Vitamin B12 Deficiency and Pernicious Anaemia

What is Vitamin B12 Deficiency?

Pernicious Anaemia (PA) is the most common cause of vitamin B12 deficiency in many countries, but it is not the only cause. Vitamin B12 deficiency is a widespread condition that can lead to serious neurological, haematological, and systemic problems if left untreated.

Prevalence of Vitamin B12 Deficiency

Vitamin B12 deficiency is a global health issue. In the United Kingdom and United States, the prevalence is around 6% in people aged under 60 years, rising to approximately 20% in those aged over 60. Estimates suggest nearly 6 million people in the UK, over 26.5 million in the USA, and more than 586 million in India may be deficient. However, these figures are likely underestimates due to significant diagnostic challenges.

Why Vitamin B12 Deficiency is Frequently Underdiagnosed

Diagnosing vitamin B12 deficiency can be surprisingly difficult for four key reasons:

  1. Frequent Misdiagnosis – Nearly 40% of patients with Pernicious Anaemia were initially told their symptoms were due to another condition.
  2. Inconsistent Diagnostic Thresholds – There is no universal agreement on what blood levels constitute a deficiency. Different countries and laboratories use varying cut-off points.
  3. Sub-clinical Deficiency – Some patients experience clear symptoms even when serum B12 levels appear “normal.”
  4. Unreliable Laboratory Tests – Many B12 assays can produce falsely high readings, particularly in cases of Pernicious Anaemia.

What is Pernicious Anaemia?

Pernicious anaemia is an autoimmune condition in which the immune system attacks the intrinsic factor or the gastric parietal cells. This leads to impaired absorption of vitamin B12 due to autoimmune atrophic gastritis. It is a specific autoimmune form of B12 malabsorption.

vitamin b12 absorption

Comparing Pernicious Anaemia to Other Causes of B12 Deficiency

Pernicious Anaemia 

  • Caused by antibodies against intrinsic factor, a lack of intrinsic factor and/or autoimmune destruction of stomach cells that produce intrinsic factor.
  • Typically requires lifelong B12 replacement therapy, preferably via injections.
  • Strongly associated with other autoimmune diseases and a family history of autoimmunity.
  • Higher rates of co-existing iron deficiency.

Other Causes of B12 Deficiency (Non-Autoimmune)

  • Dietary insufficiency (e.g., strict vegan or vegetarian diets without supplementation).
  • Intestinal malabsorption (Crohn’s disease, coeliac disease, infections, or surgery).
  • Medication side effects (e.g., metformin, proton pump inhibitors).
  • Nitrous oxide (laughing gas) exposure.
  • Rare genetic disorders.

While dietary and some post-surgical causes can often be managed with high-dose oral supplements or dietary adjustments, Pernicious Anaemia usually requires injectable B12 because intrinsic factor is absent or non-functional.

Co-existing Deficiencies: Iron, Folate & Others

Patients with Pernicious Anaemia frequently experience additional deficiencies because stomach lining damage affects absorption. Common co-deficiencies include:

  • Iron deficiency — Reported in up to 46% of patients with probable Pernicious Anaemia (significantly higher than in other B12 deficiency groups).
  • Folate deficiency.
  • Vitamin D deficiency.

These overlapping deficiencies can worsen fatigue, anaemia, and other symptoms. Testing for iron studies, folate, and vitamin D in people with PA is recommended.

Association with Other Autoimmune Conditions

Pernicious Anaemia rarely occurs alone. Patient-reported data shows that nearly half of people with PA have one or more additional autoimmune diseases. Common co-existing autoimmune conditions include:

  • Hashimoto’s thyroiditis (most common)
  • Vitiligo
  • Rheumatoid arthritis
  • Psoriasis
  • Graves’ disease
  • Coeliac disease
  • Type 1 diabetes

Approximately one-third of patients also report a family history of Pernicious Anaemia or other autoimmune diseases, suggesting a genetic predisposition.

Causes of Vitamin B12 Deficiency

There are multiple ways to become deficient in this vital nutrient:

  • Inadequate Dietary Intake – Vitamin B12 is found almost exclusively in animal-based foods. Vegans and some vegetarians are at highest risk.
  • Gastric Atrophy (Atrophic Gastritis) – Chronic inflammation of the stomach lining reduces production of intrinsic factor. This is the mechanism behind Pernicious Anaemia and can also result from ageing or Helicobacter pylori infection.
  • Intestinal Diseases and Infections – Crohn’s disease, coeliac disease, chronic pancreatitis, bacterial overgrowth, fish tapeworm, giardiasis, tropical sprue, and others.
  • Surgical Procedures – Gastric bypass, partial gastrectomy, ileal resection.
  • Certain Medications: Metformin, proton pump inhibitors (PPIs), H2-receptor antagonists, and some anticonvulsants. Warning: Never stop prescribed medication without consulting your doctor.
  • Nitrous Oxide (N₂O) Exposure – Laughing gas inactivates the body’s stores of vitamin B12.
  • Rare Genetic Conditions – Inborn errors in B12 transport or metabolism.

Need Help?

Join the Pernicious Anaemia Society for support, resources, and community.

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Frequently Asked Questions

What is the most common cause of B12 deficiency?

Pernicious Anaemia is the leading cause of vitamin B12 deficiency

Can I have both B12 and iron deficiency at the same time?

Yes. This combination is particularly common in pernicious anaemia due to stomach lining damage affecting multiple nutrients.

Is Pernicious Anaemia hereditary?

There is a familial tendency. Many patients have relatives with PA or other autoimmune conditions.

How does PA differ from dietary B12 deficiency?

Dietary deficiency can usually be corrected with oral supplements or diet changes. Pernicious Anaemia involves permanent absorption problems, requires lifelong injections and often also causes other deficiencies.

References
  1. Andres E, Serraj K. Optimal management of pernicious anemia. Journal of Blood Medicine 2012; 3:97-103
  2. Hunt A, Harrington D, Robinson S.; Vitamin B12 Deficiency; British Medical Journal 2014; 349:5226
  3. Hooper M. What You Need to Know About Pernicious Anaemia and Vitamin B12 Deficiency; Hammersmith Health Books, London; 2014.pp 32-34
  4. Hooper M, Hudson P, Porter F, McCaddon A; Patients Journeys; the diagnosis and treatment of pernicious anaemia; British Journal of Nursing 2014; 23;7;385-386
  5. Smith D, Refsum H. Do we need to reconsider the desirable blood level of vitamin B12?; Journal of Internal Medicine 2011; 271(2):179-182
  6. Carmel R, Agrawal Y; Failures of cobalamin assays in pernicious anaemia; New England Journal of Medicine 2012; 367;4:385-386
  7. R. Ahmadi & Dominic J. Harrington (2021): Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls , Critical Reviews in Clinical Laboratory Sciences, DOI: 10.1080/10408363.2021.1885339
  8. Thain A, et al. Patient-reported characteristics of pernicious anaemia: a first step to initiate James Lind Alliance Priority Setting Partnership driven research. BMC Primary Care. 2025. DOI: 10.1186/s12875-025-03036-0

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