Etiology of Megaloblastic Macrocytic Anemias The most common causes of megaloblastic states are Vitamin B12 deficiency Defective utilization of vitamin B12 Folate deficiency The most common cause of B12 deficiency is pernicious anemia due to impaired intrinsic factor secretion (usually secondary to the presence of autoantibodies—see Autoimmune Metaplastic Atrophic Gastritis).