What is Folate and What Does It Do?
Folate is an essential vitamin that functions as a critical cofactor in one-carbon metabolism, playing a vital role in DNA synthesis, RNA production, amino acid metabolism, and methylation reactions necessary for normal cell division, growth, and development. 1, 2
Biochemical Functions of Folate
Folate, as tetrahydrofolate, serves several crucial physiological functions:
- DNA and RNA synthesis - Essential for the production of purines and thymidylate, which are building blocks of DNA and RNA 1, 3
- Amino acid metabolism - Involved in the remethylation of homocysteine to methionine 1, 2
- Methylation reactions - Provides methyl groups for various biochemical processes 2
- One-carbon metabolism - Transfers one-carbon units in metabolic pathways 1
- Erythropoiesis - Maintains normal red blood cell formation 3
Forms and Absorption
- Folate refers to a family of molecules that vary in oxidation state and chemical structure 1
- Natural folate is found in foods, while folic acid is the synthetic form used in supplements and fortified foods 1, 2
- Folate is absorbed in the duodenum and jejunum through a pH-dependent carrier-mediated process 1
- Vitamin C improves folate bioavailability by protecting it from degradation in the stomach 1
Dietary Sources and Requirements
- Primary food sources: Pulses (legumes), leafy green vegetables, eggs, nuts, and whole grain products 1, 2
- Recommended intake: 250-400 μg/day of dietary folate equivalents (DFE) for the general population 1, 2
- Pregnant/lactating women: Require approximately twice the amount (500-600 μg/day) 2
- Bioavailability: Food folates have lower bioavailability than synthetic folic acid 1
Health Consequences of Folate Deficiency
Inadequate folate status can lead to:
- Megaloblastic anemia - Characterized by large, immature red blood cells 2, 3
- Neural tube defects - Including spina bifida and anencephaly in developing fetuses 2, 4
- Elevated homocysteine levels - Associated with cardiovascular risk 2, 5
- Genomic instability - Affecting DNA methylation and repair 2, 4
- Impaired brain development - Affecting brain volume, cortical thickness, and neurogenesis 6
- Other birth defects - Including cleft lip/palate and cardiac defects 2
Clinical Assessment of Folate Status
Folate status can be assessed through:
- Serum/plasma folate - Reflects recent dietary intake 1, 5
- Red blood cell folate - Indicates long-term status over preceding 3 months 1, 5
- Plasma homocysteine - Functional marker of folate status (also affected by vitamins B2, B6, B12) 1, 5
- Serum levels below 5 ng/mL - Indicate folate deficiency 3, 5
- Levels below 2 ng/mL - Usually result in megaloblastic anemia 3, 5
Supplementation Guidelines
- Women of childbearing age: 400 μg daily of folic acid to prevent neural tube defects 2
- Women with previous neural tube defect-affected pregnancy: 4 mg daily of folic acid 2
- Treatment of folate deficiency: Typically 1-5 mg daily of folic acid 2, 3
Potential Risks of Excessive Intake
- High doses (>1 mg/day) may mask vitamin B12 deficiency 2
- Excessive intake has been associated with increased risk of certain conditions including advanced adenomas 2
- Unmetabolized excessive folate may affect health adversely 4