Pernicious anaemia is an autoimmune condition that prevents the body from absorbing vitamin B12 due to a lack of intrinsic factor, a protein essential for B12 uptake in the gut. Without treatment, this leads to megaloblastic anaemia and potentially serious neurological complications. Vitamin B12 injections for pernicious anaemia are the gold-standard treatment in the UK, delivering hydroxocobalamin intramuscularly to bypass the absorption problem. This lifelong therapy rapidly corrects deficiency, restores red blood cell production, and protects nerve function. Understanding the treatment schedule, what to expect, and the importance of ongoing maintenance is essential for managing this chronic condition effectively.

What Is Pernicious Anaemia and Why B12 Injections Are Needed

Pernicious anaemia is an autoimmune condition in which the body cannot absorb vitamin B12 (cobalamin) from the diet due to a lack of intrinsic factor, a protein produced by cells in the stomach lining. Intrinsic factor is essential for B12 absorption in the terminal ileum. In pernicious anaemia, the immune system mistakenly attacks the gastric parietal cells that produce intrinsic factor, leading to B12 deficiency over time.

Diagnosis typically involves blood tests including full blood count (showing macrocytosis), anti-intrinsic factor antibodies (which are specific for pernicious anaemia), and sometimes anti-parietal cell antibodies. In unclear cases, methylmalonic acid and homocysteine levels may be measured.

Vitamin B12 is crucial for several physiological processes, including:

• Red blood cell formation – deficiency leads to megaloblastic anaemia, characterised by large, immature red blood cells

• Neurological function – B12 is required for myelin synthesis and nerve health

• DNA synthesis – essential for cell division and growth

Without adequate B12, patients may develop symptoms such as fatigue, pallor, shortness of breath, glossitis (sore tongue), paraesthesia (pins and needles), and in severe cases, neurological complications including peripheral neuropathy, ataxia, and cognitive impairment.

Intramuscular (IM) hydroxocobalamin is the recommended first-line treatment for pernicious anaemia in the UK, as advised by NICE and the British Society for Haematology. While high-dose oral B12 supplements can be effective through passive diffusion, they are not routinely recommended for pernicious anaemia management in UK practice.

Important: If neurological symptoms are present (numbness, tingling, balance problems, confusion), treatment should not be delayed. These symptoms require urgent medical attention and immediate initiation of B12 injections to prevent potentially irreversible nerve damage.

How Vitamin B12 Injections Work for Pernicious Anaemia

Vitamin B12 injections in the UK contain hydroxocobalamin, which is the standard injectable formulation used in NHS practice. Hydroxocobalamin is preferred because it has a longer half-life and is retained in the body more effectively than cyanocobalamin (which is mainly available as oral supplements in the UK).

Once administered intramuscularly (usually into the deltoid or gluteal muscle), hydroxocobalamin is rapidly absorbed into the circulation. It binds to transport proteins, primarily transcobalamin II, which delivers B12 to tissues throughout the body. The liver stores significant amounts of B12, providing a reserve that can last several months to years, depending on the individual's metabolic needs and the severity of prior deficiency.

At the cellular level, B12 acts as a cofactor for two critical enzymatic reactions:

• Methionine synthase – converts homocysteine to methionine, essential for DNA methylation and synthesis

• Methylmalonyl-CoA mutase – involved in fatty acid metabolism and myelin production

By restoring adequate B12 levels, injections enable normal red blood cell maturation in the bone marrow, correcting the megaloblastic anaemia. Haematological improvement typically occurs within days to weeks, with reticulocyte counts rising as the marrow responds. Neurological recovery may take longer—weeks to months—and in some cases, long-standing nerve damage may be only partially reversible.

The intramuscular route ensures consistent, reliable delivery of B12, independent of gastrointestinal absorption. This makes injections highly effective for pernicious anaemia and other malabsorption syndromes, including post-gastrectomy states, Crohn's disease affecting the terminal ileum, and certain medications that interfere with B12 uptake.

NHS Treatment Schedule and Dosing for B12 Injections

The NHS follows evidence-based protocols for B12 replacement therapy in pernicious anaemia, with treatment divided into two phases: loading (induction) and maintenance.

Loading phase: For patients without neurological involvement, the standard regimen is 1 mg hydroxocobalamin intramuscularly three times weekly for two weeks (total of six injections). This rapidly replenishes depleted B12 stores and corrects anaemia.

If neurological symptoms are present (such as paraesthesia, ataxia, cognitive changes, or visual disturbances), more intensive treatment is required. NICE and British National Formulary (BNF) guidance recommend 1 mg hydroxocobalamin on alternate days until no further improvement in symptoms is observed. This may continue for several weeks or even months, as neurological recovery is often slower and more variable than haematological response. Treatment should not be delayed pending test results if neurological features are present.

Maintenance phase: Once the loading phase is complete, patients transition to maintenance therapy with 1 mg hydroxocobalamin intramuscularly every two to three months for life. Following neurological involvement, maintenance injections are typically given every two months for life. This schedule maintains adequate B12 levels and prevents relapse of deficiency symptoms.

It is important to check for coexistent folate and iron deficiency. If folate deficiency is present, replacement should only be started after initiating B12 therapy to avoid worsening neurological symptoms.

Pernicious anaemia is a lifelong condition requiring indefinite treatment. Stopping injections will lead to recurrence of deficiency, as the underlying malabsorption cannot be corrected. Patients should be counselled about the importance of adherence to their maintenance schedule.

Hydroxocobalamin is safe to use during pregnancy and breastfeeding, with dosing generally following the standard schedule. In certain circumstances—such as pregnancy, concurrent illness, or rapid metabolic turnover—B12 requirements may increase, and dosing adjustments may be necessary under medical supervision.

What to Expect During and After Your B12 Injection

During the injection: Vitamin B12 injections are typically administered by a practice nurse at your GP surgery. While some NHS areas may offer self-administration after appropriate training, this depends on local policy and is not routinely available everywhere. The injection is given intramuscularly, usually into the upper arm (deltoid) or buttock (gluteal muscle). The procedure is quick, taking only a few seconds, and most patients report minimal discomfort—similar to other intramuscular injections such as vaccines.

You may experience a brief stinging sensation as the solution is injected. Hydroxocobalamin has a characteristic red colour, which is normal and may temporarily tint the urine pink or red for a day or two after injection. This is harmless and does not indicate any problem.

Immediate effects: Some patients report feeling an improvement in energy levels within 24 to 48 hours, though this varies. Haematological parameters (such as haemoglobin and red blood cell indices) typically begin to normalise within one to two weeks. Neurological symptoms may take longer to resolve—often several weeks to months—and improvement may be gradual rather than immediate.

Common side effects: B12 injections are generally very well tolerated. Possible side effects include:

• Mild pain, redness, or swelling at the injection site

• Headache or dizziness (usually transient)

• Nausea (uncommon)

• Hypokalaemia (low potassium) during initial treatment, particularly in severely deficient patients—this is rare but may require monitoring

When to seek medical advice: Serious adverse reactions are extremely rare. However, you should:

• Call 999 or go to A&E immediately if you experience signs of a severe allergic reaction (difficulty breathing, severe throat/facial swelling, or collapse)

• Contact your GP if you experience a rash, itching, persistent pain at the injection site, or worsening neurological symptoms despite treatment

If you suspect any side effects from your B12 injections, you can report them through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

Monitoring Your Treatment and Long-Term Management

Initial monitoring: After starting B12 injections, your GP will typically arrange a full blood count (FBC) to assess haematological response. A reticulocyte count may also be checked, as a rise in reticulocytes (young red blood cells) within the first week indicates effective bone marrow response. Haemoglobin levels usually normalise within four to eight weeks.

If neurological symptoms were present at diagnosis, your doctor may perform a neurological examination at follow-up appointments to assess improvement. Routine serum B12 measurement is not useful once on injection therapy; assessment should be based on clinical response and FBC if indicated.

Long-term follow-up: Once stable on maintenance therapy, routine blood monitoring is not usually necessary unless new symptoms develop. Pernicious anaemia is a lifelong condition, and patients will require B12 injections indefinitely. However, annual review with your GP is advisable to:

• Ensure adherence to the injection schedule

• Monitor for any new or worsening symptoms

• Consider testing for other autoimmune conditions if symptoms develop (particularly thyroid function, as thyroid disease is commonly associated with pernicious anaemia)

Gastric cancer risk: Pernicious anaemia is associated with a slightly increased risk of gastric cancer. Current British Society of Gastroenterology guidance suggests considering a baseline upper GI endoscopy with biopsies in adults aged 50 or over with confirmed pernicious anaemia to document autoimmune gastritis. Ongoing surveillance is only recommended if extensive gastric atrophy, intestinal metaplasia, or additional risk factors are identified.

Patient self-management: Many patients become adept at recognising early signs of B12 deficiency (such as fatigue or paraesthesia) if injections are delayed. If you notice symptoms returning before your next scheduled injection, contact your GP to discuss whether more frequent dosing is needed.

Self-administration of B12 injections at home may be available in some NHS areas, subject to local policy and appropriate training. Discuss this option with your healthcare team if interested.

Lifestyle considerations: While dietary B12 intake is not relevant in pernicious anaemia (due to malabsorption), maintaining a balanced diet supports overall health. Patients should also be aware that certain medications—such as proton pump inhibitors (PPIs) and metformin—can interfere with B12 absorption, though this is less relevant once on injection therapy.

If you have any concerns about your treatment, symptoms, or injection schedule, do not hesitate to discuss these with your GP or haematology team.

Frequently Asked Questions