A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania

Abstract

BackgroundCasein glycomacropeptide is a peptide that lacks phenylalanine, tyrosine, and tryptophan. This profile may enable it to deplete phenylalanine, tyrosine, and tryptophan, and subsequently the synthesis of dopamine and serotonin in the brain. Dopamine- and serotonin-depleting amino acid mixtures have shown promise as acute antimanic treatments. In this study, we explore the depleting effects on amino acids, dopamine and serotonin as well as its actions on manic-like and other behavior in rats.MethodsCasein glycomacropeptide and a selection of amino acid mixtures were administered orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests.ResultsCasein glycomacropeptide induced a time-dependent reduction in tyrosine, tryptophan, and phenylalanine in brain and plasma which was augmented by supplementing with leucine. Casein glycomacropeptide +leucine reduced dopamine in the frontal cortex and serotonin in the hippocampus, frontal cortex, and striatum after 2 and 4 h. Casein glycomacropeptide+leucine also had antimanic activity in the amphetamine-induced hyperlocomotion test at 2 h after a single acute treatment and after 1 week of chronic treatment.ConclusionsCasein glycomacropeptide-based treatments and a branched-chain amino acid mixture affected total tissue levels of dopamine in the frontal cortex and striatum and serotonin in the frontal cortex, striatum, and hippocampus of rats in a time-dependent fashion and displayed antimanic efficacy in a behavioral assay of mania.

BDNF+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

“…Increased immobility is associated with a depressive‐like phenotype . The two‐day FST protocol included OF testing to assess locomotor activity, an important cofounder of the FST. On day one of the FST, 4 weeks after the SAB test, rats were acclimatised to the testing room (150 lx) 1 hour prior to testing.…”

Dietary supplementation with casein glycomacropeptide, leucine and tryptophan reduces plasma amino acid levels in men

“…In preclinical studies, we found a Tyr and Phe reduction in the blood of 39-56% (Liebenberg et al, 2018). In the study by Sheehan, the reduction was 40-50% as well (Sheehan et al, 1996).…”

“…In the tap water condition, the plasma Tyr was reduced with 10% and Phe with 3%. In the study from our research group, Tyr was reduced with 50% compared to tap water (Liebenberg et al, 2018).…”

“…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 aim of this study is to build on the promising results from the rat study by performing a proof-of-concept study in healthy adults.…”

β-Lactoglobulin Elevates Insulin and Glucagon Concentrations Compared with Whey Protein—A Randomized Double-Blinded Crossover Trial in Patients with Type Two Diabetes Mellitus

“…S-free fatty acids (FFA) were measured using the in vitro enzymatic colorimetric method assay NEFA-HR(2), which quantifies the concentration of non-esterified fatty acids (FUJIFILM Wako Chemicals Europe GmbH, Germany). P-amino acids (AA) concentrations were measured by high-pressure liquid chromatography (HPLC) method using a Thermo Scientific Ultimate 3000 system, as earlier described [ 11 ]. Briefly, the samples were diluted 1.11x by adding 2 M Perchloric acid (HCIO 4 ) and then centrifuged at 14,000× g at 4 °C for 10 min.…”