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Folic acid and folinic acid are both forms of vitamin B9, essential for DNA synthesis, cell division, and growth. Folic acid is the synthetic form commonly used in supplements and food fortification. Folinic acid (also known as leucovorin or calcium folinate) is a reduced form of folic acid that does not require activation by dihydrofolate reductase to participate in cellular reactions. Folinic acid is primarily used as an antidote to counteract the toxic effects of antifolate drugs such as methotrexate and pyrimethamine by bypassing blocked metabolic steps, thus allowing normal cells to continue DNA synthesis even when dihydrofolate reductase is inhibited[1][3][4][5]. It also enhances the efficacy of fluorouracil (5-FU) chemotherapy by stabilizing its binding to thymidylate synthase, increasing cytotoxicity against cancer cells[2][4][6]. Both agents are used clinically—either alone or together—to reduce side effects from methotrexate therapy in conditions like rheumatoid arthritis or cancer treatment[8].
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