The human body needs folic acid to synthesize DNA and new cells. Folic acid deficiency typically causes megaloblastic anemia.
The signs and symptoms of folic acid deficiency are non-specific. Subtle signs such as the development of glossitis and oral sores, grey discoloration of the hair, and in case of children, growth abnormalities may be observed; however, as folic acid deficiency leads to megaloblastic anemia, an anemic presentation is most often seen.
The severity of the symptoms is linked to the degree of the anemia and the general health of the individual; for instance, in old age, the symptoms are often much more marked even with a lower deficiency. The symptoms of anemia include fatigue, shortness of breath (especially on exertion) and palpitations. In severe cases, stable angina and intermittent claudication may also result. On physical examination, the skin and conjunctiva is often pale and the patient has a high volume pulse along with tachycardia. In long standing cases, ankle edema, cardiac murmurs and other signs of heart failure also begin to manifest.
In addition to these general signs and symptoms, the clinical manifestations resulting from the underlying etiology (such as anti-folate drug toxocoty, malabsorption, chronic kidney disease, hemolytic anemias, malignancies and homocysteinuria) may also be observed. Folic acid deficiency in pregnant women can predispose to the development of neural tube defects in the developing fetus (such as anencephaly, spina bifida, etc). Women with documented folic acid deficiency or with a history of bearing one or more child with a neural tube defect carry a particularly high risk. As folic acid is necessary for DNA repair, its deficiency may be associated with the development of certain cancers in the body.
The diagnosis of folic acid deficiency is easily made through a careful history and simple physical examination of the individual. A number of simple tests can help confirm the diagnosis. These include the following.
The treatment of folic acid deficiency is folic acid supplementation which is usually done orally. For mild cases, a diet containing high levels of folate (such as citrus fruits and green, leafy vegetables) can be adequate; however, supplementation using folic acid tablets is usually carried out. The dosage of these supplements depends upon the etiology and the severity of the deficiency. In case of anemia due to folic acid deficiency, a daily dose of 1 to 5 mg is usually administered and the hemoglobin, red cell folate and serum folate levels are repeated after some duration. Once the deficiency has been overcome, a maintenance dose of 5 mg per week is often given.
The dosage and duration of folic acid supplementation in folic acid deficiency due to other etiologies is different. In case of gastrointestinal malignancies, up to 5 mg of folic acid is taken for 3 to 8 years; whereas in other malignancies, doses as high as 40 mg may be taken for the same duration depending upon the severity. Folic acid deficiency resulting from overuse of methotrexate may require doses as high as 20 mg for up to 12 weeks   . In chronic kidney disease, supplementation of up to 15 mg is taken on alternate days for several years; whereas in homocysteinuria, up to 5 mg of folic acid is required for 1 to 6 months.
In case of overuse of phenytoin, gum hypertrophy may occur which is treated by supplementation along with the topical application of folic acid over the affected gums  . Pregnancy related gum disease is also treated in a similar fashion. Prophylactic folic acid supplementation is recommended to all women of child bearing age. Supplementation starting from 2 months prior to pregnancy and during the first two months of pregnancy is very effective in preventing the development of neural tube defects in the fetus .
The prognosis of folic acid deficiency itself is very good; however, the underlying etiology (such as any malignancy) may have a prognosis of its own. In the absence of any pathology, folic acid deficiency is completely reversible and does not carry any permanent effects.
The deficiency of folic acid caused due to poor nutrition, pregnancy or lactation is easily treatable with folic acid supplementation. Similarly, folic acid deficiency resulting from excessive alcohol intake rapidly responds to alcohol withdrawal. Folic acid deficiency due to pathological states responds to folic acid supplementation; however, the recovery is not permanent and the underlying pathology always has to be dealt with. Folic acid deficiency resulting from anti-folate drug use responds to folic acid supplementation and/or drug withdrawal.
Folic acid is not stored in the human body in good amounts due to which a daily intake of folic intake is required. Males require about 400 micrograms of folic acid daily whereas females require 400 to 600 micrograms. Plant sources of folic acid in the human diet include bananas, melons, citrus fruits, green leafy vegetables, tomatoes, peas and mushrooms whereas pork, poultry and kidney and liver meat are the animal sources. By far, the most common cause of folic acid deficiency is dietary deficiency. A diet low in folic acid may lead to folic acid deficiency over the course of a few weeks.
In addition to the consumption of unbalanced diets, dietary deficiency may result from poor intake due to starvation and old age. A number of disease states such as acute hepatitis, depression and anorexia nervosa lead to decreased appetite and can also cause inadequate dietary intake of folic acid. Excessive intake of alcohol interferes with the absorption of folic acid in the gastrointestinal tract and also increases its excretion in the urine. For this reason, folic acid deficiency is common in alcoholics . Folic acid is absorbed from the entire gastrointestinal tract; therefore, malabsorption is a very rare cause of folic acid deficiency. However, a number of gastrointestinal diseases such as celiac disease, Crohn disease and cancers can lead to malabsorption severe enough to cause folic acid deficiency in advanced cases.
Deficiency of folic acid can also occur in certain physiological states involving a high folic acid demand such as pregnancy and lactation. In pregnancy, the growing fetus has many rapidly dividing cells for which folic acid is required in excess. Similarly in lactation, folic acid is secreted into the mother’s milk and excess folic acid is required in the diet to make up for this loss. Up to 200 micrograms of folic acid may be needed in addition to the basal requirement of 400 micrograms.
A number of pathological states also confer a high folic acid demand in the body due to rapid cell turnover. These include hemolytic diseases, malignancies and severe inflammatory diseases. Advanced chronic renal diseases also increase the breakdown of red blood cells and ultimately to folic acid deficiency. High levels of homocysteine (as seen in homocysteinuria) are also known to cause the deficiency of folic acid. The use of certain drugs (such as methotrexate, phenytoin, pyrimethamine, sulfasalazine and trimethoprim) can lead to folic acid deficiency . These drugs are therefore referred to as anti-folate drugs.
Dietary folic acid deficiency is more common in the people belonging to the poor social class, especially in the third world countries where people face starvation and often do not get adequate levels of folic acid in their food.
Deficiency of folic acid is much more common in women due to their increased folic acid demand in pregnancy and lactation. In developed countries, alcohol intake is a very common precipitating cause of folic acid deficiency.
Folic acid is necessary for the synthesis of DNA and RNA; and therefore, the production of new cells. It is also needed for the repair of DNA. All the processes and conditions that require a high cell turnover essentially require folic acid. In case of folic acid deficiency, DNA synthesis and cell division can not take place. The most common physiologic manifestation in adults is the development of megaloblastic anemia.
Consuming a well balanced diet with a good amount of fruits and vegetables is sufficient to prevent the deficiency of folic acid in both genders. Women of childbearing age should take folic acid supplements; especially before and during the first two months of pregnancy  . Supplementation should also be taken during the period of lactation. The people suffering from disease conditions that involve a high cellular turn over should consider taking folic acid supplementation prophylactically.
Folic acid is essential for the synthesis of DNA and the division of cells. Deficiency of folic acid usually results from inadequate dietary intake; however, a number of pathological conditions may also precipitate this deficiency. The most common manifestation of folic acid deficiency is megaloblastic anemia. Oral supplements are the mainstay for the management of folic acid deficiency.
The human body essentially requires folic acid for the synthesis of DNA and the formation of new cells. Most commonly, lack of folic acid in the diet leads to folic acid deficiency. The symptoms of folic acid deficiency develop due to reduced number of circulating red blood cells. Supplementation of folic acid using tablets or pills is often sufficient to resolve the deficiency.