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Background: Folate may be involved in the detoxification of heavy metals. This has been demonstrated in animal studies, in in vivo and in vitro studies, and clinical evaluations. However, knowledge regarding the associations between serum folate and blood concentrations of cadmium and lead is limited., Objective: We aimed to investigate the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults., Methods: Data on 15,501 adults were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and used for the analysis. Information on serum folate concentrations and blood levels of lead and cadmium was derived from laboratory measurements in the NHANES. Multivariable linear regression was used to examine the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults, controlling for confounders., Results: The serum folate concentration was negatively correlated with blood levels of cadmium and lead (P-trends <0.01). When stratified by sex (male and female) and estimated glomerular filtration rate (eGFR ≤60 and >60 mL/min/1.73 m 2 ), the association between serum folate concentrations and blood levels of cadmium and lead was found to be more stable in adults with eGFR > 60 mL/min/1.73 m 2 , both in males and females., Significance: These findings warrant future studies to explore the mechanisms responsible for the beneficial role of folate in regulating cadmium and lead concentrations in the blood., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)