Folate Deficiency

Folate deficiency occurs when there is insufficient intake of folate—primarily found in green leafy vegetables and legumes or in fortified foods or supplements in the form called folic acid. Folate deficiency can also be caused by poor absorption or excessive loss of the vitamin. A severe deficiency in folate, which is required for the synthesis of red blood cells, results in megaloblastic anemia, characterized by oversized and malformed red blood cells (Balarajan et al. 2011). In addition, folate deficiency in women during conception and early embryologic development increases the risk for neural tube defects in babies, which occurs when fusion of the tissues around the spinal cord is incomplete during the initial formation of the spinal cord. These defects are often very serious and can result in fetal or infant death (Bailey et al. 2015). While folate deficiency may impact anemia minimally, it is the risk of neural tube defects that resulted in the push for fortification with folic acid. At-risk groups for folate deficiency include pregnant and lactating women, infants, young children, and the elderly (Benoist 2008). While many countries have successfully reduced the prevalence of folate deficiency through mandatory folic acid fortification programs, based on the limited data available, folate deficiency still appears be a public health problem in some settings, particularly for women (McLean, Benoist, and Allen 2008; Bailey et al. 2015).

How is folate deficiency measured?

Serum/plasma folate and/or red blood cell folate levels are most commonly used to measure folate deficiency. The serum/plasma level of folate does not represent long-term status because it may be influenced by illness or recent ingestion of folate or folic acid; therefore, the red blood cell folate level is usually the preferred indicator to determine folate deficiency. A venous blood sample, which requires a cold chain, is the preferred way to measure serum/plasma folate and red blood cell folate levels. Several laboratory techniques can be used to assess folate status, including microbiological methods, protein-binding assays, and chromatography-based assays (WHO 2015b). The microbiological assay, using the folate-dependent microorganism Locatobacillus rhamnosus, is the most widely recommended (Bailey et al. 2015).

How is folate deficiency categorized?

A definition for what constitutes a public health problem for folate deficiency is not established, although, generally, a prevalence below 5 percent does not represent a public health problem (Bailey et al. 2015). Table 7 shows the cut-offs for defining folate deficiency using serum/plasma folate and red blood cell folate. Note that the cutoff for insufficiency to prevent neural tube defects are higher among non-pregnant women of reproductive age at the population level—red blood cell folate levels should exceed 400 ng/mL (WHO 2015a).

Table 7: Folate Deficiency Cutoffs in Serum/Plasma Folate of Red Blood Cell Folate (nanogram per milliliter or nanomole per liter)

Folate Indicator Cutoff Value Indicating Folate Deficiency ng/mL (nmol/L)
Serum/plasma folate level <4 (<10)
Red blood cell folate level <151 (<340)

Source: WHO 2015b; Bailey et al. 2015

Where can we get these data?

Folate deficiency is measured in population-based surveys and research studies for women of reproductive age and, in rare cases, children. Of the commonly administered population-based surveys, the National Micronutrient Survey is usually the only one that collects and analyzes information on the prevalence of folate deficiency.

Methodological issues

  • It is useful to report the entire distribution of values, including the lower and upper tails, especially in fortification or supplementation programs.
  • Cut-offs for pregnant women are not established, because folate status declines throughout pregnancy. However, for pregnant women, when red blood cell folate concentration fall below 1,000 nmol/L, the risk of neural tube defects begins to increase (Crider et al. 2014).