Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth defects of her baby’s brain or spine.
Foods with folic acid in them include
- Leafy green vegetables
- Fruits
- Dried beans, peas, and nuts
- Enriched breads, cereals and other grain products
If you don’t get enough folic acid from the foods you eat, you can also take it as a dietary supplement.
Certainly. Here’s a comprehensive overview of folic acid, including its biochemistry, physiological roles, uses, sources, metabolism, deficiency risks, and more.
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage.
Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods.
The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.
Folate in the form of folic acid is used to treat anemia caused by folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby.
NTDs include anencephaly and spina bifida, among other defects. Low levels in early pregnancy are believed to be the cause of more than half of babies born with NTDs. More than 80 countries use either mandatory or voluntary fortification of certain foods with folic acid as a measure to decrease the rate of NTDs.
Long-term supplementation with relatively large amounts of folic acid is associated with a small reduction in the risk of stroke and an increased risk of prostate cancer.There are concerns that large amounts of supplemental folic acid can hide vitamin B12 deficiency.
Not consuming enough folate can lead to folate deficiency. This may result in a type of anemia in which red blood cells become abnormally large. Symptoms may include feeling tired, heart palpitations, shortness of breath, open sores on the tongue, and changes in the color of the skin or hair. Folate deficiency in children may develop within a month of poor dietary intake.
In adults, normal total body folate is between 10 and 30 mg with about half of this amount stored in the liver and the remainder in blood and body tissues. In plasma, the natural folate range is 150 to 450 nM.
Folate was discovered between 1931 and 1943. It is on the World Health Organization’s List of Essential Medicines. In 2022, it was the 65th most commonly prescribed medication in the United States, with more than 10 million prescriptions. The term “folic” is from the Latin word folium (which means leaf) because it was found in dark-green leafy vegetables.
1. What is Folic Acid?
- Folic acid is the synthetic, oxidized form of vitamin B9, used in supplements and food fortification.
- The natural form in foods is called folate.
- It is water-soluble and belongs to the B-vitamin family.
- Once absorbed, folic acid is converted in the body to tetrahydrofolate (THF) and its derivatives, which are biologically active coenzymes.
2. Chemical Structure
- Chemical formula: C₁₉H₁₉N₇O₆
- It consists of:
- Pteridine ring
- Para-aminobenzoic acid (PABA)
- Glutamic acid residue
These three parts are essential for its function in one-carbon metabolism.
3.Biological Functions
Folic acid is vital for one-carbon metabolism, where it serves as a coenzyme in:
| Function | Biological Role |
|---|---|
| DNA synthesis and repair | Required for purine and pyrimidine synthesis (thymidylate) |
| Amino acid metabolism | Involved in interconversion of serine ↔ glycine and in methionine synthesis |
| Methylation reactions | Supports SAM (S-adenosylmethionine) synthesis; key for gene regulation and neurotransmitter synthesis |
| Erythropoiesis | Supports red blood cell production; deficiency leads to megaloblastic anemia |
| Neural tube development | Crucial during early pregnancy to prevent birth defects |
4. Absorption, Transport, and Metabolism
| Step | Details |
|---|---|
| Absorption | Occurs mainly in the proximal jejunum via active transport and passive diffusion |
| Conversion | Folic acid is converted to dihydrofolate (DHF) then to tetrahydrofolate (THF) by dihydrofolate reductase (DHFR) |
| Methylation | THF is converted to 5-methyltetrahydrofolate (5-MTHF), the primary circulating form |
| Storage | Stored in the liver; body stores ~5–20 mg |
| Excretion | Excess is excreted via urine; daily loss ~50–100 mcg |
5. Dietary Sources of Folate
| Food | Approx. Folate Content |
|---|---|
| Leafy greens (spinach) | 194 mcg / ½ cup cooked |
| Asparagus | 89 mcg / 4 spears |
| Lentils | 180 mcg / ½ cup cooked |
| Fortified cereals (US) | 100–400 mcg per serving |
| Orange juice | 55 mcg / ¾ cup |
| Liver (beef, chicken) | 200–300 mcg / 3 oz |
6. Recommended Dietary Allowance (RDA)
| Group | RDA (mcg DFE) |
|---|---|
| Adults (M/F) | 400 mcg |
| Pregnant women | 600 mcg |
| Breastfeeding women | 500 mcg |
| Children 1–3 years | 150 mcg |
| Adolescents (14–18) | 400 mcg |
Note: 1 mcg dietary folate equivalent (DFE) =
- 1 mcg food folate
- 0.6 mcg folic acid (from supplements/fortified foods with food)
- 0.5 mcg folic acid on empty stomach
7. Clinical Uses
A. Preventive
- Neural tube defects (NTDs): Spina bifida, anencephaly – supplementation before and during early pregnancy is critical
- Cardiovascular protection: May lower homocysteine levels (a risk factor for atherosclerosis)
- Cancer prevention: Controversial; low folate may increase cancer risk, high-dose supplementation might promote growth in established tumors
B. Therapeutic
- Megaloblastic anemia: Due to folate deficiency
- Methotrexate rescue: In cancer or autoimmune therapy, leucovorin (a folate form) is used
- Hyperhomocysteinemia: To prevent thrombosis and vascular disease
- Depression (adjunctive): Folate metabolism influences serotonin and dopamine pathways
- Infertility: Supports DNA synthesis in germ cells
8. Deficiency of Folate
Causes:
- Poor diet (especially in alcoholics, elderly)
- Malabsorption (e.g., celiac disease, inflammatory bowel disease)
- Increased needs (pregnancy, hemolytic anemia, cancer)
- Drug interference: Methotrexate, phenytoin, sulfasalazine, trimethoprim
Symptoms:
- Megaloblastic anemia (fatigue, pallor, glossitis)
- Neural tube defects in fetus
- Cognitive decline (elderly)
- Elevated homocysteine → vascular risk
9. Excess and Toxicity
- Upper Limit (UL) for folic acid (from supplements/fortification): 1000 mcg/day
- No known toxicity from food folate
- Masking of B12 deficiency is the main concern: high folic acid can correct anemia but not the neurological damage of B12 deficiency
10. Drug Interactions
| Drug | Effect |
|---|---|
| Methotrexate | Inhibits DHFR; folate antagonist |
| Phenytoin, Carbamazepine | May reduce folate absorption |
| Trimethoprim, Pyrimethamine | Antifolates; inhibit DHFR |
| Sulfasalazine | Inhibits folate absorption |
Summary
- Folic acid is an essential B vitamin critical for cell division, DNA synthesis, RBC formation, and fetal development.
- Deficiency is common in malnourishment and certain disease states.
- It plays roles in prenatal health, cardiovascular protection, and neurologic function.
- Widespread fortification has dramatically reduced neural tube defects globally.
Folate Deficiency
Folate deficiency is when your blood lacks the amount of vitamin B9 (folate) it needs to function properly. Folate deficiency can cause a wide range of symptoms and complications.
What complications can occur due to folate deficiency?
When you don’t get enough folate, several complications can occur.
Folate deficiency during pregnancy
Folate deficiency during pregnancy can cause severe complications. Folate is important for the growth of the fetus’s brain and spinal cord. Folate deficiency can cause severe birth defects called neural tube defects. Neural tube defects include spina bifida and anencephaly.
Folate deficiency can also increase your chances of placental abruption, a condition where your placenta separates from your uterus. In addition, your baby may be premature (preterm birth) and/or have a low birth weight. Studies have also shown low folate during pregnancy could lead to the development of autism in your child.
Folate deficiency anemia
Folate deficiency can also lead to folate deficiency anemia. Anemia can happen when your body doesn’t have enough healthy red blood cells. Your body needs red blood cells to carry oxygen to your body tissues. Folate deficiency anemia can also cause your body to produce abnormally large red blood cells that don’t function properly.
Other complications of folate deficiency can include:
- Infertility.
- Certain cancers.
- Cardiovascular disease.
- Depression.
- Dementia.
- Decreased cognitive function.
- Alzheimer’s disease.
Symptoms and Causes
What are the symptoms of folate deficiency?
One of the first symptoms of folate deficiency is extreme tiredness (fatigue). Other symptoms may include:
Anemia symptoms
- Paleness.
- Shortness of breath (dyspnea).
- Irritability.
- Dizziness.
Oral symptoms
- Tender, red tongue.
- Mouth sores or mouth ulcers.
- Reduced sense of taste.
Neurological symptoms
- Memory loss.
- Difficulty concentrating.
- Confusion.
- Problems with judgment.
Additional symptoms of folate deficiency may include:
- Lack of energy.
- Muscle weakness.
- Depression.
- Weight loss.
- Diarrhea.
What causes folate deficiency?
One of the most common causes of folate deficiency is not eating a healthy, balanced diet. A healthy diet includes foods that naturally contain folate or are enriched with folic acid. Other causes of folate deficiency can include:
- Digestive system diseases: Your digestive system doesn’t absorb folic acid well if you have a disease such as Crohn’s disease or celiac disease.
- Excessive alcohol use: People who drink large amounts of alcohol sometimes substitute alcohol for food. As a result, they don’t get enough folate.
- Overcooking your fruits and vegetables: When you overcook, the heat can destroy the naturally occurring folate in your produce.
- Hemolytic anemia: A blood disorder that occurs when your red blood cells are destroyed and can’t be replaced fast enough.
- Certain medications: Some anti-seizure drugs and ulcerative colitis drugs interfere with the proper absorption of folate.
- Kidney dialysis: A treatment for people with kidney failure.
Diagnosis and Tests
How is folate deficiency diagnosed?
Your healthcare provider will ask about your medical history and your symptoms. They can diagnose folate deficiency through a blood test. The blood test measures the amount of folate in your blood. A low level of folate indicates a folate deficiency.
Management and Treatment
How is folate deficiency treated?
Your healthcare provider will treat your folate deficiency with a folic acid supplement. Most adults need 400 micrograms (mcg) of folic acid each day. Your healthcare provider will let you know how much you should take.
Your healthcare provider will also advise you to eat a healthy, balanced diet. A balanced diet includes fruits, vegetables and other foods that contain folate or are enriched with folic acid.
Prevention
How can I prevent folate deficiency?
The best way to prevent folate deficiency is to eat a healthy diet that includes foods that contain folate or folic acid. Folate can be found naturally in:
- Peas, beans and legumes.
- Citrus fruits.
- Dark green leafy vegetables.
- Liver.
- Seafood.
- Eggs and dairy.
- Meat and poultry.
Folic acid can be found in enriched or fortified:
- Bread.
- Flour.
- Pasta.
- Rice.
- Cereal.
The amount of folate you need every day depends on your age and other factors. Most adults should get 400 micrograms (mcg) of folate daily. If you’re pregnant, you should take a folic acid supplement to make sure you’re getting enough folate each day. The average daily recommended amount of folate you need are:
| Age/Life Stage | Recommended Amount of Dietary Folate Equivalents (DFEs) |
|---|---|
| Birth to age 6 months | 65 mcg DFE |
| Infants ages 7 to 12 months | 80 mcg DFE |
| Children ages 1 to 3 years | 150 mcg DFE |
| Children ages 4 to 8 years | 200 mcg DFE |
| Children ages 9 to 13 years | 300 mcg DFE |
| Teenagers ages 14 to 18 years | 400 mcg DFE |
| Adults ages 19 years and up | 400 mcg DFE |
| While pregnant | 600 mcg DFE |
| While breastfeeding | 500 mcg DFE |
If you’re taking any medication that interferes with folate absorption, you should also take a folic acid supplement.