What deficiency causes pellagra? Understanding the role of niacin (vitamin B3)

December 5, 2025 •

4 min read

According to the Cleveland Clinic, pellagra is a systemic disease caused by a severe deficiency of niacin (vitamin B3). This vitamin deficiency can affect multiple parts of the body, leading to the characteristic symptoms associated with pellagra.

Quick Summary

A severe deficiency of niacin, or vitamin B3, causes pellagra. This deficiency results from inadequate dietary intake (primary) or impaired nutrient absorption (secondary) due to underlying health issues.

Key Points

Core Deficiency: The primary deficiency that causes pellagra is a lack of niacin (vitamin B3), but it can also be caused by insufficient dietary intake of the amino acid tryptophan, from which niacin is synthesized.
The Four Ds: Pellagra is characterized by its classic symptoms of dermatitis, diarrhea, dementia, and if left untreated, death.
Primary vs. Secondary: Pellagra can be either primary, resulting from a poor diet, or secondary, caused by an underlying health condition that interferes with niacin absorption or metabolism.
Key Risk Factors: Major risk factors include chronic alcoholism, gastrointestinal disorders like Crohn's disease, and reliance on untreated corn as a dietary staple.
Effective Treatment: Treatment for pellagra involves niacin supplementation and improving overall diet, while secondary cases also require management of the underlying medical issue.
Prevention is Key: Prevention focuses on ensuring a balanced, niacin-rich diet, which can be achieved through diverse food choices or fortification of staple foods.

The Cause: Niacin and Tryptophan Deficiency

Pellagra is a nutritional disorder that stems from a severe deficiency of niacin, also known as vitamin B3. While a direct lack of niacin is the most straightforward cause, the situation is more complex. The body is capable of synthesizing niacin from the essential amino acid tryptophan. This means a deficiency can arise from two distinct pathways:

Insufficient Niacin Intake: Not consuming enough niacin-rich foods.
Insufficient Tryptophan Intake: Lacking the raw material the body uses to produce its own niacin.
Impaired Conversion: A disruption in the body's ability to convert tryptophan into niacin, which requires other B vitamins like B2 and B6.

This is why historically, pellagra was prevalent in populations where corn (maize) was the staple food. Corn is low in both usable niacin (which is in a bound form unless treated with alkali) and tryptophan, making diets heavily reliant on it prone to causing pellagra. In developed nations, food fortification with niacin has made dietary-based pellagra rare, but it can still occur in specific at-risk populations.

Primary vs. Secondary Pellagra

Pellagra is typically categorized into two main types based on its origin.

Primary Pellagra

This type is caused solely by an insufficient intake of niacin and/or tryptophan in the diet. It is most common in developing countries or among populations experiencing malnutrition due to famine, poverty, or limited food choices. Individuals following highly restrictive or fad diets, as well as those with eating disorders like anorexia nervosa, are also susceptible.

Secondary Pellagra

Secondary pellagra develops when an underlying medical condition or substance interferes with the body's ability to absorb or utilize niacin and tryptophan, even if dietary intake is adequate. This form is more prevalent in developed countries. Causes include:

Chronic Alcoholism: Alcoholism interferes with the absorption and metabolism of niacin.
Gastrointestinal Diseases: Conditions like Crohn's disease, ulcerative colitis, and chronic diarrhea can impair nutrient absorption.
Certain Medications: Drugs such as isoniazid (used to treat tuberculosis), chemotherapy agents, and anticonvulsants can disrupt niacin metabolism.
Other Conditions: Hartnup disease (a genetic disorder), carcinoid syndrome (where tryptophan is diverted to make serotonin), and HIV infection can also lead to secondary pellagra.

Symptoms of Pellagra (The 4 Ds)

Pellagra is classically defined by the "4 Ds," representing its major clinical manifestations.

Dermatitis: Skin lesions are a hallmark sign, often appearing on sun-exposed skin (photosensitivity). They start as red, sunburn-like rashes and progress to rough, scaly, and hyperpigmented patches. Characteristic patterns include Casal's collar (around the neck) and symmetrical patches on the hands and feet.
Diarrhea: Gastrointestinal symptoms are common and may include abdominal discomfort, nausea, vomiting, and inflammation throughout the digestive tract. Diarrhea can be persistent and bloody in severe cases.
Dementia: Neurological and psychiatric symptoms can occur, progressing from irritability and apathy to more severe issues like confusion, memory loss, disorientation, and even hallucinations.
Death: If left untreated, pellagra can be fatal, which is why the fourth "D" is included.

Risk Factors and Diagnosis

In addition to the primary dietary factors and secondary medical conditions, several other risk factors increase the likelihood of developing pellagra, including poverty, advanced age, and specific dietary habits. Diagnosis is primarily clinical, based on a patient's diet history, symptoms, and physical examination. A favorable response to niacin supplementation can confirm the diagnosis, and urine tests may be used to measure niacin metabolites.

Treatment and Prevention

Treatment involves correcting the niacin deficiency and addressing any underlying causes.

Supplementation: Oral or intravenous niacin (typically as nicotinamide to avoid flushing side effects) is administered.
Dietary Improvements: A high-protein, balanced diet rich in niacin and tryptophan is crucial for long-term recovery.
Underlying Condition Treatment: Managing diseases like alcoholism, malabsorption disorders, or addressing medication side effects is vital for secondary pellagra.
Sun Protection: Protecting affected skin from further sun exposure is important during recovery.

Preventing pellagra can be achieved through adequate nutrition and food fortification. In areas where corn is a staple, traditional alkaline treatment (nixtamalization) makes niacin bioavailable and has been an effective prevention strategy for centuries. For more information on niacin, refer to the NIH Office of Dietary Supplements.

Primary vs. Secondary Pellagra Comparison Table


Feature	Primary Pellagra	Secondary Pellagra
Underlying Cause	Inadequate dietary intake of niacin or tryptophan.	Impaired absorption or metabolism of niacin/tryptophan due to a medical condition.
At-Risk Populations	Those in food-limited regions, experiencing famine, poverty, or following severely restricted diets.	Individuals with chronic alcoholism, GI diseases, Hartnup disease, or on specific medications.
Prevalence	Historically significant, now rare in developed countries but still an issue in some developing regions.	More common in developed nations among specific patient groups.
Treatment Focus	Dietary change and niacin supplementation.	Addressing the underlying medical cause in addition to supplementation.

Conclusion

In summary, the deficiency that causes pellagra is a lack of niacin (vitamin B3), often compounded by insufficient tryptophan, which the body uses to create niacin. While severe dietary inadequacy is the primary cause, secondary factors like alcoholism, malabsorption diseases, and certain medications are the major drivers of pellagra in developed nations. Recognizing the classic "4 D" symptoms—dermatitis, diarrhea, dementia, and death—is critical for timely diagnosis. With proper niacin supplementation, dietary adjustments, and treatment of any underlying health issues, pellagra is both preventable and treatable, though untreated cases can have irreversible and fatal consequences.

Frequently Asked Questions

The primary nutrient deficiency that causes pellagra is a lack of niacin, also known as vitamin B3. A deficiency can also arise from a lack of the amino acid tryptophan, which the body uses to create its own niacin.

Pellagra is known by the '4 Ds': dermatitis (a skin rash, often on sun-exposed areas), diarrhea, dementia (neurological issues), and eventually, death if untreated.

Yes, primary pellagra is caused by a diet that is insufficient in niacin and tryptophan. This is historically associated with populations relying heavily on corn that has not been properly processed.

Secondary pellagra can result from medical conditions that prevent the body from absorbing or utilizing niacin. Examples include chronic alcoholism, gastrointestinal diseases like Crohn's, and certain genetic disorders.

Pellagra is treated with niacin supplementation, usually in the form of nicotinamide, along with a high-protein, balanced diet. Treating any underlying cause is also essential, especially for secondary pellagra.

While rare in most developed countries due to food fortification, pellagra can still occur among at-risk populations. This includes those with chronic alcoholism, eating disorders, or certain underlying medical conditions.

Good food sources of niacin and tryptophan include meat (especially poultry and fish), eggs, milk, peanuts, legumes, and fortified bread and cereals.

Pellagra can be prevented by consuming a balanced diet rich in niacin and tryptophan. Public health initiatives, like fortifying staple foods with niacin, are also effective preventative measures in vulnerable populations.