Chapter 111 - Folic Acid

In the 1930s, first Lucy Wills and then Robert Stokstad isolated a natural component of yeast (termed ‘Wills factor’ and ‘factor U’, respectively) that prevented megaloblastic anemia of pregnancy and promoted growth in chickens. In the next decade, Herschell Mitchell, Esmond Snell, and Robert Williams isolated a factor from spinach that could support the growth of the lactic acid bacteria, Streptococcus faecalis and Lactobacillus casei. They named this factor ‘folic acid’ based on folium, the Latin word for leaf. Shortly thereafter, Stokstad isolated the pure crystalline form of the vitamin, and it was recognized that the Wills factor, factor U, and folic acid were the same substance. Elucidation of the components and details of folic acid metabolism, its metabolic interrelationships with vitamin B12 and methionine/homocysteine metabolism, its roles in pyrimidine and purine synthesis, and the determination of the molecular basis for deficiency diseases occurred through the 1950s and 1960s. In the late 1980s and 1990s, the identification of elevated plasma homocysteine (hyperhomocysteinemia) as a risk factor for vascular disease, cognitive dysfunction, and dementia renewed interest in folic acid. During this time it was also determined that periconceptional supplements of the vitamin were effective in reducing the risk of neural tube defects (NTDs). This led to wide-spread fortification of cereal and grain products with folic acid in the US and Canada beginning in the midto late1990s. Today, more than 50 countries and territories have instituted folic acid fortification programs, which have been highly effective in reducing NTDs. There are, however, lingering questions regarding the safety of excess folic acid consumption.