Folic Acid Deficiency

Folic Acid Deficiency: Overview

Alternative names: Vitamin B9 deficiency, Increased Folic Acid Requirement

Folic acid deficiency is one of the most common of all vitamin deficiencies.  Although it occurs in both males and females, folic acid deficiency anemia most often affects women over 30.  It becomes increasingly common as age impedes the body's ability to absorb folic acid, a water-soluble vitamin that is manufactured by intestinal bacteria and stored for a short time in the liver.

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Folic acid, folate and folacin refer to one of the B-vitamins required for a healthy body.  Folic acid aids in the prevention of birth defects called neural tube defects (NTDs) such as spina bifida and anencephaly.  Research has shown that adequate amounts of folic acid can prevent up to half of these birth defects, if women start taking folic acid supplements shortly before conception.

When folic acid is consumed, it is actively transported into the blood from the gastrointestinal tract, where it acts as a coenzyme for a multitude of functions and often is converted to its active form, tetrahydrofolic acid (THFA), in the presence of the niacin coenzyme (NADPH) and vitamin C.  In the body, folic acid is found mainly as methyl folate, and vitamin B12 is needed to convert it back to the active THFA.  Extra folic acid is stored in the liver, enough for six to nine months of vitamin for body use before deficiency symptoms might develop.

Folic acid or, more specifically, its coenzyme THFA, has functions very similar to those of vitamin B12.  Folic acid aids in red blood cell production by carrying the carbon molecule to the larger heme molecule, which is the iron-containing part of hemoglobin (the oxygen-carrying molecule of the red blood cells).

Alongside B12 and vitamin C, THFA helps in the breakdown and utilization of protein.  With B12, it assists in many amino acid conversions, such as the methylation of methionine, serine, histidine, and even the B vitamin cholineFolic acid is also used in the formation of the nucleic acids for RNA and DNA.  Actually, the anemia that results from folic acid deficiency comes from the lack of THFA and decreased synthesis of the purines and pyrimidines that make up the DNA.  So folic acid has a fundamental role in the growth and reproduction of all cells.

Folic acid is necessary for growth and cellular repair, since it is a critical component of DNA and RNA.  It is also essential for the formation and maturation of red blood cells.  Since folic acid is important to the division of cells in the body, it is even more essential during times of growth, such as pregnancy.  Pregnancy is a time of rapid cell multiplication.  If there is a deficiency of folic acid, there is decreased nucleic acid synthesis, and cell division is hampered.  This deficiency can lead to low birth weight or growth problems in infants.

For this reason, pregnancy is a time for concern about sufficient folic acid intake (the RDA doubles during pregnancy).  Also, those eating the standard American diet ("SAD") that is high in fats, meats, white flour, white sugar, and desserts may develop folic acid deficiency.  Eating some fresh or lightly-cooked vegetables daily will allow one to maintain normal folate levels.

We should be concerned about folate deficiency primarily in pregnancy, during breast-feeding, and in the elderly.  Folic acid absorption seems to diminish with age, and deficiency is common in the elderly, especially those in rest or nursing homes, who are unlikely to get fresh vegetables or supplements.

Incidence; Contributing Risk Factors

Folic acid deficiency is fairly common.

Alcoholics have had serious problems maintaining proper folic acid levels.  Teenagers with poor diets, who do not eat green vegetables or many vegetables at all other than fried potatoes, may more easily become folic acid deficient.

Signs and Symptoms

Often, the first manifestation of a low folate level is feeling depressed.  Folic acid deficiency is more common in people with depression or other psychological symptoms in mental institutions.

Besides causing mental symptoms, folate deficiency can also affect the skin.  As in vitamin B2 (riboflavin) deficiency, cracks or scaling at the lips and corners of the mouth (cheilosis) may occur.  Also possible with deficiency are decreased growth, fatigue, and more rapid graying of the hair.

Folic acid deficiency generates a picture similar to that of a B12 deficiency – anemia, fatigue, irritability, anorexia, weight loss, headache, sore and inflamed tongue, diarrhea, heart palpitations, forgetfulness, hostility, and a feeling of paranoia.  Often, the mental symptoms occur before the anemia, with poor memory (possibly from decreased RNA synthesis), general apathy, withdrawal, irritability, and a decrease in basic mental powers.

Diagnosis and Tests

If deficiency is suspected, it is wise to get a blood folate level test as well as a B12 level before treatment with supplements.  A red-blood-cell folate level may more accurately reflect body stores of folic acid.

Treatment and Prevention

Folic acid supplements are usually prescribed, and self-care includes avoiding:

  • alcohol
  • non-herbal tea, antacids, and phosphates (contained in beer, ice cream, and soft drinks), which restrict iron absorption
  • tobacco

Although adequate folic acid intake usually cures this condition in about three weeks.


Folic acid-deficiency anemia is not correctable with iron and, as it progresses, it will appear very different from iron-deficiency anemia.  The blood will show large, irregular red blood cells, while low iron causes small red blood cells.  In pregnancy, this megaloblastic anemia is of great concern.  Folic acid deficiency is very common during pregnancy, when the requirements are at least double those for the nonpregnant state.  Since folic acid stores in the liver can last several months, deficiency symptoms are more likely in later pregnancy.  The fetus can readily draw on the folic acid of the mother, and deficiencies can cause problems in both.  The mother's folacin-deficiency mental symptoms of indifference, lack of motivation, withdrawal, or depression may be passed over as hormonal.  The anemia may likewise not be considered a matter for concern.  Serious problems can result from a major deficiency.  Toxemia of pregnancy, premature birth, and hemorrhage are all possible in addition to the anemia of the mother.  The fetus could develop birth deformities, brain damage, or show poor growth as a child.  It is very important to supplement folic acid during pregnancy.

More recently, folic acid deficiency (along with vitamin A deficiency) has been associated with cervical dysplasia and cancer.

Severe deficiencies can result in congestive heart failure.

Signs, symptoms & indicators of Folic Acid Deficiency:

Lab Values - Cells

Lab Values - Nutrients


Symptoms - Head - Mouth/Oral

Symptoms - Nails

Conditions that suggest Folic Acid Deficiency:



Female Infertility

Folic acid deficiency can lead to infertility.


Chronic / Hidden Infection

Folic acid deficiency anemia can lead to increased susceptibility to infection.

Lab Values


Osteoporosis - Osteopenia

Folate (folic acid) and the B-vitamins involved in homocysteine conversion (such as B12 and B6) may be beneficial in reducing the risk of osteoporosis because high levels of homocysteine are implicated in chronic diseases such as osteoporosis.


Restless Leg Syndrome

Restless Leg Syndrome may be an early neurologic manifestation of folate deficiency, the most common of all the vitamin deficiencies.  Often the deficiency is not due to a poor diet, but to a genetic factor causing a folate dependency.  While not all RLS patients complain of uncomfortable sensations, folate-deficient patients always suffer from them. [Folic Acid in Neurology, Psychiatry and Internal Medicine, New York, Raven Press, 1979]

Tumors, Malignant

Acute Lymphocytic Leukemia (ALL)

Maternal folic acid supplementation during pregnancy was associated with a reduced risk of acute lymphoblastic leukemia in children in a study in Western Australia. [Lancet 2001;358(9297): pp.1935-40]

Risk factors for Folic Acid Deficiency:


Alcohol-related Problems

Alcohol interferes with the metabolism and absorption of folic acid.


Crohn's Disease

All inflammatory bowel disease patients are prone to low serum folate levels.

Ulcerative Colitis

All inflammatory bowel disease patients are prone to low serum folate levels.

Supplements, Medications, Drugs

(Past) H2-blocker antacid use

There is some evidence that H2 blockers may slightly reduce the absorption of folate.  Folate is an important nutrient and one that is commonly deficient in the diet, so if you are taking H2 blockers you should probably take folate supplements as well.

Current birth control pill use

Birth control pills reduce the folic acid content in the body.

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Folic Acid Deficiency suggests the following may be present:


Folic Acid Deficiency can lead to:

Dental / Oral

Canker Sores (Aphthous Ulcers)

Vitamin B12, folate, zinc and iron have been shown to be effective in up to 60% of patients with canker sores when such a vitamin or mineral deficiency has been documented. [Dermatologic Clinics 1996:14, pp.243-256, British Dental Journal 1985:159, pp.361-367]



There is substantial scientific evidence linking folic acid deficiency to depression.  Folate deficiency is common in depressed individuals. [Journal of Psychiatric Research 1982;20(2): pp.91-101, British Journal of Psychiatry 1991;159: pp.271-2, Nutrition Reviews 1997;55(5): pp.145-9]

Recommendations for Folic Acid Deficiency:


Folic Acid

Whether or not a woman is expecting a child, it is recommended that women of child-bearing age take folic acid every day in order to help prevent NTDs.  It is recommended that women take 0.6mg (600mcg) folic acid daily prior to conception and through the first 3 months of pregnancy.

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