The Vitamin Folic Acid 1, which occurs ubiquitously in nature, especially in yeast, liver and green vegetables, is not active as such in the mammalian body, but is reduced enzymatically to 5,6,7,8-Tetrahydrofolic Acid 2: this coenzyme form acts as a carrier for various one-carbon units.
These endogenous reduced folates participate in important metabolic reactions like the de novo purine and pyrimidine biosynthesis and also the biosynthesis of proteinogenic amino acids: for example 5-Methyl-tetrahydrofolic acid 3 acts as the methyl-group donor in the biosynthesis of Methionine.
Two main uses of reduced folates in the oncological field can be cited:
- as antidotes to Folic Acid antagonists, such as Methotrexate (“rescue therapy”), used in the treatment of certain neoplastic diseases, psoriasis and rheumatoid arthritis.
- as biochemical modulators prescribed in synergistic combination with the chemotherapy agent 5-Fluorouracil in treating colorectal cancer (FOLFOX or FOLFIRI regimen)
Folate deficiencies can typically occur in several different situations, like:
- inadequate nutrition
- absorption or utilization (i.e after treatment with high doses of the antimetabolite Methotrexate)
- increased requirements (pregnancy, lactation, malignancy).
The consequences of a folate deficiency can be: birth defects (i.e. “spina bifida”), megaloblastic anemia, some types of depression,….. (see below).
In all cases of deficiency or to prevent deficiency, the folate pool can be advantageously replenished by oral administration of a reduced folate, like Calcium Folinate 4 (see for example: “Development of Human Folate Deficiency”, V.Herbert et al., Folic Acid Metabolism in Human Health an Disease, 195-210. (1990)).