Niacin, Pellagra, and the Role of Tryptophan

Although pellagra is uncommon, it most frequently afflicts alcoholics and the elderly. Thyrotoxicosis and sepsis increase niacin requirements but rarely precipitate pellagra. Though the disease is produced by dietary insufficiency of tryptophan and niacin, the full deficiency syndrome can develop in patients who shunt tryptophan into other metabolic pathways despite a normal diet. Such is the case for patients with the carcinoid syndrome, in whom 60 times more tryptophan than normal is hydroxy-lated to serotonin (Melmon, 1981). 

Mental confusion and psychologic features such as anxiety, depression, amnesia, and hallucinations develop in patients with carcinoid syndrome. One such confused and depressed patient improved with high pro-tein/high tryptophan feeding, arguing for the causative role of a dietary deficiency in cognitive impairment (Major et al, 1973). However, it is possible that, in the carcinoid syndrome, the confusional features are not entirely related to a deficiency. Non-hydroxylated metabolites of tryptophan have been demonstrated which may explain the psychological and mental features (Melmon, 1981). 

Dietary tryptophan is an effective anti-depressant in some depressed patients (Beitman and Dunner, 1982). Thomson et al (1982) proposed 

There have been few clinical studies on the incidence of pellagra. Mitra (1971) reported low niacin levels, rash, and confusion in two nonalcoholic, elderly women living alone. Borderline vitamin stores, combined with other neurologic illness, may produce active disease. In the same British study, a number of other confused patients were reported to have low vitamin levels but no rash. 

The earliest neurologic symptoms of pellagra are reminiscent of neurasthenia, with insomnia, fatigue, nervousness, irritability, and depression with memory loss (Victor et al, 1971). A progressive dementia can develop, but this seems unlikely to be caused solely by the absence of niacin. An acute confusional syndrome also occurs in human pellagra, and this is reversible with niacin therapy. A central neuritis is prominent in the large motor cortex cells (the Betz cells). This is not a demyelinating process like Bj2 deficiency but a primary involvement of the whole neuron. 

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