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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.

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