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Human Nutrition and Metabolism

Long-Term Effects of Histidine Depletion on Whole-Body Protein Metabolism in Healthy Adults^{1 ,2}

Wantanee Kriengsinyos^*,, Mahroukh Rafii, Linda J. Wykes^**, Ronald O. Ball^*, and Paul B. Pencharz^,,3

^* Department of Nutritional Sciences and Paediatrics, University of Toronto, Toronto, Canada M5S 3E2; The Research Institute, The Hospital for Sick Children, Toronto, Canada M5G 1X8; ^** School of Dietetics and Human Nutrition, McGill University, Montreal, Canada H9X 3V9; and Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada T6G 2P5

³To whom correspondence should be addressed. E-mail: paul.pencharz{at}sickkids.ca.

The essentiality of histidine in healthy adults is a controversial topic. To study the potential metabolic effects of a lack of exogenous histidine, four healthy adults consumed a histidine-free diet, with adequate energy and 1.0 g/(kg · d) of an L-amino acid mixture for 48 d. Protein metabolism was monitored every 4 d by using indicator amino acid (L-[1-¹³C]phenylalanine) oxidation (in four subjects) and [¹⁵N]glycine (in one subject). Urine samples (24-h) were collected for measurement of urea, total nitrogen, creatinine, 3-methylhistidine (3-MH), histidine and ß-alanine. Albumin, transferrin and hematologic concentrations were measured on d 0, 24 and 48. Urinary excretion of nitrogen, urea, creatinine and 3-MH were not affected by the histidine-free diet. However, there was a significant (P < 0.001) linear decline (24–28%) in whole-body protein turnover. Significant (P < 0.05) decreases in albumin (12%), transferrin (17%) and hemoglobin (Hb) (11%) concentrations occurred slowly over the histidine depletion period. The urinary excretion of ß-alanine (an index of carnosine catabolism) generally increased in the smallest subject during the consumption of histidine-free diet. This study demonstrates that a lack of histidine in the diet for a prolonged period resulted in an accommodation of protein turnover and phenylalanine oxidation, measured by the ¹³C-phenylalanine indicator amino acid. The extensive metabolic accommodation, together with decreases in Hb, albumin and transferrin during histidine depletion, leaves unresolved the issue of whether histidine is a dietary essential amino acid in healthy adults.

KEY WORDS: • histidine • whole-body protein metabolism • indicator amino acid oxidation • healthy adults

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