Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification

Abstract

Objective

To estimate the associated risk of folate and vitamin B12 (B12) insufficiency, as well as vitamin repletion, following folic acid food fortification.

Design

Retrospective cross-sectional study over a 5-year period.

Setting

Two large laboratory databases in the provinces of Ontario and British Columbia, Canada.

Participants

Canadian women aged 65 years and over who underwent concomitant clinical testing of serum folate and B12 during the pre-fortification period of January 1996 to December 1997 in Ontario (n = 733) and British Columbia (n = 3839), and in the near-complete post-fortification period of January 1998 to December 2000 in Ontario (n = 4415) and British Columbia (n = 6677).

Measurements

Geometric mean concentrations of serum folate and B12 before and after folate fortification. Prevalence ratios (PR) were used to separately compare the post- and pre-fortification period rates of folate deficiency (below 6.0 nmol/L); B12 insufficiency (below 150 pmol/L); and B12 insufficiency in combination with supraphysiological concentrations of serum folate (above 45 nmol/L).

Results

The mean baseline folate and B12 concentrations were similar between provinces. Using the combined provincial data, the mean serum folate concentration increased by 64% after fortification, from 14.8 to 24.2 nmol/L (p < 0.001). The average B12 concentration increased from 280 to 300 pmol/L, which was more pronounced in BC (p < 0.001) than in Ontario (p = 0.16). The prevalence of folate deficiency declined from 6.3% to 0.88% after fortification (PR 0.14, 95% confidence interval [CI] 0.11-0.18), while the decline in B12 deficiency was less pronounced (PR 0.78, 95% CI 0.71-0.86). The prevalence of combined B12 insufficiency with supraphysiological concentrations of serum folate increased from 0.09% pre-fortification to 0.61% post (PR 7.0, 95% CI 2.6-19.2).

Conclusions

The introduction of folic acid food fortification was associated with a substantial improvement in the folate status of Canadian women aged 65 years and older, paralleled by a large decline in the rate of folate deficiency. Improvement in the B12 status of these women was far less pronounced. Because the prevalence of combined B12 insufficiency and supraphysiological concentrations of serum folate may have increased with folic acid food fortification, consideration should be given to confirming this finding, and possibly, to the addition of B12 to folate fortified foods.

Sponsorship

Public Health Branch, Ontario Ministry of Health and Long Term Care.

Potential conflict of interest

None

Introduction

Both folic acid and vitamin B12 (B12) are important nutrients during the aging process. A deficiency of either vitamin may lead to impaired methylation of DNA [1], [2], heightening the risk for certain forms of cancer [3] and megaloblastic anemia [4]. In the presence of poor oral intake or gastrointestinal absorption of B12 [5], excess folic acid consumption may mask the hematological (e.g., megaloblastic) and biochemical (e.g., hyperhomocysteinemic) manifestations of B12 impairment, especially in the elderly [6], [7], [8], [9]. Unrecognized B12 deficiency may also have serious neuropsychiatric sequelae [10], including progressive subacute combined generation of the spinal cord [9], [11]. On the other hand, the addition of B12 to folic acid supplements might further lower the risk of both vascular disease [12] and dementia [13].

As part of a program to reduce the rate of fetal neural tube defects [14], most Canadian cereal grains were fortified with folic acid. Early fortification began in January 1997, but near-complete fortification was achieved by January 1998, providing 0.2 mg of additional folates per day to all Canadian adults. This initiative was associated with a 45% increase in red cell folate concentrations in women of reproductive age [15]. Since B12 was not a part of the fortification initiative, however, the effect of this program on the relative distribution of folate and B12 levels in older women is unknown. We assessed the risk of having B12 and/or folate insufficiency, in association with mandatory folic acid food fortification.