What is Folic Acid
Folic acid is the synthetic form of vitamin B9, a water-soluble B vitamin that is essential for DNA synthesis, cell division, and proper fetal neural tube development, particularly critical during the first 28 days after conception. 1, 2
Chemical Nature and Forms
- Folic acid is the synthetic, manufactured form of vitamin B9 found in supplements and fortified foods, while folate is the naturally occurring form present in foods like spinach, broccoli, Brussels sprouts, beans, lentils, and oranges 3, 2
- The name derives from the Latin word "folium" (leaf), as it was first discovered in spinach leaves and synthesized in 1945 4
- Folic acid acts as a coenzyme for one-carbon transfer reactions essential for purine and pyrimidine synthesis, amino acid metabolism, and DNA/RNA production 1, 2
Critical Role in Pregnancy and Neural Tube Defect Prevention
- Neural tube closure occurs within the first 28 days after conception—often before a woman knows she is pregnant—making preconception supplementation absolutely essential 1, 5
- Folic acid supplementation reduces the risk of neural tube defects (spina bifida and anencephaly) by approximately 50-72%, preventing severe lifelong disability or death 1, 6
- Approximately 2,500 infants are born annually in the United States with neural tube defects, with all anencephalic infants dying shortly after birth and most spina bifida survivors facing paralysis and bowel/bladder incontinence 1
Recommended Dosages by Risk Category
Standard-Risk Women
- All women of childbearing age (12-45 years) capable of becoming pregnant should take 0.4-0.8 mg (400-800 μg) of folic acid daily, regardless of pregnancy plans, because over 50% of pregnancies are unplanned 1, 6
- Supplementation should begin at least 1 month before conception and continue through the first trimester 6, 7
- This dose can be obtained through multivitamin supplements, fortified foods, or dedicated folic acid tablets 8
High-Risk Women
- Women with previous neural tube defect-affected pregnancies, first- or second-degree relatives with neural tube defects, type 1 diabetes, or taking antiepileptic medications require 4-5 mg (4,000-5,000 μg) daily 1, 9, 7
- High-dose supplementation should start 3-6 months before conception and continue through 12 weeks of gestation, then reduce to 0.4-1.0 mg daily for the remainder of pregnancy 9, 7
- The 4-5 mg dose should be taken as folic acid alone, not in multivitamin format, to avoid excessive intake of other vitamins like vitamin A 3, 7
Role in Treating Anemia
- Folic acid is FDA-approved for treating megaloblastic anemias caused by folic acid deficiency, which may occur in tropical or nontropical sprue, nutritional deficiency, pregnancy, infancy, or childhood 10
- Folic acid requirements are markedly increased during pregnancy and lactation, and deficiency results in impaired DNA synthesis affecting rapidly dividing cells like red blood cells 10
Critical Safety Considerations
- Folic acid doses above 0.1 mg daily may mask vitamin B12 (pernicious anemia) deficiency by correcting the anemia while allowing irreversible neurologic damage to progress 10
- However, vitamin B12 deficiency is rare in young women of childbearing age (less than 1% have serum B12 levels below 100 pg/mL), making routine screening unnecessary before starting standard 0.4-0.8 mg doses 1, 7
- For high-dose supplementation (>1 mg), vitamin B12 deficiency should be ruled out, and taking folic acid with vitamin B12 (2.6 μg/day) in a multivitamin mitigates this concern 9, 7
- Total daily folic acid intake should remain below 1 mg unless under physician supervision to avoid masking B12 deficiency 1, 8
Mechanism of Action in Neural Tube Defect Prevention
- Folic acid participates in one-carbon transfer reactions critical for methylation reactions, DNA synthesis, histone and DNA methylation, methionine production, and homocysteine remethylation 1, 2
- Decreased blood folic acid levels inhibit DNA replication, repair, and RNA synthesis in rapidly proliferating fetal neural tissue, causing neural tube defects 2
- The exact mechanism by which folic acid prevents neural tube defects remains incompletely understood, but its role in regulating DNA synthesis and function during embryogenesis is essential 1
Public Health Impact
- Mandatory folic acid fortification programs in 71 countries have achieved up to 78% reduction in neural tube defect rates and increased red blood cell folate concentrations approximately 1.47-fold 5
- The U.S. Public Health Service has recommended folic acid supplementation for all women capable of becoming pregnant since 1992, representing 30 years of proven prevention strategy 1, 5
- Even with adequate supplementation, not all neural tube defects can be prevented due to multifactorial or monogenic etiology, but 50-72% of cases are preventable 9, 6