The prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis did not increase among older U.S. adults after mandatory folic acid fortification

Abstract

Whether folic acid fortification and supplementation at the population level have led to a higher prevalence of vitamin B-12 deficiency in the absence of anemia remains to be examined among a nationally representative sample of older U.S. adults. We assessed the prevalence of low vitamin B-12 status in the absence of anemia or macrocytosis before and after fortification among adults aged >50 y using cross-sectional data from the NHANES 1991-1994 (prefortification) and 2001-2006 (postfortification). We compared the prefortification and postfortification prevalence of multiple outcomes, including serum vitamin B-12 deficiency (<148 pmol/L) and marginal deficiency (148-258 pmol/L) with and without anemia (hemoglobin <130 g/L for men, <120 g/L for women) and with and without macrocytosis (mean cell volume >100 fL) using multinomial logistic regression, adjusting for age, sex, ethnicity, body mass index, C-reactive protein, and vitamin B-12 supplement use. Prefortification and postfortification serum vitamin B-12 deficiency without anemia [4.0 vs. 3.9%; adjusted prevalence ratio (aPR) (95% CI): 0.98 (0.67, 1.44)] or without macrocytosis [4.2 vs. 4.1%; aPR (95% CI): 0.96 (0.65, 1.43)] remained unchanged. Marginal deficiency without anemia [25.1 vs. 20.7%; aPR (95% CI): 0.82 (0.72, 0.95)] or without macrocytosis [25.9 vs. 21.3%; aPR (95% CI): 0.82 (0.72, 0.94)] were both significantly lower after fortification. After fortification, higher folic acid intake was associated with a lower prevalence of low serum B-12 status in the absence of anemia or macrocytosis. Results suggest that the prevalence of low serum B-12 status in the absence of anemia or macrocytosis among older U.S. adults did not increase after fortification. Thus, at the population level, we found no evidence to support concerns that folic acid adversely affected the clinical presentation of vitamin B-12 deficiency among older adults.

FIGURE 1

Prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis among U.S. adults aged >50 y in NHANES before and after mandatory folic acid fortification. Bars denote 95% CIs. *P < 0.001 based on prevalence estimate differences in serum vitamin B-12 deficiency (<148 pmol/L) and marginal deficiency (148–258 pmol/L) without anemia (hemoglobin ≥ 130 g/L for men, ≥120 g/L for women) or without macrocytosis (MCV ≤ 100 fL) using multinomial logistic regression adjusted for age, sex, race/ethnicity, BMI, C-reactive protein, smoking, and oral vitamin B-12 supplement use. Participants with liver disease, renal dysfunction, heavy alcohol use, and treatment of anemia <3 mo before survey participation were excluded from the analyses. Analyses were weighted to account for the complex sampling design of NHANES. MCV, mean cell volume; Serum B-12 def + no anemia, serum vitamin B-12 <148 pmol/L without anemia; serum B-12 def + no macrocytosis, serum vitamin B-12 <148 pmol/L without macrocytosis; serum B-12 marg def + no anemia, serum vitamin B-12 of 148–258 pmol/L without anemia; serum B-12 def + no macrocytosis, serum vitamin B-12 of 148–258 pmol/L without macrocytosis.

FIGURE 2

Postfortification prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis among U.S. adults aged >50 y in NHANES by folic acid intake group (A) and folic acid supplement intake group (B). Bars denote 95% CIs. Estimates with RSEs ≥30% were considered statistically unreliable and were reported with a dagger for RSE = 30–39%. Values across folic acid intake groups and folic acid supplement intake groups are significantly different and marked by different superscript letters (a > b > c) at P < 0.04 using multinomial logistic regression adjusting for age, race/ethnicity, BMI, and C-reactive protein. Participants with liver disease, renal dysfunction, heavy alcohol use, and treatment of anemia <3 mo before survey participation were excluded from the analyses. ECGP, enriched cereal grain product; RSE, relative standard error; RTE, ready-to-eat cereal; serum B-12 def + no anemia, serum vitamin B-12 <148 pmol/L without anemia; serum B-12 def + no macrocytosis, serum vitamin B-12 <148 pmol/L without macrocytosis; serum B-12 marg def + no anemia, serum vitamin B-12 of 148–258 pmol/L without anemia; serum B-12 def + no macrocytosis, serum vitamin B-12 of 148–258 pmol/L without macrocytosis; SUP, supplement containing folic acid; 0 µg/d, non-users and users of supplements containing no folic acid.