Managing Vitamin B12 Deficiency

Oct 09, 2018

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.

These are:

The synthesis of succinyl coenzyme A from methylmalonic acid
The synthesis of methionine from homocysteine
The demethylation of 5-methyl tetrahydrofolate to tetrahydrofolate

Early Dagnosis

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
Pregnancy

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.

Supplementation

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.

Prevention