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Megaloblastic Anemia: Symptoms and Risk Factors

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.  


  • 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 >>