11.1 Folate & Folic Acid

Folate is a B vitamin that exists in either its reduced form (folate) or oxidized form (folic acid). When folate is used in this section, we are referring to the reduced form, not the vitamin itself. Another key distinction between the 2 terms is that folic acid refers to the synthetic form, while folate refers to the natural form. Folic acid is only found in certain foods because they have been fortified with it, not because they produce it. The structure of folic acid is shown below.

Figure 11.11 Structure of Folic Acid1

Another key difference between folate and folic acid is the number of glutamates in their tails. Notice that glutamate is boxed in the structure of folic acid above. Folic acid always exists as a monoglutamate, meaning it only contains 1 glutamate. On the other hand, about 90% of the folate found in foods are polyglutamates, meaning there is more than 1 glutamate in their tail. Folic acid is more stable than folate, which can be destroyed by heat, oxidation, and light2. Table 11.11 summarizes the key differences between folate and folic acid.

Table 11.11 Comparison of folate to folic acid

Folate Folic Acid
Reduced Form Oxidized Form
Natural Synthetic
Polyglutamate Monoglutamate
More Stable

The bioavailability of folate was believed to be much lower than folic acid.3 To account for these differences, the DRI committee created dietary folate equivalents (DFEs) to set the RDAs4. DFEs are defined as follows:

1 DFE = 1 ug food folate = 0.6 ug food folic acid = 0.5 ug folic acid on an empty stomach

DFE = ug food folate + (ug folic acid X 1.7)

The 1.7 came from research suggesting that folic acid from food was 85% bioavailable, compared to 50% for folate (85%/50% = 1.7)4. This was established in 1998 by the DRI committee, and it is likely that these conversions & the requirements will change based on the newer evidence suggesting folate’s bioavailability from food is higher (80% of folic acid) than previously believed3. With this data, the new conversion factor for folic acid would be 1.25 (100%/80%). This conversion factor means that food folate levels are probably contributing more towards our dietary needs than currently being estimated by the DFE, but the DRI for folate/folic acid has not been updated.

Before folate (polyglutamates) can be taken up into the enterocyte, the extra glutamates must be cleaved prior to uptake into the enterocyte by the reduced folate transporter (RFT, aka reduced folate carrier)5-7. Folic acid, because it is a monoglutamate, requires no cleavage for uptake before it is taken up through the RFT. Once inside the enterocyte, the monoglutamate form is methylated and transported into circulation through an unresolved carrier5. This series of events is depicted in the figure below.

Figure 11.12 The uptake and absorption of folate and folic acid (orange boxes represent glutamate)

Thus, the methylated monoglutamate form is the circulating form. This is transported to the liver where it is converted back to the polyglutamate form for storage. Folate is excreted in both the urine and feces5.


11.11 Folate Functions

11.12 Folate Deficiency & Toxicity

References & Links

1. http://en.wikipedia.org/wiki/File:Folat.svg

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

3. Winkels R, Brouwer I, Siebelink E, Katan M, Verhoef P. (2007) Bioavailability of food folates is 80% of that of folic acid. Am J Clin Nutr 85(2): 465-473.

4. Anonymous. (1998) Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington D.C.: National Academies Press.

5. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. (2006) Modern nutrition in health and disease. Baltimore, MD: Lippincott Williams & Wilkins.

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

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