Indications
Folic acid is primarily indicated for the treatment of folic acid deficiency and megaloblastic anemia, which can occur due to various nutritional deficiencies. Additionally, it is recommended during periods of increased physiological demand such as pregnancy, infancy, or childhood, where the risk of anemia due to nutritional deficiencies is heightened.
Pharmacodynamics
Folic acid, also known as Vitamin B9, is a water-soluble B-complex vitamin crucial for various biochemical processes. It serves as an essential cofactor for enzymes involved in the synthesis of DNA and RNA, specifically necessary for the creation of purines, pyrimidines, and methionine which are integral to DNA and protein synthesis. Converted into tetrahydrofolic acid within the body, folic acid facilitates transformylation reactions critical for nucleotide biosynthesis. Deficiencies in folic acid can impair DNA synthesis, leading to the development of megaloblastic and macrocytic anemias due to the formation of defective megaloblasts. This vitamin is especially important during periods of rapid cell division, such as pregnancy, infancy, and red blood cell production, and plays a protective role in cancer prevention. Since humans cannot synthesize folic acid endogenously, it must be obtained through diet or supplements. The conversion of folic acid in the body is mediated by the enzyme dihydrofolate reductase (DHFR), which reduces it to the active forms dihydrofolate (DHF) and tetrahydrofolate (THF). This process is crucial for the synthesis of nucleic acids and amino acids and is susceptible to disruption by antifolates like Methotrexate, which inhibit DHFR to halt DNA synthesis in rapidly dividing cells. Serum folate levels below 5 ng/mL are indicative of deficiency, and levels falling under 2 ng/mL can lead to megaloblastic anemia.
Absorption
Folic acid is absorbed efficiently from the small intestine, predominantly from its proximal section. Before absorption, naturally occurring conjugated folates are converted enzymatically to folic acid within the gastrointestinal tract. Following oral administration, folic acid appears in plasma approximately 15 to 30 minutes thereafter, with peak levels typically reached within one hour.
Metabolism
The metabolism of folic acid primarily occurs in the liver, where it is converted into its active enzyme cofactors, dihydrofolate (DHF) and tetrahydrofolate (THF), through the action of dihydrofolate reductase (DHFR). This conversion is critical for the proper functioning of metabolic pathways essential for cell growth and division.
Mechanism of Action
Folic acid, initially inactive in its biochemical form, undergoes conversion to tetrahydrofolic acid and methyltetrahydrofolate through the action of the enzyme dihydrofolate reductase (DHFR). These derivatives are then transported into cells via receptor-mediated endocytosis, where they play crucial roles in supporting normal erythropoiesis, synthesizing purine and thymidylate nucleic acids, interconverting amino acids, methylating tRNA, and managing formate levels. Moreover, with vitamin B12 acting as a cofactor, folic acid facilitates the remethylation of homocysteine to methionine through the enzyme methionine synthetase, thereby helping to normalize elevated homocysteine levels.
