Food additive and naturally occurring glutamate and risk of cardiovascular diseases in the NutriNet-Santé prospective cohort.

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

During follow-up (median = 7.92 y), 2397 CVD, 1113 CVA, and 1284 IHD cases were diagnosed. Higher intakes of food additive glutamate [hazard ratio (HR) per 200 mg/d: 1.05; 95% confidence interval: 1.01, 1.09; P = 0.02], naturally occurring glutamic acid (HR3000 mg/d: 1.13; 95% CI: 1.03, 1.25; P = 0.009), and total glutamate (HR3000 mg/d = 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.