11.12 Folate Deficiency & Toxicity

Folate deficiency is a vitamin deficiency that affects some Americans. The hallmark symptom of folate deficiency is megaloblastic (aka macrocytic) anemia. Megaloblastic anemia, as the name suggests, is characterized by large, nucleated (most red blood cells do not have a nucleus), immature red blood cells. This occurs because folate is needed for DNA synthesis; without it red blood cells are not able to divide properly1. As a result, fewer and poorer functioning red blood cells are produced that cannot carry oxygen as efficiently as normal red blood cells2.

A maternal folate deficiency can lead to neural tube defects in infants. The exact cause of neural tube defects is unknown, but folate supplementation has been shown to decrease the incidence of neural tube defects3. The most common of these neural tube defects is spina bifida (1 out of 2500 babies born in the United States), which is a failure of the neural tube to close and the spinal cord and its fluid protrude out the infant’s back, as shown below4,5.

Figure 11.121 Spina bifida

The neural tube closes 21-28 days after conception1, and with 50% of pregnancies estimated to be unplanned, many women aren’t aware they are pregnant during this period1,2. Thus, it is recommended that women of childbearing age consume 400 ug of folic acid daily1. In addition, in 1998 the FDA mandated that all refined cereals and grains be fortified with 140 ug folic acid /100 grams of product7. As you can see below, spina bifida prevalence rates declined during the optional fortification years and declined further once fortification became mandatory in the United States.

Figure 11.122 Neural tube defect prevalence 1995-20118

However, more recent research has found that folic acid supplementation begun before conception reduced the occurrence and severity of neural tube defects9.

The following link is an interesting account of the history that led up to the folic acid fortification. It is debatable whether folic acid fortification was fully responsible for the decrease in spina bifida rates shown above, but the rates are lower than they were pre-fortification.

Web Link

Folic Acid Fortification: Fact and Folly

Folate/Folic acid is not toxic, but it can mask a vitamin B12 deficiency and prevent its diagnosis. This effect will be discussed further in the vitamin B12 deficiency section.

References & Links

1. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.

2. Whitney E, Rolfes SR. (2008) Understanding nutrition. Belmont, CA: Thomson Wadsworth.

3. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.

4. http://www.cdc.gov/ncbddd/birthdefects/SpinaBifida.htm

5. http://www.nlm.nih.gov/medlineplus/ency/imagepages/19087.htm

6. https://www.cdc.gov/ncbddd/spinabifida/facts.html

7. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

8. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a2.htm

9. Bergman JEH, Otten E, Verheij JBGM, de Walle HEK. (2016) Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study. Reprod Toxicol. 59:96-100.


Folic Acid Fortification: Fact and Folly – http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SelectionsFromFDLIUpdateseriesonFDAHistory/ucm091883.htm