Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post-folic acid fortification period than in the pre-folic acid fortification period

Background: Large intakes of folic acid may delay the diagnosis of vitamin B-12 deficiency, which could lead to irreversible neuropathy. Objective: The objective of this study was to determine whether the proportion of individuals with low serum vitamin B-12 without macrocytosis (undiagnosed vitamin B-12 deficiency) has increased in the post-folic acid fortification period. Design: Individuals aged >= 19 y with low serum vitamin B-12 (<258 pmol/L) and mean corpuscular volume (MCV) measured between 1995 and 2004 were identified from medical records. The proportion and odds ratios of individuals with low serum vitamin B-12 without macrocytosis by sex, race, and age according to pre-fortification (n = 86), perifortification (n = 138), and postfortification (n = 409) periods were determined. Results: MCV was significantly lower in the postfortification period (88.6 fL) than in the prefortification (94.4 fL; P < 0.001) and perifortification (90.6 fL; P = 0.007) periods. The proportion of subjects with low serum vitamin B-12 without macrocytosis was significantly higher in the postfortification (approximate to 87%) and perifortification (approximate to 85%) periods than in the prefortification period (approximate to 70%; P < 0.001). In a sex-, race-, and age-adjusted analysis, the odds ratio for having low serum vitamin B-12 without macrocytosis was 3.0 (95% Cl: 1.7, 5.2) in the postfortification period relative to the prefortification period. Conclusions: Subjects with low serum vitamin B-12 were likely to be without macrocytosis in the postfortification period. MCV should not be used as a marker for vitamin B-12 insufficiency. It is possible that folic acid fortification may have led to a correction of macrocytosis associated with vitamin B-12 insufficiency.