What deficiency causes low-grade fever? Uncovering the nutritional links

September 26, 2025 •

4 min read

While often assumed to be from infection, studies have noted that fever can occur in patients with megaloblastic anemia, a condition often caused by vitamin B12 or folate deficiency. Uncovering what deficiency causes low-grade fever is important, though it is considered a rare cause and a medical evaluation is always warranted.

Quick Summary

Severe deficiencies in vitamins B12 and D, along with folate, can be linked to a persistent low-grade fever, often alongside anemia and impaired immune function. Nutritional deficits are a rare but documented cause of fever and should be confirmed by a healthcare provider after ruling out other more common causes.

Key Points

Rare Cause: Nutritional deficiencies are an uncommon reason for persistent low-grade fever, with infections and autoimmune diseases being far more frequent causes.
Vitamin B12 and Folate: Severe deficiency can cause megaloblastic anemia, which is associated with low-grade fever, possibly due to increased bone marrow activity.
Vitamin D: Crucial for immune function, a deficiency can weaken the immune system, increasing susceptibility to infections that cause fever and potentially driving chronic inflammation.
Other Nutrients: Deficiencies in iron and zinc can also affect the immune system and thermoregulation, though these are less likely to be the sole cause of fever.
Chronic Inflammation: Multiple micronutrient deficiencies can contribute to chronic inflammation, a state of systemic stress that may manifest as a low-grade fever.
Medical Evaluation is Key: It is vital to consult a healthcare provider for any persistent fever to rule out serious underlying conditions before considering a nutritional cause.

The Nutritional Link to Persistent Low-Grade Fever

Persistent low-grade fever can be a perplexing and concerning symptom, often prompting a search for underlying infection or inflammation. While infections and autoimmune disorders are more common culprits, nutritional deficiencies are a documented, though less common, cause. Research has highlighted that deficiencies in key vitamins and minerals can impair bodily functions, including the immune response and thermoregulation, potentially leading to a low-grade fever.

Vitamins B12 and D: The Primary Suspects

The Link to Megaloblastic Anemia

Deficiencies in vitamin B12 and folate are a well-documented, albeit rare, cause of fever. These deficiencies lead to megaloblastic anemia, a condition where the bone marrow produces abnormally large, immature, and nonfunctional red blood cells. In patients with severe megaloblastic anemia, a low-grade fever can be a presenting symptom. The exact mechanism isn't fully understood, but it's believed that the fever may result from increased metabolic activity and cellular turnover within the hyperplastic (overactive) bone marrow. Treating the underlying vitamin B12 deficiency with supplementation typically resolves the fever, as confirmed by various case studies.

The Role of Vitamin D in Immune Function

Vitamin D is crucial for the proper functioning of the immune system. It modulates both innate and adaptive immune responses, helping the body fight off pathogens. When vitamin D levels are low, the immune system can become compromised, making an individual more susceptible to infections that could cause a low-grade fever. Additionally, some studies suggest that vitamin D deficiency is linked to increased inflammation, another potential driver of fever. While a direct causal relationship solely due to deficiency is debated, it is a risk factor for illnesses that cause fever.

Other Micronutrient Impacts

Iron's Influence on Thermoregulation

Iron deficiency, the most common nutritional deficiency globally, can affect the body's ability to maintain a stable temperature. Research on both animals and humans has shown that iron-deficient subjects have an impaired ability to maintain normal body temperature, especially in cool environments, and can have altered thyroid hormone and catecholamine responses. While this primarily manifests as cold sensitivity, the disruption in thermoregulation can, in some cases, be associated with minor fever, especially in the context of anemia.

Zinc Deficiency and Immune Response

Zinc is a critical mineral involved in numerous cellular processes, particularly those of the immune system. A deficiency can impair immune cell function, alter cytokine production, and increase susceptibility to infections, potentially leading to chronic, low-grade inflammatory states that could include fever. Zinc is a cofactor for many enzymes, and its absence can hinder the body's ability to mount an effective and appropriately regulated immune response.

Magnesium and Body Temperature Regulation

Magnesium deficiency, or hypomagnesemia, can have a variety of symptoms, including neuromuscular and cardiac issues. Interestingly, some observations have noted that patients with severe magnesium deficiency often have an increased surface body temperature and altered perspiration, indicating a potential role in thermoregulation. This suggests that imbalances in magnesium could contribute to subtle shifts in body temperature, although it is not typically considered a primary cause of fever.

How Deficiencies Drive Inflammation

Many micronutrient deficiencies, even if subclinical, can lead to impaired immune responses and altered cytokine production, which are the chemical messengers of the immune system. Chronic undernutrition and multiple micronutrient deficiencies can lead to increased inflammatory mediators in the body. This state of chronic, low-level inflammation can, in turn, cause a persistent low-grade fever. While not as direct as an infection, it represents a state of systemic stress on the body's systems.

Comparison: Deficiency-Related vs. Common Fever Causes


Feature	Deficiency-Related Fever	Common Infectious Fever
Onset	Often gradual, insidious onset over weeks or months.	Typically abrupt, with clearly defined start and end points.
Duration	Persistent or recurrent low-grade temperature.	Usually short-term, resolving with illness.
Associated Symptoms	Often accompanied by fatigue, weakness, mood changes, anemia symptoms (pale skin, heart palpitations), or neurological signs.	Typically accompanied by cold/flu symptoms (cough, sore throat), localized pain, or systemic illness indicators.
Diagnostic Markers	Low blood levels of specific vitamins or minerals, presence of megaloblastic anemia indicators (high MCV, pancytopenia).	Elevated white blood cell count, positive infectious disease tests, high C-reactive protein (CRP), or other infection-specific markers.
Resolution	Improves with targeted nutritional supplementation.	Resolves with recovery from infection or antibiotic/antiviral treatment.

When to Consult a Doctor

It is critical to emphasize that nutritional deficiencies are a rare cause of a persistent low-grade fever. A proper medical evaluation is necessary to rule out more serious and common conditions, such as chronic infections (e.g., tuberculosis), autoimmune disorders (e.g., lupus), or other inflammatory diseases. You should always consult with a healthcare provider for any unexplained fever to get an accurate diagnosis and treatment plan. A blood test to check for vitamin B12, vitamin D, and other nutrient levels is part of a comprehensive diagnostic workup for pyrexia of unknown origin (PUO).

Conclusion: Connecting the Nutritional Dots

While nutritional deficiencies are an unusual cause for a persistent low-grade fever, particularly B12 and folate, their potential link highlights the importance of a comprehensive health evaluation. These deficiencies can impact the immune system, contribute to inflammation, and alter thermoregulation. Recognizing the broader context of symptoms is key. For more in-depth information on vitamin deficiency, refer to the National Institutes of Health nutritional studies. Always seek professional medical advice to determine the true cause of any unexplained fever and ensure appropriate treatment.

Frequently Asked Questions

Yes, in rare cases of severe deficiency leading to megaloblastic anemia, a low-grade fever can occur. The fever usually resolves with B12 supplementation.

While not a direct cause, vitamin D deficiency can impair immune function, making a person more susceptible to infections and inflammation that can, in turn, cause a fever.

Deficiencies can disrupt bodily processes, particularly the immune system and thermoregulation. In conditions like severe megaloblastic anemia, increased metabolic activity can cause fever. Impaired immunity can also lead to chronic inflammation, which may manifest as a low-grade fever.

The most common causes are infections, inflammatory or autoimmune conditions, or malignancy. Nutritional deficiencies are much less common and require other serious conditions to be ruled out by a doctor.

Symptoms can vary depending on the deficiency but often include fatigue, weakness, pale skin, shortness of breath, neurological symptoms (tingling), and general malaise.

No, you should not self-medicate. Always consult a healthcare provider for a proper diagnosis before starting any supplement regimen, as treating the wrong cause could delay treatment for a more serious condition.

Yes, severe anemia, particularly megaloblastic anemia caused by B12 or folate deficiency, can be associated with a low-grade fever due to abnormal bone marrow activity.