Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS: Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (ß -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (ß -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (ß -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (ß -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (ß -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (ß 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (ß 77.08 µmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (ß -1.79 µIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (ß -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (ß -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.

The correlation of helios and neuropilin-1 frequencies with parkinson disease severity.

OBJECTIVES: Parkinson disease (PD), a neurodegenerative disease, has also some immunologic basis in which several regulatory factors, like Helios and Neuropilin-1 (NRP-1) may show some roles in its pathogenesis. We aimed to evaluate the circulatory frequency of T regulatory cells (Tregs) expressing Helios and NRP-1 in PD. PATIENTS AND METHODS: In this case-control study, 83 patients with PD and 83 healthy controls were enrolled. The diagnosis of PD was accomplished in accordance with clinical diagnostic criteria of the UK Parkinson Disease Society Brain Bank. The modified Hoehn and Yahr (H and Y) were used to measure the severity of PD. Flow cytometry was used to evaluate the circulatory frequency of CD4+CD25+Foxp3+Tregs expressing and Helios and NRP-1 in all participants. Also, correlation of H and Y with such frequencies was evaluated. RESULTS: Our findings showed that frequency of CD4+CD25+Foxp3+Tregs expressing NRP-1 (P = 0.04) and Helios (P = 0.01) in patients with PD was significantly higher than those in healthy subjects. The frequency of Tregs expressing Helios and NRP-1 showed a negative correlation with H and Y criteria and disease duration. Multiple linear regression analysis indicated that the severity of PD is the only effective factor on the frequency of CD4+CD25+Foxp3+NRP-1+Tregs (P = 0.012) and CD4+CD25+FoxP3+ Helios + Tregs (P = 0.038). CONCLUSION: Our study showed that the increased frequency of Tregs expressing Helios and NRP-1 is associated with the severity of PD.

The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: A critical, systematic review and metaanalysis of randomized controlled trials.

In this meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on the scores for the expanded disability status scale (EDSS) in people with multiple sclerosis (MS) are assessed. The following databases were search up to January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI). Six studies were included in this meta-analysis. The findings demonstrated that supplementation with vitamin D alone and vitamin D plus calcium did not affect the EDSS score (WMD -0.11 (-0.33, 0.11); P = 0.32). In addition, subgroup analysis showed that vitamin D supplementation alone, when compared to the use of a placebo, and vitamin D plus calcium supplementation compared with the control did not affect EDSS (WMD -0.13 (-0.30, 0.11); P = 0.29) and (WMD -0.08 (-0.57, 0.41); P = 0.29), respectively. Overall, this meta-analysis indicated that taking vitamin D in people with MS had no significant effect on EDSS.

Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD). METHODS: The study is randomized, double-blind, placebo-controlled clinical trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 109 CFU/day probiotic or placebo (n = 30 each group) that lasted 12 weeks. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was recorded at pre- and post-intervention. RESULTS: Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P < 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3 µmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7 µmol/L, P = 0.03) in comparison with the placebo. Additionally, probiotic consumption resulted in a statistically significant reduction in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1 µIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles. CONCLUSIONS: Our study evidenced that 12 weeks of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. CONCLUSIONS: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.

Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity.

Different immune-mediated mechanisms involved in the pathogenesis of Parkinson disease (PD) as a neurodegenerative and inflammatory disease. According to our knowledge, there is no report evaluating Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We analyzed the correlation of the serum levels and circulatory gene expression of TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40 healthy subjects were enrolled. The diagnosis of PD was performed byclinical diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. The severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum levels and gene expression of TIPE2 were assessed by Elisa and real time PCR, respectively. The mean serum levels and gene expression of TIPE2 in patients with PD did not have significant difference compared to healthy subjects. Linear multiple regression analysis showed that increased serum levels of TIPE2 are positively related to age and severity of PD (P ≤ 0.0001). In addition, the gene expression of TIPE2 was found to be associated with age (P < 0.0001). Our study showed that the serum levels of TIPE2 and its gene expression might be important prognostic biomarkers of PD.

The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin and Lipid in Patients with Parkinson's Disease: A Randomized, Double-blind, PlaceboControlled Trial.

BACKGROUND: This study was conducted to evaluate the effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted in 50 patients with PD as a pilot study. Participants were randomly allocated into two groups to take either 8×109 CFU/day probiotic supplements or placebo (n = 25 each group, one capsule daily) for 12 weeks. Gene expression related to inflammation, insulin, and lipid was quantified in peripheral blood mononuclear cells (PBMC) of PD patients, with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, probiotic intake downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), IL-8 (P < 0.001) and tumor necrosis factor alpha (TNF-α) (P=0.04) in PBMC of subjects with PD. In addition, probiotic supplementation upregulated transforming growth factor beta (TGF-ß) (P = 0.02) and peroxisome proliferatoractivated receptor gamma (PPAR-γ) (P = 0.03) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of probiotic intake on gene expression of low-density lipoprotein receptor (LDLR) and vascular endothelial growth factor (VEGF) in PBMC of patients with PD. CONCLUSION: Overall, probiotics supplementation for 12 weeks in PD patients significantly improved gene expression of IL-1, IL-8, TNF-α, TGF-ß and PPAR-γ, but did not affect gene expression of VEGF and LDLR, and biomarkers of inflammation and oxidative stress.

The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

The current research was performed to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on clinical signs and metabolic status in people with Parkinson's disease (PD). This randomized double-blind placebo-controlled clinical trial was conducted in 60 patients with PD. Participants were randomly assigned into two groups to receive either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Unified Parkinson's disease rating stage (UPDRS) were recorded at baseline and the after 3-month intervention. After 12 weeks' intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation led to a significant improve in UPDRS (-3.3 ± 10.0 vs. +4.4 ± 14.9, P = 0.02). Furthermore, co-supplementation decreased high-sensitivity C-reactive protein (hs-CRP) (-0.3 ± 0.6 vs. +0.3 ± 0.3 µg/mL, P < 0.001), and increased total antioxidant capacity (TAC) (+65.2 ± 68.7 vs. +16 ± 52.4 µmol/L, P = 0.003) and glutathione (GSH) concentrations (+41.4 ± 80.6 vs. -19.6 ± 55.9 µmol/L, P = 0.001) compared with the placebo. Additionally, co-supplementation meaningfully decreased insulin (-2.1 ± 4.9 vs. +1.4 ± 6.2 µIU/mL, P = 0.01), homeostasis model of assessment-estimated insulin resistance (-0.7 ± 1.8 vs.+0.3 ± 1.6, P = 0.02) and Beta cell function (-5.9 ± 13.9 vs. +5.7 ± 25.5, P = 0.03), and increased quantitative insulin sensitivity check index (+0.009 ± 0.02 vs. -0.006 ± 0.03, P = 0.03) compared with the placebo. Overall, our study demonstrated that omega-3 fatty acids and vitamin E co-supplementation in people with PD had favorable effects on UPDRS, hs-CRP, TAC, GSH and markers of insulin metabolism.

Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: This trial was performed to evaluate the effects of probiotic intake on disability, mental health and metabolic condition in subjects with multiple sclerosis (MS). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted among 60 MS patients. Participants were randomly allocated into two groups to receive either a probiotic capsule (n = 30) or placebo containing starch (n = 30) for 12 weeks. Expanded disability status scale (EDSS) scoring and parameters of mental health were recorded at the baseline and 12 weeks after the intervention. RESULTS: Compared with the placebo, probiotic intake improved EDSS (-0.3 ± 0.6 vs. +0.1 ± 0.3, P = 0.001), beck depression inventory (-5.6 ± 4.9 vs. -1.1 ± 3.4, P < 0.001), general health questionnaire (-9.1 ± 6.2 vs. -2.6 ± 6.4, P < 0.001) and depression anxiety and stress scale (-16.5 ± 12.9 vs. -6.2 ± 11.0, P = 0.001). In addition, changes in high-sensitivity C-reactive protein (-1.3 ± 3.5 vs. +0.4 ± 1.4 µg/mL, P = 0.01), plasma nitric oxide metabolites (+1.0 ± 7.9 vs. -6.0 ± 8.3 µmol/L, P = 0.002) and malondialdehyde (MDA) (+0.009 ± 0.4 vs. +0.3 ± 0.5 µmol/L, P = 0.04) in the probiotic group were significantly different from the changes in these parameters in the placebo group. Additionally, the consumption of probiotic capsule significantly decreased serum insulin (-2.9 ± 3.7 vs. +1.1 ± 4.8 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (-0.6 ± 0.8 vs.+0.2 ± 1.0, P = 0.001), Beta cell function (-12.1 ± 15.5 vs. +4.4 ± 17.5, P < 0.001) and total-/HDL-cholesterol (-0.1 ± 0.3 vs.0.1 ± 0.3, P = 0.02), and significantly increased quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. -0.005 ± 0.01, P < 0.001) and HDL-cholesterol levels (2.7 ± 3.4 vs. 0.9 ± 2.9 mg/dL, P = 0.02) compared with the placebo. CONCLUSIONS: Our study demonstrated that the use of probiotic capsule for 12 weeks among subjects with MS had favorable effects on EDSS, parameters of mental health, inflammatory factors, markers of insulin resistance, HDL-, total-/HDL-cholesterol and MDA levels.

Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial.

Alzheimer's disease (AD) is associated with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind, and controlled clinical trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n = 30 in each group) treating with either milk (control group) or a mixture of probiotics (probiotic group). The probiotic supplemented group took 200 ml/day probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 CFU/g for each) for 12 weeks. Mini-mental state examination (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to determine the related markers. After 12 weeks intervention, compared with the control group (-5.03% ± 3.00), the probiotic treated (+27.90% ± 8.07) patients showed a significant improvement in the MMSE score (P <0.001). In addition, changes in plasma malondialdehyde (-22.01% ± 4.84 vs. +2.67% ± 3.86 µmol/L, P <0.001), serum high-sensitivity C-reactive protein (-17.61% ± 3.70 vs. +45.26% ± 3.50 µg/mL, P <0.001), homeostasis model of assessment-estimated insulin resistance (+28.84% ± 13.34 vs. +76.95% ± 24.60, P = 0.002), Beta cell function (+3.45% ± 10.91 vs. +75.62% ± 23.18, P = 0.001), serum triglycerides (-20.29% ± 4.49 vs. -0.16% ± 5.24 mg/dL, P = 0.003), and quantitative insulin sensitivity check index (-1.83 ± 1.26 vs. -4.66 ± 1.70, P = 0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose, and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 weeks positively affects cognitive function and some metabolic statuses in the AD patients. CLINICAL TRIAL REGISTRATION: http://www.irct.ir/, IRCT201511305623N60.