Development of a Dietary Methyl Donor Food Frequency Questionnaire to Assess Folate and Vitamin B₁₂ Status in Children with Chronic Hepatitis B Virus Infection

Objective: To develop a dietary methyl donor food frequency questionnaire (DMD-FFQ) that is validated in a cohort of US children and to determine whether the consumption of folate and vitamin B₁₂, principal DMDs, correlates with HBV DNA levels and its methylation density. Study design: We developed a semiquantitative DMD-FFQ to estimate intake of folate and vitamin B₁₂ and validated this instrument against a 24-hour dietary recall and biomarkers—red blood cell folate, serum vitamin B₁₂, and homocysteine—in 35 children with chronic HBV infection without other medical comorbidities. Estimates of DMD, as well as the serum biomarkers, were correlated with the methylation density of HBV CpG island 2 and HBV DNA levels. Results: Folate per kilogram of body weight by the DMD-FFQ correlated positively with 24-hour recall (r = 0.60; P <.001) and red blood cell folate (r = 0.40; P =.02), and negatively with homocysteine (r = -0.54; P <.001). Vitamin B₁₂ per kilogram by DMD-FFQ also correlated positively with 24-hour recall (r = 0.57; P <.001) and serum vitamin B₁₂ (r = 0.36, P =.04), and negatively with homocysteine (r = -0.44; P =.008). Neither DMD intake (from DMD-FFQ or 24-hour recall) nor serum biomarkers correlated with HBV DNA levels or its methylation density. Conclusions: Our DMD-FFQ correlates well with a 24-hour recall and circulating biomarkers. Although little evidence existed that consumption of these micronutrients correlated with HBV replication, this tool could prove useful for investigating epigenetic modification by diet for several pediatric diseases.