Abstract

The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes. The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days. Administration of CGMP produced a dose-dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine--tryptophan was CGMP (20 g): 3.648 [SE:0.3281]; CGMP (40 g): 2.368 [SE:0.1858]; and CGMP (60 g)1.887 [SE:0.2591]. A comparison of the groups showed a dose-dependent statistical difference, with a one-way ANOVA summary (Dunnett) F = 11.87, p = 0.0003, CGMP 20 g versus CGMP 40 g, p = 0.0042, CGMP 20 g versus CGMP 60 g, p = 0.0002. No significant side effects were observed. This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g of CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 h. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.

Highlights

  • There is a great need for more efficient treatments of the manic condition

  • Preclinical studies in rats from our research group showed that an intake of casein glycomacropeptide (CGMP) lowered the precursors of dopamine, tyrosine (Tyr) and phenylalanine (Phe) in the blood and in the brain and had an anti-manic effect (Liebenberg et al, 2018)

  • A comparison of the groups showed a dose-dependent statistical difference, one-way ANOVA F = 11.87, p = 0.0003, CGMP 20 g versus CGMP 40 g, p = 0.0042, CGMP 20 g versus CGMP 60 g, p = 0.0002. In this double-blind, randomised dose–response study, we investigated the plasma amino acid, and psychological responses in healthy human adults following the consumption of three doses of a mixture of CGMP with added Leu and Trp

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Summary

Introduction

There is a great need for more efficient treatments of the manic condition. Preclinical studies in rats from our research group showed that an intake of casein glycomacropeptide (CGMP) lowered the precursors of dopamine, tyrosine (Tyr) and phenylalanine (Phe) in the blood and in the brain and had an anti-manic effect (Liebenberg et al, 2018). The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine and tyrosine, in plasma, and be a potential new intervention to treat acute manic episodes. Conclusions: This study demonstrate CGMP is a welltolerated and effective mixture, and that 60 g of CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). We conclude that this dose should be the one considered for future studies involving CGMP in humans

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