Vitamin B12 for Anemia

B12 treats the anaemia it causes, and nothing else. That distinction is the single most important thing on this page, because iron deficiency, thalassaemia and anaemia of chronic disease are all far more common and none of them respond to B12. When the anaemia is megaloblastic and B12 is low, replacement works decisively. Reticulocytes rise within a week, haemoglobin normalises over one to two months, and the macrocytosis resolves. The evidence also overturns an old assumption: high-dose oral B12, 1000 to 2000 mcg daily, matches intramuscular injection for most causes of deficiency, including pernicious anaemia, because roughly one per cent absorbs by passive diffusion independent of intrinsic factor. The cause still needs identifying. Pernicious anaemia, metformin, long-term proton pump inhibitors, gastric or ileal surgery, strict veganism and small bowel disease all require different follow-up, and pernicious anaemia means lifelong treatment.

One caveat has permanent consequences. Neurological damage from B12 deficiency can progress even while the blood count looks better, and folate given alone corrects the anaemia while the spinal cord deterioration continues. Always check B12 before starting folate. Deficiency also frequently coexists with iron deficiency, which masks macrocytosis and produces a normal mean cell volume. A normal MCV does not exclude B12 deficiency.

B12 is a cofactor for exactly two human enzymes. Methionine synthase converts homocysteine to methionine using methylcobalamin, regenerating tetrahydrofolate in the process. Without it, folate is trapped as methyltetrahydrofolate, DNA synthesis in dividing erythroblasts stalls, nuclear maturation lags behind cytoplasmic growth, and the marrow produces the large, ineffective cells of megaloblastic anaemia. The second enzyme, methylmalonyl-CoA mutase, uses adenosylcobalamin and explains the neurology. Its failure raises methylmalonic acid, which disrupts myelin synthesis and produces subacute combined degeneration of the cord, peripheral neuropathy and cognitive change. Because methylmalonic acid rises specifically in B12 deficiency and not folate deficiency, it is the confirmatory test when serum B12 is borderline.

For dietary or drug-induced deficiency, 1000 to 2000 mcg of oral cyanocobalamin daily corrects levels within weeks. Cyanocobalamin is the best-studied form and is entirely adequate; methylcobalamin is not superior for correcting anaemia despite marketing claims. Injections remain the right choice in specific circumstances: neurological involvement, severe symptomatic anaemia, malabsorption after bowel resection, or poor adherence. UK practice for neurological presentation is hydroxocobalamin 1 mg on alternate days until improvement, then 1 mg every two to three months. Once the marrow starts producing cells rapidly, potassium can fall, so severe cases need monitoring in the first week.

A 2018 Cochrane systematic review comparing oral with intramuscular B12 found no significant difference in serum B12 normalisation or haematological response for most patients, which is the basis for oral-first treatment in uncomplicated deficiency. A 1998 randomised trial had already shown effective correction of cobalamin deficiency with oral cobalamin, including in patients lacking intrinsic factor. A 2016 cohort analysis from the Diabetes Prevention Program Outcomes Study documented the association between long-term metformin use and B12 deficiency, establishing one of the common modern causes. What the evidence does not cover well: patients with severe neurological disease, where trials are absent and injections remain standard, and long-term adherence to daily tablets outside trial conditions.

Oral B12 is one of the safest supplements available. It is water-soluble, excess is excreted in urine, there is no established upper limit, and no toxicity has been demonstrated even at gram-level doses. Injections can cause local reactions, and hypersensitivity to cobalamin is rare. Two practical issues deserve care. In severe megaloblastic anaemia, brisk marrow response consumes potassium and can precipitate hypokalaemia in the first days of treatment. And high-dose supplementation makes future serum B12 testing uninterpretable, so establish the diagnosis before starting.

B12 has almost no pharmacological interactions. Nearly every entry below is a drug that causes deficiency rather than one that reacts with the supplement.