Understanding the Primary and Secondary Causes of Pellagra Disease

December 29, 2025 •

4 min read

While largely eliminated in developed nations, outbreaks of pellagra have still been reported in regions facing famine or during emergencies, affecting vulnerable populations. Pellagra is a systemic nutritional disease caused by a severe deficiency of niacin, also known as vitamin B3, or its essential amino acid precursor, tryptophan. The condition is classically defined by the '4 Ds': dermatitis, diarrhea, dementia, and, if left untreated, death.

Quick Summary

Pellagra stems from a lack of niacin or tryptophan, leading to primary deficiencies from poor diet or secondary deficiencies from malabsorption issues. Contributing factors include alcoholism, specific medications, and certain genetic disorders affecting nutrient metabolism. Effective management targets the underlying cause.

Key Points

Primary Deficiency: Pellagra can be caused by a diet that is severely lacking in niacin (vitamin B3) and its precursor, tryptophan.
Secondary Impairment: It can also arise from underlying medical conditions that prevent the body from properly absorbing or metabolizing niacin.
Maize-Based Diets: Diets with untreated maize as a staple are a classic cause of primary pellagra due to the niacin being in a non-bioavailable form.
Alcohol Abuse: Chronic alcoholism is a leading cause of secondary pellagra in developed countries, impairing nutrient absorption and utilization.
Genetic and Disease Factors: Hartnup disease, carcinoid syndrome, and chronic gastrointestinal issues like Crohn's can all lead to pellagra by disrupting tryptophan or niacin pathways.
Medication Interference: Certain drugs, such as isoniazid, can interfere with niacin synthesis and cause secondary pellagra.
Correct the Root Cause: Treatment requires not only niacin supplementation but also addressing the specific primary or secondary cause to ensure a full recovery.

What are the causes of pellagra disease?

Pellagra is a serious condition arising from a severe cellular deficiency of niacin (vitamin B3), a nutrient crucial for cell metabolism, DNA repair, and signaling. The causes can be broadly categorized into primary and secondary factors, each stemming from a different mechanism leading to insufficient niacin in the body.

Primary causes: Inadequate dietary intake

Primary pellagra is the result of insufficient niacin and tryptophan consumption in the diet. This is the historical cause of pellagra and continues to be a concern in food-insecure populations.

Maize-based diets: Diets heavy in maize (corn) are a significant risk factor for primary pellagra. Although maize contains niacin, it is in a bound, non-bioavailable form that the human body cannot easily absorb without an alkaline treatment, such as the traditional nixtamalization process used in Latin America. Additionally, maize is low in the amino acid tryptophan, which the body can convert into niacin.
Limited food variety: In areas of poverty, famine, or crisis, dietary options are often limited and may lack sufficient protein and other B vitamins, compounding the risk of niacin deficiency. Milk and eggs, for instance, contain enough tryptophan to protect against pellagra even if low in niacin.
Chronic alcoholism: Heavy alcohol use is the most common cause of pellagra in industrialized nations. It leads to poor nutrition and damages organs, causing malabsorption that prevents the body from properly utilizing nutrients.
Fad diets and malnutrition: Severe food restriction, such as that seen in anorexia nervosa or certain fad diets that eliminate niacin-rich foods, can also precipitate a deficiency.

Secondary causes: Impaired absorption or metabolism

Secondary pellagra occurs when a person's diet is adequate, but an underlying condition prevents the body from absorbing or effectively using the niacin. A variety of medical conditions can impair niacin metabolism.

Gastrointestinal diseases: Chronic gastrointestinal conditions that cause malabsorption, such as Crohn's disease, inflammatory bowel disease (IBD), cirrhosis of the liver, and chronic diarrhea, can prevent the body from absorbing niacin from food.
Hartnup disease: This rare genetic disorder impairs the absorption of neutral amino acids, including tryptophan, in the intestine and kidneys, leading to decreased niacin synthesis.
Carcinoid syndrome: In this condition, tumors divert excessive tryptophan away from niacin synthesis to produce serotonin, leaving insufficient tryptophan for the body to create niacin.
Certain medications: Some drugs, particularly those used to treat tuberculosis like isoniazid, interfere with niacin metabolism or synthesis. Isoniazid, for example, binds to vitamin B6, which is a required cofactor for the conversion of tryptophan to niacin. Other medications, including certain chemotherapy drugs and antiepileptics, can also disrupt the process.
HIV infection: In individuals with HIV, plasma tryptophan levels can be decreased, potentially leading to a pellagra-like state.
Sorghum-based diets: While less common than maize, diets heavily reliant on millet with a high leucine content have been linked to pellagra. Excessive leucine interferes with the enzymatic conversion of tryptophan to niacin.

A comparison of primary and secondary pellagra


Feature	Primary Pellagra	Secondary Pellagra
Underlying Cause	Inadequate dietary intake of niacin and/or tryptophan.	Impaired absorption or metabolism of niacin and/or tryptophan, despite adequate intake.
Dietary Context	Typically associated with restricted diets, often maize-based, common in food-insecure regions.	Can occur in individuals with a normal, balanced diet, indicating a medical issue.
Common Risk Factors	Poverty, famine, restricted food supply, maize-staple diets, and chronic alcoholism.	Gastrointestinal diseases (Crohn's, cirrhosis), genetic disorders (Hartnup disease), carcinoid syndrome, HIV, and specific medications.
Prevalence	Historically widespread, now more common in developing nations or during humanitarian crises.	More prevalent in industrialized countries, often in conjunction with chronic diseases or substance abuse.
Treatment Focus	Niacin supplementation and dietary improvement.	Treating the underlying medical condition while supplementing with niacin.

Diagnosing and treating the root cause

Because pellagra's symptoms (dermatitis, diarrhea, dementia) can be non-specific, identifying the root cause is critical for effective treatment. A thorough medical and dietary history can help distinguish between primary and secondary cases. In cases of dietary deficiency (primary pellagra), niacin supplementation combined with an improved diet rich in protein and B-vitamins is typically curative. However, with secondary pellagra, simply increasing dietary niacin might not be enough if the body cannot absorb or utilize it. In these instances, treating the underlying medical condition is necessary, in addition to supplementation.

For example, if the cause is chronic alcoholism, addressing the alcohol abuse is a vital part of the recovery process. For a person with a malabsorption condition like Crohn's disease, managing the GI issue is paramount. In cases involving medications, a doctor might adjust the prescription or manage the side effects with supplementation. Recovery times vary depending on the severity and cause, but improvement is often seen within days of beginning treatment.

Conclusion

Pellagra is a serious nutritional disease caused by a lack of niacin or tryptophan. Understanding its causes—whether from a primary dietary deficiency or secondary medical conditions—is fundamental for proper diagnosis and treatment. While primary pellagra is linked to poor, restrictive diets often seen in less developed regions, secondary pellagra is more common in industrialized countries, typically associated with chronic illnesses, alcoholism, or specific medications. Early recognition and targeted intervention with niacin supplementation and management of any underlying issues are crucial for preventing long-term complications and ensuring recovery. This comprehensive approach highlights the need for clinicians to consider both nutritional and systemic factors when diagnosing this once-epidemic condition, which still exists in various forms today.

For more detailed information, consult the Cleveland Clinic website on pellagra, a trusted resource on the topic.

Frequently Asked Questions

In industrialized countries, chronic alcoholism is the most common cause of pellagra, leading to poor nutrition and malabsorption of niacin.

A diet based primarily on corn can cause pellagra because much of the niacin in untreated corn is in a 'bound' form that the body cannot easily absorb, and corn is also low in the amino acid tryptophan.

Yes, some medications can induce secondary pellagra by interfering with niacin metabolism. Examples include the tuberculosis drug isoniazid and certain chemotherapy agents.

Hartnup disease is a genetic disorder that impairs the absorption of neutral amino acids, including tryptophan. Since the body can produce niacin from tryptophan, this defect leads to a niacin deficiency and pellagra.

Primary pellagra results from a direct lack of niacin or tryptophan in the diet. Secondary pellagra occurs when an underlying medical condition impairs the body's ability to absorb or utilize niacin, even if dietary intake is sufficient.

While rare in developed nations due to food fortification, pellagra still poses a risk in food-insecure regions and for specific high-risk populations, including chronic alcoholics and those with malabsorptive diseases.

Conditions like Crohn's disease that cause chronic diarrhea and other malabsorptive states can lead to pellagra by preventing the proper absorption of niacin and other nutrients from the intestinal tract.