[11] Standard therapy for treatment of vitamin B12 deficiency has been intramuscular (IM) or intravenous (IV) injections of hydroxocobalamin (OHCbl), since the majority of cases are due to malabsorption by the enteral route (gut).

[13] In a newly diagnosed vitamin B12-deficient patient, normally defined as when serum levels are less than 200 pg/ml, daily IM injections of hydroxocobalamin up to 1,000 μg (1 mg) per day are given to replenish the body's depleted cobalamin stores.

[citation needed] Although less common in this form than cyanocobalamine and methylcobalamine, hydroxocobalamine is also available as pills for oral or sublingual administration.

However, one study on the treatment of children with methylmalonic acidemia and homocystinuria found oral hydroxocobalamine at 1 mg daily to be ineffective in reducing levels of homocysteine.

In a trial on adult volunteers, this dose did not lead to a significant increase in serum vitamin B12 levels when given thrice daily for one week.

The use of hydroxocobalamin became first line due to its low adverse risk profile, rapid onset of action, and ease of use in the prehospital setting.

The literature data on the acute toxicity profile of hydroxocobalamin show it is generally regarded as safe with local and systemic exposure.

[citation needed] Vitamin B12 refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms.

The variable R group gives rise to the four most commonly known cobalamins: cyanocobalamin (CNCbl), methylcobalamin (MeCbl), adenosylcobalamin (AdCbl, also known as cobamamide or 5-deoxyadenosylcobalamin), and hydroxocobalamin (OHCbl).

The folate-cobalamin interaction is pivotal for normal synthesis of purines and pyrimidines and the transfer of the methyl group to cobalamin is essential for the adequate supply of tetrahydrofolate, the substrate for metabolic steps that require folate.

In a state of vitamin B12 deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of methyltetrahydrofolate.