Association of dietary folate intake with endometriosis in US participants :a retrospective cross-sectional study

Abstract Objective To investigate the dose-response relationship between dietary folate intake and endometriosis risk among U.S. women of reproductive age. Methods This cross-sectional study analyzed 4,024 women (aged 20–54 years) from the 1999–2006 NHANES cycles. Dietary folate intake was quantified via 24-hour recall and categorized into quartiles (Q1-Q4: 0–206, 207–300, 301–429, and 430–2,827 µg/day). Multivariable logistic regression models adjusted for sociodemographics, lifestyle factors, and dietary confounders evaluated the folate-endometriosis association. Restricted cubic splines assessed nonlinear trends. Results Among participants, 8.0% (321/4,024) reported endometriosis. Higher folate intake exhibited a dose-dependent inverse association with endometriosis risk. Compared to Q1 (reference), adjusted odds ratios (95% CI) for Q2–Q4 were 0.82 (0.59–1.14), 0.75 (0.52–1.08), and 0.63 (0.42–0.96), respectively (P for trend = 0.032). A linear threshold effect was observed, with intake ≥ 400 µg/day associated with 37% reduced risk (OR = 0.63, 95% CI:0.46–0.86; P = 0.003). Subgroup analyses revealed no significant interactions by age, BMI, or lifestyle factors (P interaction > 0.05). Conclusion Dietary folate intake demonstrates a significant inverse linear relationship with endometriosis risk in U.S. women, suggesting adequate folate consumption (≥ 400 µg/day) may mitigate disease burden.