Recurrent mouth ulcers can significantly impact quality of life, causing pain and difficulty eating. Whilst minor trauma and stress are common triggers, vitamin B12 deficiency represents an important yet often overlooked cause of persistent oral ulceration. Vitamin B12 (cobalamin) is essential for DNA synthesis and cell division, processes critical for maintaining the rapidly renewing oral mucosa. When B12 levels fall, the delicate tissues lining the mouth become vulnerable to damage and impaired healing. Research demonstrates that individuals with recurrent aphthous stomatitis frequently present with lower B12 levels, and correcting this deficiency can reduce ulcer frequency and severity. Understanding this connection is particularly relevant for at-risk groups including vegans, older adults, and those with malabsorption conditions.

Understanding the Link Between Vitamin B12 Deficiency and Mouth Ulcers

Mouth ulcers, medically termed aphthous ulcers (sometimes called canker sores), are painful lesions that develop on the soft tissues inside the mouth. Whilst these ulcers can arise from various causes—including minor trauma, stress, or certain foods—nutritional deficiencies represent an important and often overlooked contributing factor. Among these, vitamin B12 deficiency has been associated with recurrent mouth ulceration.

Vitamin B12 (cobalamin) is an essential water-soluble vitamin crucial for DNA synthesis, red blood cell formation, and neurological function. The body cannot produce B12 independently, making dietary intake or supplementation necessary. When B12 levels fall below optimal ranges, the rapidly dividing cells of the oral mucosa become particularly vulnerable to damage and impaired healing.

Research has shown that individuals with recurrent aphthous stomatitis (RAS)—characterised by repeated mouth ulcer episodes—often present with lower serum B12 levels compared to healthy controls. Studies have found that correcting B12 deficiency can lead to improvement in ulcer frequency and severity in affected patients. However, it is important to emphasise that not all mouth ulcers are caused by B12 deficiency, and other factors such as immune dysfunction, genetic predisposition, and local trauma also play important roles.

Understanding this connection is particularly relevant in the UK, where certain population groups—including vegans, older adults, and individuals with malabsorption conditions—face increased risk of B12 deficiency. Recognising the potential link between nutritional status and oral health enables both patients and healthcare professionals to consider appropriate investigation and management strategies.

Recognising Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency presents with a diverse range of symptoms that extend well beyond oral manifestations. The condition typically develops gradually, and early signs may be subtle or attributed to other causes. Recognising the full spectrum of symptoms is essential for timely diagnosis and treatment.

Oral and mucosal symptoms often provide early clues. Beyond mouth ulcers, patients may experience:

• A sore, red, or swollen tongue (glossitis)

• Burning sensation in the mouth

• Altered taste perception

• Angular cheilitis (cracks at the corners of the mouth)

Haematological manifestations arise from impaired red blood cell production. Patients commonly report:

• Persistent fatigue and weakness

• Breathlessness, particularly on exertion

• Palpitations

• Pale or jaundiced skin

These symptoms reflect the development of megaloblastic anaemia, where red blood cells become abnormally large and dysfunctional.

Neurological symptoms can be particularly concerning and may become irreversible if deficiency persists. These include:

• Paraesthesia (pins and needles) in hands and feet

• Difficulty walking or balance problems

• Memory impairment and cognitive changes

• Mood disturbances, including depression and irritability

• Visual disturbances (rare, such as optic neuropathy)

Gastrointestinal symptoms such as diarrhoea, constipation, or loss of appetite may also occur, particularly when deficiency results from malabsorption.

It is important to recognise that symptom severity does not always correlate with the degree of deficiency. Some individuals with significantly low B12 levels may present with minimal symptoms initially, whilst others experience pronounced manifestations. If you experience persistent mouth ulcers alongside any of these symptoms, contact your GP for appropriate assessment and blood testing. Seek urgent same-day assessment for rapidly progressive neurological symptoms, and emergency care for severe breathlessness, chest pain, or fainting.

How Vitamin B12 Deficiency Causes Mouth Ulcers

The mechanism linking vitamin B12 deficiency to mouth ulcer development involves several interconnected pathological processes affecting the oral mucosa. Understanding these mechanisms helps explain why B12 supplementation can prove therapeutic in susceptible individuals.

Impaired DNA synthesis represents the primary mechanism. Vitamin B12 serves as an essential cofactor for methionine synthase, an enzyme critical for DNA production and cell division. The oral epithelium has one of the highest cell turnover rates in the body, with complete renewal occurring approximately every 7–14 days. When B12 deficiency impairs DNA synthesis, the rapidly dividing epithelial cells cannot regenerate effectively, leading to mucosal thinning, increased fragility, and susceptibility to ulceration.

Megaloblastic changes affect not only red blood cells but also epithelial cells throughout the body. In the oral cavity, these abnormal cells demonstrate impaired maturation and function, compromising the protective barrier function of the mucosa. This renders the tissue more vulnerable to minor trauma and inflammatory triggers that would normally be well tolerated.

Altered immune function may contribute to ulcer formation. Research suggests that B12 may play a role in regulating inflammatory responses and maintaining immune homeostasis. Deficiency could potentially lead to dysregulated local immune responses in the oral mucosa, possibly triggering or perpetuating ulcerative lesions.

Impaired tissue repair further compounds the problem. Even when ulcers form from other triggers, B12 deficiency hampers the healing process. The vitamin is essential for proper cell division and epithelial regeneration—processes fundamental to wound healing. Consequently, ulcers may persist longer, recur more frequently, and cause greater discomfort in B12-deficient individuals compared to those with adequate nutritional status.

Diagnosing and Testing for Vitamin B12 Deficiency in the UK

In the UK, diagnosis of vitamin B12 deficiency follows guidance from the British Society for Haematology (BSH) and NICE, emphasising a combination of clinical assessment and laboratory investigation. If you present to your GP with recurrent mouth ulcers and other suggestive symptoms, a systematic diagnostic approach will be undertaken.

Initial blood tests typically include:

• Serum B12 level: The first-line investigation, though interpretation requires caution. The BSH defines deficiency as serum B12 <148 pmol/L, whilst levels between 148–258 pmol/L are considered borderline and may warrant further investigation, particularly if symptoms are present.

• Full blood count (FBC): May reveal macrocytic anaemia (elevated mean cell volume) and reduced haemoglobin, though these changes are not always present, especially in early deficiency.

• Serum folate and ferritin: Important to assess as folate deficiency can coexist with B12 deficiency, and iron deficiency can mask macrocytosis. Important safety note: If folate deficiency is detected alongside B12 deficiency, B12 replacement must be started before folate to avoid worsening neurological symptoms.

• Blood film: Can demonstrate megaloblastic changes and hypersegmented neutrophils characteristic of B12 deficiency.

When serum B12 results are equivocal or clinical suspicion remains high despite normal B12 levels, additional tests may be requested:

• Methylmalonic acid (MMA): Elevated levels indicate functional B12 deficiency at the cellular level, though availability may be limited in primary care and levels can be elevated in renal impairment

• Homocysteine: Also elevated in B12 deficiency, though less specific and also affected by renal function

• Intrinsic factor antibodies: To investigate pernicious anaemia, the most common cause of B12 deficiency in the UK

• Anti-parietal cell antibodies: May be tested if pernicious anaemia is suspected but intrinsic factor antibodies are negative

Identifying the underlying cause is crucial for appropriate management. Your GP will explore:

• Dietary history (particularly relevant for vegans and vegetarians)

• Gastrointestinal symptoms suggesting malabsorption

• Medication history (metformin, proton pump inhibitors, and H2-receptor antagonists can impair B12 absorption)

• Previous gastric surgery

• Family history of pernicious anaemia

Important: If neurological symptoms are present, treatment should be started immediately without waiting for test results.

Referral to secondary care may be appropriate if the cause remains unclear, if neurological symptoms are present, or if initial treatment proves ineffective. Gastroenterology referral might be considered to investigate malabsorption disorders such as coeliac disease or Crohn's disease. Urgent referral (two-week wait) is required for mouth ulcers persisting for more than three weeks, as per NICE suspected cancer guidelines.

Treatment Options: Vitamin B12 Supplements and Injections

Treatment of vitamin B12 deficiency in the UK follows NICE Clinical Knowledge Summary guidance, with the approach tailored to the underlying cause, severity of deficiency, and presence of neurological symptoms. For patients experiencing recurrent mouth ulcers related to B12 deficiency, appropriate replacement therapy often leads to significant improvement in oral symptoms.

Intramuscular B12 injections represent the standard treatment for deficiency due to malabsorption (such as pernicious anaemia) or when neurological symptoms are present. The typical regimen involves:

• Loading dose for patients without neurological involvement: Hydroxocobalamin 1mg intramuscularly three times weekly for two weeks

• Loading dose for patients with neurological involvement: Hydroxocobalamin 1mg on alternate days until no further improvement, then

• Maintenance therapy: 1mg every two to three months (or every two months if neurological involvement)

Lifelong maintenance therapy is necessary for irreversible causes such as pernicious anaemia or following gastric surgery.

Hydroxocobalamin is preferred in the UK over cyanocobalamin due to its superior retention in the body. These injections are administered by practice nurses in GP surgeries and are generally well tolerated, with minimal adverse effects beyond occasional injection site reactions.

Oral B12 supplementation may be appropriate in specific circumstances:

• Dietary deficiency in individuals with normal absorption capacity (typically 50-150 micrograms daily)

• Patient preference (after discussion of relative efficacy)

• Maintenance therapy in selected cases

Higher oral doses (1000–2000 micrograms daily) may be used in some cases, as only a small percentage is absorbed through passive diffusion when intrinsic factor-mediated absorption is impaired.

Sublingual and nasal preparations are available but are not routinely recommended in NHS practice due to limited evidence and cost considerations.

Monitoring response to treatment involves:

• Clinical assessment of symptom improvement, including mouth ulcer frequency

• FBC to confirm resolution of anaemia and reticulocyte response

• Ongoing monitoring of neurological symptoms if present

Routine repeat measurement of serum B12 levels shortly after starting injections is not generally recommended as results may be misleadingly high.

Patient safety considerations:

• If you experience worsening neurological symptoms or develop new symptoms despite treatment, contact your GP promptly.

• In combined B12 and folate deficiency, B12 replacement must be started before folate supplementation to avoid precipitating or worsening neurological damage.

• Whilst rare, hypokalaemia can occur during initial treatment as cells rapidly take up potassium during recovery—your doctor may monitor potassium levels if you have risk factors.

• Report any suspected side effects to the MHRA Yellow Card Scheme.

Preventing Mouth Ulcers Through Adequate B12 Intake

Prevention of B12 deficiency-related mouth ulcers centres on ensuring adequate vitamin intake through diet, appropriate supplementation when necessary, and addressing underlying risk factors. A proactive approach is particularly important for individuals in high-risk groups.

Dietary sources of vitamin B12 are exclusively animal-derived, making awareness crucial for dietary planning:

• Meat and poultry: Beef, lamb, pork, and chicken (particularly liver and organ meats)

• Fish and seafood: Salmon, trout, tuna, sardines, and shellfish

• Dairy products: Milk, cheese, and yoghurt

• Eggs: Particularly the yolk

The NHS recommends approximately 1.5 micrograms of B12 daily for adults, a requirement easily met through a varied diet including animal products. However, certain groups require particular attention:

Vegans and strict vegetarians must obtain B12 through:

• Fortified foods (plant-based milk alternatives, breakfast cereals, nutritional yeast)

• Regular B12 supplementation (typically 10–25 micrograms daily or 2000 micrograms weekly)

The Vegan Society recommends that all vegans supplement B12, as plant-based sources are unreliable and insufficient.

Older adults (over 65 years) face increased risk due to reduced stomach acid production and intrinsic factor secretion. Regular monitoring and consideration of supplementation may be appropriate.

Individuals taking certain medications should discuss B12 status with their GP:

• Metformin (commonly prescribed for type 2 diabetes)

• Proton pump inhibitors and H2-receptor antagonists (for acid reflux)

Additional preventive measures for mouth ulcer management include:

• Maintaining good oral hygiene with a soft-bristled toothbrush

• Considering sodium lauryl sulphate-free toothpastes if you notice sensitivity (evidence is mixed)

• Identifying and avoiding individual trigger foods

• Managing stress through appropriate techniques

• Ensuring adequate intake of other nutrients (folate, iron, zinc) that support oral health

When to seek medical advice:

• If you experience recurrent mouth ulcers (more than three episodes annually)

• If ulcers last longer than three weeks (requires urgent referral to rule out oral cancer)

• If you develop a persistent unexplained neck lump or suspicious oral lesions

• If ulcers become increasingly severe or frequent

Early identification and correction of nutritional deficiencies can significantly improve quality of life and prevent potential long-term complications of B12 deficiency.

Frequently Asked Questions