Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

symptomatic

1st line – parenteral cyanocobalamin or hydroxocobalamin

Back
ACUTE
|
symptomatic
|
severe symptoms
1st line – 

parenteral cyanocobalamin or hydroxocobalamin

Patients with severe haematological (pancytopenia and marked symptomatic anaemia) or neurological (sub-acute combined spinal degeneration, dementia, or cognitive impairment) symptoms of vitamin B12 deficiency require hospital admission and acute and urgent treatment.[90]

An acute regimen of parenteral cyanocobalamin is given daily for 1 to 2 weeks, and then once a week for up to 1 month, until significant reticulocytosis is seen in the marrow.[91]

Brisk bone marrow reticulocytosis can be measured in 1 to 2 weeks as a response to treatment. Other markers of deficiency, including methylmalonic acid, homocysteine, and mean corpuscular volume, should normalise in 8 weeks with adequate treatment.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once daily for 1-2 weeks, followed by 1000 micrograms once weekly for 1 month

OR

hydroxocobalamin: 1000 micrograms intramuscularly three times weekly for 2 weeks, followed by 1000 micrograms once every 3 months

Plus – referral to neurologist and/or haematologist

Back
ACUTE
|
symptomatic
|
severe symptoms
Plus – 

referral to neurologist and/or haematologist

Treatment recommended for ALL patients in selected patient group

Patients with severe neurological symptoms may require neurological and psychogeriatric referral and evaluation while commencing the acute parenteral treatment regimen. In some cases, neurological symptoms may be irreversible despite serum vitamin B12 levels returning to normal.

Patients with symptomatic anaemia and pancytopenia require hospital admission and haematological consultant referral.

Pregnant women should be managed in consultation with their obstetrician.

Consider – blood transfusion ± diuretic

Back
ACUTE
|
symptomatic
|
severe symptoms
Consider – 

blood transfusion ± diuretic

Additional treatment recommended for SOME patients in selected patient group

Patients with symptomatic anaemia and pancytopenia require hospital admission and haematological consultant referral and, rarely, may require red blood cell (RBC) transfusion.

If there are signs of congestive cardiac failure, cardiac monitoring is advised and packed RBCs should be given together with low-dose diuretic therapy.

Diuretics should generally be avoided in pregnancy unless the benefits outweigh the risks, and only under consultant guidance.

Primary options

bumetanide: 0.5 to 2 mg orally/intravenously once or twice daily initially, increase according to response, maximum 10 mg/day

Consider – oral folic acid

Back
ACUTE
|
symptomatic
|
severe symptoms
Consider – 

oral folic acid

Additional treatment recommended for SOME patients in selected patient group

Folate supplementation can help reverse the haematological abnormalities.

Primary options

folic acid: 1 mg orally once daily

Plus – lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
symptomatic
|
severe symptoms
Plus – 

lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Treatment recommended for ALL patients in selected patient group

Most patients identified with vitamin B12 deficiency require lifelong maintenance therapy with once-daily oral cyanocobalamin or once-monthly parenteral cyanocobalamin.

Oral cyanocobalamin is generally well tolerated for maintenance therapy. Parenteral cyanocobalamin is often reserved for those who cannot take daily pills or have documented failure to oral therapy. It may also be considered when there are concerns about adherence to oral vitamin B12 replacement therapy.[98]

Some clinicians may attempt to lower the effective dose of maintenance oral cyanocobalamin. Periodic monitoring after replacement may be able to identify patients who may maintain serum levels with oral doses <1000 micrograms/day.[99] However, absorption may be variable, and some patients may experience less than maximal clinical and laboratory response with oral cyanocobalamin doses <1000 micrograms/day.[100][101][102]

Absorption can be maximised by administration on an empty stomach.

A response with daily oral cyanocobalamin should be seen within 8 weeks. If serum vitamin B12 does not significantly rise after this time, clinicians should switch to parenteral cyanocobalamin (if not already used) or consider other causes.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms orally once daily

Secondary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

1st line – oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
symptomatic
|
mild to moderate symptoms
1st line – 

oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Treatment of patients with mild to moderate symptoms of vitamin B12 deficiency (e.g., mild anaemia, dysaesthesia/paraesthesias, polyneuropathy, depression) is with once-daily oral cyanocobalamin or once-monthly parenteral cyanocobalamin, depending on clinician preference.

In patients treated with oral cyanocobalamin, a response should be seen within 8 weeks. If serum vitamin B12 does not significantly rise after this time, clinicians should switch to parenteral cyanocobalamin (if not already used) or consider other causes.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms orally once daily; 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

Plus – lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
symptomatic
|
mild to moderate symptoms
Plus – 

lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Treatment recommended for ALL patients in selected patient group

Most patients identified with vitamin B12 deficiency require lifelong maintenance therapy with once-daily oral cyanocobalamin or once-monthly parenteral cyanocobalamin.

Oral cyanocobalamin is generally well tolerated for maintenance therapy. Parenteral cyanocobalamin is often reserved for those who cannot take daily pills or have documented failure to oral therapy. It may also be considered when there are concerns about adherence to oral vitamin B12 replacement therapy.[98]

Some clinicians may attempt to lower the effective dose of maintenance oral cyanocobalamin. Periodic monitoring after replacement may be able to identify patients who may maintain serum levels with oral doses <1000 micrograms/day.[99] However, absorption may be variable, and some patients may experience less than maximal clinical and laboratory response with oral cyanocobalamin doses <1000 micrograms/day.[100][101][102]

Absorption can be maximised by administration on an empty stomach.

A response with daily oral cyanocobalamin should be seen within 8 weeks. If serum vitamin B12 does not significantly rise after this time, clinicians should switch to parenteral cyanocobalamin (if not already used) or consider other causes.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms orally once daily

Secondary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

asymptomatic or borderline deficiency

1st line – dietary supplementation + multivitamins

Back
ACUTE
|
asymptomatic or borderline deficiency
|
patients aged >65 years with poor diet
1st line – 

dietary supplementation + multivitamins

About 5% to 35% of older people have evidence of vitamin B12 deficiency.[11][12][13][14][15][16]

Low serum vitamin B12 (<148 picomols/L; <200 picograms/mL) may not be associated with symptoms. But dietary advice on the importance of eating animal-derived foods (such as meat, fish, eggs, and milk), and taking multivitamin supplements, is recommended as first-line treatment in this group.

Combined diet and multivitamins should meet the recommended dietary allowance of 2.4 micrograms/day.[58]

2nd line – lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
asymptomatic or borderline deficiency
|
patients aged >65 years with poor diet
2nd line – 

lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

If diet and multivitamin supplements do not help, or if the diet cannot be improved, cyanocobalamin treatment is advised.

Most patients identified with vitamin B12 deficiency require lifelong maintenance therapy with once-daily oral cyanocobalamin or once-monthly parenteral cyanocobalamin.

Oral cyanocobalamin is generally well tolerated for maintenance therapy. Parenteral cyanocobalamin is often reserved for those who cannot take daily pills or have documented failure to high-dose oral therapy. It may also be considered when there are concerns about adherence to oral vitamin B12 replacement therapy.[98]

Some clinicians may attempt to lower the effective dose of maintenance oral cyanocobalamin. Periodic monitoring after replacement may be able to identify patients who may maintain serum levels with oral doses <1000 micrograms/day.[99] However, absorption may be variable, and some patients may experience less than maximal clinical and laboratory response with oral cyanocobalamin doses <1000 micrograms/day.[100][101][102]

Absorption can be maximised by administration on an empty stomach.

A response with daily oral cyanocobalamin should be seen within 8 weeks. If serum vitamin B12 does not significantly rise after this time, clinicians should switch to parenteral cyanocobalamin (if not already used) or consider other causes.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms orally once daily

More

Secondary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

1st line – dietary supplementation + multivitamins

Back
ACUTE
|
asymptomatic or borderline deficiency
|
vegan or strict vegetarian diet
1st line – 

dietary supplementation + multivitamins

Vegans or strict vegetarians should be counselled to supplement their diet with appropriate vitamin B12-fortified foods and multivitamin supplements in order to meet the recommended dietary allowance of 2.4 micrograms/day.[58][93]

Pregnant and breastfeeding women who have a strict vegetarian or vegan diet should be counselled about adequate intake of vitamin B12 and supplementation.[103] Breastfeeding women who adhere to a vegan diet will only provide adequate vitamin B12 for her infant if the mother satisfies vitamin B12 requirements through supplementation.[97]

2nd line – lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
asymptomatic or borderline deficiency
|
vegan or strict vegetarian diet
2nd line – 

lifelong oral or parenteral cyanocobalamin or parenteral hydroxocobalamin

Lifelong maintenance treatment with once-daily oral cyanocobalamin or once-monthly parenteral cyanocobalamin is advised.

Oral cyanocobalamin is generally well tolerated for maintenance therapy. Parenteral cyanocobalamin is often reserved for those who cannot take daily pills or have documented failure to oral therapy. It may also be considered when there are concerns about adherence to oral vitamin B12 replacement therapy.[98]

Some clinicians may attempt to lower the effective dose of maintenance oral cyanocobalamin. Periodic monitoring after replacement may be able to identify patients who may maintain serum levels with oral doses <1000 micrograms/day.[99] However, absorption may be variable, and some patients may experience less than maximal clinical and laboratory response with oral cyanocobalamin doses <1000 micrograms/day.[100][101][102]

Absorption can be maximised by administration on an empty stomach.

A response with daily oral cyanocobalamin should be seen within 8 weeks. If serum vitamin B12 does not significantly rise after this time, clinicians should switch to parenteral cyanocobalamin (if not already used) or consider other causes.

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms orally once daily

More

Secondary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

1st line – parenteral cyanocobalamin or hydroxocobalamin

Back
ACUTE
|
asymptomatic or borderline deficiency
|
with chronic gastrointestinal illness
1st line – 

parenteral cyanocobalamin or hydroxocobalamin

Patients with a chronic gastrointestinal (GI) illness that can cause malabsorption or inadequate absorption (e.g., pernicious anaemia, Crohn's disease, coeliac disease) or who have undergone gastric surgery or terminal ileectomy should be treated with parenteral cyanocobalamin.[1][94]

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 1000 micrograms intramuscularly/subcutaneously once monthly

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

1st line – oral, parenteral, or intranasal cyanocobalamin or parenteral hydroxocobalamin

Back
ACUTE
|
asymptomatic or borderline deficiency
|
after bariatric surgery
1st line – 

oral, parenteral, or intranasal cyanocobalamin or parenteral hydroxocobalamin

Patients who have had bariatric surgery may not be able to adequately maintain serum vitamin B12 levels with multivitamins; therefore, oral, parenteral, or intranasal cyanocobalamin should be given.[74][95]​ An oral multivitamin supplement optimised for bariatric surgery has shown potential benefit in reducing vitamin deficiencies following Roux-en-Y gastric bypass surgery, but the evidence is limited.[96]

In Europe, hydroxocobalamin is more commonly used than cyanocobalamin. Hydroxocobalamin is retained longer in the body than cyanocobalamin, but superiority to cyanocobalamin has not been established in clinical trials.

Primary options

cyanocobalamin: 350-1000 micrograms orally once daily; or 1000 micrograms intramuscularly/subcutaneously once monthly; or 3000 micrograms intramuscularly/subcutaneously every 6 months; or 500 micrograms intranasally once weekly

More

OR

hydroxocobalamin: 1000 micrograms intramuscularly once every 3 months

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer