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

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.

Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre-registration of a review protocol, we systematically searched the PubMed, EMBASE, and Cochrane databases for literature covering themes of 'lactate', 'the brain', and 'microcirculation'. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty-eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose-dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD+ /NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose-dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg. OPEN SCIENCE BADGES: This article has received a badge for *Pre-registration* because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.