Pellagra is a disease that we now recognize as being caused by a deficiency in nicotinic acid (niacin). It is characterized by development of a dermatitis, which appears on areas of the body exposed to strong sunlight; by diarrhea, associated with malabsorption of nutrients; and by a severe confusional state. This disease was first described by Gaspar Casal, who wrote of the diet of Spanish peasants with pellagra or mal de la rosa, as it was then called (the book was published posthumously in 1762).
Because the Spanish peasants who had this disease subsisted on cornmeal, and because corn, particularly moldy corn, was also the dietary staple of other poverty-stricken populations in southern Europe that developed pellagra, it was believed that the disease was caused by eating a corn-based diet, particularly when the corn had been improperly stored and became moldy. It was also observed that the diet of those with pellagra was especially lacking in animal protein.
It was not until 1914, when pellagra had become a problem in the southern United States, that Gold-berger began his studies, which ultimately demonstrated that the nutritional etiology of pellagra produced a comparable condition in dogs called “black tongue” and identified foods that were pellagrapreventing (Roe 1973). Later investigators extracted some of these foods, including liver, and attempted isolation of nutrients lacking in the diets of those with the disease. During this period, independent studies by Otto Heinrich Warburg and Walter Christian identified nicotinic acid as one of the substances forming “coferment,” which was thought to be important in normal metabolism. Shortly after this discovery, nicotinic acid was found to be an essential factor for the growth of certain bacteria.
Conrad Elvehjem and his co-workers, who carried out extensive studies at the University of Wisconsin in the 1930s, tested various liver-extract fractions for activity as growth factors in experimental animals. One sample was found to contain a substance that was identified by Wayne Woolley as nicotinic acid. Subsequently, others in Elvehjem’s laboratory cured “black tongue” in dogs by feeding them the nicotinic acid obtained from such liver extracts (Kline and Baumann 1971).
Once it was known that nicotinic acid could cure this disease in dogs, Tom Spies gave nicotinic acid to several subjects with pellagra and found that the human disease responded to it as well. The nutrient nicotinic acid was subsequently given the alternate name of niacin in order to avoid lay confusion of the term with nicotine.
Later studies of the metabolism of niacin in experimental animals showed that they could synthesize it from a precursor, which proved to be the amino acid tryptophan. Because animal proteins are particularly rich in tryptophan, this finding helped to explain the old observation that diets of pellagrins were invariably low in meat and milk (Goldsmith 1964).
Nicotinic acid is active biochemically in several coenzyme forms, and it is necessary for the synthesis and breakdown of fatty acids, carbohydrates, and amino acids. In human studies conducted soon after the discovery of its activity as a vitamin, it was found that when large doses of niacin were administered, individuals became flushed. Although this observation was an early indication that niacin might be toxic if given in excessive amounts, it also suggested that high doses might relieve conditions associated with constriction of blood vessels. In fact, the vitamin failed to yield the hoped-for therapeutic advantage, but it was found later that niacin in high doses could reduce blood cholesterol levels (Havel and Kane 1982).
World History
