Long-Term Effects of Histidine Depletion on Whole-Body Protein Metabolism in Healthy Adults

Abstract

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-(13)C]phenylalanine) oxidation (in four subjects) and [(15)N]glycine (in one subject). Urine samples (24-h) were collected for measurement of urea, total nitrogen, creatinine, 3-methylhistidine (3-MH), histidine and beta-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 beta-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 (13)C-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.

An open label study to determine the effects of an oral proteolytic enzyme system on whey protein concentrate metabolism in healthy males

“…Results of IAA indicate that Aminogen ® supplementation may contribute to decreased whole body protein metabolism. Decreased flux of IAA levels such as phenylalanine and valine have been reported to be indicators of decreased whole body protein metabolism and decreased N2 excretion [ 1 , 14 ]. Fluctuations in tyrosine, phenylalanine and BCAAs were compared using average percent AUC.…”

The urine proteome as a biomarker of radiation injury

“…Selective oxidation of histidine as an early effect of irradiation has significant implications. Histidine is an essential amino acid for humans and rats and its deficiency affects whole-body protein turnover rate and levels of hemoglobin, albumin, and transferrin [35]. The neutral pK a of its imidazole side chain allows participation in acid/base catalysis and proton transfer reactions at physiological pH.…”

Effects of L‐histidine depletion and L‐tyrosine/L‐phenylalanine depletion on sensory and motor processes in healthy volunteers

“…In a standard reference work on dietary requirements (Institute of Medicine, 2006), histidine is listed as an indispensable (essential) amino acid. However, this has been challenged in long‐term depletion studies (Kriengsinyos et al. , 2002).…”