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Pharmacology · Antianaemia agents (iron, folic acid, vitamin B12)

Folic acid !

The synthetic form of folate. It treats folate-deficiency megaloblastic anaemia and, taken before and early in pregnancy, prevents neural tube defects.

Updated 2026-11-01

Also called: pteroylglutamic acid

The figure shows folic acid itself in the active site of human dihydrofolate reductase, the enzyme that reduces it to its active tetrahydrofolate form.

Target in 3D: Dihydrofolate reductase (activates folic acid). PDB structure 1DHF (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Folic acid is inactive as taken. Dihydrofolate reductase reduces it to tetrahydrofolate, which carries one-carbon units needed to make thymidylate and purines. Without it, dividing cells cannot copy DNA, red cell precursors grow large (megaloblasts) and the neural tube may fail to close in the embryo. It corrects the anaemia of B12 deficiency too, but not its nerve damage.

  1. Folic acid is absorbed in the small intestine
  2. DHFR reduces it to tetrahydrofolate
  3. Tetrahydrofolate donates carbons for thymidylate and purines
  4. DNA synthesis and normal red cells return

Pharmacokinetics

Absorption
Well absorbed by mouth in the proximal small intestine
Metabolism
Reduced in tissues to tetrahydrofolate

Indications

Adverse effects

Common

  • Usually well tolerated
  • Rash and itching (allergy, rare)

Contraindications

  • Untreated vitamin B12 deficiency (pernicious anaemia) as the only therapy
  • Hypersensitivity

Key interactions

Phenytoin, phenobarbital, primidone
Large amounts of folic acid may lower their antiseizure effect
Methotrexate, trimethoprim, pyrimethamine
They inhibit dihydrofolate reductase and can cause folate deficiency; folic acid needs this enzyme, so methotrexate toxicity is rescued with calcium folinate instead

What is monitored

  • Haemoglobin, MCV and reticulocytes
  • Vitamin B12 level before treating megaloblastic anaemia

Administration and safety

  • Usually oral, once daily
  • Parenteral forms exist for patients who cannot take it by mouth

Nursing care

  • Advise people who may become pregnant about starting it before conception
  • Confirm that B12 deficiency has been excluded before it is used alone for macrocytic anaemia
  • Give dietary advice: leafy green vegetables, fruit, liver

Pregnancy and breastfeeding

Recommended before conception and through early pregnancy to reduce neural tube defects; higher amounts are advised after a previous affected pregnancy.

Test yourself

Think of the answer, then tap the question to see it.

Which enzyme converts folic acid into its active form?

Dihydrofolate reductase.

Why should B12 deficiency be excluded before giving folic acid alone?

Folic acid corrects the anaemia but the neurological damage of B12 deficiency progresses.

When should folic acid start to prevent neural tube defects?

Before conception, continuing through the first trimester.

Why is calcium folinate, not folic acid, used for methotrexate rescue?

Folic acid needs DHFR, which methotrexate blocks; folinate is already reduced.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Folic Acid: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 45 (McGraw Hill, 2023); Farmacología básica y clínica (Katzung), 16.ª ed., cap. 33 (McGraw Hill, 2025); DailyMed - HYDROXOCOBALAMIN injection, solution (DailyMed (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.