Vitamin B6 nutritional status of pellagrins and their leucine tolerance

Abstract

Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required.

Mechanisms of the Pellagragenic Effect of Leucine: Stimulation of Hepatic Tryptophan Oxidation by Administration of Branched-Chain Amino Acids to Healthy Human Volunteers and the Role of Plasma Free Tryptophan and Total Kynurenines

“…The kynureninase inhibition demonstrated in rats using methylene 14 C-Trp 7 may also occur in pellagrins, evidenced indirectly from increased urinary excretion of 3-HK and XA. 10 , 18 Levels of this transamination product (XA) and of kynurenic acid ( Fig. 1 ) rise when there is an increased flux of Trp down the kynurenine pathway after acute Trp loading or enhanced TDO activity and also after kynurenine loading or kynureninase inhibition.…”

“…Indeed plasma pyridoxal 5′-phosphate levels are significantly lower in pellagrins than in controls. 18 Leu may also inhibit kynureninase by a similar (functional vitamin B 6 deficiency) mechanism. Leu is metabolized initially by BCAA aminotransferase (BCAT).…”

Effect of L-Leucine Therapy on Hematopoietic Function in Elderly Myelodysplastic Syndrome Patients

“…Patients diagnosed with MDS classified as refractory anemia (RA), refractory anemia with ring sideroblasts, refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia with excess blasts type 1 (RAEB-1), unclassified MDS, or 5q-syndrome according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, 4th edition 11) were enrolled in the present study. The patients were aged 40-90 years, and informed consent was obtained from each patient prior to study participation.…”

Nutritional Adequacy, Nutrient Availability and Needs

“…incidence by sex, age and season and the composition of family dietaries. The explanation for the Indian results may lie in the finding of vitamin Bli-deficiency in the subjects and/or a connection with alcohol ism (Bapurao & Krishnaswamy, 1978). Looking at data from the World as a whole, a greater incidence amongst men than women has always been associated elsewhere with alcoholism (Harris, 1941).…”