Does B12 Deficiency Cause Low-Grade Fever?

October 23, 2025 •

3 min read

According to past studies, fever occurs in about 40% of patients with megaloblastic anemia, a condition often caused by vitamin B12 deficiency. While typically low-grade, this symptom can be a surprising and often missed sign that a person's B12 levels are critically low.

Quick Summary

This article explores the connection between vitamin B12 deficiency and low-grade fever, detailing how the resulting megaloblastic anemia can cause temperature elevations. It examines the underlying mechanisms, other associated symptoms, and important information regarding diagnosis and treatment.

Key Points

Causal Link: A low-grade fever can be caused by vitamin B12 deficiency, typically when it leads to megaloblastic anemia.
Megaloblastic Anemia: The fever is believed to result from ineffective red blood cell production and increased activity within the bone marrow.
Accompanying Symptoms: A low-grade fever is often accompanied by fatigue, weakness, pale skin, and neurological issues like tingling or confusion.
Diagnosis: Diagnosing a B12 deficiency involves a blood test to check serum levels and potentially other markers like MMA and homocysteine.
Treatment: B12 deficiency is treated with supplements (oral, injections, or nasal gel) that often resolve the fever and other related symptoms.
Overlooked Symptom: Because fever is common, the connection to B12 deficiency can be missed, making it a possible cause of pyrexia of unknown origin (PUO).

Understanding the Link Between Vitamin B12 and Fever

While a fever is most commonly associated with infections, a low-grade fever can be a less-known symptom of severe vitamin B12 deficiency. This connection is not a new discovery; historical medical literature has documented cases of pyrexia (fever) resolving only after treatment for megaloblastic anemia caused by B12 deficiency. The link is primarily understood through the resulting blood disorder, megaloblastic anemia, which affects the production of healthy blood cells.

The Role of Megaloblastic Anemia

Megaloblastic anemia, caused by insufficient B12 or folate, is characterized by the production of abnormally large, immature red blood cells. This process is highly inefficient and leads to the destruction of these cells within the bone marrow, a process known as intramedullary hemolysis. The increased activity and cell destruction in the bone marrow are believed to cause the systemic pyrexia (fever). The level of fever can often correlate with the severity of the anemia.

Why the Fever is Often Overlooked

Because fever is a non-specific symptom, physicians may not immediately connect it to a nutritional deficiency, especially if the patient also presents with other more common symptoms of B12 deficiency, such as fatigue and neurological issues. Case studies, however, have highlighted that B12 deficiency should be considered as a cause of pyrexia of unknown origin (PUO) after infectious and inflammatory causes have been ruled out. In these cases, the fever resolves quickly after B12 supplementation begins.

Other Symptoms of B12 Deficiency

A low-grade fever rarely occurs in isolation due to B12 deficiency. It is typically accompanied by a range of other physical, neurological, and psychological symptoms.

Common Symptoms of B12 Deficiency:

Chronic fatigue and weakness
Tingling or numbness in the hands and feet (paresthesia)
Cognitive issues, including memory loss and confusion
Pale or yellowish skin (jaundice)
Sore, red, and smooth tongue (glossitis)
Irritability and mood swings
Loss of appetite and weight loss

Diagnosing and Treating B12 Deficiency

Diagnosing B12 deficiency involves a blood test to measure serum B12 levels. Additional tests, such as checking for elevated methylmalonic acid (MMA) and homocysteine levels, may be necessary to confirm the diagnosis. Treatment is straightforward and highly effective once the deficiency is identified.

Table: Treatment Options for Vitamin B12 Deficiency


Treatment Method	Typical Application	Benefits	Considerations
Oral Supplements	Mild deficiency, especially due to dietary insufficiency.	Non-invasive and effective for correcting milder deficiencies.	High doses may be needed to achieve sufficient absorption.
Intramuscular Injections	Severe deficiency, malabsorption issues (like pernicious anemia), or significant neurological symptoms.	Bypasses potential absorption problems in the gut; leads to rapid improvement in symptoms.	Requires regular injections, potentially for life.
Nasal Spray/Gel	Alternative option for some patients, prescribed by a doctor.	Effective and convenient for certain patients who cannot tolerate injections.	Less common and not suitable for all cases.

The Importance of Prompt Diagnosis

Allowing a B12 deficiency to persist can lead to serious and potentially irreversible complications, particularly affecting the nervous system. Neurological damage can manifest as long-term issues with balance, vision, and cognitive function. For individuals presenting with unexplained low-grade fever and other suggestive symptoms, investigating B12 levels is a crucial step that can prevent unnecessary and extensive diagnostic procedures for pyrexia of unknown origin. Early diagnosis and treatment can resolve the fever and prevent the progression of more serious symptoms. For example, the case reported in the International Journal of Innovative Research in Medical Science describes a patient whose fever resolved within 48 hours of starting parenteral B12 therapy, suggesting a direct causal link.

Conclusion

Yes, vitamin B12 deficiency can cause a low-grade fever, particularly when it leads to megaloblastic anemia. This temperature elevation is a documented symptom, though it is often misattributed to other causes due to its non-specific nature. The fever is believed to be linked to the increased and ineffective activity within the bone marrow, which is attempting to produce red blood cells. For individuals with unexplained low-grade fever, especially when accompanied by fatigue, paleness, and neurological symptoms, a B12 deficiency should be considered. Treating the underlying deficiency with supplements or injections typically resolves the fever and other symptoms, underscoring the importance of proper diagnosis.

For additional information on Vitamin B12 deficiency, please consult the factsheet from the Office of Dietary Supplements at the National Institutes of Health.

Frequently Asked Questions

The link arises from megaloblastic anemia, a blood disorder caused by B12 deficiency. The ineffective production and breakdown of red blood cells in the bone marrow generate heat, leading to a low-grade fever.

No, it is typically a low-grade fever, meaning the body temperature is slightly elevated but usually not dangerously high. Higher temperatures are rare and usually only seen in severe, complicated cases.

The fever can persist for days or weeks if the underlying deficiency is not addressed. It typically resolves quickly, often within 48 hours, once B12 supplementation begins.

It is possible to have a deficiency without obvious symptoms, especially in milder cases. However, symptoms like fatigue, weakness, and neurological issues typically appear as the deficiency worsens.

B12 deficiency is treated with supplementation, which can include oral tablets, intramuscular injections, or a nasal gel, depending on the severity and cause. Injections are often used for severe deficiencies or malabsorption issues.

You should see a doctor if a low-grade fever persists for more than a few days, especially if accompanied by other B12 deficiency symptoms like extreme fatigue, paleness, or tingling. This is crucial to rule out other serious conditions.

Severe B12 deficiency can sometimes cause nerve damage and other issues even without classic anemia. However, the most direct link to fever is through the resulting megaloblastic anemia and the bone marrow activity it causes.