Lead exposure is related to hypercortisolemic profiles and allostatic load in Brazilian older adults

Lead levels (Pb) have been linked to both hyper- and hypo-reactivity of hypothalamic-pituitary-adrenal axis (HPA) axis to acute stress in animals and humans. Similarly, allostatic load (AL), the 'wear and tear' of chronic stress, is associated with inadequate HPA axis activity. We examined whether Pb levels would be associated with altered diurnal cortisol profile, as a primary mediator of AL, during aging. Pb levels were measured from blood samples (BPb) of 126 Brazilian individuals (105 women), between 50 and 82 years old. Six neuroendocrine, metabolic, and anthropometric biomarkers were analyzed and values were transformed into an AL index using clinical reference cut-offs. Salivary samples were collected at home over 2 days at awakening, 30-min after waking, afternoon, and evening periods to determine cortisol levels. A multiple linear regression model showed a positive association between BPb as the independent continuous variable and cortisol awakening response (R²=0.128; B=0.791; p=0.005) and overall cortisol concentration (R²=0.266; B=0.889; p<0.001) as the outcomes. Repeated measures ANOVA showed that individuals with high BPb levels showed higher cortisol at 30min after awakening (p=0.003), and in the afternoon (p=0.002) than those with low BPb values. Regarding AL, regression model showed that BPb was positively associated with AL index (R²=0.100; B=0.204; p=0.032). Correlation analyzes with individual biomarkers showed that BPb was positively correlated with HDL cholesterol (p=0.02) and negatively correlated with DHEA-S (p=0.049). These findings suggest that Pb exposure, even at levels below the reference blood lead level for adults recommended by the National Institute for Occupational Safety and Health and by the Center for Disease Control and Prevention, may contribute to AL and dysregulated cortisol functioning in older adults. Considering these findings were based on cross-sectional data future research is needed to confirm our exploratory results.