The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Imbalances in immune regulation are important features of migraine pathophysiology. In line with this, the current study investigated the efficacy of omega-3 fatty acids supplementation on inflammatory and anti-inflammatory markers in patients with migraines. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial consisted of 40 patients that were prone to experiencing episodic migraines. For two months, participants were randomized into one group that received omega-3 supplementation (n= 20), 600 mg of EPA and 300 mg of DHA, twice daily) or another group that received a placebo (n= 20). Transforming growth factor ß (TGF-ß), interleukin (IL)-4, interferon-gamma (IFN-γ), and interleukin (IL)-17 serum levels were assessed using enzyme-linked immunosorbent assay methods at baseline and following the intervention. The current study was registered on ClinicalTrials.gov with the registration number NCT02532023. RESULTS: After two months of intervention, the administration of omega-3 fatty acids resulted in a significant rise in the concentrations of anti-inflammatory cytokine IL-4 (p=0.010) as well as a significant reduction in concentrations of pro-inflammatory cytokine IFN-γ (p=0.001) compared with the placebo. However, no significant changes were observed in serum TGF-ß and IL-17 levels. DISCUSSION: Our findings indicated consumption of omega-3 fatty acids may have a potentially beneficial response on the inflammatory immune response in patients with migraines. Larger trials are needed to corroborate these findings.

The Effects of Nano-curcumin Supplementation on Leptin and Adiponectin in Migraine Patients: A Double-blind Clinical Trial Study from Gene Expression to Clinical Symptoms.

BACKGROUND: Migraine is a disabling neurogenic disorder characterized by recurrent headache attacks. Adipokines act as inflammatory and pain mediators that contribute to migraine pathogenesis. Leptin and adiponectin levels change in migraine patients and are associated with headache attacks. Curcumin can exert modulatory and analgesic effects on adipokines through several mechanisms, from gene expression to suppressing pain. The aim of the present study was to evaluate the effects of nano-curcumin supplementation on leptin and adiponectin gene expression, their serum levels and migraine symptoms in patients with migraine. METHODS: Forty-four episodic migraine patients enrolled in this trial were divided into two groups as nano-curcumin (80 mg/day) and placebo group, over a two-month period. At the beginning and the end of the study, the mRNA expression of leptin and adiponectin from isolated PBMCs and their serum levels were measured using real-time PCR and ELISA method, respectively. The headache frequencies, severity and duration of pain were also recorded. RESULTS: The results of the present research showed that nano-curcumin can up-regulate adiponectin mRNA and increase its serum level significantly (P < 0.05). In the case of leptin, a reduction in gene expression and concentration was found in the nano-curcumin group but it was not statistically significant (P > 0.05). Nano-curcumin also significantly reduced the frequency, severity and duration of headaches (P < 0.05). CONCLUSION: These findings indicate that nano-curcumin supplement can be considered as a promising approach to migraine management and clinical symptoms improvement.

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial.

AIM: In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-ß in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-ß in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively. RESULTS: Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-ß (p < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 (p < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-ß gene expression, while the serum levels of IL-4 was observed to be increased significantly (p = 0.03) following two month nano-curcumin supplementation. CONCLUSION: The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-ß. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.

The effects of nano-curcumin supplementation on adipokines levels in obese and overweight patients with migraine: a double blind clinical trial study.

OBJECTIVE: The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine. RESULTS: Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.

The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial.

OBJECTIVE: The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. RESULTS: In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. TRIAL REGISTRATION: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

Evaluation of the Effect of Vitamin D Supplementation on Anthropometric Indicators and Dietary Intake of Patients with Type 2 Diabetes.

BACKGROUND: Various studies have shown that diabetes and its complications are associated with vitamin D deficiency. Due to the possible role of vitamin D in reducing the complications of diabetes and the high prevalence of its deficiency in Iran, this study was designed to investigate the effect of vitamin D supplementation on anthropometric indices and dietary intake of patients with type 2 diabetes. METHODS: This randomized clinical trial (RCT) study was performed on 74 patients with type 2 diabetes (T2DM). Patients randomly divided into two groups to receive vitamin D (VD) supplementation (100 µg or 4000 IU/day) or placebo for three months, randomization was based on the permutated-block method. Anthropometric indices including body weight (BW), body mass index (BMI) and waist circumference (WC) and physical activity, dietary intake were assessed by validated methods at the beginning and end of the trial. RESULTS: VD supplementation had not any significant differences in anthropometric indices, dietary intake and physical activity between the two groups. CONCLUSION: Finally, it can be concluded, receiving 100 micrograms/day of VD for three months had no favourable effects on patients with T2DM.

The effects of vitamin D3 supplementation on TGF-ß and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial.

BACKGROUND: Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients. METHODS AND MATERIALS: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-ß) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method. RESULTS: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-ß was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-ß (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study. CONCLUSION: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).

The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial.

Introduction: Migraine is a disabling neurovascular disorder characterized by increasing levels of pro-inflammatory cytokines and oxidative stress biomarkers. Curcumin and coenzyme Q10 (CoQ10) can exert neuroprotective effects through modulation of inflammation and oxidative stress. The aim of the present study was to evaluate the combined effects of nano-curcumin and CoQ10 supplementation on migraine symptoms and quality of life in migraine patients.Methods: One-hundred men and women (mean age 32 years) with episodic migraine based on the International Headache Society (IHS) criteria participated in this study. The subjects were randomly divided into four groups as (1) combination of nano-curcumin (80 mg) plus CoQ10 (300 mg), (2) nano-curcumin (80 mg), (3) CoQ10 (300 mg) and (4) the control (nano-curcumin and CoQ10 placebo included oral paraffin oil) beside usual prophylactic drugs for 8 weeks. Frequency, severity, duration of headache attacks, the headache diary results (HDR) and headache disability based on migraine-specific questionnaires were assessed at the baseline and end of the study.Results: Ninety-one of 100 patients completed the study. The results showed a significant effect of nano-curcumin and CoQ10 supplementation on frequency, severity, duration of migraine attacks and HDR compared to other groups (All P < 0.001). Nano-curcumin and CoQ10 group also had better scores in migraine-specific questionnaires at the end of the study compared to other groups (All P < 0.001). There were no side effects reported by the participants.Conclusions: These findings suggest a possible synergistic effect of nano-curcumin and CoQ10 on clinical features of migraine.Trial registration number: IRCT2017080135444N1.

Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano- Curcumin on Migraine Patients from Cellular to Clinical Insight: A Randomized, Double-Blind and Placebo-Controlled Trial.

BACKGROUND AND OBJECTIVES: Migraine is an exhausting neuro-inflammatory disorder recognized as recurrent headache attacks. Evidence has shown that Interleukin (IL)-1ß plays a substantial role in the neuro-immunity pathogenicity of migraine. n-3 fatty acids and curcumin revealed neuromodulatory and anti-inflammatory effects through several pathways, of which the suppression of IL-1ß gene expression is an important inflammatory pathway. The aim of this study was the investigation of synergistic relation of n -3 fatty acids and nano-curcumin on IL-1ß gene expression and serum levels in migraine patients. METHODS: This study was performed as a randomized, double-blind, placebo-controlled trial in a period of two months. A total of 80 episodic migraines were assigned into 4 groups of 1) n-3 fatty acids and curcumin combination; 2) n -3 fatty acids; 3) nano-curcumin; and 4) n-3 fatty acids and curcumin placebo. The gene expression and serum level of IL-1ß were measured by real-time PCR and ELISA methods respectively, at the beginning and the end of the interventions. RESULTS: Results showed the n-3 fatty acids and nano-curcumin combination significantly reduced the attack frequency in a synergistic status (P < 0.001). A significantly greater reduction in the serum level of IL-1ß was observed in the combination group, and the differences in the other groups were not statistically significant. The IL-1ß gene expression in the combination group showed a significant reduction for other treatment groups (P < 0.05), but these significant differences were absent after multiple testing Bonferroni corrections. CONCLUSION: Present findings revealed that n -3 fatty acids and curcumin co-supplementation can be suggested as a promising new approach in migraine headache management, but further studies are needed to confirm these findings.

The effects of nano-curcumin supplementation on Th1/Th17 balance in migraine patients: A randomized controlled clinical trial.

BACKGROUND: The present study was aimed to evaluate the nano-curcumin supplementation on Th1/Th17 balance by assessment of gene expression and serum level of interferon gamma (IFN-γ) and interleukin-17 (IL-17) in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. The expression of IFN-γ and IL-17 from peripheral blood mononuclear cells and IFN-γ and IL-17 serum levels were measured, using a real-time PCR and ELISA methods, respectively. RESULTS: Compared to placebo group, two month nano-curcumin supplementation led to a significant reduction in serum levels and expression of IL-17 mRNA (P = 0.006 & 0.04, respectively), while there was no statistical difference regarding serum levels and expression of IFN-γ mRNA. CONCLUSION: Nano-curcumin supplementation in migraine patients led to a significant reduction in gene expression and plasma levels of IL-17 compared to control group.

Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.

OBJECTIVES: Cyclic AMP (adenosine monophosphate) response element-binding protein (CREB) and Brain-derived neurotrophic factor (BDNF) are reported to broadly involve in learning capacity and memory. BDNF exerts its functions via tropomyosin receptor kinase B (TrkB). BDNF transcription is regulated by stimulating CREB phosphorylation. The CREB-TrkB-BDNF pathway is reported to be affected by diabetes, which may contribute to its cognitive deficits. This study was conducted to investigate the effect of vitamin D supplementation on the hippocampal fraction of this pathway in an animal model of type-1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were randomly divided into 4 groups as follows: Group 1: normal healthy rats (n=8); group 2: normal healthy rats receiving sesame oil supplementation as placebo (n=8); Group 3: diabetic rats receiving sesame oil (n=10); and Group 4: diabetic rats treated with 4300 IU/kg/week vitamin D dissolved in sesame oil (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Blood and hippocampal samples were acquired at the end of the experiment. RNA was extracted from the hippocampus, and real-time PCR (polymerase chain reaction) was performed for BDNF and TrkB gene expression. RESULTS: Administration of vitamin D (4300 IU/kg/week) in a T1DM animal model increased CREB phosphorylation in the hippocampus, but the serum and hippocampal BDNF levels and TrkB and BDNF gene expression did not change significantly. CONCLUSION: Vitamin D increased hippocampal CREB phosphorylation in a T1DM animal model. Our findings showed that vitamin D might be protective against central nervous system complications in diabetes. However, future studies are warranted.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

BACKGROUND: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

INTRODUCTION: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs. METHODS AND MATERIALS: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 µg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method. RESULTS: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055). CONCLUSION: Based on the results of this study, we found that 2000 IU (50 µg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

The effect of l-carnitine supplementation on serum levels of omentin-1, visfatin and SFRP5 and glycemic indices in patients with pemphigus vulgaris: A randomized, double-blind, placebo-controlled clinical trial.

Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l-carnitine (LC) on secreted frizzled-related protein-5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [-14.718, -0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [-1.125, 3.056], p = .426), fasting blood sugar (95% CI [-4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [-0.305, 0.528], p = .729), and quantitative insulin-sensitivity check index (95% CI [-0.016, -0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin-1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.

Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials.

Objective: Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results. The aim of this systematic review and meta-analysis was to evaluate the impact of Coenzyme Q10 supplementation on the frequency, severity, and duration of migraine attacks. Methods: A systematic review of the literature was conducted using ISI Web of Science, PubMed, Cochrane library and Scopus to identify eligible studies up to April 2018. Studies included were randomized clinical trials of Coenzyme Q10 supplementation that reported the frequency, severity, or duration of migraine attacks as a primary outcome. A meta-analysis of eligible studies was performed using the fixed effects model or the random effects model to estimate pooled effect size. Results: Four randomized clinical trials with 221 participants were included. Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05, p < 0.001) without significant heterogeneity among the studies (I 2 = 36.6%, p = 0.192). Coenzyme Q10 supplementation had no significant effect on severity (weighted mean difference: -2.35 visual analog scale score, 95% CI: -5.19 to 0.49, p = 0.105) and duration of migraine attacks (weighted mean difference: -6.14 h, 95% CI: -13.14 to 0.87, p = 0.086) with high heterogeneity. Conclusion: Pooled analyses of available randomized clinical trials suggest that Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.

Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial.

BACKGROUND: Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants. METHODOLOGY: 48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively. RESULTS: This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group. CONCLUSION: In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing.Trial registration NCT03008057. Registered December 2016.

Effects of vitamin D supplementation on depressive symptoms in type 2 diabetes mellitus patients: Randomized placebo-controlled double-blind clinical trial.

AIM: Diabetes increases the odds of depression and depression is often associated with poor glycemic control and complications of diabetes. Vitamin D is also believed to improve glycemic control and ameliorate depressive symptoms. Therefore, we examined effects of vitamin D monotherapy (without antidepressant drugs) on depressive symptoms in Type 2 diabetic patients with mild to moderate depressive symptoms. METHODS: We conducted 12 weeks, placebo-controlled, double-blind, randomized trial on 68 subjects with T2DM and mild to moderate depressive symptoms. Subjects received 100 µg (4000 IU) vitamin D (n = 32) or placebo (n = 34) daily. Beck Depression Inventory-II (BDI-II-PERSIAN) was applied for assessment of the severity of depression. Depression scores and metabolic profiles were measured at the beginning and end of trail. RESULTS: after 3 months of vitamin D supplementation, mean values of 25(OH) D increased from 15.5 ±â€¯8.8 to 32.2 ±â€¯8.9 ng/ml (p-value <0.001) in the vitamin D group. Moreover, BDI-II scores decreased from 15.2 ±â€¯9.6 to 9.8 ±â€¯7.2 (p-value <0.001) in the vitamin D group and 15.5 ±â€¯11.2 to 13.7 ±â€¯11.5 (p-value = 0.03) in placebo group. This decrease in BDI-II scores were significant (27.6% vs 10.8%) compared with placebo (p-value = 0.02). In term of metabolic profiles, mean change in level of Hemoglobin A1c (HbA1c), insulin and triglycerides (TG) were significantly higher in response to the treatment with vitamin D compared to placebo (p-value <0.02). CONCLUSIONS: In conclusion, supplementation of vitamin D in T2DM patients may protect these patients against the onset of major depressive disorder (MDD), with noticeable favorable effects on measures of metabolic profiles. TRIAL REGISTRATION: NCT03008057.

Effects of l-carnitine supplementation on cardiovascular and bone turnover markers in patients with pemphigus vulgaris under corticosteroids treatment: A randomized, double-blind, controlled trial.

Pemphigus vulgaris (PV) is a severe, bullous, autoimmune disease of the skin and mucous membranes. Corticosteroids are usually the main core treatment for controlling PV, which could lead to several side effects such as insulin resistance, osteoporosis, and cardiovascular disorders. The aim of this study is to evaluate the protective effects of l-carnitine (LC) supplementation in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 48 patients with PV were divided randomly into two groups to receive 2 g LC (n = 24) or a placebo (n = 24) for 8 weeks, respectively. Serum levels of osteopontin (OPN), bone morphogenic protein 4 (BMP4), cystatin C, systolic and diastolic blood pressure, 25 hydroxyvitamin D3, and LC were evaluated at the beginning and at the end of the study. LC supplementation demonstrated a significant increase in serum carnitine (p < .001). In addition, at the end of the trial, LC supplementation significantly decreased serum BMP4 (p = .003), OPN (p = .03), and cystatin C (p = .001) levels. There was no significant effect on blood pressure in comparison with the placebo. During study, no harmful side effects were reported by patients. These findings indicate that LC supplementation significantly leads to favorable changes in OPN, BMP4, and cystatin C in PV patients under corticosteroid therapy. However, further investigations are required to confirm these results.

Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: A randomized, placebo-controlled, double-blind clinical trial.

AIM: Diabetic patients predispose to vascular diseases such as nephropathy, and retinopathy. Poor adherence to medical treatment and dietary recommendations in uncontrolled diabetes leads to vascular damages. Vitamin D has been extensively studied and found to be protective against diabetes mellitus. YKL-40 and Monocyte chemoattractant protein-1 (MCP-1) are considered to exert crucial role in diabetes and its complications. Therefore, this study was designed to investigate effects of vitamin D supplementation on serum levels of YKL-40 and MCP-1 involved in the development of diabetic complications. METHODS: For 12 weeks, 48 type 2 diabetic patients enrolled in the trial and randomly were divided into two groups (n = 24 per group), receiving one of the following: 100 µg (4000 IU) vitamin D or placebo. Before and after intervention, serumYKL-40, MCP-1, insulin, IL-6, TNF-α, 25- (OH) vitamin D and HbA1c were measured. RESULTS: Our results revealed that serum levels of 25 (OH) vitamin D significantly increased in vitamin D group (p < 0.001). Vitamin D supplementation also significantly reduced serum YKL-40 levels (-22.7 vs. -2.4 ng/ml; (p-value = 0.003)). There was a significant decline in MCP-1 concentration in intervention group at the end of the study (-45.7 vs. -0.9 pg/ml; (p = 0.001)). Furthermore, there was a significant decrease in IL-6, fasting insulin and HOMA-IR in intervention group after 3 months supplementation. CONCLUSIONS: Daily vitamin D supplementation effectively reduced circulatory YKL-40 and MCP-1 levels in patients with type-2 diabetes and vitamin D deficiency. Vitamin D might contribute in reducing diabetic complications via modulating YKL-40 and MCP-1 signaling pathways.

Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials.

The reduction of brain-derived neurotrophic factor (BDNF) affects cognitive function, learning, and memory and also causes behavioral disorders. Several randomized controlled trials have examined the neuroprotective effects of curcumin and its ability to increase BDNF levels, with inconclusive results. The aim of this systematic review was to evaluate the impact of curcumin supplementation on serum BDNF levels. A systematic review of the literature was conducted using PubMed, Scopus, ISI Web of Science, Cochrane library, and Google scholar to identify eligible studies up to January 2019. The studies included were randomized control trials of curcumin supplementation that reported the serum BDNF level as a primary outcome. A dose-response meta-analysis of eligible studies was performed using the random-effects model to estimate pooled effect size. Four randomized control trials with 139 participants were included. Curcumin supplementation dose and duration ranged from 200 to 1820 mg/d and 8 to 12 weeks, respectively. Curcumin supplementation significantly increased serum BDNF levels (weighted mean difference: 1789.38 pg/mL, 95% confidence interval: 722.04-2856.71, P < .01) with significant heterogeneity among the studies (I2 = 83.5%, P < .001). Subgroup analysis showed that sex, mean age of participants, curcumin dosage, and trial duration were potential sources of heterogeneity. The significant positive impact of curcumin supplementation on BDNF levels indicates its potential use for neurological disorders that are associated with low BDNF levels.