Why Does Pellagra Occur? Unraveling the Causes of Niacin Deficiency

November 21, 2025 •

5 min read

According to the Cleveland Clinic, pellagra is a systemic disease caused by a severe deficiency of niacin (vitamin B3), often leading to the classic '3 Ds': dermatitis, diarrhea, and dementia. Understanding why does pellagra occur is key to both preventing and treating this condition effectively.

Quick Summary

Pellagra is a nutritional disorder resulting from insufficient niacin or tryptophan. It can arise from dietary inadequacies, poor absorption due to medical conditions, chronic alcoholism, and inherited metabolic defects.

Key Points

Niacin Deficiency: The core reason why pellagra occurs is a severe lack of niacin (vitamin B3), often alongside tryptophan deficiency.
Two Primary Avenues: Pellagra can be either primary, caused by poor diet, or secondary, resulting from other health conditions that impair nutrient absorption or metabolism.
Corn is a Classic Culprit: Historically, reliance on diets based on untreated corn, which has low tryptophan and unavailable niacin, was a major cause of primary pellagra.
Alcoholism is a Modern Risk: In developed countries, chronic alcoholism is a leading cause of secondary pellagra due to poor diet and malabsorption.
Malabsorption and Genetics: Secondary pellagra can also stem from gastrointestinal diseases like Crohn's, genetic disorders like Hartnup disease, or medication side effects.
The '3 Ds': The classic symptoms are dermatitis, diarrhea, and dementia, reflecting the impact of niacin deficiency on high-cell-turnover tissues like skin, the gut, and the brain.
Treatment is Simple: The condition is treated by correcting the underlying cause and supplementing with niacin, usually leading to rapid symptom improvement.

The Foundational Role of Niacin

Niacin, also known as vitamin B3, is a water-soluble vitamin essential for hundreds of metabolic reactions in the body. It is converted into the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are critical for converting food into energy. This energy is vital for cellular function, especially in rapidly reproducing cells found in the skin, gastrointestinal tract, and brain. When the body lacks sufficient niacin, these high-energy-demand systems are the first to show symptoms, which are famously known as the “3 Ds”: dermatitis, diarrhea, and dementia. A fourth “D,” death, can occur if the condition is left untreated for an extended period.

Primary Causes: Inadequate Dietary Intake

Primary pellagra is the result of not getting enough niacin or the amino acid tryptophan from the diet. The body can convert tryptophan into niacin, so a diet low in both can quickly lead to deficiency. Historically, this was the most common cause, particularly in populations where maize (corn) was a dietary staple without proper preparation.

The Problem with Maize

Maize is rich in niacin, but the vitamin is in a chemically bound form that the human body cannot easily absorb. This is why pellagra was once widespread among poor maize-dependent communities in parts of Europe, Africa, and the southern United States. However, Central and South American cultures traditionally prepared corn through a process called nixtamalization, soaking the maize in an alkaline solution (limewater). This process releases the bound niacin, making it bioavailable and preventing pellagra. The subsequent fortification of foods like bread and cereals with niacin has made primary pellagra rare in industrialized nations today.

Other Nutritional Deficiencies

Certain diets, such as those relying heavily on sorghum (millet), can also cause pellagra. Although sorghum contains adequate tryptophan, it has high levels of the amino acid leucine, which interferes with the conversion of tryptophan to niacin. Pellagra also frequently occurs alongside other B vitamin and protein deficiencies in contexts of widespread malnutrition, such as famines or refugee crises.

Secondary Causes: Malabsorption and Metabolism Issues

In developed nations, secondary pellagra is more common. It occurs when the body's ability to absorb or utilize niacin is compromised, even with sufficient dietary intake.

Common Secondary Causes

Chronic Alcoholism: Alcohol use disorder is a leading cause of pellagra in developed countries. It can induce pellagra through general malnutrition, poor dietary habits, and organ damage that impairs nutrient absorption.
Gastrointestinal Diseases: Conditions that cause malabsorption, like Crohn's disease, ulcerative colitis, or severe and prolonged diarrhea, can prevent the body from absorbing niacin and tryptophan from food.
Genetic Disorders: Rare hereditary diseases can affect tryptophan metabolism. Hartnup disease, an autosomal recessive disorder, impairs the intestinal absorption and renal reabsorption of neutral amino acids, including tryptophan, leading to a pellagra-like syndrome.
Carcinoid Syndrome: This syndrome is characterized by neuroendocrine tumors that divert large amounts of dietary tryptophan to produce serotonin, leaving insufficient tryptophan to be converted into niacin.
Certain Medications: Some drugs can interfere with niacin metabolism. This includes the tuberculosis treatment isoniazid and certain chemotherapy agents like 5-flurouracil and 6-mercaptopurine.
HIV Infection: HIV can deplete tryptophan levels, contributing to niacin deficiency and pellagra.

Comparing Primary and Secondary Pellagra Causes


Feature	Primary Pellagra	Secondary Pellagra
Core Cause	Insufficient dietary intake of niacin and/or tryptophan.	Impaired absorption or metabolism of niacin and/or tryptophan, despite adequate intake.
Common in Developed Nations?	No, rare due to food fortification.	Yes, more common than primary pellagra.
Historical Context	Widespread in impoverished populations relying on untreated maize.	Associated with chronic diseases, substance abuse, and modern medical treatments.
Underlying Factors	Poverty, limited food choices, reliance on pellagragenic grains (e.g., untreated corn).	Non-dietary medical issues: Alcoholism, GI disorders, genetic conditions, medications, carcinoid tumors.
Treatment Focus	Dietary change and niacin supplementation.	Addressing the underlying medical condition, in addition to supplementation.

The Role of Tryptophan

While niacin can be obtained directly from the diet, tryptophan is an essential amino acid that serves as a precursor for niacin synthesis. About half of the body's niacin requirements are met through this conversion process. This helps to explain why conditions affecting tryptophan intake (like poor diet) or its metabolism (like Hartnup disease and carcinoid syndrome) can cause pellagra. Foods rich in tryptophan include:

Poultry (chicken, turkey)
Cheese
Fish (salmon, tuna)
Legumes and seeds
Eggs
Nuts (peanuts, pumpkin seeds)

Conclusion

Pellagra occurs due to a profound deficiency of niacin, which can be traced back to two main paths: insufficient dietary intake (primary) and poor absorption or metabolism (secondary). While primary causes were historically tied to poverty and maize-based diets, modern cases in developed countries are more frequently linked to conditions such as chronic alcoholism, gastrointestinal diseases, and rare metabolic or drug-related issues. Treatment involves correcting the niacin deficiency with supplementation and addressing the underlying cause. For comprehensive information on preventing and controlling pellagra in emergency situations, the World Health Organization offers detailed guidance.

Authoritative Source

World Health Organization (WHO): Pellagra and its prevention and control in major emergencies

Additional Considerations

Symptoms Often Appear Alone: Not all of the '3 Ds' appear at once or in every patient. GI symptoms like diarrhea often manifest before skin or cognitive changes.
Recovery is Possible: With early treatment, most people recover from pellagra, with symptoms improving within days or weeks of starting niacin supplementation. However, some severe neurological damage can be permanent.
Fortification is a Lifesaver: The widespread fortification of grains with niacin has been a major public health victory, virtually eradicating primary pellagra in many regions.

How to Prevent Pellagra

Preventing pellagra primarily revolves around ensuring adequate intake or absorption of niacin and tryptophan.

Strategies for Prevention

Balanced Diet: Consuming a diverse and balanced diet rich in niacin and tryptophan is the best defense. Good sources include meat, fish, poultry, eggs, milk, fortified grains, and peanuts.
Food Fortification: Supporting and implementing food fortification programs in at-risk areas is crucial.
Treatment of Underlying Conditions: For those with secondary causes, managing chronic diseases like alcoholism, gastrointestinal disorders, or HIV is essential.
Medication Monitoring: Patients on medications that can interfere with niacin synthesis should be monitored for potential deficiency.
Proper Food Preparation: In regions where maize is a staple, traditional nixtamalization methods should be practiced to increase niacin bioavailability.

Who is at Risk?

While rare in many places, specific populations remain at risk for pellagra:

Individuals with chronic alcoholism
Those with malabsorptive diseases
Patients with anorexia nervosa
People with certain genetic disorders or carcinoid tumors
Populations in food-insecure regions where maize is a staple
Patients on specific long-term medications

Diagnosis and Management

Diagnosing pellagra often relies on clinical presentation, including the characteristic '3 Ds' and a patient's dietary and medical history. Lab tests can measure niacin levels, but a favorable response to niacin supplementation can also help confirm the diagnosis. Treatment involves high-protein, calorie-adequate diets and niacin supplementation, typically with nicotinamide to avoid flushing side effects. Addressing any underlying secondary causes is also critical for a complete recovery.

Frequently Asked Questions

The main reason pellagra occurs is a severe deficiency of niacin (vitamin B3) and/or its precursor, the amino acid tryptophan. This can happen due to inadequate dietary intake (primary pellagra) or issues with the body's ability to absorb or process these nutrients (secondary pellagra).

Yes, diets based on untreated maize (corn) are a classic cause of primary pellagra because the niacin is in a bound, non-absorbable form and the grain is low in tryptophan. Diets high in leucine, such as those rich in sorghum, can also interfere with niacin synthesis and cause pellagra.

No, pellagra is not only caused by diet. Secondary pellagra can occur even with adequate niacin intake if the body cannot absorb or utilize it properly. Causes include chronic alcoholism, gastrointestinal diseases, certain medications, and genetic disorders.

Several medical conditions can lead to secondary pellagra, including chronic alcoholism, malabsorptive disorders (such as Crohn's disease or chronic diarrhea), and rare genetic conditions like Hartnup disease. Liver cirrhosis, carcinoid syndrome, and HIV infection are also associated with it.

Chronic alcoholism is a major risk factor because it often involves poor nutrition and a lack of B vitamins. Heavy alcohol use can also damage organs, impairing the body's ability to absorb nutrients like niacin and tryptophan.

Hartnup disease is a rare genetic disorder that affects the transport of neutral amino acids, including tryptophan, in the intestines and kidneys. This leads to low levels of tryptophan available for the synthesis of niacin, causing a pellagra-like syndrome.

Pellagra is treated by supplementing the missing niacin, usually with nicotinamide to reduce side effects like flushing. For secondary pellagra, it is also crucial to address and manage the underlying medical condition that is causing the deficiency.