Vitamin B12 Deficiency
Vitamin B12 is used in the treatment of pernicious anemia and other vitamin B12 deficiency states. Cyanocobalamin is usually considered the vitamin B12 preparation of choice. Hydroxocobalamin may, however, be preferred for the initial treatment of vitamin B12 deficiencies. Although hydroxocobalamin produces a more sustained increase in plasma vitamin B12 concentrations after parenteral administration than does parenteral administration of cyanocobalamin, hydroxocobalamin offers no therapeutic advantage over cyanocobalamin when given for maintenance in recommended doses every 2 or 4 weeks; serum cobalamin concentrations attained using these intervals are about the same with both drugs.
Vitamin B12 deficiency is likely to occur in patients with conditions characterized by abnormalities of the gastric or ileal mucosa. Common causes of vitamin B12 deficiency in temperate climates are Crohn's disease, colitis, and pernicious anemia. Other populations at risk for vitamin B12 deficiency include the elderly, individuals with human immunodeficiency virus (HIV) infection, vegans, and those who have undergone partial or total gastrectomy.
Parenteral cyanocobalamin or hydroxocobalamin is usually indicated in patients with malabsorption of vitamin B12, such as those with tropical or nontropical sprue (idiopathic steatorrhea, gluten-induced enteropathy); partial or total gastrectomy; regional enteritis; gastroenterostomy; ileal resection; or malignancies, granulomas, strictures, or anastomoses involving the ileum. When secretion of intrinsic factor (IF) is decreased by lesions that destroy the gastric mucosa (e.g., following ingestion of corrosives or in patients with extensive GI neoplasia) or by gastric atrophy secondary to multiple sclerosis, certain endocrine disorders, or iron deficiency, or when antibodies to IF are present in gastric juice, absorption of vitamin B12 is decreased and cyanocobalamin or hydroxocobalamin may be required. Malabsorption of vitamin B12 may also be caused by competition for vitamin B12 by bacteria (blind loop syndrome) or by the fish tapeworm, Diphyllobothrium latum, or by administration of certain drugs.
(See Drug Interactions.)Megaloblastic anemia associated with malabsorption syndromes characteristically results from folate deficiency; however, patients may also be deficient in vitamin B12 and combined therapy may be warranted.
Cyanocobalamin nasal spray is used to maintain hematologic status in patients with pernicious anemia with no nervous system involvement who have responded (i.e., are in remission) to initial parenteral therapy with a vitamin B12 preparation. Cyanocobalamin nasal spray also is used as a supplement for vitamin B12 deficiency due to any of the following conditions: dietary vitamin B12 deficiency associated with a vegan diet; malabsorption of vitamin B12 secondary to structural or functional damage to the stomach or ileum, as can occur in individuals with HIV infection, Crohn's disease, tropical sprue, or nontropical sprue (i.e., idiopathic steatorrhea, gluten-induced enteropathy); inadequate secretion of IF resulting from lesions that have destroyed gastric mucosa (e.g., following ingestion of corrosives or in patients with extensive GI neoplasia), conditions associated with gastric atrophy (e.g., HIV infection, multiple sclerosis, certain endocrine disorders, iron deficiency, subtotal gastrectomy), total gastrectomy, regional ileitis, or ileal resection or malignancy; competition for vitamin B12 by intestinal parasites (e.g., the fish tapeworm, D. latum) or bacteria; or inadequate utilization of vitamin B12 following the use of an antimetabolite for antineoplastic therapy.
Long-term therapy with cyanocobalamin may not be necessary when other therapeutic measures (e.g., treatment of fish tapeworm, discontinuance of concomitant therapy, use of a gluten-free diet in patients with nontropical sprue) correct the underlying cause of the deficiency.
Increased vitamin B12 requirements during pregnancy or in patients with thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic impairment, or renal impairment generally can be met by oral or intranasal administration of cyanocobalamin.
The National Academy of Sciences (NAS) has issued a comprehensive set of Recommended Dietary Allowances (RDAs) as reference values for dietary nutrient intakes since 1941. In 1997, the NAS Food and Nutrition Board (part of the Institute of Medicine [IOM]) announced that they would begin issuing revised nutrient recommendations that would replace RDAs with Dietary Reference Intakes (DRIs). DRIs are reference values that can be used for planning and assessing diets for healthy populations and for many other purposes and that encompass the Estimated Average Requirement (EAR), the Recommended Dietary Allowance (RDA), the Adequate Intake (AI), and the Tolerable Upper Intake Level (UL).
The NAS has established an EAR and RDA for vitamin B12 for adults based on the amount needed to maintain hematologic status and normal serum vitamin B12 concentrations. The EAR and RDA for children and adolescents 1-18 years of age were established based on data in adults, since data in children and adolescents currently are not available. An AI has been set for infants 6 months of age and younger based on the observed mean vitamin B12 intake of infants fed principally human milk. An AI for infants 7-12 months of age has been set based on the AI for younger infants and data from adults.
The principal goal of maintaining an adequate intake of vitamin B12 in the US and Canada is to prevent vitamin B12 deficiency and the neurologic complications associated with vitamin B12 deficiency. Adequate intake of vitamin B12 usually can be accomplished through consumption of foodstuffs; however, about 10-30% of geriatric individuals are unable to absorb naturally occurring vitamin B12 and should consume vitamin B12-fortified food or supplements. In the US, vitamin B12 principally is obtained from mixed foods whose main ingredient is meat, fish, or poultry; milk and milk drinks; and fortified ready-to-eat cereals.
For specific information on currently recommended AIs and RDAs of vitamin B12 for various life-stage and gender groups, see
Dosage: Dietary and Replacement Requirements, under Dosage and Administration.
Although an adequate amount of vitamin B12 is usually obtained from dietary sources in patients with normal GI absorption, dietary vitamin B12 deficiency can occur in some individuals, especially in strict vegetarians and their breast-fed infants. Cyanocobalamin or hydroxocobalamin is useful in preventing vitamin B12 deficiency in these individuals. Increased vitamin B12 requirements may rarely be associated with pregnancy, oral contraceptive use, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, and/or hepatic and renal disease; however, dietary deficiency of vitamin B12 is rare and nutritional megaloblastic anemia more often results from folate deficiency. Megaloblastic anemia in association with the puerperium, infancy, or alcoholism usually results from folate deficiency; however, vitamin B12 deficiency may also occur and combined therapy may be warranted. Folic acid should be administered with vitamin B12 if both folic acid and vitamin B12 concentrations are inadequate. Malabsorption syndromes should be corrected, if present, and an adequate, well-balanced diet should be prescribed.
Cyanocobalamin has been used in the management of familial selective B12 malabsorption and hereditary deficiency of transcobalamin II. Large doses of cyanocobalamin have been used in the management of methylmalonic aciduria in infants and in pregnant women when amniocentesis shows methylmalonic acidemia in the fetus.
Parenteral cyanocobalamin and hydroxocobalamin are used in conjunction with cyanocobalamin Co 57 in the Schilling test to study vitamin B12 absorption. Cyanocobalamin nasal spray is not used in the Shilling test.
Hydroxocobalamin (Cyanokit) is used for the treatment of known or suspected cyanide poisoning. In an open-label study in individuals older than 15 years of age treated with hydroxocobalamin for suspected smoke inhalation-associated cyanide poisoning, 67% of those with pretreatment cyanide levels considered potentially toxic survived. Survival rates of 42 or 56% were reported in 2 additional studies in subjects exposed to cyanide from fire or smoke inhalation. In a retrospective review undertaken to assess safety and efficacy of hydroxocobalamin for cyanide poisoning from sources other than fire or smoke (i.e., ingestion or inhalation), 71% of patients treated with hydroxocobalamin survived. Individuals in these studied received 5-20 g of hydroxocobalamin.
Vitamin B12 is ineffective in the treatment of psychiatric disorders unless they can be proven to be a consequence of vitamin B12 deficiency.