Main functions. Folate is an essential micronutrient for normal development and metabolic function as a cofactor for enzymes in one-carbon metabolism, thus important for the biosynthesis of nucleotides (RNA and DNA) (Bjørke-Monsen & Ueland, 2023a). Folates are also necessary for the conversion of homocysteine to methionine (Bjørke-Monsen & Ueland, 2023a; EFSA, 2014f). Supplemental folic acid (in addition to dietary folate intake) before pregnancy prevents neural tube defects (spina bifida and anencephaly) in infants (Bjørke-Monsen & Ueland, 2023a).
Indicator for recommended intake. Serum or plasma folate and folate in red blood cells are the primary biomarkers of dietary intake.
Main data gaps. Lack of biomarker cut-offs for adverse health effects.
Deficiency and risk groups. Deficiency is manifested mainly as megaloblastic anaemia. People with low folate intake, malabsorption or increased folate requirements have a risk of developing folate deficiency. Individuals who are homozygous for the C677C→T-polymorphism (TT genotype) in the methylene tetrahydrofolate reductase (MTHFR) gene have increased requirements (Bjørke-Monsen & Ueland, 2023a). Alcohol use disorder is associated with severe folate deficiency linked to poor dietary intake, intestinal malabsorption, impaired hepatic uptake with reduced storage of folates, and increased renal excretion. Children and pregnant and lactating females also have an increased demand for folate and may be at risk of inadequate intake.
Dietary reference values. The AR for adults was derived from the level of intake required to maintain serum and red blood cell folate concentrations of ≥10 and 340 nmol/L, respectively. AR is set to 250 µg/day in females and males. RI is set to 330 µg/day (females and males). No AR is set for pregnant females due to insufficient evidence. Instead, an AI is set to 600 µg/day for pregnant females, and a provisional AR is set to 480 µg/day, derived from the AI set by EFSA (EFSA, 2014f), which is based on a controlled metabolic study in pregnant females (Caudill et al., 1997). In most Nordic and Baltic countries, females of reproductive age are recommended to take a supplement of 400 µg/day from planned pregnancy and throughout the first trimester of pregnancy. The UL of folic acid (synthetic) is 1000 µg/d.