Possible role for dietary leucine in the pathogenesis of pellagra

Abstract

The traditional view of the pathogenesis of pellagra is that it is a nutritional deficiency disease caused by the consumption of maize, a staple which is deficient in tryptophan and in which nicotinic acid is present in "bound" form. But cases of pellagra seen in populations whose staple is "jowar" (a millet with tryptophan content close to that of rice) throws doubt on this hypothesis. Jowar has an abnormally high leucine content, as does maize. L-leucine was found to interfere with tryptophan and nicotinic-acid metabolism, and leucine supplements induced "black tongue" (the canine equivalent of pellagra) in dogs. Leucine seems to act by distorting the nicotinamide-nucleotide pattern of red blood-cells, though total nucleotide levels are not affected. Supplements of this amino acid seem to exacerbate the mental symptoms associated with pellagra. Pellagra may, therefore, be thought of as a human nutritional deficiency disease mediated by leucine imbalance. The disease could be brought under control by identification and selective propagation of strains of jowar which are low in leucine.