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.

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

Background: Casein 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. Methods: Casein 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. Results: Casein 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. Conclusions: Casein 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.

Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression.

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.

Experiences of wake and light therapy in patients with depression: A qualitative study.

Wake therapy can reduce depressive symptoms within days, and response rates are high. To sustain the effect, it is often combined with light therapy. Few studies have focussed on factors related to patients' adherence to the regime, and none has used qualitative methods to examine their experience of these combined interventions. Therefore, the aim of the present study was to illuminate patients' experiences with wake and light therapy and factors related to adherence. Thirteen inpatients with depression were included. They participated in an intervention consisting of three wake therapies during the first week, 30 min of daily light treatment for the entire 9 weeks, and ongoing psychoeducation regarding good sleep hygiene. Patients kept a diary, and individual semistructured interviews were conducted. Data were analysed using qualitative content analysis. The participants' overall experience with the treatment was positive. Some experienced a remarkable and rapid antidepressant effect, whereas others described more long-term benefits (e.g. improved sleep and diurnal rhythm). Yet recovery was fragile, and patients were only cautiously optimistic. Social support was important for maintaining the motivation to stay awake and receive daily light therapy. Overall, participants found the treatment worthwhile and would recommend it to others with depression. The study revealed a lack of knowledge among participants about the connection between regular sleep patterns and depression. In conclusion, this study provides insight into patients' experiences, and knowledge that can contribute to guidelines for future adherence-promoting organization of wake and light therapy.

Vitamin D and calcium supplementation prevents severe falls in elderly community-dwelling women: a pragmatic population-based 3-year intervention study.

BACKGROUND AND AIMS: We evaluated the effect of two programs for the prevention of falls leading to acute hospital admission in a population of elderly community-dwelling Danish residents. METHODS: This was a factorial, pragmatic, intervention study. We included 9605 community-dwelling city residents aged 66+ years. We offered a prevention program consisting of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin-D3 to a total of 4957 participants. The remaining 5063 participants were offered home safety inspection with dietary and health advice, or no intervention. RESULTS: The Calcium and Vitamin D program was followed by 50.3% and the Environmental and Health Program by 46.4%. According to a multivariate analysis including age, marital status and intervention program, female residents who followed the Calcium and Vitamin D Program had a 12% risk reduction in severe falls (RR 0.88; 95% CI 0.79-0.98; p < 0.05; NNT 9). CONCLUSIONS: The present study supports the hypothesis that vitamin D and calcium supplementation prevent falls leading to acute hospitalization in community-dwelling elderly females in a northern European region known to be deficient in vitamin D.

Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study.

UNLABELLED: This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D, especially during winter periods. INTRODUCTION: We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents. MATERIALS AND METHODS: This was a factorial, cluster-randomized, pragmatic, intervention study. We included 9605 community-dwelling residents aged 66+ years. We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin D3 to a total of 4957 participants. Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants. Both programs included revision of the resident's current pharmaceutical treatment. We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Database. We defined osteoporotic fractures as low energy fractures of the proximal humerus, distal forearm, vertebral column, pelvis, cervical femur, and intertrochanteric femur. RESULTS: Active participation was 50.3% in the Calcium and Vitamin D Program and 46.4% in the Environmental and Health Program. We observed a 16% reduction in fracture incidence rate (relative risk [RR], 0.84; CI, 0.72-0.98; p < 0.025) among male and female residents offered the Calcium and Vitamin D Program (intention-to-prevent analysis). CONCLUSIONS: This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D, especially during winter periods.