treatment of vitamin B12 deficiency (2023)

Last edition on 5/2022 and last modification on 9/2022

Vitamin B12 deficiency is usually treated with vitamin B12 supplements.

If B12 levels are particularly low, it is necessary to administer B12 intramuscularly and refer to hematology:

treatment of pernicious anemia and other macrocytic anemias with neurological involvement: five to six 1000 mcg loading doses over a period of one to two weeks, followed by 1000 mcg every three months (see BNF for full details)

If B12 levels are borderline, the response to oral B12 may be diagnostic and treatment should be discussed with the local hematology department:

treatment with vitamin B12 from food, cyanocobalamin 50-150 mcg daily in 1-3 divided doses

Patients generally feel better within 24 to 48 hours of starting treatment, and then normal hematopoiesis is established in the bone marrow. The reticulocyte count in the blood usually rises after a week in parallel with the platelet count, which may temporarily return to abnormally high levels. The response may be slower if there is a parallel disease.

A more detailed treatment algorithm is summarized (1,2,3):

Soro s B12 > 180then Normal level: no further testing required

If the neurological symptoms are:

if Leber's optic atrophy or tobacco amblyopia then:

hydroxocobalamin 1000 mcg IM daily for 2 weeks, then twice weekly until unresponsive, then every 3 months for life and investigate underlying cause

if peripheral neuropathy, dementia then:

hydroxocobalamin 1000 mcg IM 3 times weekly for 2 weeks, then every 3 months for life and investigate underlying cause

If the serum vit B12 is > 150 and there are no symptoms, then:

recheck serum vitamin B12 level after 2 months
if the repeat level remains low, a significant proportion of these patients will develop symptomatic vitamin B12 deficiency in the future. There is a choice between:

(1) monitor the level of vitamin B12 every six months for 12 months, and then once a year or
(2) treat with oral vitamin B12 supplements and monitor serum vitamin B12 and CBC levels after 2 to 3 months to see if they improve; this is the initial treatment option most likely to be used in the primary care setting for asymptomatic B12 deficiency rather than self-monitoring

Note: This option is explained in more detail below.

If serum vit B12 < 150 and macrocytosis +/- anemia [if pancytopenia, talk to hematologist]

if there is evidence of pernicious anemia (anti-GPC [gastric parietal cells] or especially anti-IF [intrinsic factor] Abs positive)so:

hydroxocobalamin 1000 mcg IM 3 times weekly for 2 weeks, then every 3 months for life -a diagnosis of PA (pernicious anemia) is assumed.
note: youPernicious anemiathere is evidence that oral therapy with high doses of vitamin B12 taken daily has similar efficacy in improving the symptoms and haematological parameters of B12 deficiency; however, it is not preferred for the initial treatment of patients with severe symptoms due to the potential for a slower response compared to intramuscular injection.

found that oral therapy can be used for the long-term treatment of pernicious anemia (3)
with adequate B12 supplementation:

reticulocyte count usually rises and peaks within a week
in 8 weeks - removal of anemia and normalization of macrocytosis
if there is neurological involvement, recovery is usually slower and less predictable

if there is no evidence of pernicious anemia then:

consider other causes of vitamin B12 deficiency, eg malabsorption, medications, diet

for malabsorption: hydroxocobalamin 1000 mcg IM 1-3 times weekly (depending on severity of deficiency) for 2 weeks, then every 3 months for life
if dieting: try oral vitamin B12 50-100 mcg daily and recheck serum vitamin B12 and CBC (to see if MCV +/- corrected anemia) after 2 months (2)

if there is no evidence of vitamin B12 deficiency related to malabsorption, medication or diet, reassess if you have considered other causes of macrocytosis +/- anemia not related to vitamin B12 deficiency, e.g. liver dysfunction, folate deficiency, hypothyroidism, hemolysis, myelodysplasia, antimetabolic drugs, etc.

if the above is ruled out, consider treatment with 50-100 mcg po daily vit B12 and recheck serum vit B12 and CBC (to see if MCV +/- anemia is corrected) after 2 months. If still no response, try hydroxocobalamin 1000 mcg IM 1-3 times weekly (depending on severity of deficiency) for 2 weeks, recheck CBC and vitamin B12 after 4 weeks, and consider referral to a hematologist (2)

If serum vit B12 < 150 and NO (macrocytosis +/- anemia), then:

consider treatment with 50-100 mcg vit B12 orally daily and recheck serum vit B12 and CBC after 2 months OR
hydroxocobalamin 1000 mcg IM 1-3 times weekly (depending on severity of deficiency) for 2 weeks, then every 3 months for life OR
monitor serum vitamin B12 level every 6 months for 1 year, then once a year for 2-5 years (2)

Blood transfusion is rarely indicated for vitamin B12 deficiency, except in cases of severe anemia or when other causes of anemia, such as bleeding, coexist. Transfusion carries the risk of fluid overload, especially in the elderly (1).

Treatment of asymptomatic B12 deficiency (2):

treatment of patients with apparently asymptomatic vitamin B12 deficiency is a source of considerable debate

these patients often havevitamin B12 in serum >150ng/l

it is worth confirming 'deficiency' by repeating the serum vitamin B12 level (caution: requests for vitamin 12 levels may be automatically rejected by the laboratory's computer system within 42 days of the previous request; please indicate clearly on the request why you are repeating the test in the short term)

if the repeat level remains low, a significant proportion of these patients will develop symptomatic vitamin B12 deficiency in the future. So there is an option:

(1) monitor the level of vitamin B12 every six months for 12 months, and then once a year or
(2) treat with oral vitamin B12 supplements and monitor serum vitamin B12 and CBC levels after 2 to 3 months to see if they improve; this is the initial treatment option most likely to be used in the primary care setting for asymptomatic B12 deficiency rather than self-monitoring
the initial strategy of treating these patients with parenteral vitamin B12 supplementation would seem quite cumbersome (2)

Grades:

if low erythrocyte folate levels are associated and dietary deficiency is unlikely, seek to rule out chronic inflammatory conditions or malabsorption
Evidence from limited studies suggests that high-dose oral vitamin B12 may be as effective as intramuscular administration in producing short-term hematologic and neurologic responses in patients with vitamin B12 deficiency (1).
It is not necessary to monitor the serum vitamin B12 level in patients who are on parenteral vitamin B12 therapy for 3 months (2).
suggested folic acid supplements of 5 mg orally daily for 4 weeks for patients with vitamin B12 deficiency anemia. This avoids the possibility of inducing folate deficiency, which is a consequence of the increased production of normoblastic red blood cells, which should occur after feeding a previously deficient source of vitamin B12 (2).
Hydroxocobalamin has replaced the use of cyanocobalamin as the vitamin B12 form of choice for parenteral therapy: it remains in the body longer than cyanocobalamin (2).
The rationale for treatment of patients with apparently asymptomatic but significantly reduced (<150 ng/L) serum vitamin B12 levels is that some of these patients have biochemical evidence of subclinical vitamin B12 deficiency, for example, elevated plasma homocysteine levels and methylmalonic acid, and some will develop symptomatic problems if left untreated
patients treated with oral replacement therapy should monitor their initial response to treatment with vitamin B12 levels after 2-3 months, followed by 6-12 monthly tests to ensure a sustained response
gastroscopy is initially recommended in patients diagnosed with pernicious anemia for the diagnosis of atrophic gastritis and for evaluation of gastric malignancies (3)

Reference:

primary health care criteria - lack of vitamin B12