The deficiency in its classical form, pellagra, is encountered chiefly in population groups in which corn furnishes the staple cereal of the diet. The association of pellagra with diets high in corn has been explained to a large extent by recent research. It has been shown that the amino acid, tryptophan, is converted by the body through a series of chemical reactions to the vitamin, niacin (95). One of the proteins of corn, zein, is known to be low in tryphtophan. The low tryptophan and niacin content of corn diets accounts in large part for their pellagragenic effect. The possibility that corn contains some inhibitory factor which influences niacin requirement has not been ruled out completely but if such a factor is present, it is of little practical importance (96). There is evidence that some of the niacin in corn is present in bound form which may be unavailable for absorption.
Since tryptophan is a precursor of niacin, it is necessary to estimate the tryptophan as well as the niacin con-tent of diets in determining the adequacy of niacin in-take. The ratio of conversion of tryptophan to niacin compounds is in the neighborhood of 60 to 1, that is, about 1.0 mg. of niacin is formed from 60 mg. of dietary tryptophan. Pellagra-preventive foods include liver, lean meat, peanuts, potatoes, legumes, milk and eggs; the last two foods furnish little niacin but are excellent sources of trpytophan. Since niacin is stable to heat, loss in food preparation is minimal.
The minimum niacin requirement of the adult is about 9.0 to 12.0 mg. daily including that formed from tryptophan, assuming a conversion ratio of 60 to 1. The requirement of the infant is about 5 mg. daily. Requirement appears to be related to body size and to caloric intake. Approximately 4.4 mg. of niacin is needed for every 2000 calories furnished by the diet, but with low caloric intakes not less than 9 mg. should be supplied. In terms of body weight, about 0.15 mg. total niacin per kilogram will prevent pellagra.
Infants have been maintained satisfactorily for several months on purified diets high in tryptophan and free of niacin. Whether the body’s niacin requirement can be met solely by tryptophan remains unknown. Recommended allowances of niacin are about fifty per cent greater than minimum needs calculated on the basis of body weight or caloric intake.
Niacin functions in the body as a component of two important coenzymes: Coenzyme I, diphosphopyridine nucleotide, and coenzyme II, triphosphopyridine nucleotide. These enzymes, which are found in all cells, are concerned in glycolysis and tissue respiration.
Early signs of niacin deficiency are lassitude, anorexia, mild digestive disturbances, especially “heartburn,” glossitis, diarrhea, and psychic and emotional changes such as anxiety, irritability and depression. The tongue is sore, red, often swollen and there is hypertrophy or atrophy of the papillae. Cheilosis, angular stomatitis and seborrheic dermatitis of the nasolabial folds have been observed in experimental niacin deficiency, although the diet contained an adequate amount of riboflavin (37, 96). The occurrence of similar lesions in niacin and riboflavin deficiency attests the close metabolic relationship of these vitamins.
In severe or prolonged deficiency, characteristic dermatitis, extensive inflammation of mucous membranes and marked mental disturbances are observed. The dermatitis involves the skin surfaces exposed to sun light or subjected to trauma or irritation. In classical pellagra, the dermatitis in the early stages resembles sunburn; subsequently, bleb formation, secondary infection and pigmentation occur. At times, the skin is so extensively involved that bullae break and exfoliate leaving large denuded areas similar to those of a severe burn. The lesions are bilateral, symmetrical and clearly demarcated from the normal skin. Areas most often involved are the backs of the hands and forearms, anterior surfaces of the feet and lower legs, and the neck (Casal’s necklace). The face may be involved and, also, the axilla, groin, perineum, genitalia, elbows, knees and the area under the breasts. In mild, chronic pellagra, only thickening, hyperkeratinization, pigmentation and scaling of the skin may be evident, particularly over points of pressure.
Severe inflammation of the entire gastrointestinal tract is found in advanced niacin deficiency: glossitis, stomatitis, esophagitis with dysphagia, gastritis, diarrhea, usually watery but occasionally containing blood, and proctitis. Involvement of other mucous membranes is evidenced by vaginitis and urethritis. The psychiatric manifestations of severe pellagra include confusion, delusions, hallucinations, disorientation and stupor.
Deficiency of riboflavin, thiamine and other B-complex vitamins may complicate the clinical picture of endemic pellagra. Achlorhydria frequently accompanies niacin deficiency and an anemia, either macrocytic or hypochromic, may be observed. The macrocytic anemia responds to folic acid, rather than to niacin, while the hypochromic anemia usually represents deficiency of iron.
A neurologic syndrome consisting of progressive stupor, grasping and sucking reflexes, and cogwheel rigidity of the extremities has been ascribed to acute niacin deficiency. This syndrome has been noted in association with febrile illness and prolonged parenteral feeding with glucose and has been reported to respond to niacin (98).
The diagnosis of mild niacin deficiency is not easy in the absence of characteristic dermatitis. The presence of glossitis, diarrhea and mild mental changes in a subject whose diet has been low in niacin and good protein is highly suggestive. Laboratory findings may assist in corroborating the diagnosis. Niacin is excreted in the urine largely as N1 – Methylnicotinamide (N1Me) and the 6-pyridone of N1Me (pyridone). In subjects maintained on diets low in niacin and tryptophan, excretion of pyridone falls rapidly to less than 1 mg. and excretion of N1Me decreases gradually to 0.5-0.8 daily. Signs of niacin deficiency appear shortly after this low level is reached.
Estimation of urinary excretion of N1Me and pyridone for 24 hours on a standard diet which furnishes about 10.0 mg. of niacin and 1000 mg. of tryptophan gives consider-able information relative to niacin nutrition. Patients with pellagra excrete less than 3.0 mg. with this regimen and well nourished subjects 7.0 to 37.0 mg. (99). This test would seem to merit further study. The number of days required for maximum urinary excretion to be attained by subjects receiving the above standard diet, supplemented with 10.0 mg. of niacinamide, has been suggested as a method of estimating the extent of depletion of tissue stores.
A number of test dose procedures have been suggested for evaluating niacin nutrition. One that has been used widely is estimation of urinary excretion of N1Me during a period of four to five hours after administering 50.0 mg. of niacinamide. Such tests have not been satisfactory when applied to individuals but have given some information in nutrition surveys. A smaller test dose, 10.0 mg., and at least a 12-hour period of urine collection would be more informative. Measurement of excretion of N1Me and pyridone in random urine specimens in relation to creatinine output is being explored as a test for evaluating nutritional status of population groups.
Measurement of total nicotinic acid or of coenzymes in blood has not proved useful in detecting niacin deficiency. Normal concentrations have been found in patients with pellagra.
Niacin deficiency occurs as a complication of a number of pathologic states in which food intake is restricted or in which there is interference with absorption or utilization of nutrients. Subjects with chronic alcoholism, cirrhosis of the liver, prolonged febrile illness, diarrheal diseases, diabetes mellitus and neoplasia often develop signs of niacin inadequacy. Prolonged parenteral feeding with-out niacin supplementation has led to acute pellagra.