Fundamentals of Human Nutrition/Folate

< Fundamentals of Human Nutrition

8.4 FolateEdit

Folate is a water-soluble B Vitamin. It is the term used for its natural occurring forms and is also known as pteroylglutamic acid [1]. Folate’s natural form is a polyglutamate which is how the body receives it, this also known as its ‘bound’ form. Enzymes within the intestine hydrolyze it until it is a monoglutamate. The vitamin is then methylated and delivered to the liver and other cells within the body. The methylated form of folate is inactive and can only be activated by removing the methyl group using an enzyme and the vitamin B12.

In the United States, Folic Acid is one of the five fortified vitamins and minerals in grain. This fact alone demonstrates the pivotal part that folate plays in the human body. The Food and Drug Administration (FDA) began to mandate that manufacturers fortify folic acid in flours, pastas, breads, and rice in 1998 (National Institutes of Health, 2012). The four other vitamins are minerals are Thiamin, Niacin, Riboflavin, and Iron, which are also crucial nutrients for the performance and structure of the body.

It is important to note that the Folic Acid we supplement in our diet is different from the Folate we find in nature. In nature, Folate is bound up into polyglutamates. Similar to monosaccharaides making up polysaccharides, a polyglutamate is simply many glutamates linked together. Folic acid is a singular glutamate. The reason the FDA required enrichment of Folic Acid rather than Folate is that the polyglutamate is already broken up into singular glutamates and therefore the digestive system does not have to do as much work. Folic acid is found in supplements and in enriched products. Folate is found in dark green vegetables, legumes, and some citrus products (Medline Plus, 2015). Specifically, some foods that are very high in their percent of dietary folate are beef liver, spinach, and black-eyed peas (National Institutes of Health, 2012).

The synthetic form of folate is referred to as folic acid, a monoglutamate, which is found in supplements and fortified foods. Folate is primarily used in the coenzyme THF (tetrahydrofolate) that transfers 1-carbon compounds in metabolism [2].

8.4.1 SourcesEdit

Folate cannot be synthesized by the body, so we must consume it to get an adequate intake. From the diet, folate is found in high quantities in legumes, fruits and vegetables. Of these, lentils and asparagus have an exceptional amount of folate [1].

Folate is critical for pregnant women because of its effects on growing infants and its ability to prevent major birth defects. Because of this the government has mandated that food be fortified with folic acid. The majority of these enriched foods are grains such as bread, pasta, rice and cereal [3].

Being the monoglutamate form, folic acid is a lot easier to absorb into the body then folate. This is why supplements are actually encouraged for folic acid, especially for pregnant women.

8.4.2 FunctionsEdit

Folate is important in one-carbon metabolism

1-carbon metabolism

As a part of THF, folate accepts and donates 1-carbon groups for the synthesis of thymidine and purines as well as being involved in the regeneration of homocysteine to methionine, with the assistance of Vitamin B12 [4]. It is thus important for cell maintenance, DNA and RNA synthesis, and maturation of red blood cells. This is what makes it so critical for pregnant women and infants.

8.4.3 RequirementsEdit

Folate is absorbed about 50% from foods eaten and 100% from supplements [1]. The RDA for folate is 400 μg/day DFE for ages 14 and up [5]. Children need roughly 200 μg/day of DFE (dietary folate equivalent). However, since it is so critical for pregnant and nursing women, their RDA is 600 μg/day DFE. The upper limit of folate is 1000 μg/day for adults.

Folate is heavily involved with the Vitamin B12. Both are activated by the other and both are involved in the conversion of homocysteine to methionine. This is why the healthy function of folate cannot occur without adequate B12 supply.

8.4.4 DeficiencyEdit

Folate is seen as very important for women of child bearing age, especially those who are pregnant. If a pregnant woman does not meet her folate requirements, it is highly likely her child will be born with a neural tube defect, which is when the brain and spinal cord are not developed properly-- leading to disability or even death to the infant.

Often, in the past folate has only been seen as a necessary nutrient to prevent megaloblastic anemia. The importance of folate has been underestimated so much that in 1989, the Food and Nutrition Board reduced the recommended dietary allowance simply because the incidence rate of anemia was low (American Heart Association, 2002). However as the field of nutritional science grows, it is evident that folate is necessary for preventing Neural Tube defects in pregnancy and reducing the likelihood of cardiovascular disease.

During DNA synthesis, vitamin B12 and folic acid work together. When folic acid is stored, a methyl group (CH4) is added. Folic acid remains in cells in this inactive form until it is activated. Folic Acid is activated by the vitamin B12. The amino acid, homocysteine, which is attached to the B12 removes the methyl group from the folic acid. This methyl transfer to homocysteine generates methionine, which then sets off a series of reactions. Without folic acid, homocysteine will not be used in the body and can accumulate. Accumulated homocysteine is very dangerous. High levels of homocysteine lead to atherosclerosis. Atherosclerosis is the enlargement of artery walls caused by lipid stores and muscle cell proliferation (The American Journal of Clinical Nutrition, 2000). The amino acid homocysteine contributes to the thrombogenicity of blood, or the ability for blood to clot. Simply, homocysteine in a way makes blood thicker and more clot-like. Thrombogenic blood is more likely to clog in arteries and cause atherosclerosis. Atherosclerosis then leads to blocked arteries and can cause heart attacks and strokes. To summarize, accumulated homocysteine increases the risk of cardiovascular disease and proves the necessity for adequate folic acid intake. In conclusion, it is critical to understand the importance of folate in the diet. Whether acquired from enriched products, supplementation, or naturally in foods, folate is vital for healthy body function.

Folate deficiency also leads to a decrease in red blood cell and GI tract cell production. Because of this, the onset of a folate deficiency is characterized by anemia and GI tract deterioration. The anemia of a folate deficiency is called macrocytic or megaloblastic anemia. Folate’s presence is required for DNA to properly replicate red blood cells, so a lack of folate leads to a damaged DNA and immature red blood cells. The end result is very large red blood cells that cannot carry oxygen properly, travel through the bloodstream inefficiently and occasionally have nuclei.

Folate is implicated in many anticancer treatments, so it is very easy to develop a secondary folate deficiency. If a person is taking drugs with anticancer properties, many of them have similar structures to folate and they overtake folate and impede normal metabolism. Moreover, anticancer drugs affect both healthy and unhealthy cells, leading to a folate deficiency throughout the body [1][5].

8.4.5 ToxicityEdit

Research hasn’t found much diseases from ingesting too much folate. However, there is an upper limit set because folate can mask a B12 deficiency. A B12 deficiency leads to nerve damage which in turn leads to irreversible damage to the brain and spinal cord. Furthermore, there are tentative claims that folate can lead to various forms of cancer [5].


  1. a b c d Whitney, E., & Rolfes, S. (2013). The Water-Soluble Vitamins: B Vitamins and Vitamin C. Understanding Nutrition (14th ed.). Belmont, CA: Thomson/Wadsworth.
  2. S. Tibbetts and D. R. Appling (2010). Compartmentalization of mammalian folate-mediated one-carbon metabolism,Annual Review of Nutrition, 30, 57–81.
  3. Junod, S. (2001). Folic Acid Fortification: Fact and Folly. Update,(4).
  4. Kamen, B. (1997). Folate and antifolate pharmacology. Seminars in Oncology, 24(5 Suppl 18), S18-30-S18-39.
  5. a b c Dietary Supplement Fact Sheet: Folate (2013). National Institutes of Health.