Overview

Vitamin B12 is essential for various different biological processes. A deficiency in this can cause a variety of issues. This deficiency can be caused by a few factors. Understanding the differences between pernicious anaemia and other causes of vitamin B12 deficiency is essential for accurate diagnosis and treatment.

Pernicious Anaemia is a disorder that causes a deficiency of vitamin B12, but it is not the only cause of vitamin B12 deficiency. There are also other causes, including both dietary and malabsorption-related deficiency.

This article breaks down the key differences between these various causes.

What is vitamin B12?

Vitamin B12, also known as cobalamin, is a vitamin that is often found in animal foods such as,

• Red meat
• Eggs
• Poultry, such as chicken and turkey
• Dairy products, including cheese and milk¹

It is needed for a variety of functions in the body.¹ 

What role does vitamin B12 play in the body?

Vitamin B12 plays important roles in the body, including:

Neurological function – Vitamin B12 is required for the function and development of brain cells as well as the central nervous system.^1,2

DNA synthesis – Vitamin B12 is important in the production of DNA.^1,2

Red blood cell formation – It is vital for the production of healthy red blood cells.²

Energy metabolism – It also works with enzymes involved in metabolic function.³

Now that we know the role of vitamin B12 in the body, it can be said that a deficiency in this can lead to negative effects. 

What are the symptoms of vitamin B12 deficiency?

Some symptoms of vitamin B12 deficiency include:³

• Fatigue and pallor
• Jaundice
• Diarrhoea
• Headaches
• Neurological symptoms such as numbness and balance problems

How is vitamin B12 absorbed into the body?

In order to understand vitamin B12 deficiency, we must understand how vitamin B12 is absorbed in the body.

Vitamin B12 is attached to a protein in food, where it must be released before it can be absorbed by the body.² This process starts in your mouth, when a protein in your saliva called haptocorrin binds to the vitamin B12 to protect it from being broken down.^2,4

The food then reaches the stomach, where enzymes and stomach acid break the vitamin B12 away from the haptocorrin, allowing it to bind to a protein called intrinsic factor, which is produced in the stomach.

This vitamin B12 now attached to intrinsic factor travels down to the small intestine, specifically the terminal ileum, where it is then absorbed by the body.²

What causes vitamin B12 deficiency?

The 4 main classifications of vitamin B12 deficiency include:

Autoimmune

An autoimmune condition called pernicious anaemia, where anti-intrinsic antibodies bind to intrinsic factor and prevent intrinsic factor from binding to vitamin B12, which stops it from being absorbed into the small intestine.³

Malabsorption-related

There are cells in the stomach called gastric parietal cells that produce intrinsic factor.³

Individuals with a history of gastric bypass surgery may be at risk for developing vitamin B12 deficiency as the part of the stomach responsible for producing intrinsic factor has been removed.³

Vitamin B12 deficiency can also be caused by any damage to the small intestine, specifically the terminal ileum, which is the final section of the small intestine that absorbs vitamin B12.³

Dietary insufficiency

Excess vitamin B12 is stored in the liver.³ Individuals who have followed a long-term strict vegan diet may develop a deficiency of vitamin B12 from lack of dietary intake and failure to take vitamin supplements³

 Due to vitamin B12 mainly being found in animal foods.

Toxin exposure

Exposure to toxins such as nitrous oxide can cause a vitamin B12 deficiency and neurological symptoms.³

Autoimmune-related: pernicious anaemia

What is pernicious anaemia?

Pernicious anaemia, also known as Biermer’s disease and Addisonian anaemia, is a rare autoimmune disorder that causes vitamin B12 deficiency, as it affects the body’s ability to absorb it, leading to symptoms such as fatigue, jaundice and diarrhoea.^4,3,6

How does pernicious anaemia cause vitamin B12 deficiency?

There are a few ways this condition can affect the absorption of vitamin B12:

The first way is the autoimmune destruction of gastric parietal cells, which is when the immune system accidentally attacks the parietal cells that are responsible for producing intrinsic factor, which is needed for vitamin B12 absorption.⁵ This leads to decreased production of intrinsic factor, causing vitamin B12 deficiency.⁵

Another way is that antibodies are being formed against the intrinsic factor.⁵ On top of attacking parietal cells, the immune system can directly target the intrinsic factor by binding antibodies to it, so they can’t bind to vitamin B12 for absorption.^3,5

Finally, vitamin B12 absorption can be damaged, as the lack of intrinsic factor means that it cannot form a bond with vitamin B12, which is necessary for it to be absorbed in the small intestine, specifically the terminal ileum.^3,5 As a consequence, even with enough vitamin B12 in the diet, there will still be a deficiency as the vitamin B12 is not being absorbed.^3,5 

What are the consequences of pernicious anaemia?

Vitamin B12 deficiency caused by pernicious anaemia can result in:

Megaloblastic anaemia is the production of abnormally large and immature blood cells, which leads to defective DNA synthesis.⁶

Neurological symptoms such as numbness, balance issues, and tingling can also occur due to nerve damage caused by vitamin B12 deficiency.^3,6

Early treatment and diagnosis are crucial for individuals with pernicious anaemia in order to prevent permanent damage.³

Malabsorption-related

Vitamin B12 deficiency can also be caused by factors affecting the malabsorption of vitamin B12.³ These include:

• Gastrointestinal surgeries
• Chronic gastrointestinal disorders
• Infection
• Medication-induced malabsorption

Gastrointestinal surgeries

Gastrointestinal surgeries such as gastric bypass can cause a decrease in intrinsic factor production, as these surgeries can alter the stomach's ability to release vitamin B12 from haptocorrin.³

Ileum resection, the removal of the ileum, is also another surgery that causes vitamin B12 deficiency, as the ileum is the main site of vitamin B12 absorption.³

Chronic gastrointestinal disorders

Disorders affecting the stomach, such as Crohn’s Disease, can cause inflammation or the need for the surgical removal of the ileum, leading to decreased vitamin B12 absorption.³

Celiac disease is another disease that can cause vitamin B12 absorption to be defective.³

Infection

Infections such as Diphyllobothrium latum, known as a fish tapeworm, compete with the body for vitamin B12, leading to deficiency.⁷ 

Medication-induced malabsorption

Some medications can prevent vitamin B12 from being absorbed.⁸ Long-term treatments of medications, including proton pump inhibitors (PPIs), can cause a decrease in stomach acid, which is essential for releasing vitamin B12 from food proteins.⁸

Dietary insufficiency

Another cause of vitamin B12 deficiency is an insufficient diet. This deficiency arises when individuals consume inadequate amounts of foods rich in vitamin B12.⁷

The main cause is a strict vegetarian or vegan diet. Vitamin B12 is naturally found in foods from animals, such as cheese, eggs, fish and meat.^8,9 Vegans, who do not consume any animal products at all, have a higher risk of vitamin B12 deficiency.⁹

Vegetarians are also at a risk of vitamin B12 deficiency, even though they consume animal products, they do not eat meat, so the intake of vitamin B12 may be limited.⁹

Vitamin B12 supplements may need to be taken to reach the required intake of vitamin B12 for a healthy person and reverse the deficiency.⁹ There are studies that prove plant-based diets cause an increased risk of vitamin B12 deficiency.⁹

In some countries, animal-sourced food consumption is limited due to cultural practices or economic constraints, therefore increasing the risk of deficiency.¹⁰

Comparison of pernicious anaemia vs. other B12 deficiency causes

Underlying mechanism

Pernicious anaemia occurs when the body produces antibodies that attack intrinsic factor or parietal cells, leading to decreased vitamin B12 absorption, while dietary and malabsorption-related causes typically involve external factors such as a vegan diet or chronic illnesses.

Progression

Pernicious anaemia typically develops slowly over a few years, which allows the body to compensate for the decreasing levels of vitamin B12 until very low.⁴ Though this delayed development means that symptoms do not appear until the pernicious anaemia is severe, making it more difficult to treat.⁴

Malabsorption-related causes, such as ileum removal, can lead to a faster decrease in vitamin B12 levels, as the body can’t absorb vitamin B12 as well.^3,10 This leads to symptoms presenting earlier.¹⁰

For dietary insufficiency-related vitamin B12 deficiency, the symptoms can take years and years to appear as the body stores excess vitamin B12 in the liver.^3,9,10

Summary

Understanding the differences between pernicious anaemia and other causes of vitamin B12 deficiency is essential for accurate diagnosis and treatment. Vitamin B12, also known as cobalamin, is found in animal-derived foods and is an essential vitamin. It is involved in processes such as DNA synthesis and red blood cell formation. 

A deficiency in this vitamin can cause a variety of symptoms, including fatigue, jaundice and neurological symptoms. The underlying causes of this deficiency can vary, from autoimmune conditions to dietary insufficiencies and malabsorption-related issues.

The comparison of these causes shows the difference in the underlying mechanisms and progression of the vitamin B12 deficiency. Autoimmune causes, such as pernicious anaemia, can lead to lifelong issues, while diet-related causes develop far more slowly and can be reversed with supplements. Malabsorption-related deficiency is more complex, as there are several different causes.

Ultimately, defining the cause of the vitamin B12 deficiency is crucial in treating it.