Folic Acid Supplementation: A Public Health Dilemma
Starting in January 1998, all products made from enriched grains in the United States and Canada were required to be supplemented with folic acid. These rulings were issued to reduce the incidence of congenital neural tube defects (NTDs). Epidemiologic studies show a strong correlation between maternal folic acid deficiency and the incidence of NTDs such as spina bifida and anencephaly. The requirement for folic acid supplementation is a public health mea-sure aimed at the significant number of women who do not receive prenatal care and are not aware of the importance of adequate folic acid ingestion for preventing birth defects in their infants. Observational studies from countries that supplement grains with folic acid have found that supplementation is associated with a significant (20–25%) reduction in NTD rates. Observational studies also suggest that rates of other types of congenital anomalies (heart and orofacial) have fallen since supplementation began.
There may be an added benefit for adults. N5-Methyltetrahy-drofolate is required for the conversion of homocysteine to methionine (Figure 33–2; Figure 33–3, reaction 1). Impaired syn-thesis of N5-methyltetrahydrofolate results in elevated serum concentrations of homocysteine. Data from several sources sug-gest a positive correlation between elevated serum homocysteine and occlusive vascular diseases such as ischemic heart disease and stroke. Clinical data suggest that the folate supplementation program has improved the folate status and reduced the preva-lence of hyperhomocysteinemia in a population of middle-aged and older adults who did not use vitamin supplements. There is also evidence that adequate folic acid protects against several cancers, including colorectal, breast, and cervical cancer.
Although the potential benefits of supplemental folic acid during pregnancy are compelling, the decision to require folic acid in grains was controversial. As described in the text, inges-tion of folic acid can partially or totally correct the anemia caused by vitamin B12 deficiency. However, folic acid supple-mentation does not prevent the potentially irreversible neuro-logic damage caused by vitamin B12 deficiency. People with pernicious anemia and other forms of vitamin B12 deficiency are usually identified because of signs and symptoms of anemia, which typically occur before neurologic symptoms. Some oppo-nents of folic acid supplementation were concerned that increased folic acid intake in the general population would mask vitamin B12 deficiency and increase the prevalence of neurologic disease in the elderly population. To put this in perspective, approximately 4000 pregnancies, including 2500 live births, in the United States each year are affected by NTDs. In contrast, it is estimated that over 10% of the elderly population in the United States, or several million people, are at risk for the neu-ropsychiatric complications of vitamin B12 deficiency. In acknowl-edgment of this controversy, the FDA kept its requirements for folic acid supplementation at a somewhat low level. There is also concern based on observational and prospective clinical trials that high folic acid levels can increase the risk of some diseases, such as colorectal cancer, for which folic acid may exhibit a bell-shaped curve. Further research is needed to more accurately define the optimal level of folic acid fortification in food and recommendations for folic acid supplementation in different populations and age groups.