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Folic acid is known to be associated with inflammatory diseases, but the relationship between folic acid and allergic diseases is unclear.The purpose of the study was to examine the relationship between serum folate levels and markers of atopy, wheeze, and asthma.Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey in which serum folate and total IgE levels were measured in 8083 subjects 2 years of age and older. A high total IgE level was defined as greater than 100 kU/L. Allergen-specific IgE levels were measured for a panel of 5 common aeroallergens. Atopy was defined as at least 1 positive allergen-specific IgE level. Doctor-diagnosed asthma and wheeze in the previous 12 months were assessed by means of questionnaire.Serum folate levels were inversely associated with total IgE levels (P< .001). The odds of a high total IgE level, atopy, and wheeze decreased across quintiles of serum folate levels, indicating a dose-response relationship between serum folate levels and these outcomes. Each of these associations remained statistically significant after adjusting for age, sex, race/ethnicity, and poverty index ratio. Adjusted odds ratios associated with the fifth quintile of folate relative to the first quintile were as follows: high IgE level, 0.70 (95% CI, 0.53-0.92); atopy, 0.69 (95% CI, 0.57-0.85); and wheeze, 0.60 (95% CI, 0.44-0.82). Higher folate levels were also associated with a lower risk of doctor-diagnosed asthma, but this finding was not statistically significant (odds ratio for fifth quintile vs first quintile, 0.84 [95% CI, 0.70-1.02]).Serum folate levels are inversely associated with high total IgE levels, atopy, and wheeze.