Goldberger had demonstrated the curative effects of dietary protein and proposed that pellagra was caused by a lack of specific amino acids (see Terris). Now it is known that pellagra may result from a deficiency of either nicotinic acid or tryptophan, the amino acid precursor of nicotinic acid. One milligram of nicotinic acid is formed from 60 mg of tryptophan, a process for which pyridoxine is essential. The relationship of niacin to tryptophan metabolism explains the frequent occurrence of pellagra in persons who subsist mainly on corn, which contains only small amounts of tryptophan and niacin, some of the niacin being in bound form and unavailable for absorption.
It should be pointed out that in experimental subjects, only the cutaneous-gastrointestinal-neurasthenic manifestations of pellagra have been produced by diets that are tryptophan or niacin deficient; neurologic abnormalities have not resulted from these diets (Goldsmith). As a corollary, only the dermal, gastrointestinal, and neurasthenic manifestations respond to treatment with niacin and tryptophan; neurologic disturbances in affected individuals have proved to be recalcitrant to prolonged treatment with the vitamin, although the peripheral nerve disorder may subsequently respond to treatment with thiamine. In monkeys, degeneration of peripheral nerves and the cerebrocortical changes of pellagra were induced by a deficiency of pyridoxine (Victor and Adams, 1956). Swank and Adams described degeneration of the peripheral nerves in pyridoxineand pantothenic acid-deficient swine, and Vilter and colleagues produced polyneuropathy in human subjects rendered pyridoxine deficient; these subjects also showed seborrheic dermatitis and glossitis (indistinguishable from that of niacin deficiency) and the cheilosis and angular stomatitis that are usually attributed to riboflavin deficiency. The foregoing observations indicate that certain lingual and cutaneous manifestations of pellagra may be produced by a deficiency of pyridoxine or other B vitamins, and that the neurologic manifestations of pellagra are most likely caused by pyridoxine deficiency.
In the special case of Hartnup disease in infants (which resembles pellagra in most respects including the dermatitis), a secondary niacin deficiency is believed to result from the high excretion of indicans and indole metabolites (see Chap. 36).
The administration of niacin 500 mg per day for approximately 3 weeks reverses the process. If the patient is unable to take oral medications, intravenous doses of 100 mg per day for 5 to 7 days are utilized. If the patient is simultaneously deficient in pyridoxine, as for example when INH is used for tuberculosis treatment, the pyridoxine must also be replaced in order to allow the conversion of dietary tryptophan to endogenous niacin.
Under this title, Jolliffe and coworkers, in 1940, described an acute cerebral syndrome in alcoholic patients consisting of clouding of consciousness, progressing to extrapyramidal rigidity and tremors (“cogwheel” rigidity) of the extremities, uncontrollable grasping and sucking reflexes, and coma. Some of their patients showed overt manifestations of nutritional deficiency, such as