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


Journal

PLoS medicine
ISSN: 1549-1676
Titre abrégé: PLoS Med
Pays: United States
ID NLM: 101231360

Informations de publication

Date de publication:
03 2022
Historique:
received: 08 11 2021
accepted: 23 02 2022
entrez: 24 3 2022
pubmed: 25 3 2022
medline: 21 4 2022
Statut: epublish

Résumé

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). 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. 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. ClinicalTrials.gov NCT03335644.

Sections du résumé

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.

Identifiants

pubmed: 35324894
doi: 10.1371/journal.pmed.1003950
pii: PMEDICINE-D-21-04643
pmc: PMC8946744
doi:

Substances chimiques

Sweetening Agents 0
Aspartame Z0H242BBR1

Banques de données

ClinicalTrials.gov
['NCT03335644']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1003950

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: SG is co-founder of Open Food Facts, a non-profit project developed by thousands of volunteers from around the world. It is a free and open-data food product database designed to help citizens make better food choices.

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Auteurs

Charlotte Debras (C)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Eloi Chazelas (E)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Bernard Srour (B)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Nathalie Druesne-Pecollo (N)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Younes Esseddik (Y)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Fabien Szabo de Edelenyi (F)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Cédric Agaësse (C)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Alexandre De Sa (A)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Rebecca Lutchia (R)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Stéphane Gigandet (S)

Open Food Facts, Saint-Maur-des-Fossés, France.

Inge Huybrechts (I)

French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.
International Agency for Research on Cancer, World Health Organization, Lyon, France.

Chantal Julia (C)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
Public Health Department, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France.

Emmanuelle Kesse-Guyot (E)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Benjamin Allès (B)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Valentina A Andreeva (VA)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.

Pilar Galan (P)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Serge Hercberg (S)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.
Public Health Department, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France.

Mélanie Deschasaux-Tanguy (M)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

Mathilde Touvier (M)

Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.

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Classifications MeSH