Folate Deficiency

What folate does

Folate is a B vitamin needed to build DNA and RNA and for cell division. Tissues that renew quickly, such as bone marrow, the gut lining and a developing baby, are most affected by a shortage. Folate also helps convert homocysteine into methionine; low folate raises homocysteine levels.

Folate is the natural form found in foods. Folic acid is the synthetic form used in supplements and fortified foods, and it is absorbed more efficiently. In the US, enriched grain products have been fortified with folic acid since 1998, which made deficiency much less common.

The body stores only enough folate for a few months, so deficiency can develop within 3 to 4 months of poor intake.

Causes

Low intake

• diets low in fruits, vegetables, beans and fortified grains
• older adults living alone, people with eating disorders, and poverty
• overcooking vegetables destroys folate

Increased needs

• pregnancy and breastfeeding
• conditions with rapid cell turnover: hemolytic anemia, sickle cell disease, severe psoriasis or exfoliative skin disease
• dialysis

Poor absorption

• celiac disease
• Crohn's disease and other small bowel conditions
• bowel surgery

Alcohol

Heavy drinking reduces intake, impairs absorption, and increases loss. Alcohol use disorder is one of the most common causes in the US.

Medicines

• methotrexate
• some anti-seizure medicines: phenytoin, carbamazepine, valproate, phenobarbital
• trimethoprim and sulfasalazine
• pyrimethamine

Genetics

Common variants of the MTHFR gene slightly reduce folate processing, but they rarely cause folate deficiency by themselves when intake is adequate.

Symptoms

Symptoms develop gradually:

• fatigue, weakness and lack of energy
• shortness of breath and palpitations on exertion
• pale skin or mild yellowing
• a sore, red, smooth tongue (glossitis)
• mouth ulcers and cracks at the corners of the mouth
• diarrhea and loss of appetite
• irritability, poor concentration and low mood

Unlike vitamin B12 deficiency, folate deficiency does not usually cause nerve damage. Numbness, tingling or balance problems point to B12 deficiency.

Folate deficiency in pregnancy

The neural tube, which becomes the brain and spinal cord, closes within the first 4 weeks of pregnancy, often before a person knows they are pregnant. Low folate at this time increases the risk of neural tube defects such as spina bifida and anencephaly.

The CDC and US Preventive Services Task Force recommend that everyone who could become pregnant take 400 micrograms of folic acid daily, starting at least 1 month before conception and continuing through early pregnancy. People with a previous pregnancy affected by a neural tube defect, or taking certain anti-seizure medicines, may be advised by their doctor to take a higher dose.

Diagnosis

• Complete blood count: anemia with large red cells (high MCV).
• Blood smear: large oval red cells and white cells with extra nuclear lobes.
• Serum folate and sometimes red cell folate, which reflects longer-term status.
• Vitamin B12 level: always checked, because the anemia looks identical and treating with folic acid alone can mask B12 deficiency while nerve damage progresses.
• Homocysteine and methylmalonic acid: homocysteine is raised in both deficiencies; methylmalonic acid is raised only in B12 deficiency.
• Tests for the cause: celiac antibodies, liver tests, and review of medicines and alcohol.

Treatment

• Folic acid tablets, usually taken daily for about 4 months to replenish stores, at a dose prescribed by your doctor. Longer-term treatment if the cause continues.
• Check and treat vitamin B12 deficiency first or at the same time.
• Treat the cause: reduce alcohol, manage celiac or Crohn's disease, adjust medicines where possible. People on methotrexate are often prescribed folic acid to reduce side effects.
• Diet: include folate-rich foods:

Blood counts usually start improving within 1 to 2 weeks and return to normal within about 2 months.

Complications

• worsening anemia and, in older people, heart strain
• neural tube defects in pregnancy
• raised homocysteine, which is associated with cardiovascular disease
• masked B12 deficiency if folic acid is given alone

Frequently asked questions

What are the symptoms of folate deficiency?

Common symptoms are tiredness, weakness, shortness of breath, pale skin, a sore red tongue, mouth ulcers, diarrhea and irritability. They develop gradually as anemia worsens. Numbness or tingling suggests vitamin B12 deficiency instead or as well.

What causes low folate?

The main causes are a diet low in fruits, vegetables and fortified grains, heavy alcohol use, conditions that reduce absorption such as celiac or Crohn's disease, increased needs in pregnancy or hemolytic anemia, and medicines such as methotrexate and some anti-seizure drugs.

How long does it take to correct folate deficiency?

With folic acid tablets, people often feel better within days to weeks. Blood counts improve within 1 to 2 weeks and usually normalize within about 2 months. Treatment typically continues for around 4 months to rebuild stores.

What is the difference between folate and B12 deficiency?

Both cause the same type of anemia with large red blood cells. B12 deficiency can also damage nerves, causing numbness, tingling and memory problems, while folate deficiency usually does not. Both must be tested, because treating with folic acid alone can hide B12 deficiency.