Am J Clin Nutr. 2026 Aug 8:101462. doi: 10.1016/j.ajcnut.2026.101462. Online ahead of print.
ABSTRACT
BACKGROUND: The potential cardiac toxicity of glutamate is debated and has been suggested by some epidemiological and experimental studies. To our knowledge, none investigated the links between both naturally occurring and food additive glutamate and cardiovascular disease (CVD) risk.
OBJECTIVE: Our objective was to assess the associations between intakes of total, food additive and naturally occurring glutamate, and the risk of CVD, including cerebrovascular (CVA) and coronary heart (CHD) diseases, in a large population-based study.
METHODS: Participants (n= 108,932, NutriNet-Santé prospective cohort, 2009-2023, France, mean age=42.4y (SD=14.5), 79.3% females) completed repeated 24h-dietary records (mean = 21 (SD=18), up to 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 CHD were investigated using multivariable Cox models.
RESULTS: During follow-up (median=7.92y), 2397 CVD, 1113 CVA, and 1284 CHD cases were diagnosed. Higher intakes of food additive glutamate (Hazard Ratio=1.05, 95%Confidence Interval (1.01, 1.09), p-value=0.02), naturally occurring glutamic acid (HR=1.13(1.03, 1.25), p-value=0.009), and total glutamate (HR=1.15(1.05, 1.26), p-value=0.004) were associated with higher risks of CHD. For CVD, corresponding HRs were 1.03(1.00, 1.06; p-value=0.07), 1.09(1.01, 1.18; p-value=0.02) and 1.10(1.02, 1.18; p-value=0.01). No association was detected for CVA (all p-values≥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 CHD 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.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.
PMID:42570865 | DOI:10.1016/j.ajcnut.2026.101462