Author: federico barbero
Date: 01/12/2010


Federico Barbero e Emanuele Quaglia


Pellagra is a disease due to deficiency of NIACIN, a B-complex vitamin, or its precursor TRYPTOPHAN. It is characterized by scaly DERMATITIS which is often associated with DIARRHEA and DEMENTIA (the three D's)."

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Pellagra is a disease that depend from the nutrition, so there aren’t difference between men and women, or between young and old people, and no racial predilection for the development of pellagra is recognized.
Pellagra can be common in people who obtain most of their food energy from maize ( or corn) an example is the rural South America where maize is a staple food. Maize is a poor source of tryptophan as well as niacin if it is not nixtamalized. Nixtamalization of the corn corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, like Mississippi and Alabama.
Pellagra is common in Africa, Indonesia, and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol dependent, or psychiatric patients who refuse food. It can be found in cases of chronic alcoholism. In addition, pellagra is a micronutrient deficiency disease that frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely on limited sources of niacin provided to them, such as groundnuts.


Pellagra is classically described by "the three D's": diarrhea, dermatitis and dementia. More symptoms are:

  • High sensitivity to sunlight
    • Aggression
    • Dermatitis, alopecia, oedema
    • Smooth, beefy red glossitis
    • Red skin lesions
    • Insomnia
    • Weakness
    • Mental confusion
    • Ataxia, paralysis of extremities, peripheral neuritis
    • Diarrhea
    • Dilated cardiomyopathy
    • Eventually dementia


When all symptoms and signs are present, the clinical diagnosis is simple. In most cases, however, there are only a few symptoms present. The diagnosis is confirmed by measuring the urinary excretion of N´-methylnicotinamide (NMN). NMN excretion of <0.8 mg/day suggests niacin deficiency. Patients with pellagra also have increased urinary excretion of coproporphyrins. In clinical practice, a successful test-therapy will confirm the original diagnosis.
It is possible for a diagnosis of pellagra to be delayed or missed because symptoms, such as headache, rash, itching, apathy and diarrhea, can be mild or vague and/or attributed to other conditions. These include psoriasis, eczema, migraine headache and depression. The rash associated with pellagra may look like a sunburn.
Some symptoms of pellagra, such as confusion, dementia and disorientation may be associated with the aging process, Alzheimer's disease or with mental illness or other vitamin deficiencies


Pellagra can develop according to several mechanisms, all of which ultimately revolve around niacin deficiency. The first is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan, an essential amino acid found in soybeans, meat, poultry, fish, and eggs that the body converts into niacin. Third, it may be caused by excess leucine, though the relationship is unclear.
Niacin (also known as vitamin B3, nicotinic acid and vitamin PP) is an organic compound with the formula C6H5NO2 and, depending on the definition used, one of the forty to eighty essential human nutrients. This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The terms niacin, nicotinamide, and vitamin B3 are often used interchangeably to refer to any member of this family of compounds, since they have the same biochemical activity.
Niacin cannot be directly converted to nicotinamide, but both compounds could be converted to NAD and NADP in vivo. Although the two are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects as niacin, which occur as side effects of niacin's conversion. Nicotinamide does not reduce cholesterol or cause flushing. Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.
Niacin is essential for adequate cellular function because of its required roles in 2 similar but distinct coenzymes (NAD and NADP) .


-Chronic alcoholism

-Hartnup disease: This is an autosomal recessive disorder that compromises renal and intestinal transport of neutral amino acids.5 The gene for this condition, which severely depletes tryptophan (the substrate for niacin synthesis), has been found by homozygosity mapping to be located on chromosome 5p15.

-Isoniazid therapy: Treatment with the antituberculosis drug isoniazid can lead to pyridoxine depletion. Pyridoxine, another B vitamin, is required as a coenzyme for the conversion of tryptophan to niacin. Isoniazid therapy is a well-recognized contributor to pellagra.

-Carcinoid tumors: Patients with carcinomas have excessive serotonin production. Niacin and serotonin are products of competing pathways of tryptophan metabolism. Increased diversion of tryptophan towards serotonin production results in a deficiency of substrate available for niacin synthesis.


Compromised ability to absorb ingested niacin and tryptophan

  • Malabsorptive states
    • Reference
  • Prolonged diarrhea


Death is the result of the depletion of the coenzyme required to generate sufficient energy to support vital body functions. Untreated pellagra results in death from multiorgan failure, the disease can kill within four or five years.


As there is seldom a deficiency of only one vitamin, treatment should obviously include a polyvitamin preparation in addition to a balanced diet. Specifically for pellagra, nicotinamide (precursor of niacin) is given as a supplement in a dose ranging from 300 to 1000 mg daily using divided doses. A rapid improvement of the skin lesions and the general condition is usually seen. Neurological improvement is rather slow. A balanced diet is essential for prophylaxis. In some countries flour is systematically enriched with extra niacin.


2013-03-19T21:24:42 - Caterina Franco

Other psychological symptoms of pellagra

Frostig and Spies (acc. to Cleary and Cleary) described more specific psychological symptoms of pellagra as:

* Psychosensory disturbances (impressions as being painful, annoying bright lights, odors intolerance causing nausea and vomiting, dizziness after sudden movements)
* Psychomotor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action)
* Emotional disturbances
Despite clinical symptoms, blood level of tryptophan or unrinary metabolites such as 2-pyridone/N-methylniacinamide ratio <2 or NAD/NADP ratio in erythrocytes could be used to diagnose pellagra. Diagnosis could be confirmed after rapid improvements in the symptoms in patients using high doses of niacin (50-500 mg/day) or niacin enriched food.

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