Helicobacter pylori Seropositivity’s Association with Markers of Iron, 1-Carbon Metabolism, and Antioxidant Status among US Adults: A Structural Equations Modeling Approach

OBJECTIVES: We tested a model in which Helicobacter pylori seropositivity (Hp(s)) predicted iron status, which in turn acted as a predictor for markers of 1-C metabolism that were then allowed to predict antioxidant status. METHODS: National Health and Nutrition Examination Surveys (NHANES 1999–2000) cross-sectional data among adults aged 20–85 y were analyzed (n = 3,055). Markers of Hp(s), iron status (serum ferritin and transferrin saturation (TS)); 1-C metabolism (serum folate (FOL(serum)), B-12, total homocysteine (tHcy), methylmalonic acid (MMA)) and antioxidant status (vitamins A and E) were entered into a structural equations model (SEM). RESULTS: Predictors of Hp(s) included older age, lower education and income, racial/ethnic groups (lowest among Non-Hispanic Whites), and lifetime cigarette smoking. SEM modeling indicated that Hp(s) had a direct inverse relationship with iron status (combining serum ferritin and TS) which in turn was positively related to 1-C metabolites (higher serum folate, B-12 or lower tHcy/MMA) that were positively associated with antioxidant status (combining serum vitamins A and E). Another pathway that was found bypassed 1-C metabolites (Hps → Iron_st → Antiox). The sum of all indirect effects from Hp(s) combining both pathways and the other indirect pathways in the model (Hps → Iron_st → OneCarbon; Hps →OneCarbon →Antiox) was estimated at β = -0.006±0.003, p<0.05. CONCLUSIONS: In sum, of the total effect of H. pylori seropositivity on antioxidant status, two significant indirect pathways through Iron status and 1-Carbon metabolites were found. Randomized controlled trials should be conducted to uncover the concomitant causal effect of H. pylori eradication on improving iron status, folate, B-12 and antioxidant status among H. pylori seropositive individuals.