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

• Published in: Environment international 2024-01, Vol.183, p.108375-108375, Article 108375
• Main Authors: India Aldana, Sandra, Colicino, Elena, Cantoral Preciado, Alejandra, Tolentino, Maricruz, Baccarelli, Andrea A., Wright, Robert O., Téllez Rojo, Martha María, Valvi, Damaskini
• Format: Article
• Language: English
• Subjects: Body Mass Index; Cardiometabolic health; Cardiovascular Diseases; Child; Child, Preschool; Children; Cross-Sectional Studies; Endocrine-disrupting chemicals; Female; Fluoride; Fluorides; Glucose; Glycated Hemoglobin; Humans; Leptin; Male; Obesity; Risk Factors; Triglycerides; Waist Circumference
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2023.108375

•We evaluated longitudinal associations between repeated fluoride measures and cardiometabolic outcomes in children.•Dietary fluoride altered levels of lipids, adipokines, and diabetes-related biomarkers in children during 4–8 years of age.•Dietary fluoride increased zBMI and odds of overweight/obesity status in children at age 8.•Fewer, though consistent, associations were observed with respect to urinary fluoride.•Stronger fluoride-induced associations were observed in boys at age 8 and in girls prior to age 8. 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. We studied ∼ 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. Dietary fluoride intake at age 4 was associated with annual increases in triglycerides [β per-fluoride-doubling = 2.02 (95 % CI: 0.37, 3.69)], cholesterol [β = 1.46 (95 % CI: 0.52, 2.39)], HDL [β = 0.39 (95 % CI: 0.02, 0.76)], LDL [β = 0.87 (95 % CI: 0.02, 1.71)], and HbA1c [β = 0.76 (95 % CI: 0.28, 1.24)], and decreased leptin [β = -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