Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests Part II: Normalisation of the Tryptophan and the Tyrosine Plus Phenylalanine to Competing Amino Acid Ratios in a New Control Formulation

Abstract

Current formulations for acute tryptophan (Trp) or tyrosine (Tyr) plus phenylalanine (Phe) depletion and loading cause undesirable decreases in ratios of Trp or Tyr + Phe to competing amino acids (CAA), thus undermining the specificities of these tests. Branched-chain amino acids (BCAA) cause these unintended decreases, and lowering their content in a new balanced control formulation in the present study led to normalization of all ratios. Four groups (n = 12 each) of adults each received one of four 50 g control formulations, with 0% (traditional), 20%, 30%, or 40% less of the BCAA. The free and total [Trp]/[CAA] and [Phe + Tyr]/[BCAA + Trp] ratios all decreased significantly during the first 5 h following the traditional formulation, but were fully normalized by the formulation containing 40% less of the BCAA. We recommend the latter as a balanced control formulation and propose adjustments in the depletion and loading formulations to enhance their specificities for 5-HT and the catecholamines.

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 the ratios of free tryptophan (Trp) to competing amino acids (CAA; panel a), total Trp to CAA (panel b), and phenylalanine (Phe) plus tyrosine (Tyr) to the BCAA plus total Trp (panel c) as a function of time after intake of 50 g of the original balanced-control formulation (F0) and the formulation (F3) with 40% less of the branched-chain amino acids (isoleucine, leucine, and valine; BCAA). In this latter formulation, the contents of Phe, Tyr and Trp were held constant. Error bars represent SEM for n = 12 participants per group, except for F1, where a mean of 10 subjects is presented. The asterisk denotes a significant difference from the baseline value (P = 0.05–0.0009). For other statistical comparisons, see Table 3 and the relevant text in the Results section.