Objectives:Unexpectedly high serum B-12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B-12 intake, serum B-12 concentrations, and predictors of vitamin B-12 status in children with CF and PI.Study Design:Serum B-12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B-12 above reference range for age and sex [Hi-B-12]) or within reference range (serum B-12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B-6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed.Results:A total of 106 subjects, mean age 10.43.0 years, participated in the study. Median serum B-12 was 1083pg/mL, with 56% in the Hi-B-12 group. Dietary and supplement-based B-12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B-12 group had significantly greater supplement-based B-12 intake than the serum B-12 within reference range for age and sex group (1000% vs 583% RDA, P<0.001). Multiple logistic regression analysis showed that high supplement-based B-12 intake and age >12 years increased the risk of Hi-B-12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R-2=0.18, P<0.001).Conclusions:Serum B-12 was elevated in the majority of children with CF and PI. Supplement-based B-12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B-12 status. The health consequences of lifelong high supplement-based B-12 intake and high serum B-12 are unknown and require further study, as does the inversed correlation between serum B-12 and forced expiratory volume at 1 second.