Folic acid anemia occurs most often in infants, adolescents, pregnant and lactating females, alcoholics, the elderly, and in those with malignant or intestinal diseases.
Folic acid is needed for the orderly production of deoxyribonucleic acid (DNA) in all tissue cells and is a component of three of the four DNA bases – thymine, adenine, and guanine – (the fourth is cytosine). In bone marrow, it is required for the normal production of the red blood cells and for RNA synthesis.
Folic acid circulates through, and is stored in, the liver and a deficiency is almost always because of insufficient amounts in the diet.
Absorption of folic acid occurs primarily in the upper small intestine and does not depend on intrinsic factor as does vitamin B12. A deficiency of folic acid is more common than a B12 deficiency.
Folic acid stores are also depleted more rapidly than cobalamin (B12) stores and, without proper dietary intake, a megaloblastic anemia will develop.
Clinical manifestations of folic acid anemia are similar to those of pernicious (B12) anemia except for the lack of neurologic symptoms common in a B12 deficiency. Evaluation is based on blood tests, measurement of serum folate levels, and signs and symptoms.
Diagnosis is made following the Schilling test and a therapeutic trial of vitamin B12 injections to distinguish between folic acid deficiency anemia and pernicious anemia. Significant blood test findings include macrocytosis, decreased reticulocyte count, abnormal platelets, and a serum folate less than 4 mg/ml.
The elderly are particularly at risk for developing this type of anemia as their diets often wane for one reason or another, including a lack of interest in food, poverty, immobility, and/or ill-fitting dentures. Interestingly, when folate supplements are given to the elderly, good medical supervision must be undertaken as folate supplements can mask the megaloblastic anemia of B12 deficiency. Since the elderly are already at risk for B12 deficiency, giving folate supplementation by mistake, or by design, can aggravate an additional problem of B12 deficiency.
Alcohol abuse also contributes to this type of anemia since alcohol interferes with folate metabolism in the liver, resulting in a profound depletion of folate stores. Patients with neoplastic diseases and such skin diseases as chronic exfoliative dermatitis are also are at risk for folic acid anemia.
Folic acid deficiency anemia is common during pregnancy. Both folate and iron are essential for red cell production and during pregnancy there is an increased need to supply both the mother and the developing infant(s). This type of anemia is common in newborns because of the increasing survival rates of premature infants. Not only can it be a danger to the mother, but also contributes to fetal malformations. The most common birth defect resulting from a deficiency of this vitamin is spina bifida.
During the 1980s, a considerable body of evidence accumulated stating that spina bifida and other neural tube defects were associated with folate deficiency. It is now widely recognized that folate supplements are necessary and best started before pregnancy occurs since closure of the neural tube occurs by day 28 of pregnancy. This is generally long before the woman knows she is pregnant.
It was also established that receiving enough folate from fortified foods was nearly impossible and supplements were highly recommended. Even though the studies successfully used the folate monoglutamate form of folic acid, it is pteroylmonoglutamic acid form that is used in vitamin supplements and fortified foods. Most naturally occurring folates are pteroylpolyglutamates.
According to one source, adding folate to foods may even be dangerous if vitamin B12 is not also included (see a report by Victor Herbert, MD). Folate supplements will mask the megaloblastic anemia of vitamin B12 deficiency and may hasten the development of irreversible nerve damage.
This is a significant problem of the elderly, who may already suffer from an impaired absorption of vitamin B12. The addition of relatively large amounts of B12 to foods, as well as folate, would permit passive absorption of adequate amounts of vitamin B12 to prevent deficiency from developing. However, B12 requires Intrinsic Factor for absorption and the elderly are often not able to produce it. Catch 22.
Folic acid deficiency is also common in tropical areas where poverty results in a poor diet. In North America and other regions of the world where access to food is rarely a problem, folic acid deficiency still occurs because dietary needs are not met, especially during the growth of children and adolescents and during pregnancy. These age groups are more prone to folic acid deficiency anemia because of their heavy use of folate-deficient cow’s milk, which also inhibits the absorption of iron, causing an additional risk of iron-deficiency anemia as well.
Causes of folic acid deficiency anemia include:
- alcohol abuse (alcohol prevents absorption of several nutrients especially the B vitamins)
- poor diets (common in alcoholics, the elderly, those living alone or in poverty, and infants, especially those with infections or diarrhea)
- impaired absorption because of intestinal dysfunction from such disorders as celiac disease, tropical sprue, regional jejunitis, Crohn’s disease, or bowel resection
- bacteria competing for available folic acid
- overcooking of food, destroying valuable water-soluble nutrients, including a high percentage of folic acid
- limited storage capacity in infants
- prolonged drug therapy, especially from anticonvulsants and estrogens
- not addressing increased folic acid needs of certain age groups, as well as in patients with neoplastic diseases and some skin disorders (eg. chronic exfoliative dermatitis).
Signs and symptoms of folic acid deficiency anemia gradually produces clinical features similar to other megaloblastic anemias, but without neurologic manifistations of B12 deficiency. Symptoms include the following:
- progressive fatigue
- shortness of breath
- heart palpitations
- weakness
- glossitis (inflammation of the tongue)
- nausea
- anorexia
- headache
- fainting
- irritability
- forgetfulness
- pallor
- slight jaundice
Conventional treatment consists primarily of folic acid supplements and, more importantly, the elimination of contributing causes. Oral administrations of folate preparations are 1 to 5 mg daily. Prophylactic doses are given in pregnancy or those considering getting pregnant. Parenteral administration of folic acid can relieve acute symptoms within 48 hours. Blood transfusions are given to treat severe cardiac or respiratory distress as a result of severe deficiency.
