Food additive and naturally occurring glutamate and risk of cardiovascular diseases in the NutriNet-Santé prospective cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The potential cardiac toxicity of glutamate is debated and has been suggested by some epidemiological and experimental studies. To our knowledge, none have investigated the links between both naturally occurring and food additive glutamate and cardiovascular disease (CVD) risk. OBJECTIVES: Our objective was to assess the associations between intakes of total, food additive, and naturally occurring glutamate and risk of CVD, including cerebrovascular (CVA) and ischemic heart diseases (IHDs), in a large population-based study. METHODS: Participants {n = 108,932, NutriNet-Santé prospective cohort, 2009-2023, France, mean age = 42.4 y [standard deviation (SD) = 14.5], 79.3% females} completed repeated 24-h dietary records [mean = 21 (SD = 18), ≤84], including brands of industrial food consumed. Exposure to food additive glutamate was evaluated through multiple composition databases and ad hoc laboratory assays in food matrices. Associations between time-dependent continuous exposures to total, naturally occurring, and food additive glutamate and risk of CVD, CVA, and IHD were investigated using multivariable Cox models. RESULTS: = 1.15; 95% CI: 1.05, 1.26) P = 0.004) were associated with higher risks of IHD. For CVD, corresponding HRs were 1.03 (1.00, 1.06; P = 0.07), 1.09 (1.01, 1.18; P = 0.02), and 1.10 (1.02, 1.18; P = 0.01). No association was detected for CVA (all P ≥ 0.5). Residual confounding cannot be entirely ruled out, and causality cannot be established based on this single observational study. CONCLUSIONS: This large prospective study showed positive linear associations between higher glutamate intakes and increased risks of CVD. In particular, food additive glutamate, naturally occurring glutamic acid, and total glutamate intakes were all associated with higher IHD risk. This adds to previous experimental data showing a role of glutamate in regulating heart functioning at physiological doses, while also suggesting heart rate dysfunction at higher exposures. This trial was registered at clinicaltrials.gov as NCT03335644.
Authors: Anaïs Hasenböhler, Guillaume Javaux, Marie Payen de la Garanderie, Fabien Szabo de Edelenyi, Laurent Bourhis, Cédric Agaësse, Alexandre De Sa, Inge Huybrechts, Fabrice Pierre, Xavier Coumoul, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Léopold K Fezeu, Serge Hercberg, Pilar Galan, Mélanie Deschasaux-Tanguy, Benoit Chassaing, Bernard Srour, Mathilde Touvier
Institutions: Conservatoire National des Arts et Métiers, Inserm, Université Paris Cité, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Université Sorbonne Paris Nord, Equipe de Recherche en Epidémiologie Nutritionnelle, Centre de Recherche Épidémiologie et Statistique, Centre international de recherche sur le cancer, Université Toulouse III - Paul Sabatier, École Nationale Vétérinaire de Toulouse, Toxicologie Alimentaire, Université de Toulouse, Health and Functional Exposomics, Assistance Publique – Hôpitaux de Paris, Institut Pasteur
Language: English
Topic: Nutritional Studies and Diet
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Funders: Institut National de la Santé et de la Recherche Médicale, Ministère de la Santé, Institut National Du Cancer, Fondation Bettencourt Schueller, Conservatoire National des Arts et Métiers, Ministère des Solidarités et de la Santé, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, European Research Council
OpenAlex ID: W7201984005