Vitamin B12 deficiency: How to assess and treat it?

The prevalence of vitamin B12 (B12) deficiency is approximately 6-12% in people under the age of 60, and approximately 17% in all adults with macrocytic anemia. However, the elderly, pregnant women, and vegans are more likely to have B12 deficiency, so a higher index of suspicion should be used in populations with suggestive signs and symptoms.

Patient assessment

When to suspect a vitamin B12 deficiency?

B12 deficiency should be suspected in patients with suggestive signs and symptoms, especially if they have the risk factors.

However, because neurological sequelae can occur in the absence of anemia, B12 levels should be measured in any patient with early neurological signs and symptoms.

In the absence of specific characteristics or if the patient does not have a defined risk factor, routine testing of B12 levels has limited clinical utility and may lead to a therapeutic dilemma.

What to look for in a physical examination

Perform a clinical examination to look for signs of anemia and neuropsychiatric disorders. In the most severe form of B12 deficiency, subacute combined degeneration of the spinal cord may develop.

It presents as slowly progressive symmetrical weakness and paresthesia of the lower extremities (peripheral sensory neuropathy) accompanied by sensory ataxia. In the early stages, this can be detected as an alteration in vibratory proprioceptive sensitivity.

What are the first investigations?

The first-line tests to be prescribed in primary care for suspected B12 deficiency are as follows:

– Determination of serum vitamin B12.

– Determination of serum folate.

– Complete blood count and hemocyte indices.

– Anti-intrinsic factor antibody (in case of clinical suspicion of pernicious anemia).

– Holotranscobalamin

When are specialized investigations needed?

Suspicion of pernicious anemia

The prevalence of pernicious anemia is about 4% in European countries and increases with age. It is a form of atrophic gastritis with autoimmune destruction of the parietal cells of the stomach, with loss of intrinsic factor production, resulting in reduced B12 absorption.

There is an association with other autoimmune diseases, although they may occur in isolation. It is suggested that patients with clinical manifestations of B12 deficiency (hematologic or neurologic symptoms) independent of B12 levels, as well as those with low serum B12 levels without obvious cause or risk factors, be considered for pernicious anemia.


Consider treatment with vitamin B12, with the primary goal of alleviating the symptoms and signs caused by B12 deficiency. The authors recommend following the British Society of Haematology recommendations on the management of patients with suspected B12 deficiency, which are divided into patients with clinically defined disease and patients with nonspecific symptoms.

In short, the available B12 replacement modalities are as follows:

– Parenteral B12 (hydroxycobalamin injection, intramuscular or deep subcutaneous): It is recommended to follow the dosing guidelines outlined in the British National Formulary (1 mg, 3 times/week, for 2 weeks, then once every 3 months). However, if neurological features are present, initial treatment should be given every other day until symptoms improve, followed by maintenance treatment every two months. The duration of treatment will depend on the reversibility of any underlying cause and may be lifelong, especially in cases of pernicious anemia.

– Oral B12: In asymptomatic individuals without evidence of malabsorption or for maintenance therapy after correction of signs or symptoms with parenteral B12; 50-150 μg/day of oral cyanocobalamin can be tried, except in pernicious anemia.

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