Pellagra was a major problem in parts of India where jowar (Sorghum vulgare) is the dietary staple, despite the fact that the tryptophan content of sorghum proteins is higher than that of maize, the cereal traditionally associated with endemic pellagra. The intake of tryptophan and niacin was as great among people whose dietary staple was jowar as that of rice eaters, yet pellagra was common among jowar eaters and not in rice-eating communities, suggesting that the relatively high content of leucine in the proteins of jowar might be a contributory factor.
A number of studies have demonstrated a pellagragenic effect of excess dietary leucine in experimental animals and in human beings (Gopalan and Rao, 1975), although other studies failed to show any effect (Manson and Carpenter, 1978a, 1978b). Magboul and Bender (1983) showed that, when rats were fed diets that were only marginally adequate with respect to tryptophan and niacin, the addition of 1.5% leucine led to a significant depletion of liver and blood nicotinamide nucleotides. This effect was only apparent when the niacin content of the diet was such that it provided less than half the minimum requirement and was most marked when the diets provided virtually no preformed niacin, suggesting that the effect of leucine is on the metabolism of tryptophan and not on the utilization of niacin.
Studies with [14C]tryptophan in animals and isolated hepatocytes show that leucine does inhibit the synthesis of NAD from tryptophan, inhibiting metabolism at the level of kynurenine hydroxylase and kynureninase, causing the accumulation of intermediates. In isolated hepatocytes, the more important effect seems to be at the level of uptake of tryptophan into the cells; leucine and tryptophan share a common transport mechanism with the other large neutral amino acids (Bender, 1983,1989a; Salter et al., 1985).
It is likely that leucine is only a factor in the etiology of pellagra when the dietary intakes of both tryptophan and niacin are extremely low - a condition that may occur when sorghum is the dietary staple, especially during food shortage.
Was this article helpful?