THE URINARY-EXCRETION OF TRYPTOPHAN AND TRYPTOPHAN-METABOLITES IN THE CHRONIC ETHANOL-FED RAT

An investigation was made into the hypothesis that chronic ethanol ingestion disturbs the metabolism of tryptophan which is reflected by alterations in the urinary excretion of the metabolites 5-hydroxyindoleacetic acid (5-HIAA), anthranillic acid (AA) and indoleacetic acid (IAA). In particular, we investigated whether experimental chronic alcoholism is associated with a decrease in the tryptophan metabolite ratios as suggested in the literature. Male Wistar rats were chronically fed a nutritionally-complete liquid diet in which ethanol comprised 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At 6 weeks, 24 h urine samples were collected for the analysis of tryptophan, 5-HIAA, AA and IAA by HPLC. During ethanol-feeding there were reductions in the daily urinary excretion (i.e. mumol/24 h) of tryptophan (-57%, P=0.026) and concomitant increases in 5-HIAA excretion (62%, P=0.057). Expression of data in terms of lean tissue mass (i.e. urinary creatinine) revealed identical conclusions. An analysis was performed on the molar ratios of these urinary analytes. The tryptophan: total metabolite ratio was significantly decreased (by -53 %), but the AA: total metabolite ratio was not significantly altered (P=0.102). The ratios 5-HIAA/AA and 5-HIAA/IAA were slightly increased, but they did not attain statistical significance (P>0.351). It was concluded that chronic ethanol feeding is associated with significant changes in the urinary excretion of tryptophan and its related metabolites. Many of the above changes were contrary to previous clinical data and this may be due to dietary and nutritional deficiencies or to alterations in the diurnal pattern of 5-hydroxytryptamine and tryptophan metabolism.