Vitamin B12 (Cobalamin)
Vitamin B12 is unique among the vitamins because it is the first essential nutrient identified to contain cobalt, an essential mineral element. It is the only vitamin that contains a mineral as part of its structure. Vitamin B12 is found almost exclusively in animal-derived foods, particularly animal protein. Vegetarians may obtain small amounts through microbial synthesis or from legume root nodules where it is produced by microorganisms.
Vitamin B12 is required for normal metabolism of nerve tissue and plays a role in protein, fat, and carbohydrate metabolism. It works together with folic acid in several metabolic pathways, including the synthesis of choline, and helps facilitate the proper placement of vitamin A into body tissues.
Absorption of vitamin B12 is complex and depends on the presence of intrinsic factor, a mucoprotein secreted by the stomach. Autoimmune reactions may interfere with intrinsic factor by binding to it directly or by damaging the gastric cells that produce it. Absorption of B12 tends to decrease with age and may be impaired in individuals with iron, calcium, or vitamin B6 deficiencies. Absorption is increased during pregnancy.
Pernicious anemia develops slowly as the large stores of vitamin B12 in the liver are gradually depleted, a process that may take five to six years. Symptoms often appear mild relative to the severity of the deficiency due to physiologic adaptation. Enlargement of the spleen or liver may occasionally be present. Gastrointestinal symptoms can include loss of appetite, alternating constipation and diarrhea, vague abdominal pain, and significant weight loss.
Neurological involvement is common and may occur even in the absence of anemia. Peripheral nerve involvement is frequent, followed by spinal cord changes beginning in the dorsal columns. These changes may lead to loss of vibratory sensation in the lower extremities, impaired position sense, and ataxia. As the condition progresses, involvement of the lateral columns may occur, resulting in spasticity, exaggerated reflexes, and a positive Babinski sign. Neuropsychiatric symptoms such as irritability, mild depression, or paranoia may also be present. In rare cases, yellow-blue color blindness has been reported.
An unusual presentation of vitamin B12 deficiency is fever of unknown origin, which may resolve rapidly with B12 therapy. When pernicious anemia is associated with deficiencies of endocrine glands—particularly the thyroid or adrenal glands—this supports an autoimmune basis for gastric mucosal atrophy. Hypogammaglobulinemia may also be observed.
The anemia associated with vitamin B12 deficiency is macrocytic, typically with a mean corpuscular volume (MCV) greater than 100. Laboratory testing is available to measure serum B12 levels. The Schilling test was historically used to assess B12 absorption by measuring uptake of radioactive vitamin B12 with and without intrinsic factor.
