Novel Nutritional Treatment for Manic and Psychotic Disorders: a Review of Tryptophan and Tyrosine Depletion Studies and the Potential of Protein-based Formulations Using Glycomacropeptide

Rationale: Current amino acid (AA) mixtures used in acute tryptophan (Trp) and tyrosine (Tyr) plus phenylalanine (Phe) depletion and loading tests are unpalatable and lack specificity. Specificity is improved by reducing content of branched-chain amino acids (BCAA) and palatability to a certain extent by dose reduction.

Objectives: This study aims to identify a palatable naturally occurring alternative(s) to amino acids with the desired BCAA content for use in the above tests.

Methods: A palatable alternative lacking in Trp, Tyr and Phe has been identified in the whey protein fraction caseino-glycomacropeptide (c-GMP). The absence of these three aromatic amino acids renders GMP suitable as a template for seven formulations for separate and combined depletion or loading and a placebo control. The absence of Phe and Tyr enables GMP to provide a unique nutritional therapy of manic and psychotic disorders by inhibition of cerebral dopamine synthesis and release and possibly also by enhancing glutamatergic function, in general, and in patients resistant to anti-psychotic medication, in particular.

Results: Seven GMP-based formulations for the above tests are proposed, two of which can be used in the above nutritional therapy and a third formulation as a placebo control in clinical trials.

Conclusions: Development of these formulations should advance the above research and diagnostic tests, open new avenues for neuroscience research on monoamine function, and improve the therapy of bipolar and psychotic disorders and enhance the quality of life of sufferers.