Megaloblastic anemia is a disorder of abnormally large red blood cells. It is usually caused by deficiency of vitamin B₁₂ or folic acid. These vitamin deficiencies impair the normal function of DNA and can cause numerous abnormalities of the blood, the brain, and the nervous system.  

Symptoms

• Anemia
• Painful tingling of the hands and feet
• Weakness
• Fatigue
• Loss of coordination
• Irritability and mental status changes
• Gastrointestinal problems (e.g., diarrhea)
• Decreased appetite
• Changes of taste perception
• Weight loss

Risk Factors

Vitamin B₁₂ deficiency may result from:

• Deficiency of Intrinsic factor (IF): Intrinsic factor is a molecule produced in the stomach and required for absorption of vitamin B₁₂. Deficiencies can occur due to stomach surgery, autoimmune disease, and as a result of aging.
• Malabsorption: Small bowel and pancreatic disease and alcohol abuse contribute to poor absorption of dietary vitamin B₁₂. Elderly persons may also have reduced vitamin B₁₂ absorption.
• Other gastric disease: Occasionally, individuals with gastritis, surgical removal of the stomach, or "stomach stapling" surgery may develop a vitamin B₁₂ deficiency.
• Medications: Metformin, proton pump inhibitors (e.g., omeprazole), H2-blockers (e.g., Zantac), antacids, and antibiotics may inhibit vitamin B₁₂ absorption.
• HIV infection: Weight loss and diarrhea caused by HIV/AIDS are associated with vitamin B₁₂ deficiency.
• Fish tapeworm infection
• Dietary deficiency: See Nutritional Considerations.

Folic acid deficiency may result from:

• Alcohol abuse: Alcohol directly interferes with the absorption of folic acid.
• Malabsorption: Malabsorption diseases, such as inflammatory bowel disease and celiac sprue, decrease folic acid absorption.
• Pregnancy and breast-feeding: Because fetal and infant growth requires increased folic acid, pregnancy and breast-feeding may deplete a woman's stores. In turn, an exclusively breast-fed infant whose mother is deficient in folic acid will not receive adequate amounts.
• Medications: Intake of certain medications, such as methotrexate, phenytoin, and trimethoprim, may lead to folic acid deficiency.
• Vitamin B₁₂ deficiency: Because Vitamin B₁₂ is responsible for the conversion of folic acid to its metabolically active form, its deficiency can lead to folic acid deficiency.
• Dietary deficiency: See Nutritional Considerations.

Megaloblastic Anemia: Diagnosis and Treatment

Diagnosis

• A medical history and physical examination are the first steps.
• Blood testing diagnoses these disorders and distinguishes between the two.
  
  Note that the tests for vitamin B₁₂ and folic acid levels may be rendered unreliable by pregnancy, alcohol intake, recent nutritional changes, or certain medications.
• Bone marrow biopsy is usually not necessary for diagnosis, but may be recommended in some cases.

Treatment

• The underlying cause of vitamin B₁₂ or folate deficiency must be identified to ensure adequate long-term treatment.
• Vitamin B₁₂ injections are usually given daily for one week, then weekly for four weeks, and then monthly until vitamin levels have stabilized. Patients with continued risk of deficiency should remain on monthly injections. Oral vitamin B₁₂ pills may be used in some patients.
• Oral folic acid pills taken daily for several months usually correct the deficiency.
• Alcohol use should be restricted. In individuals with alcoholic tendencies, psychiatric treatment along with substance abuse counseling and Alcoholics Anonymous meetings or other community support may be necessary.

Megaloblastic Anemia: Nutritional Considerations

The following steps may reduce the risk of megaloblastic anemia:

• Vitamin B₁₂ supplementation: Individuals following mixed diets generally have adequate vitamin B₁₂ intake. However, many individuals, particularly elderly persons, have less than adequate B₁₂ absorption and may benefit from supplementation. Persons at risk for deficiency include those who have had "stomach stapling" surgery, alcoholics, and individuals who follow unsupplemented vegan diets for many years and their breast-fed infants. In these groups, the risk for vitamin B₁₂ deficiency is easily eliminated with supplementation. Common multiple vitamins, B₁₂ supplements, fortified breakfast cereals, fortified soymilk, and fortified meat analogues contain a reliable source of the vitamin.
• Increased intake of folic acid: Due to fortification of grain products with folic acid, anemia resulting from folic acid deficiency is becoming less common. However, alcoholism often leads to deficiency and may require supplementation. In addition, people with epilepsy who are taking anticonvulsant medications may benefit from folic acid supplementation.
  
  Increased intake of foods rich in folic acid is a wise choice for all. These include beans, legumes, citrus fruits and juices, wheat bran, whole grains, and dark green leafy vegetables.