Association between dietary and circulating folate markers and kidney stones in American adults: A cross-sectional...

The relationship between folate status and kidney stone disease (KSD) is poorly understood, despite folate's essential role in one-carbon metabolism, which is related to pathways of stone formation. Given the limited and inconsistent findings from previous research, this study aimed to comprehensively investigate the association between both dietary folate intake and multiple circulating folate biomarkers with the prevalence of KSD in a large, nationally representative US adult population. We conducted a cross-sectional analysis of 9208 adult participants from the National Health and Nutrition Examination Survey, 2017 to 2020. Dietary folate was assessed using a 24-hour recall. Circulating biomarkers included total serum folate, 5-methyltetrahydrofolate, tetrahydrofolate (THF), and red blood cell (RBC) folate. Multivariable logistic regression models were used to estimate odds ratios and 95% confidence intervals for KSD across quartiles of each folate measure, adjusting for potential confounders. The overall weighted prevalence of KSD was 9.4%. In unadjusted models, higher RBC folate and THF concentrations were associated with increased odds of KSD. However, after adjusting for sociodemographic, lifestyle, and clinical confounders (Model 3), no significant associations were observed between dietary folate intake (Q4 vs Q1: odds ratio 0.94, 95% confidence interval: 0.57-1.55) or any circulating folate biomarkers (RBC folate, 5-methyltetrahydrofolate, serum folate, and THF) and the prevalence of KSD. Furthermore, no significant linear or nonlinear dose-response trends were detected. In this large, nationally representative study using rigorous survey-weighted analysis, folate status was not independently associated with the prevalence of kidney stone disease. These findings suggest that folate intake and metabolism may not be major drivers of stone formation in the general US adult population.