How a person gets pernicious anemia

November 30, 2025 •

4 min read

According to a 2012 study, pernicious anemia occurs in 0.1% of the general population and 1.9% of those over 60, making it a relatively rare but significant autoimmune disease. It is not contracted like an infection but develops when the body's immune system mistakenly attacks the cells in the stomach that produce intrinsic factor, a protein essential for vitamin B12 absorption. This leads to a severe vitamin B12 deficiency and can cause debilitating symptoms if left untreated.

Quick Summary

The condition develops primarily due to an autoimmune response that prevents the absorption of vitamin B12 by destroying intrinsic factor or the cells that produce it. Key risk factors include genetics and a history of other autoimmune disorders. Without adequate treatment, the resulting deficiency can lead to severe neurological and hematological issues.

Key Points

Autoimmune Attack: The most common cause is the immune system attacking stomach cells that produce intrinsic factor, a protein vital for vitamin B12 absorption.
Intrinsic Factor Deficiency: Without intrinsic factor, the body cannot absorb enough vitamin B12 from food, regardless of dietary intake.
Genetic Predisposition: A family history significantly increases the risk, with rare congenital forms affecting infants from birth.
Delayed Onset: The body's ability to store B12 means symptoms may not appear for years, leading to a potential for delayed diagnosis and increased risk of complications.
Associated Conditions: People with other autoimmune diseases, like type 1 diabetes and thyroid issues, have a higher risk of developing pernicious anemia.
Requires Lifelong Treatment: Treatment typically involves regular vitamin B12 injections to bypass the digestive absorption process.
Not Just a Dietary Problem: Pernicious anemia is a malabsorption issue, distinct from simple dietary B12 deficiency often seen in vegans.

Understanding the autoimmune response in pernicious anemia

For most people, a person gets pernicious anemia because of an autoimmune response, a process where the body's immune system mistakenly targets and attacks its own healthy cells. In this specific case, the immune system produces antibodies that attack the parietal cells in the stomach lining. These parietal cells are critical for two functions: producing hydrochloric acid to release vitamin B12 from food and secreting a special protein called intrinsic factor. Intrinsic factor is vital because it binds to vitamin B12, forming a complex that can be absorbed in the small intestine.

When the immune system destroys these parietal cells, the production of intrinsic factor ceases. Without intrinsic factor, vitamin B12 cannot be absorbed, regardless of how much is consumed through diet. This leads to a chronic and worsening vitamin B12 deficiency that, in turn, causes megaloblastic anemia, a condition characterized by abnormally large, underdeveloped red blood cells.

Other pathways leading to pernicious anemia

While the autoimmune mechanism is the most common cause, there are other ways a person can develop this condition or a similar vitamin B12 malabsorption issue:

Genetic predisposition: In rare cases, some infants are born with a congenital defect that prevents them from producing intrinsic factor. This results in pernicious anemia from a very young age. There is also a family history link, as relatives of those with the autoimmune form are at a higher risk.
Surgical procedures: Operations that remove all or part of the stomach (gastrectomy) or parts of the small intestine (ileectomy), where intrinsic factor is produced and B12 is absorbed, can directly cause a deficiency. Gastric bypass surgery for weight loss is a known risk factor.
Infections and digestive disorders: Certain gastrointestinal conditions can interfere with absorption. For instance, small intestinal bacterial overgrowth (SIBO) can cause bacteria to consume B12 before the body can absorb it. A fish tapeworm infection can have a similar effect. Inflammatory bowel diseases like Crohn's and celiac disease also impair absorption.
Medications: The long-term use of certain drugs, including proton pump inhibitors (PPIs) and metformin (used for diabetes), can lead to vitamin B12 deficiency by reducing stomach acid, which is necessary to free B12 from food proteins.

Associated autoimmune conditions

People with pernicious anemia often have other autoimmune diseases, suggesting a shared genetic predisposition and immune system malfunction. A significant percentage of individuals with pernicious anemia also have conditions such as:

Type 1 diabetes mellitus
Autoimmune thyroid disease (Hashimoto's or Graves' disease)
Addison's disease
Vitiligo, a condition causing skin depigmentation

Comparing causes of vitamin B12 deficiency

It is important to differentiate the autoimmune cause of pernicious anemia from other reasons for a lack of vitamin B12. Not all B12 deficiencies are pernicious anemia.


Feature	Pernicious Anemia	Other Vitamin B12 Deficiency
Underlying Cause	Autoimmune destruction of parietal cells, leading to a lack of intrinsic factor.	Can be due to diet (veganism), digestive disorders, surgery, or medication.
Intrinsic Factor	Functionally absent due to autoimmune attack.	Production is often normal, but absorption may be inhibited for other reasons.
Treatment Response	Requires parenteral (injectable) or high-dose oral supplementation to bypass the gut absorption block.	Can often be corrected with dietary changes or standard oral supplements.
Risk Profile	Strong association with other autoimmune conditions and genetic factors.	Risk is higher in vegans, older adults, alcoholics, and those with certain medication usage.
Chronic Condition	A lifelong condition that requires continuous monitoring and treatment.	Can sometimes be resolved once the underlying cause is addressed.

The delayed onset and progression

Pernicious anemia often has an insidious and slow onset. The body can store several years' worth of vitamin B12 in the liver, so a deficiency may not become symptomatic for 3 to 5 years after the intrinsic factor production stops. This delay can lead to misdiagnosis or late treatment, increasing the risk of serious complications, particularly irreversible nerve damage. Over time, the chronic atrophic gastritis that defines the autoimmune form can also increase the risk of gastric cancer.

Diagnosis and treatment

Diagnosing pernicious anemia involves blood tests to measure B12 levels and check for specific antibodies against intrinsic factor and parietal cells. Treatment typically involves lifelong vitamin B12 injections, as the faulty absorption process prevents oral supplements from being effective in standard doses. However, very high-dose oral B12 has shown some efficacy in bypassing the need for intrinsic factor.

Conclusion

In summary, a person gets pernicious anemia primarily through an autoimmune process where the body attacks the very cells needed to absorb vitamin B12, leading to a severe, chronic deficiency. While genetic factors, certain surgeries, and other digestive disorders can also cause malabsorption, the autoimmune form is the most prevalent. Early diagnosis is crucial for preventing severe neurological and hematological complications, highlighting the importance of recognizing the symptoms and risk factors associated with this condition.

Disclaimer: This article is for informational purposes only and should not replace professional medical advice. Always consult a healthcare provider for diagnosis and treatment.

Frequently Asked Questions

Pernicious anemia can have a genetic component, with a family history of the disease increasing a person's risk. While not always directly inherited, a genetic predisposition is often involved, and some rare congenital forms result in the inability to produce intrinsic factor from birth.

No, pernicious anemia cannot be cured with diet changes alone. Because the problem lies in the body's inability to absorb vitamin B12 due to a lack of intrinsic factor, simply eating more B12-rich foods will not solve the issue. The malabsorption must be bypassed, usually with injections or high-dose oral supplements.

The earliest signs are often subtle and non-specific, which can delay diagnosis for years. Common symptoms include fatigue, weakness, a sore and red tongue, and digestive issues like constipation or diarrhea.

Diagnosis involves several tests, including a complete blood count (CBC) to check for large red blood cells (macrocytes) and low hemoglobin, a serum B12 level test, and blood tests for antibodies targeting intrinsic factor or parietal cells.

Yes, surgical removal of part or all of the stomach (gastrectomy) or parts of the small intestine can lead to pernicious anemia. This is because these procedures remove the areas responsible for producing intrinsic factor and absorbing B12.

Pernicious anemia was once considered deadly before treatments were available. If left untreated, the severe vitamin B12 deficiency can cause irreversible neurological damage, heart problems, and increase the risk of gastric cancer.

The chronic inflammation of the stomach lining (atrophic gastritis) caused by the autoimmune attack is linked to an increased risk of developing gastric polyps and, subsequently, stomach cancer. Regular monitoring is advised for affected individuals.