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Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study

Debras, Charlotte, Chazelas, Eloi, Srour, Bernard, Druesne-Pecollo, Nathalie, Esseddik, Younes, Szabo de Edelenyi, Fabien, Agaësse, Cédric, De Sa, Alexandre, Lutchia, Rebecca, Gigandet, Stéphane, Huybrechts, Inge, Julia, Chantal, Kesse-Guyot, Emmanuelle, Allès, Benjamin, Andreeva, Valentina A., Galan, Pilar, Hercberg, Serge, Deschasaux-Tanguy, Mélanie, Touvier, Mathilde·2022·PLOS Medicine
DOI 10.1371/journal.pmed.1003950PMC PMC8946744
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Abstract

Background: The food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site). Methods and findings: Overall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009–2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer ( n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P -trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer ( n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers ( n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns. Conclusions: In this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally. Trial registration: ClinicalTrials.gov NCT03335644 .

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Metadata

Authors
Debras, C., Chazelas, E., Srour, B., Druesne-Pecollo, N., Esseddik, Y., Szabo de Edelenyi, F., Agaësse, C., De Sa, A., Lutchia, R., Gigandet, S., Huybrechts, I., Julia, C., Kesse-Guyot, E., Allès, B., Andreeva, V. A., Galan, P., Hercberg, S., Deschasaux-Tanguy, M., & Touvier, M.
ORCID
Venue
PLOS Medicine
Publisher
Public Library of Science (PLoS)
Published
2022-03-24
Volume
19
Issue
3
Pages
e1003950
ISSN
1549-1676
DOI
10.1371/journal.pmed.1003950
PMC
PMC8946744
Cited by
333
References
11
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Ministère de la Santé
  • Santé Publique France
  • Institut National de la Santé et de la Recherche Médicale
  • Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
  • Conservatoire National des Arts et Métiers (CNAM) and Université Sorbonne Paris Nord
  • Institut National Du Cancer (2019-158, INCa_14059)
  • University Sorbonne Paris Nord
  • H2020 European Research Council (864219)
  • French Ministry of Health (arrêté 29.11.19)
  • IdEx Université de Paris (ANR-18-IDEX-0001)

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