Folic Acid


Folic acid is a member of the water-soluble B vitamin group. Isolated in 1946 from spinach leaves, its name comes from folium, the Latin word for leaf. In the body, folic acid is converted to its biologically active form tetrahydrofolic acid (THFA). Niacin and vitamin C are necessary for this conversion. Structurally, folic acid consists of a pteridine nucleus (containing two rings), conjugated with para-aminobenzoic acid, and glutamic acid. Hence, its chemical name is pteroylmonoglutamate.

Dosage Info

Dosage Range

200-800mcg daily. However, physicians may occasionally administer doses to severely deficient patients ranging from 5,000-15,000mcg daily. (1)

Most Common Dosage

400mcg daily.

Dosage Forms

Tablets, capsules, liquids, liposomal sprays, and effervescent tablets.

Adult RDI


Adult ODA



  • RDA listed as dietary folate:
  • Infants 14 years: 400mcg
  • Pregnancy: 600mcg
  • Lactation: 500mcg

Interactions and Depletions



Active Forms

Folic acid (also known as folate) and folinic acid (also known as 5-methyl tetrahydro-folate).


Folic acid absorption occurs primarily in the first part of the small intestine via two separate mechanisms, which include:
a) active transport, which requires a folate-binding protein (FBP)
b) passive diffusion, which accounts for 20 to 30 percent of folate absorption

Toxicities & Precautions


There are no known toxicities associated with folic acid.

Large doses of folic acid can mask an underlying vitamin B12 deficiency, which if undetected, could result in irreversible nerve damage. (2) Consequently, folic acid is limited to 800mcg in OTC nutritional supplements and 1mg in prescription products.

Functions in the Body

DNA and RNA Synthesis:

Like vitamin B12, folic acid is necessary for the synthesis of both DNA and RNA. Hence, it is essential for proper cellular division and the transmission of the genetic code to all newly formed cells.


Necessary for decreased incidence of neural tube defects during pregnancy. (3) , (4)

Red Blood Cells:

Essential for the healthy maturation of red blood cells. (5)

Methylation Reactions:

Required for some methylation reactions such as the conversion of homocysteine to methionine.

Protein and Amino Acid Synthesis:

Involved in the synthesis of proteins and various amino acids.

Clinical Applications

Alzheimer's Disease

Relative folate deficiency may precede Alzheimer disease and vascular dementia onset. (6)


Many patients with major depression and schizophrenia improve with folic acid therapy. (7)

Pregnancy And Lactation

Doubles the requirements for folic acid. (8)


Homocysteine concentrations, when elevated, are a risk factor for atherosclerotic disease. Folic acid lowers homocysteine levels, which decreases atherogenesis. (9) , (10) , (11) , (12) , (13) , (14) . The same effect has been noted when folic acid is given in conjunction with vitamin B6 and vitamin B12. (15) , (16) , (17) Lipid lowering medications known as "fibrates" have been shown to increase homocysteine levels. A study was conducted in which fenofibrate was given either with placebo or with vitamins including vitamin B6, vitamin B12 and folic acid. The homocysteine measurements with the vitamins were significantly lower than the measurements taken without the vitamins. (18) Dietary supplementation with the B-vitamins prevented hyperhomocysteinemia but did not prevent the development of vascular dysfunction or atherosclerotic lesions. (19)

In patients who have undergone angioplasty, benefit has been documented with therapy consisting of vitamin B6, vitamin B12 and folic acid. In a prospective, double-blind, randomized trial, 205 patients who had undergone a successful coronary angioplasty were given a combination of folic acid, vitamin B12 and pyridoxine or placebo for six months. Treatment significantly lowered plasma homocysteine levels and at follow-up, the minimal luminal diameter was significantly larger in the treatment group, the degree of stenosis was less severe, the rate of restenosis was significantly lower and the need for revascularization of the target lesion was less in patients assigned to folate treatment. (20)

Another randomized, double-blind placebo-controlled trial involving 553 patients was designed to evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention. After successful angioplasty of at least 1 significant coronary stenosis, patients were enrolled and randomized to either a combination of folic acid, vitamin B12, and vitamin B6 or a placebo for 6 months. After 1 year, the endpoints (death, nonfatal myocardial infarction, or revascularization) were lower in patients receiving the homocysteine lowering therapy. (21)

Birth Defects

Adequate folic acid is necessary to prevent neural tube birth defects such as spina bifida. (22)

Cervical Dysplasia

Often due to a folic acid deficiency, many hysterectomies can be prevented with adequate folic acid supplementation. (23)


Folic acid lowers homocysteine levels. Homocysteine interferes with collagen crosslinking, which leads to a defective bone matrix. (24)


Alcohol inhibits folate absorption and alcoholics are usually deficient. (25)

Cognitive Enhancement

A literature review of recent research has noted subclinical differences in nutritional status of certain B vitamins among older adults may influence certain aspects of cognitive performance. Supplementation with folate, vitamin B12 and vitamin B6 has been effective in enhancing cognitive performance in older adults. (26)

Of note, a study evaluating 370 nondemented people 75 years old or older for three years, noted that subjects with low levels of vitamin B12 or folate had twice the risk of developing Alzheimer's disease. A clearer association was noted when both vitamins were taken into consideration. (27)


Effectively treated using 0.1% folate solution as a mouthwash. (28)

Symptoms and Causes of Deficiency

Folic acid deficiency disrupts DNA metabolism, which causes abnormal cellular development, especially in cells with the most rapid rates of turnover which includes red blood cells, leukocytes, and epithelial cells of the stomach, intestine, vagina, and uterine cervix.

    Folic acid is one of the most common vitamin deficiencies. Substantial destruction occurs during food processing and heat, light, and oxygen easily destroy it. Folic acid needs are greatly increased during pregnancy. (29) Megaloblastic anemia (abnormally large red blood cells) is a result of a folic acid or vitamin B12 deficiency. Symptoms of folic acid deficiency include headache, fatigue, hair loss, insomnia, birth defects, cervical dysplasia, and elevated homocysteine. The following drugs can cause folic acid depletion: oral contraceptives, triamterene, anticonvulsants, H-2 receptor antagonists, trimethoprim, cholestyramine, anti-inflammatory drugs, methotrexate, aspirin, antacids, and alcohol.

Dietary Sources

Folic acid occurs in a wide variety of foods. Best sources include dark green leafy vegetables, brewer’s yeast, liver, and eggs. Other good sources are beets, broccoli, brussels sprouts, orange juice, cabbage, cauliflower, cantaloupe, kidney and lima beans, wheat germ, and whole grain cereals and breads. The "friendly" intestinal bacteria also synthesize folic acid.


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  3. View Abstract: Evans MI, Llurba E, Landsberger EJ, OBrien JE, Harrison HH. Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values. Obstet Gynecol. Mar2004;103(3):474-9.
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