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Associations of saccharin intake with all-cause, cardiovascular and cancer mortality risk in USA adults

Published online by Cambridge University Press:  04 November 2024

Ya Gao ,
Li Yin ,
Yuntao Zhang ,
Xianzhi Li  and
Lin Liu Open the ORCID record for Lin Liu [Opens in a new window]
Ya Gao
Affiliation:
Department of Clinical Pharmacy, The First People’s Hospital of Xianyang, Shaanxi, 712000, People’s Republic of China
Li Yin
Affiliation:
Meteorological Medical Research Center, Panzhihua Central Hospital, Panzhihua, People’s Republic of China Clinical Medical Research Center, Panzhihua Central Hospital, Panzhihua, People’s Republic of China
Yuntao Zhang
Affiliation:
MED-X institute, Center for Immunological and Metabolic Diseases (CIMD), The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
Xianzhi Li*
Affiliation:
Meteorological Medical Research Center, Panzhihua Central Hospital, Panzhihua, People’s Republic of China Clinical Medical Research Center, Panzhihua Central Hospital, Panzhihua, People’s Republic of China
Lin Liu*
Affiliation:
Zhejiang Provincial Center for Cardiovascular Disease Control and Prevention, Zhejiang Hospital, Hangzhou, People’s Republic of China
*
*Corresponding authors: Xianzhi Li, email [email protected]; Lin Liu, email [email protected]
*Corresponding authors: Xianzhi Li, email [email protected]; Lin Liu, email [email protected]
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Abstract

Saccharin is a widely used sugar substitute, but little is known about the long-term health effects of saccharin intake. Our study aimed to examine the association between saccharin intake and mortality in diabetic and pre-diabetic population and overweight population from NHANES 1988–1994. Cox proportional hazard models were used to evaluate the association between saccharin intake and CVD, cancer and all-cause mortality. After multivariable adjustment, increased absolute saccharin intake was associated with the risk of all-cause mortality (hazard ratio (HR): 1·41, 95 % CI: 1·05, 1·90), CVD mortality (HR: 1·93, 95 % CI: 1·15, 3·25) and cancer mortality (HR: 2·26, 95 % CI: 1·10, 4·45) in diabetic and pre-diabetic population. Among overweight population, higher absolute saccharin intake was associated with the risk of cancer mortality (HR: 7·369, 95 % CI: 2·122, 25·592). Replacing absolute saccharin intake with total sugar significantly reduced all-cause mortality by 12·5 % and CVD mortality by 49·7 % in an equivalent substitution analysis in the diabetic and pre-diabetic population. Aspartame substitution reduced all-cause mortality by 29·2 % and cancer mortality by 30·2 %. Notably, the relative daily intake of saccharin also had similar effects as the absolute intake on all-cause, cardiovascular and cancer mortality in all analyses. This was despite the fact that the relative daily intake in our study was below the Food and Drug Administration limit of 15 mg/kg. In conclusion, our study showed a considerable risk of increased saccharin intake on the all-cause, CVD mortality and cancer mortality.

Keywords

CancerCVDDiabetic and pre-diabetic populationMortalityOverweightSaccharin intake
Type
Research Article
Information
British Journal of Nutrition , Volume 132 , Issue 9 , 14 November 2024 , pp. 1205 - 1213
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

†

These authors contributed equally to this work.

References

Byard, JL & Goldberg, L (1973) The metabolism of saccharin in laboratory animals. Food Cosmet Toxicol 11, 391–402.CrossRefGoogle ScholarPubMed
Bowman, SA, Friday, JE & Moshfegh, A (2008) MyPyramid Equivalents Database, 2.0, for USDA Survey Foods, 2003–2004. Beltsville, MD: Food Surveys Research Group, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture.Google Scholar
Ionescu, E, Rohner-Jeanrenaud, F, Proietto, J, et al. (1988) Taste-induced changes in plasma insulin and glucose turnover in lean and genetically obese rats. Diabetes 37, 773–779.CrossRefGoogle ScholarPubMed
Suez, J, Korem, T, Zeevi, D, et al. (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186.CrossRefGoogle ScholarPubMed
Whitehouse, CR, Boullata, J & McCauley, LA (2008) The potential toxicity of artificial sweeteners. AAOHN J 56, 251–259.CrossRefGoogle ScholarPubMed
Cooper, PL, Wahlqvist, ML & Simpson, RW (2010) Sucrose v. saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects. Diabetic Med 5, 676–680.CrossRefGoogle Scholar
Serrano, J, Smith, KR, Crouch, AL, et al. (2021) High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome 9, 11.CrossRefGoogle ScholarPubMed
Horwitz, DL, McLane, M & Kobe, P (1988) Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care 11, 230–234.CrossRefGoogle ScholarPubMed
Whysner, J & Williams, GM (1996) Saccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion. Pharmacol Ther 71, 225–252.CrossRefGoogle ScholarPubMed
Arnold, DL (1984) Toxicology of saccharin. Fundam Appl Toxicol Offic J Soc Toxicol 4, 674–685.Google ScholarPubMed
Wang, Y, Xu, Z-L, Xie, Y-Y, et al. (2011) Development of polyclonal antibody-based indirect competitive enzyme-linked immunosorbent assay for sodium saccharin residue in food samples. Food Chem 126, 815–820.CrossRefGoogle Scholar
IDA (2019) IDF Diabetes Atlas. Available at https://www.diabetesatlas.org/en/ (accessed December 2021).Google Scholar
Tabák, AG, Herder, C, Rathmann, W, et al. (2012) Prediabetes: a high-risk state for diabetes development. Lancet 379, 2279–2290.CrossRefGoogle ScholarPubMed
Palmer, JR, Boggs, DA, Krishnan, S, et al. (2008) Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Arch Intern Med 168, 1487–1492.CrossRefGoogle ScholarPubMed
Malik, VS, Popkin, BM, Bray, GA, et al. (2010) Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 121, 1356–1364.CrossRefGoogle ScholarPubMed
Vos, MB & Lavine, JE (2013) Dietary fructose in nonalcoholic fatty liver disease. Hepatology 57, 2525–2531.CrossRefGoogle ScholarPubMed
Malik, VS, Pan, A, Willett, WC, et al. (2013) Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Am J Clin Nutr 98, 1084–1102.CrossRefGoogle ScholarPubMed
U.S. Department of Health and Human Services and U.S. Department of Agriculture (2015) 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. https://health.gov/our-work/food-nutrition/previous-dietary-guidelines/2015 (accessed March 2022).Google Scholar
World Health Organization (2015) Guidelines for Sugar Intake in Adults and Children 2015. ––https://www.who.int/news/item/04–03–2015-who-calls-on-countries-to-reduce-sugars-intake-among-adults-and-children (accessed March 2022).Google Scholar
Centers for Disease Control and Prevention (CDC) & National Center for Health Statistics (NCHS) (1997) National Health and Nutrition Examination Survey NHANES Questionnaires, Datasets, and Related Documentation. https://wwwn.cdc.gov/nchs/nhanes/Default.aspx (accessed May 2022).Google Scholar
American Diabetes Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1), S67–S74.CrossRefGoogle Scholar
National Center for Health Statistics (2019) Public Use Linked Mortality File. Atlanta, GA: Centers for Disease Control and Prevention. https://ftpcdcgov/pub/Health_Statistics/NCHS/datalinkage/linked_mortality/ (accessed July 2021).Google Scholar
Administration FaD (2023) Aspartame and Other Sweeteners in Food. https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states (accessed July 2023).Google Scholar
Agullo, V, Dominguez-Perles, R, Moreno, DA, et al. (2020) Alternative sweeteners modify the urinary excretion of flavanones metabolites ingested through a new maqui-berry beverage. Foods 9, 41.CrossRefGoogle ScholarPubMed
Huentupil, Y, Pena, L, Novoa, N, et al. (2019) New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases. J Enzyme Inhib Med Chem 34, 451–458.CrossRefGoogle ScholarPubMed
Mazarati, A, Siddarth, P, Baldwin, RA, et al. (2008) Depression after status epilepticus: behavioural and biochemical deficits and effects of fluoxetine. Brain 131, 2071–2083.CrossRefGoogle ScholarPubMed
Higgins, KA & Mattes, RD. (2019) A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity. Am J Clin Nutr 109, 1288–1301.CrossRefGoogle ScholarPubMed
Malek, AM, Hunt, KJ, DellaValle, DM, et al. (2018) Reported consumption of low-calorie sweetener in foods, beverages, and food and beverage additions by US Adults: NHANES 2007–2012. Curr Dev Nutr 2, nzy054.CrossRefGoogle Scholar
Hasan, HM, Alkass, SY & de Oliveira, DSP (2023) Impact of long-term cyclamate and saccharin consumption on biochemical parameters in healthy individuals and type 2 diabetes mellitus patients. Medicina (Kaunas) 59, 698.CrossRefGoogle ScholarPubMed
Bayindir Gumus, A, Keser, A, Tuncer, E, et al. (2022) Effect of saccharin, a non-nutritive sweeteners, on insulin and blood glucose levels in healthy young men: a crossover trial. Diabetes Metab Syndr 16, 102500.CrossRefGoogle Scholar
Hinkle, SN, Rawal, S, Bjerregaard, AA, et al. (2019) A prospective study of artificially sweetened beverage intake and cardiometabolic health among women at high risk. Am J Clin Nutr 110, 221–232.CrossRefGoogle ScholarPubMed
Jang, HJ, Kokrashvili, Z, Theodorakis, MJ, et al. (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104, 15069–15074.CrossRefGoogle ScholarPubMed
Suez, J, Cohen, Y, Valdes-Mas, R, et al. (2022) Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 185, 3307–3328. e19.CrossRefGoogle ScholarPubMed
Saccharin and Bladder Cancer. (1980) Lancet (London, England) 1, 855–856.Google Scholar
Weihrauch, MR & Diehl, V (2004) Artificial sweeteners--do they bear a carcinogenic risk? Ann Oncol 15, 1460–1465.CrossRefGoogle Scholar
Fulgoni, VL & Drewnowski, A (2022) No association between Low-Calorie Sweetener (LCS) use and overall cancer risk in the nationally representative database in the US: analyses of NHANES 1988–2018 Data and 2019 public-use linked mortality files. Nutrients 14, 4957.CrossRefGoogle ScholarPubMed
Pearson-Stuttard, J, Bennett, J, Cheng, YJ, et al. (2021) Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care records. Lancet Diabetes Endocrinol 9, 165–173.CrossRefGoogle ScholarPubMed
Ling, S, Brown, K, Miksza, JK, et al. (2020) Association of type 2 diabetes with cancer: a meta-analysis with bias analysis for unmeasured confounding in 151 cohorts comprising 32 million people. Diabetes Care 43, 2313–2322.CrossRefGoogle Scholar
Pearson-Stuttard, J, Papadimitriou, N, Markozannes, G, et al. (2021) Type 2 diabetes and cancer: an umbrella review of observational and Mendelian randomization studies. Cancer Epidemiol Biomarkers Prev 30, 1218–1228.CrossRefGoogle ScholarPubMed
Giovannucci, E, Harlan, DM, Archer, MC, et al. (2010) Diabetes and cancer. Diabetes Care 33, 1674–1685.CrossRefGoogle ScholarPubMed
Lega, IC & Lipscombe, LL (2020) Review: diabetes, obesity, and cancer-pathophysiology and clinical implications. Endocr Rev 41, 33–52.CrossRefGoogle ScholarPubMed
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