[1] This can occur as a result of alcoholism, long-term diarrhea, carcinoid syndrome, Hartnup disease, and a number of medications such as isoniazid.

Since NAD and its phosphorylated NADP form are cofactors required in many body processes, the pathological impact of pellagra is broad and results in death if not treated.

Second, it may result from deficiency of tryptophan,[3] an essential amino acid found in meat, poultry, fish, eggs, and peanuts,[8] which the body uses to make niacin.

Inflammation of the jejunum or ileum can prevent nutrient absorption, leading to pellagra, and this can in turn be caused by Crohn's disease.

[10] Chronic alcoholism can also cause poor absorption, which combined with a diet already low in niacin and tryptophan produces pellagra.

Anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction.

These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis,[11] and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine.

Nixtamalization corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn, but most especially in Mexico and the countries of Central America.

In addition, pellagra, as a micronutrient deficiency disease, frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid.

[24] Native American cultivators who first domesticated corn (maize) prepared it by nixtamalization, in which the grain is treated with a solution of alkali such as lime.

[28] With pellagra affecting over 100,000 people in Italy by the 1880s, debates raged as to how to classify the disease (as a form of scurvy, elephantiasis or as something new), and over its causation.

[30] Louis Sambon, an Anglo-Italian doctor working at the London School of Tropical Medicine, was convinced that pellagra was carried by an insect, along the lines of malaria.

Later, the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop, led researchers to investigate processing techniques in that region.

It was established in 1914 with a special Congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research.

[34] Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra.

By modifying the diet served in these institutions with "a marked increase in the fresh animal and the leguminous protein foods," Goldberger was able to show that pellagra could be prevented.

[34] By 1926, Goldberger established that a diet that included these foods, or a small amount of brewer's yeast,[35] prevented pellagra.

[36] Goldberger started feeding them a restricted diet of grits, syrup, mush, biscuits, cabbage, sweet potatoes, rice, collards, and coffee with sugar (no milk).

His reform efforts were not realized, but crop diversification in the Southern United States, and the accompanying improvement in diet, dramatically reduced the risk of pellagra.

In 1937, Conrad Elvehjem, a biochemistry professor at the University of Wisconsin-Madison, showed that the vitamin B3 cured pellagra (manifested as black tongue) in dogs.

Later studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men of the Year in comprehensive science.

[32] Poverty and consumption of corn were the most frequently observed risk factors, but the exact cause was not known, until groundbreaking work by Joseph Goldberger.

Allow the grits to settle a full minute, tilt the pan, and skim off and discard the chaff and hulls with a fine tea strainer.

[55] Casimir Funk, who helped elucidate the role of thiamin in the etiology of beriberi, was an early investigator of the problem of pellagra.

Funk suggested that a change in the method of milling corn was responsible for the outbreak of pellagra,[56] but no attention was paid to his article on this subject.