Vitamin B12 (cobalamin) is a water-soluble vitamin which is important for several physiological functions. It is involved in three enzymatic processes that are crucial in many tissues.
- The synthesis of succinyl coenzyme A from methylmalonic acid
- The synthesis of methionine from homocysteine
- The demethylation of 5-methyl tetrahydrofolate to tetrahydrofolate
Asymptomatic adults who have any of the risk factors for vitamin B12 deficiency may be considered for a screening assay of serum vitamin B12, or better, serum methylmalonic acid or homocysteine. If they present with low vitamin B12 levels, confirmation may be sought by further testing with serum methylmalonic acid or homocysteine levels before treatment is given. The former test is more specific, but many conditions may lead to falsely increased values of methylmalonic acid. The presence of risk factors may modify the decision to test, because these assays are expensive.
Another test being studied analyzes serum holotranscobalamin levels (holoTC), which is decreased if vitamin B12 is deficient.
Identification of Etiological or Contributing Factors
It is necessary to evaluate a patient for the presence of any risk factors, such as:
- Reduced absorption from the ileum
- Crohn’s disease
- Tapeworm infestation
- Strictures or blind loops of the ileum, often following ileal resection
- Atrophic gastritis
- Pernicious anemia
- Postgastrectomy syndrome
- Genetic deficiency of transcobalamin
- Dietary deficiency as in vegetarians (including exclusively breastfed infants of vegetarian mothers), elderly people with fastidious dietary restrictions, or alcohol abuse
- Prolonged use of H2-receptor blockers, or proton pump inhibitors such as omeprazole
- Use of metformin
Diagnosis and Management
A patient with signs of vitamin B12 deficiency is diagnosed on the basis of a complete blood count, including a peripheral smear, and a serum vitamin B12 assay. Confounding factors include:
Conditions which lower B12 levels falsely
- Use of oral contraceptives
- Multiple myeloma
- Folate deficiency
Conditions which present false normal levels
- Liver disease
- Bone marrow disorders
- Renal disease
Healthcare guidelines for the management of patients with asymptomatic cobalamin deficiency are lacking, but these patients may be treated orally and monitored for improvement in the MMA or homocysteine levels. Other healthcare providers opt to follow up such individuals with regular measurements of these markers.
Vitamin B12 deficiency is managed by oral or intramuscular administration of the vitamin. Both routes have proved effective in raising serum cobalamin levels, even with associated intrinsic factor (IF) deficiency. This is because there is an alternative pathway for oral absorption which is not IF-dependent, which results in the absorption of sufficient vitamin provided the dose is high enough. This being so, oral supplementation is a reasonable option, given that it is easier to tolerate and requires less skilled manpower.
One traditional intramuscular regimen comprises 1000 mcg weekly for 8 weeks, followed by 1000 mcg monthly lifelong. Oral vitamin B12 is given as 100-1000 mcg daily for 3-4 months, and then on alternate days lifelong. The hematologic response is quick, and hematocrit normalization occurs within a few weeks. However, spinal cord degeneration is usually irreversible.
Vitamin B12 in Dementia and Cardiovascular Prophylaxis
Because of the raised homocysteine levels associated with vitamin B12 deficiency, the use of supplementary vitamin B12 has been recommended in patients with mild cognitive decline due to Alzheimer’s, but it does not alter the course and should not be advised.
Similarly, B12 supplementation does not reduce mortality from cardiovascular causes in high-risk patients and is not recommended at present.
According to some research, the absorption of vitamin B12 decreases with age. Since at least 2.4 mcg of the vitamin must be ingested to prevent deficiency, it is recommended that older patients (over 50 years of age) get their recommended daily allowance from fortified foods or supplements, as their dietary absorption may not be sufficient.