The impact of probiotics and vitamin C on the prevention of upper respiratory tract symptoms in two preschool children cohorts.

BACKGROUND/OBJECTIVES: The efficacy of Lab4 probiotic and vitamin C combination on the prevention of upper respiratory tract infections (URTIs) was investigated in two studies with children. Our objective was to pool dataset of 57 preschool children from the PROCHILD study (ISRCTN28722693) and the dataset of 50 preschool matched cohort from the PROCHILD-2 study (ISRCTN26587549) to evaluate the impact of probiotic/vitamin C combination on the prevention of upper respiratory tract symptoms and provide a more robust assessment of effect using detailed individual level data. SUBJECTS/METHODS: The children were supplemented daily for 6 months with either the multistrain probiotic (1.25×1010 cfu/tablet consisting of two strains of Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) plus 50 mg vitamin C or a placebo. RESULTS: In the pooled analysis of the individual participant data (per protocol population), significant reductions were observed for the incidence (-25%; 95% confidence interval [CI], 0.66, 0.85; P < 0.0001) and duration (-14.9 days; 95% CI, -24.8, -5.1; P = 0.0030) of typical URTI symptoms in the active group compared with the placebo. The incidence rates of absenteeism from preschool (IR ratio, 0.75; 95% CI, 0.66, 0.86; P < 0.0001), paediatric visits (IR ratio, 0.56; 95% CI, 0.47; 0.68; P < 0.0001) and antibiotic usage (IR ratio, 0.53; 95% CI, 0.39, 0.71; P < 0.0001) were also significantly reduced. CONCLUSION: The pooled analysis findings of comparable preschool cohorts from two studies indicate that the supplementation with probiotic and vitamin C combination is beneficial in the prevention and management of URTI symptoms.

The kynurenine and serotonin pathway, neopterin and biopterin in depressed children and adolescents: an impact of omega-3 fatty acids, and association with markers related to depressive disorder. A randomized, blinded, prospective study.

Depressive disorder is a severe mental condition. In addition to genetic factors, immunological-inflammatory factors, oxidative stress, and disturbances in neurotransmitter metabolism, kynurenine and serotonin pathways may play a role. The exact mechanisms, especially in depressed children and adolescents, are not fully understood. Our primary hypothesis was whether the metabolites of tryptophan degradation in children and adolescents with depressive disorder might be influenced by omega-3 FAs compared to omega-6 FAs during a 12-week supplementation. A secondary hypothesis was to investigate whether tryptophan metabolites in children and adolescents are associated with markers of inflammatory response, oxidative stress, cortisol, and the serum omega-6/omega-3 FA ratio. Metabolites of tryptophan degradation and pteridines, neopterin, and biopterin in urine were analyzed with an HPLC system. Surprisingly, omega-3 FAs stimulated both kynurenine (kynurenine/tryptophan ratio) and serotonin (5-hydroxytryptophan) pathways, whereas omega-6 FAs only increased the kynurenine/tryptophan ratio. Neopterin and biopterin were not different from the healthy controls. Biopterin increased after omega-3 FA supplementation. Serotonin was positively correlated with lipoperoxidation and a marker of oxidative protein damage. Of the monitored tryptophan metabolites, only 5-hydroxyindolacetic acid was positively correlated with the severity of depression, total cholesterol, and negatively with brain-derived neurotrophic factor and glutathione peroxidase. In conclusion, in children and adolescents, both supplemented FAs stimulated the kynurenine pathway (kynurenine/tryptophan ratio) and kynurenine formation. However, the serotonin pathway (5-hydroxytryptophan) was stimulated only by omega-3 FA. Tryptophan metabolism is associated with oxidative stress, inflammation, total cholesterol, and cortisol. We are the first to point out the association between the kynurenine pathway (KYN/TRP ratio) and the omega-6/omega-3 FA ratio. The metabolite 5-HIAA could play a role in the pathophysiology of depressive disorder in children and adolescents. Clinical Trial Registration: https://www.isrctn.com/ISRCTN81655012, identifier ISRCTN81655012.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. METHODS: The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. RESULTS: OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. CONCLUSION: The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial.

Oxidative stress (OS) is thought to play a role in mental disorders. However, it is not clear whether the OS is the cause or consequence of the disorder. We investigated markers of oxidative stress (8-isoprostane (8-IsoP-U), lipoperoxides (LP), advanced oxidation protein products (AOPP) and nitrotyrosine (NT)) and antioxidant protection (Trolox equivalent antioxidant capacity (TEAC), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in 60 paediatric and adolescent patients with depressive disorder (DD) compared to healthy controls. The patients were divided into two groups (1:1). One group received an emulsion of omega-3 fatty acid (FA), and the other group an emulsion of sunflower oil with omega-6 FA for 12 weeks. The levels of 8-IsoP-U, AOPP and NT were increased, and GPx activity was decreased in patients compared to the controls. We found a significant positive correlation of the Children's Depression Inventory score with NT and a negative correlation with TEAC, SOD and GPx. NT correlated positively with the baseline omega-6/omega-3 FA ratio and a negatively with SOD. A supplementation with omega-3 FA, but not with omega-6 FA, decreased 8-IsoP-U, AOPP, NT levels and increased TEAC and SOD activity. Our results suggest that NT may play a role in the pathophysiology of DD, while elevated isoprostane is likely caused by the high omega-6/omega-3 FA ratio. Omega-3 FA supplementation reduces oxidative stress in patients with DD. This study was registered with the ISRCTN registry (ISRCTN81655012).

The Effect of Omega-3 Fatty Acids on Thromboxane, Brain-Derived Neurotrophic Factor, Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial.

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child's Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).

Methionine metabolism and multiple sclerosis.

CONTEXT: Methylation reactions are particularly important in the brain and their inhibition can lead to a number of serious pathologies. Multiple sclerosis is one of the most common neurological disorders caused by interaction of genetic and environmental factors, but little is known about its cause or factors that contribute to the disorder. Although multiple sclerosis is primarily regarded as demyelinating disorder, there are no many articles focusing on methionine determination. OBJECTIVE: The aim of this work was to investigate whether serum methionine and its related compounds like homocysteine, cysteine, glutathione and asymmetric dimethylarginine were changed in multiple sclerosis patients. MATERIALS AND METHODS: Sulphur-containing compounds were determined by using high-performance liquid chromatography with electrochemical detection in a single run for providing more complex view on methionine metabolism and asymmetric dimetylarginine was measured by a commercial enzyme-linked immunosorbent assay kit. RESULTS: Methionine and glutathione were decreased, but homocysteine, asymmetric dimethylarginine and cysteine were unchanged in patients with multiple sclerosis compared with controls. CONCLUSIONS: Methionine and glutathione seem to be potential biomarkers for prognosis of the disease.

Oxidative stress in women with perimenopausal symptoms.

OBJECTIVE: In this study, we examined the relationships between perimenopausal symptoms, biochemical parameters, and markers of oxidative stress in women in perimenopause and compared them with those of premenopausal women. METHODS: Sixty-two women (age, 53.2 ± 5.7 y) with perimenopausal symptoms were recruited to participate in our study. The control group consisted of 18 women without perimenopausal symptoms (age, 40 ± 5 y).Clinical perimenopausal symptoms were evaluated via the questionnaire of the Menopausal Rating Scale. Our participants were checked for basic biochemical parameters. The oxidative status of our samples was determined through the examination of lipoperoxides, 8-oxoguanine (8-oxoG) levels, and the total antioxidant status (TAS). RESULTS: Perimenopausal women had higher total cholesterol values and lower paraoxonase-1 (PON1) activity compared to reference values. Other biochemical parameters as well as 8-oxoG levels were unchanged compared with those of healthy control women. Lipoperoxide levels were significantly increased compared with those of premenopausal women. We found an indirect correlation between PON1 arylesterase (PON1 A) activity and lipoperoxide levels, between PON1 A activity and atherogenic index, between age and TAS, and between age and 8-oxoG levels. DNA repair ability and the total antioxidant status of women in perimenopause were significantly increased compared with women in premenopause. Hypercholesterolemic women had significantly increased low-density lipoprotein cholesterol levels when compared with normocholesterolemic individuals, but these values were still within the reference range. Normocholesterolemic women had significantly decreased high-density lipoprotein cholesterol levels, below the reference range. We found no correlations between perimenopausal symptoms and biochemical parameters or oxidative stress markers. CONCLUSIONS: We found that women in perimenopause are under increased oxidative stress manifested by reduced PON1 A activity and elevated lipoperoxidation, DNA repair ability, and TAS. Nutritional antioxidant supplementation may be an effective approach in improving menopausal symptoms.

WITHDRAWN: Natural polyphenols modify trace element status and improve clinical symptoms of attention-deficit hyperactivity disorder.

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