Homocysteine and Folate Status in an Era of Folic Acid Fortification: Balancing Benefits, Risks, and B-vitamins

Abstract

Mandatory folic acid (vitamin B9) fortification of flour products to a level of 140–150 μg/100g was implemented in the US and Canada in 1998. The rationale was to improve folate status in women of childbearing age and thereby decrease the incidence of neural tube defects (NTDs). Studies with complete ascertainment of prenatally diagnosed NTD cases indicate that fortification has prevented up to 50% of NTDs(1). Fortification has therefore been highly successful in achieving its primary objective. Folate concentration in serum and erythrocytes is a marker of folate status, which is inversely associated with the plasma concentration of total homocysteine (tHcy). Cobalamin (vitamin B12) status and renal function are also strong determinants of plasma tHcy(2), and moderate hyperhomocysteinemia is associated with an increased risk of chronic diseases, including cardiovascular disease, dementia, and impaired cognition(3). In this issue of Clinical Chemistry , Pfeiffer and colleagues(4) report on concentrations of tHcy in approximately 26 000 participants in the National Health and Nutrition Examination Survey (NHANES) from 1991 through 1994, and from 3 postfortification surveys (1999–2004). When comparing the postfortification to the prefortification period, Pfeiffer and colleagues found a tHcy decrease of approximately 10%, and a pronounced decrease in the prevalence of individuals with elevated tHcy (>13 μmol/L). These observations complement recent data published by the same authors, which demonstrate an increase in serum and erythrocyte folates, and no change in serum cobalamin in NHANES samples during the same time period(5). Results from these recent studies by Pfeiffer et al. confirm previous studies on folate and homocysteine in NHANES(6)(7) and the Framingham cohort(8). A slight decrease in blood folate between the first (1999–2000) and third (2003–2004) postfortification periods(5 …