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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^1,2

¹ From Rush University Medical Center, Chicago, IL (KFW), and the Division of Nutrition, College of Health and Human Sciences, Georgia State University, Atlanta, GA (VG)

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 prefortification (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 (87%) and perifortification (85%) periods than in the prefortification period (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% CI: 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.

Key Words: Anemia • folic acid fortification • mean corpuscular volume • MCV • macrocytosis • masking of vitamin B-12 deficiency • megaloblastic anemia • serum vitamin B-12

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Folic acid fortification: is masking of vitamin B-12 deficiency what we should really worry about?

Ingeborg Brouwer and Petra Verhoef
AJCN 2007 86: 897-898. [Full Text]  

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				P. M. Ueland and S. Hustad Homocysteine and Folate Status in an Era of Folic Acid Fortification: Balancing Benefits, Risks, and B-vitamins Clin. Chem., May 1, 2008; 54(5): 779 - 781. [Full Text] [PDF]

				I. Brouwer and P. Verhoef Folic acid fortification: is masking of vitamin B-12 deficiency what we should really worry about? Am. J. Clinical Nutrition, October 1, 2007; 86(4): 897 - 898. [Full Text] [PDF]