Associations between acrylamide and brain-derived neurotrophic factor levels in children in a European biomonitoring study

BACKGROUND: Acrylamide (AA), a probable carcinogen and neurotoxicant in heat-processed foods, and its metabolite glycidamide (GA) can experimentally alter brain-derived neurotrophic factor (BDNF), critical for cognition and neurodevelopment. METHODS: In a cross-sectional study using two studies (NAC II, Italy, 2014-2016: n = 294, 7 years; NEB II, Norway, 2016-2017: n = 470, 7-11 years), AA metabolites N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) and BDNF were measured in urine samples. We assessed associations between creatinine standardised AAMA and GAMA, their sum (∑AA), the GAMA:AAMA ratio and BDNF using multiple linear regression per study and random effects meta-analysis. Sex and thyroid-stimulating hormone (TSH) levels were tested as effect modifiers, TSH for mediation. RESULTS: Among girls, AAMA, GAMA and ∑AA metabolites were associated with lower BDNF levels (β = -0.14, 95% CI: -0.23, -0.06, β = -0.34, 95% CI: -0.62, -0.05 and β = -0.17, 95% CI: -0.27, -0.07, per interquartile range increase in exposure, respectively), GAMA:AAMA ratio positively associated (β = 0.46, 95% CI: 0.06, 0.86). In boys, BDNF was higher with GAMA (β = 0.42, 95% CI: 0.19, 0.65) and ∑AA (β = 0.12, 95% CI: -0.04, 0.27), albeit with confidence intervals crossing 0. Boys in the older NEB II study showed opposite trends to girls (p-value for interaction between sex and each of AAMA, GAMA and ∑AA = 0.01). TSH did not mediate or modify the effect. CONCLUSION: AA metabolites were linked to lower urinary BDNF levels among girls, while boys showed a positive association with GAMA and an imprecise estimate with ∑AA. Findings suggest sex-specific differences around puberty onset, warranting longitudinal investigations and children's exposure monitoring.