Response to challenge dose among young adults vaccinated for hepatitis B as infants: importance of detectable residual antibody to hepatitis B surface antigen.

OBJECTIVE: To determine whether a difference in antibody to hepatitis B surface antigen (anti-HBs) response to a hepatitis B vaccine challenge dose existed among persons with a baseline anti-HBs level of 0 mIU/mL (group 1) and those with "non-zero" levels of 0.1-4.9 (group 2) and 5.0-9.9 (group 3) mIU/mL, according to the VITROS ECi anti-HBs assay. DESIGN: Subanalysis of randomized clinical trial. Response was defined as a postchallenge anti-HBs level of at least 10 mIU/mL and 4-fold rise in anti-HBs level 2 weeks after a single challenge dose of 10 vs 20 µg Engerix-B. Baseline was defined as the anti-HBs level immediately before administration of the challenge dose. SETTING: Pediatric integrated healthcare system near Houston, Texas. PARTICIPANTS: Three hundred nineteen US-born 16-19-year-olds who completed the hepatitis B vaccine series during the first year of life. RESULTS: One hundred seventy-eight persons had zero (group 1) and 141 (114 group 2 and 27 group 3) had non-zero anti-HBs levels at baseline. Response to the challenge dose was significantly higher among those with non-zero vs zero anti-HBs levels, irrespective of challenge dosage; only 1 person with a non-zero anti-HBs level failed to respond to the challenge dose (group 3, 27/27 [100%] vs group 2, 113/114 [99%] vs group 1, 145/178 [82%]; P<.0001). CONCLUSIONS: Among participants with residual anti-HBs levels less than 10 mIU/mL 16-19 years after primary hepatitis B vaccination during infancy, non-zero anti-HBs levels, with rare exception, indicated persistence of immune memory to HBsAg. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01341275

Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age.

Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.

Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial.

BACKGROUND: There are no large randomized trials of the effect of folic acid dosing regimens on blood folate and homocysteine concentrations. OBJECTIVE: We aimed to evaluate the changes in folate and homocysteine concentrations in response to different folic acid doses and to withdrawal in young women not exposed to other sources of folic acid. DESIGN: Women (n = 1108) were randomly assigned to 1 of 6 intervention groups for which daily intakes of folic acid for 6 mo were 100 microg 1 time/d, 25 microg 4 times/d, 400 microg 1 time/d, 100 microg 4 times/d, 4000 microg 1 time/d, or 4000 microg 1 time/wk. Plasma and red blood cell folate and homocysteine concentrations were measured at baseline; at 1, 3, and 6 mo; and 3 mo after the discontinuation of folic acid. RESULTS: Folate and homocysteine concentrations were not different at baseline between the groups who had the same daily intake of folic acid as a single dose or multiple doses (P = 0.058). Plasma folate concentrations plateaued at 3 mo with 108% (95% CI: 97.7%, 120%), 259% (95% CI: 240%, 279%), 460% (95% CI: 417%, 503%), and 142% (95% CI: 123%, 162%) observed increases for the folic acid groups receiving 100, 400, and 4000 microg/d and 4000 microg/wk, respectively. The rate of reduction in folate concentrations during the 3 mo after cessation of folic acid was dose-dependent-higher intakes were associated with faster reductions. CONCLUSIONS: Changes in folate and homocysteine concentrations were unaffected by different dosing schedules. After folic acid cessation, blood folate declined rapidly, which indicated that the intervention-enhanced folate status was rapidly diminished.