Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children

Background/Aim: Fluoride is a natural mineral present in food, water, and dental products, constituting ubiquitous long-term exposure in early childhood and across the lifespan. Experimental evidence shows fluoride -induced lipid disturbances with potential implications for cardiometabolic health. However, epidemiological studies are scarce. For the first time, we evaluated associations between repeated fluoride measures and cardiometabolic outcomes in children. Methods: We studied similar to 500 Mexican children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with measurements on urinary fluoride at age 4, and dietary fluoride at ages 4, 6, and 8 years approximately. We used covariate-adjusted linear mixed-effects and linear regression models to assess fluoride associations with multiple cardiometabolic outcomes (ages 4-8): lipids (total cholesterol, HDL, LDL, and triglycerides), glucose, HbA1c, adipokines (leptin and adiponectin), body fat, and age-and sex-specific z-scores of body mass index (zBMI), waist circumference, and blood pressure. Results: Dietary fluoride intake at age 4 was associated with annual increases in triglycerides [beta per-fluoride -doubling = 2.02 (95 % CI: 0.37, 3.69)], cholesterol [beta = 1.46 (95 % CI: 0.52, 2.39)], HDL [beta = 0.39 (95 % CI: 0.02, 0.76)], LDL [beta = 0.87 (95 % CI: 0.02, 1.71)], and HbA1c [beta = 0.76 (95 % CI: 0.28, 1.24)], and decreased leptin [beta =-3.58 (95 % CI:-6.34,-0.75)] between the ages 4 and 8. In cross-sectional analyses at age 8, higher tertiles of fluoride exposure were associated with increases in zBMI, triglycerides, glucose, and leptin (p-tertile trend < 0.05). Stronger associations were observed in boys at year 8 and in girls prior to year 8 (p-sex interaction < 0.05). Fewer but consistent associations were observed for urinary fluoride at age 4, indicating increased annual changes in HDL and HbA1c with higher fluoride levels. Conclusion: Dietary fluoride exposures in early-and mid-childhood were associated with adverse cardiometabolic outcomes in school-aged children. Further research is needed to elucidate whether these associations persist at later ages.