Specificity of the acute tryptophan and tyrosine plus phenylalanine depletion and loading tests I. Review of biochemical aspects and poor specificity of current amino Acid formulations

Abstract

The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

Keywords: acute tryptophan depletion and loading; acute tyrosine depletion test; amino acid formulations; branched-chain amino acids; catecholamines; competing amino acids; dopamine; isoleucine; leucine; noradrenaline; phenylalanine; tryptophan; tyrosine; valine.

Figure 1.

Time-course of changes in plasma competing amino acid conentrations following oral intake of a 50 g dose of the control formulation for the acute tryptophan depletion and loading tests. Note: Values are means ± SEM for each group of 12 subjects. Adapted from the data in Table 3 in Dougherty et al (2008).