Background: There has been a concern regarding the masking of vitamin B-12 deficiency in the post-fortification period (after January 1, 1998).

Objective: The objective of this study was to investigate the potential masking of vitamin B-12 deficiency by comparing the proportion of individuals with low serum B-12 without macrocytosis between pre- and post-fortification periods using data from the National Health and Nutrition Examination Survey (NHANES).

Methods: The study included 7242 individuals from NHANES III (pre-fortification group) and combined NHANES 1999-2000, 2001-2002, 2003-2004, 2005-2006 (post-fortification group). Vitamin B-12 deficiency and macrocytosis were defined as having <148 pmol/L of serum vitamin B-12 and mean corpuscular volume (MCV) of>98 fL, respectively. A multivariate logistic regression was performed to estimate the likelihood of being low serum B-12 without macrocytosis in the post-fortification period in relation to the pre-fortification period.

Results: Between pre- and post-fortification periods, there was no significant difference in the proportion of individuals with low serum vitamin B-12 without macrocytosis. However, odds of having low serum vitamin B-12 without macrocytosis in the post fortification era increased in men (OR=2.65, 1.24-5.65), non-Hispanic blacks (OR=3.12, 1.04-9.35), Non-smokers (OR=4.63, 1.90-11.27), and those aged 55 and older (OR=2.183, 1.01-4.74) compared their respective counterparts in the pre-fortification period.

Conclusions: No significant difference in the proportion of individuals with vitamin B-12 deficiency without macrocytosiss was seen between the pre and post-fortification periods suggesting no making of vitamin B-12 deficiency. In the post-fortification period, serum folate was found to be a predictor of the masking effect. The impact of increased folic acid intake in the post-fortification period needs to be evaluated on a periodic basis especially, in non-target population.