Folic acid is a water-soluble B vitamin essential in the human diet. It is an important cofactor in the synthesis of DNA and RNA of dividing cells, particularly during pregnancy and infancy when there is an increase in cell division and growth.
Folic acid is important to the field of oncology in two ways. First, prior to neoplasm formation, folic acid is important in the synthesis of DNA and RNA and the repair of damaged DNA. Second, after a tumor develops, a form of folic acid is used to counter the side effects of methotrexate and fluorouracil.
Prior to tumor formation
Since folic acid is a cofactor in DNA replication and biosynthesis of purines and also in DNA repair, there is an increasing amount of research (epidemiological, clinical, and experimental) that suggests a folic acid deficiency
After tumors form
Once a neoplasm forms, folic acid levels need to be decreased. In neoplasms, DNA replication and cell division are both occurring in an uncontrolled manner. Folate, which assists in this process, needs to be inhibited, causing an interruption in DNA synthesis and slowing the growth of the tumor. Chemotherapeutic agents called antimetabolites, or folic acid antagonists, such as methotrexate and 5-fluorouracil (5-FU), inhibit the enzymatic pathways for biosynthesis of nucleic acids by substituting for folic acid and sabotaging the reaction. Unfortunately, drugs that inhibit the biosynthesis of cancer cells also inhibit the biosynthesis of normal cells, resulting in extremely toxic side effects. To counter the side effects, a drug called leucovorin (a form of folate also known as Wellcovorin, Citrovorum and folinic acid) opposes the toxic effects of methotrexate on normal tissue. Leucovorin also increases the anticancer effect of 5-FU.
Non-cancer individuals supplementing their diet with folic acid may reduce the risk of cancer. Supplemental folic acid can be purchased over the counter and is also fortified in breakfast cereals and whole grain products produced in the United States. The recommended intake for adults is 400 micrograms (mcg) each day. While the risk of upper limit toxicity is low, adult men and women should not exceed the advised upper limit of 1, 000 mcg per day. It is especially important that individuals diagnosed with cancer seek the advice of medical professionals before commencing or continuing supplemental folic acid use because it may interact with chemotherapy.
Cancer patients treated with methotrexate may be given leucovorin as a "rescue" treatment approximately 24 hours later to counteract the toxic side effects on normal tissues of the gastrointestinal system and bone marrow. Leucovorin is only available by prescription. It is a systemic drug available in oral form (tablets) or via injections. The dosage varies from person to person and is based on body size.
Patients should inform their physician of the following conditions before they begin to take leucovorin:
- Pregnancy or breast-feeding.
- Pernicious anemia.
- Allergies to leucovorin or any other drugs.
- Vitamin B12 deficiency. Folic acid may mask hematologic signs of B12 deficiency while neurologic damage progresses.
Folic acid in general and specifically leucovorin are usually well-tolerated. However, there are some uncommon side effects that include skin rashes, itching, vomiting, nausea, diarrhea, and difficulty breathing. Although extremely rare, seizures have occurred in some patients taking leucovorin. Since leucovorin is taken with chemotherapeutic drugs, some side effects may be due to drug interaction.
Supplemental folic acid can interact with anti-convulsant medications such as dilantin, phenytoin, and primidone. It also complicates the effects of metformin (used in individuals with type 2 diabetes), sulfasalazine (used in individuals with Crohn's disease), and triamterene (a diuretic).
Sally C. McFarlane-Parrott
Folic acid antagonist
—a drug that interferes with the action of folic acid
—abnormal tissue growth that is not controlled by normal stimuli and lacks normal structural organization
—a substance that is part of the structure of guanine and adenine, molecules that combine to form DNA