697.] [[PubMed][Google Scholar]
2. Weihrauch MR, Diehl VArtificial sweeteners - do they bear a carcinogenic risk? Ann Oncol. 2004;15(10):1460–1465. doi: 10.1093/annonc/mdh256.] [[PubMed][Google Scholar]
3. Helgren FJ, Lynch MJ, Kirchmeyer FJA taste panel study of the saccharin off-taste. J Am Pharm Assoc Am Pharm Assoc. 1955;44(6):353–355. doi: 10.1002/jps.3030440613.] [[PubMed][Google Scholar]
4. Moskowitz HR, Klarman LThe tastes of artificial sweeteners and their mixtures. Chem Senses Flav. 1975;1:411–421. doi: 10.1093/chemse/1.4.411.[PubMed][Google Scholar]
5. Sylvetsky AC, Welsh JA, Brown RJ, Vos MBLow-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012;96(3):640–646. doi: 10.3945/ajcn.112.034751.] [[Google Scholar]
6. Lindley MGNew developments in low-calorie sweeteners. World Rev Nutr Diet. 1999;85:44–51. doi: 10.1159/000059701.] [[PubMed][Google Scholar]
7. Morrison AS, Buring JEArtificial sweeteners and cancer of the lower urinary tract. N Engl J Med. 1980;302(10):537–541. doi: 10.1056/NEJM198003063021001.] [[PubMed][Google Scholar]
8. Sturgeon SR, Hartge P, Silverman DT, Kantor AF, Linehan WM, Lynch C, Hoover RNAssociations between bladder cancer risk factors and tumor stage and grade at diagnosis. Epidemiology. 1994;5(2):218–225. doi: 10.1097/00001648-199403000-00012.] [[PubMed][Google Scholar]
9. Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, Campbell D. et al. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev. 2006;15(9):1654–1659. doi: 10.1158/1055-9965.EPI-06-0203.] [[PubMed]
10. Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich DConsumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr. 2012;96(6):1419–1428. doi: 10.3945/ajcn.111.030833.] [[Google Scholar]
11. Chen AY, Jemal A, Ward EMIncreasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer. 2009;115(16):3801–3807. doi: 10.1002/cncr.24416.] [[PubMed][Google Scholar]
12. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl Jet al. SEER Cancer Statistics Review, 1975-2017, National Cancer Institute. Bethesda, MD. , based on November 2019 SEER data submission, posted to the SEER web site, April 2020.
13. Haugen BR2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed? Cancer. 2017;123(3):372–381. doi: 10.1002/cncr.30360.] [[PubMed][Google Scholar]
14. U.S. Food & Drug Administration. May 19, 2014. Additional information about high-intensity sweeteners permitted for use in food in the United States. .[PubMed]
15. Franz MDiet soft drinks: how safe are they? Diabetes Self Manag. 2010;27(2):8, 11–13.[PubMed][Google Scholar]
16. Cohen SM, Anderson TA, de Oliveira LM, Arnold LLTumorigenicity of sodium ascorbate in male rats. Cancer Res. 1998;58(12):2557–2561.[PubMed][Google Scholar]
17. Species differences in thyroid, kidney and urinary bladder carcinogenesis. Proceedings of a consensus conference. Lyon, France, 3-7 November 1997. IARC Sci Publ. 1999;147:1–225.[PubMed]
18. Wagner MWCyclamate acceptance. Science. 1970;168(3939):1605. doi: 10.1126/science.168.3939.1605.] [[PubMed][Google Scholar]
19. Price JM, Biava CG, Oser BL, Vogin EE, Steinfeld J, Ley HLBladder tumors in rats fed cyclohexylamine or high doses of a mixture of cyclamate and saccharin. Science. 1970;167(3921):1131–1132. doi: 10.1126/science.167.3921.1131.] [[PubMed][Google Scholar]
20. Renwick AGThe metabolism of intense sweeteners. Xenobiotica. 1986;16(10-11):1057–1071. doi: 10.3109/00498258609038983.] [[PubMed][Google Scholar]
21. Bopp BA, Sonders RC, Kesterson JWToxicological aspects of cyclamate and cyclohexylamine. Crit Rev Toxicol. 1986;16(3):213–306. doi: 10.3109/10408448609037465.] [[PubMed][Google Scholar]
22. Roberts A, Renwick AGThe pharmacokinetics and tissue concentrations of cyclohexylamine in rats and mice. Toxicol Appl Pharmacol. 1989;98(2):230–242. doi: 10.1016/0041-008X(89)90228-7.] [[PubMed][Google Scholar]
23. Whysner J, Williams GMSaccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion. Pharmacol Ther. 1996;71(1-2):225–252. doi: 10.1016/0163-7258(96)00069-1.] [[PubMed][Google Scholar]
24. Takayama S, Renwick AG, Johansson SL, Thorgeirsson UP, Tsutsumi M, Dalgard DW, Sieber SMLong-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. Toxicol Sci. 2000;53(1):33–39. doi: 10.1093/toxsci/53.1.33.] [[PubMed][Google Scholar]
25. Takayama S, Sieber SM, Adamson RH, Thorgeirsson UP, Dalgard DW, Arnold LL, Cano M. et al. Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. J Natl Cancer Inst. 1998;90(1):19–25. doi: 10.1093/jnci/90.1.19.] [[PubMed]
26. Olney JW, Farber NB, Spitznagel E, Robins LNIncreasing brain tumor rates: is there a link to aspartame? J Neuropathol Exp Neurol. 1996;55(11):1115–1123. doi: 10.1097/00005072-199611000-00002.] [[PubMed][Google Scholar]
27. Shephard SE, Wakabayashi K, Nagao MMutagenic activity of peptides and the artificial sweetener aspartame after nitrosation. Food Chem Toxicol. 1993;31(5):323–329. doi: 10.1016/0278-6915(93)90186-3.] [[PubMed][Google Scholar]
28. Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin SAspartame consumption in relation to childhood brain tumor risk: results from a case-control study. J Natl Cancer Inst. 1997;89(14):1072–1074. doi: 10.1093/jnci/89.14.1072.] [[PubMed][Google Scholar]
29. Palkowska-Gozdzik E, Bigos A, Rosolowska-Huszcz DType of sweet flavour carrier affects thyroid axis activity in male rats. Eur J Nutr. 2018;57(2):773–782. doi: 10.1007/s00394-016-1367-x.] [[Google Scholar]
30. Patel KG, Bhatt HV, Choudhury ARAlteration in thyroid after formaldehyde (HCHO) treatment in rats. Ind Health. 2003;41(3):295–297. doi: 10.2486/indhealth.41.295.] [[PubMed][Google Scholar]
31. Sachmechi I, Khalid A, Awan SI, Malik ZR, Sharifzadeh MAutoimmune Thyroiditis with Hypothyroidism Induced by Sugar Substitutes. Cureus. 2018;10(9):e3268. doi: 10.7759/cureus.3268.] [[Google Scholar]
32. Mori K, Nakagawa Y, Ozaki HDoes the gut microbiota trigger Hashimoto's thyroiditis? Discov Med. 2012;14(78):321–326.[PubMed][Google Scholar]
33. Schiffman SS, Rother KISucralose, a synthetic organochlorine sweetener: overview of biological issues. J Toxicol Environ Health B Crit Rev. 2013;16(7):399–451. doi: 10.1080/10937404.2013.842523.] [[Google Scholar]
34. Zeng F, Lerro C, Lavoue J, Huang H, Siemiatycki J, Zhao N, Ma S. et al. Occupational exposure to pesticides and other biocides and risk of thyroid cancer. Occup Environ Med. 2017;74(7):502–510. doi: 10.1136/oemed-2016-103931.] [