Vitamin B12 deficiency anaemia occurs when insufficient vitamin B12 (cobalamin) prevents the body from producing adequate healthy red blood cells. This essential vitamin is crucial for DNA synthesis, red cell formation, and neurological function. When B12 levels fall, the bone marrow produces abnormally large, immature red blood cells called megaloblasts, which cannot effectively transport oxygen. The condition develops gradually, often over months or years, and is particularly common among older adults in the UK. Early recognition and treatment are vital, as prolonged deficiency can cause potentially irreversible nerve damage. Symptoms include fatigue, weakness, pale skin, shortness of breath, and neurological manifestations such as numbness, tingling, memory problems, and difficulty walking.

What Is Vitamin B12 Deficiency Anaemia?

Vitamin B12 deficiency anaemia is a condition in which the body lacks sufficient vitamin B12 (cobalamin) to produce adequate healthy red blood cells. This essential water-soluble vitamin plays a crucial role in DNA synthesis, red blood cell formation, and neurological function. When B12 levels fall below normal ranges, the bone marrow produces abnormally large, immature red blood cells called megaloblasts, which cannot function effectively to transport oxygen throughout the body.

This type of anaemia belongs to the broader category of megaloblastic anaemias, characterised by the presence of these enlarged red blood cells. The condition develops gradually, often over months or years, as the body's B12 stores become depleted. Importantly, B12 deficiency can occur without anaemia, and some patients may present with neurological symptoms despite having normal haemoglobin levels.

Vitamin B12 deficiency is common in the UK, particularly among older adults. Early recognition and treatment are essential, as prolonged deficiency can lead to potentially irreversible nerve damage. Red flag symptoms requiring urgent assessment include progressive neuropathy, ataxia (balance problems), cognitive changes, and visual disturbances.

Typical symptoms include fatigue, weakness, pale skin, shortness of breath, and neurological manifestations such as numbness, tingling in the extremities, memory problems, and difficulty walking.

Key characteristics of B12 deficiency anaemia include:

• Macrocytic red blood cells (larger than normal)

• Reduced red blood cell count

• Potential neurological symptoms (even with normal blood counts)

• Gradual onset of symptoms

• Reversible with appropriate treatment when caught early

Causes and Risk Factors

Vitamin B12 deficiency anaemia arises from various mechanisms that prevent adequate absorption, intake, or utilisation of the vitamin. Pernicious anaemia represents the most common cause in the UK. This autoimmune condition occurs when the body produces antibodies against intrinsic factor, a protein secreted by gastric parietal cells that is essential for B12 absorption in the terminal ileum. Without intrinsic factor, dietary B12 cannot be absorbed effectively, regardless of intake levels.

Dietary insufficiency is another significant cause, particularly among strict vegans and vegetarians, as vitamin B12 is naturally found almost exclusively in animal products including meat, fish, eggs, and dairy. Whilst dietary deficiency is less common in the UK than in developing countries, it remains an important consideration in certain populations. Malabsorption disorders represent a substantial risk category, including conditions such as coeliac disease, Crohn's disease affecting the terminal ileum, and bacterial overgrowth in the small intestine.

Gastrointestinal surgery significantly increases risk, particularly procedures involving the stomach (gastrectomy) or terminal ileum resection, as these remove or bypass critical absorption sites. Patients who have undergone bariatric surgery require lifelong B12 monitoring and often routine supplementation according to British Obesity and Metabolic Surgery Society (BOMSS) guidelines.

Certain medications interfere with B12 absorption, most notably metformin (used for type 2 diabetes), proton pump inhibitors (PPIs), and H2-receptor antagonists when used long-term, as they reduce stomach acid production necessary for B12 release from food proteins.

Nitrous oxide exposure can inactivate vitamin B12. If neurological symptoms develop after nitrous oxide use, exposure should be stopped immediately and urgent medical assessment sought.

Additional risk factors include:

• Age over 60 years (reduced stomach acid production)

• Autoimmune conditions (thyroid disease, vitiligo, type 1 diabetes)

• Family history of pernicious anaemia

• Chronic alcohol consumption

Diagnosis and Testing

Diagnosis of vitamin B12 deficiency anaemia requires a combination of clinical assessment, laboratory investigations, and sometimes specialist testing. Initial presentation typically prompts a full blood count (FBC), which may reveal macrocytic anaemia characterised by elevated mean corpuscular volume (MCV >100 fL) and reduced haemoglobin levels. The blood film often shows hypersegmented neutrophils and oval macrocytes, distinctive features of megaloblastic anaemia.

Serum vitamin B12 measurement forms the cornerstone of diagnosis, with levels below 148 pmol/L (200 ng/L) generally considered deficient, though symptoms can occur at higher levels. The interpretation requires clinical context, as levels between 148–258 pmol/L represent a 'grey zone' where deficiency may still be present. Reference ranges vary between laboratories, so local laboratory guidance should be consulted.

In cases where B12 levels are borderline or clinical suspicion remains high despite normal results, additional tests may be valuable. Methylmalonic acid (MMA) and homocysteine levels become elevated in B12 deficiency, but these tests are not routinely available in all NHS laboratories and can be confounded by renal impairment. Some centres may offer holotranscobalamin (active B12) testing as an alternative.

According to NICE guidance, investigation should include testing for intrinsic factor antibodies when pernicious anaemia is suspected, as positive results confirm the diagnosis with high specificity (>95%). However, a negative test does not exclude pernicious anaemia due to limited sensitivity. Gastric parietal cell antibodies may also be measured, though these are less specific.

Important: If neurological symptoms suggest subacute combined degeneration of the spinal cord, treatment should be started urgently and not delayed for test results.

Recommended investigations include:

• Full blood count with blood film examination

• Serum vitamin B12 level

• Serum folate (to exclude combined deficiency)

• Intrinsic factor antibodies

• Thyroid function tests (autoimmune association)

• Consider MMA and homocysteine if diagnosis uncertain and available

Neurological examination should be performed in all patients, assessing for peripheral neuropathy, proprioception loss, and signs of subacute combined degeneration of the spinal cord.

Treatment Options for B12 Deficiency Anaemia

Treatment of vitamin B12 deficiency anaemia depends on the underlying cause, severity of deficiency, and presence of neurological symptoms. For patients with pernicious anaemia or malabsorption disorders, intramuscular hydroxocobalamin injections represent the standard treatment in the UK, as oral supplementation cannot overcome the absorption defect.

According to NICE Clinical Knowledge Summaries and the British National Formulary (BNF), the recommended treatment regimens are:

For patients without neurological involvement:

• Initial treatment: hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks

• Maintenance: hydroxocobalamin 1 mg intramuscularly every 3 months for life

For patients with neurological involvement:

• Initial treatment: hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement

• Maintenance: hydroxocobalamin 1 mg intramuscularly every 2 months for life

If neurological symptoms are present, treatment should be started urgently to prevent irreversible damage.

For dietary deficiency in the absence of malabsorption, oral cyanocobalamin supplementation (50–150 micrograms daily) may suffice, though compliance and absorption must be monitored. Sublingual and nasal spray formulations exist but are not routinely recommended by NICE.

Some patients prefer oral therapy even with pernicious anaemia; high-dose oral B12 (1000–2000 micrograms daily) can achieve adequate absorption through passive diffusion. However, this approach is off-label and not routinely recommended by NICE. If used (e.g., when injections are unsuitable), it requires close monitoring and agreement between the patient and healthcare provider.

Treatment considerations include:

• Concurrent folate supplementation if deficient (never give folate alone, as it may precipitate neurological deterioration)

• Potassium monitoring during initial treatment in severe anaemia or at-risk patients (e.g., those with heart failure)

• Response assessment: reticulocyte count peaks at 5–7 days, haemoglobin normalises within 6–8 weeks

• Neurological symptoms may take 6–12 months to improve and may not fully resolve

Patients should be advised that treatment for pernicious anaemia or post-surgical deficiency is lifelong. Those experiencing injection site reactions may benefit from rotating injection sites. Suspected adverse reactions should be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Prevention and Long-Term Management

Prevention of vitamin B12 deficiency anaemia focuses on identifying at-risk populations and implementing appropriate monitoring and supplementation strategies. Dietary prevention is straightforward for omnivores, as B12 is abundant in animal products including meat, fish, poultry, eggs, and dairy. The recommended daily intake for adults is 1.5 micrograms, easily achieved through a balanced diet. However, vegans and strict vegetarians require particular attention, as plant-based foods contain negligible B12 unless fortified.

For those following plant-based diets, regular consumption of fortified foods (breakfast cereals, plant-based milk alternatives, nutritional yeast) or daily oral B12 supplements is essential. Pregnant and breastfeeding women following vegan diets may require higher supplementation; they should discuss appropriate supplement choices with their midwife, GP, or dietitian. Healthcare professionals should proactively discuss B12 supplementation with patients adopting plant-based diets.

Long-term management of diagnosed B12 deficiency requires lifelong treatment for most patients with pernicious anaemia or malabsorption disorders. Regular serum B12 monitoring is not routinely necessary once stable on replacement therapy, as levels become artificially elevated and unreliable. Instead, clinical assessment focusing on symptom resolution provides adequate monitoring, with blood tests performed only if clinically indicated.

Patients should be educated about the importance of maintaining treatment adherence, as discontinuation leads to recurrent deficiency within months to years. Intramuscular injections are typically administered by healthcare professionals in the UK; self-administration is only appropriate if agreed and properly trained by NHS services.

Specific populations requiring enhanced surveillance include:

• Patients on long-term metformin (test if deficiency is suspected; consider periodic monitoring in at-risk patients)

• Those taking PPIs or H2-antagonists for extended periods

• Post-bariatric surgery patients (routine supplementation according to BOMSS guidelines)

• Elderly individuals with atrophic gastritis

• Patients with inflammatory bowel disease affecting the terminal ileum

Patient safety advice includes recognising warning signs of deficiency recurrence: increasing fatigue, neurological symptoms (numbness, tingling, balance problems), or mood changes. Patients should contact their GP if symptoms develop between scheduled injections or if they miss appointments. Annual review should include symptom enquiry and consideration of associated autoimmune conditions, particularly thyroid disease, which may co-exist with pernicious anaemia.

Frequently Asked Questions