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.

Effects of eicosapentaenoic acid supplementation on heat shock protein 27, glycemic status and anthropometric indices in type 2 diabetes patients.

Purpose: Heat shock proteins (HSP-27) are reported to be involved in the pathophysiology of diabetes complications. The purpose of the current study is to assess the effects of eicosapentaenoic acid (EPA) supplementation on serum HSP-27, glycemic status and anthropometric indices in type 2 diabetes mellitus (T2DM) patients. Methods: Thirty-six patients with T2DM were randomly allocated to obtain 2 g per day EPA (n = 18) or placebo (n = 18) for 8 weeks in a randomized, double-blind, placebo-controlled clinical trial. Fasting serum levels of HSP 27, fasting blood sugar, hemoglobin A1C, as well as anthropometric indices were measured. Results: EPA supplementation reduces the serum level of HSP 27 in the EPA group compared with the placebo (P < 0.03). Although waist circumference (WC) decreased significantly in the EPA group at the end of the trial (P < 0.02), there was no significant difference in weight, WC, body mass index (BMI), and glycemic markers in both groups after intervention (P > 0.05). Conclusions: We found that EPA supplementation reduces HSP 27 serum level in T2DM patients. However, future large-scale trials are needed.

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.

Are levels of adipokines and micronutrients different in male adult smokers and non-smokers? A case-control study.

OBJECTIVE: Smoking is a common public problem leading to increases in oxidative stress and decreases in the levels of some micronutrients, finally affecting adipokine levels. The aim of this study was to compare the serum levels of omentin (intelectin-1), chemerin, TNF-α, and some micronutrient intakes in male smokers and non-smokers. METHODS: 40 male smokers and 40 male non-smokers with a mean age of 38.6±14.1 years were included in this study. Serum levels of omentin, chemerin, and TNF-α were measured. To calculate the daily intake of energy, carbohydrate, protein, fat, and some of the micronutrients, the 24-h recall and semi-quantitative food frequency questionnaire (FFQ) was used. RESULTS: Omentin, chemerin, and TNF-α levels in male smokers were lower than non-smokers, but these differences were not statistically significant. However, after adjustment for total and saturated fat intakes and age, omentin (ß=138.4, p=0.027) and TNF-α (ß=144.5, p=0.015) revealed significant differences. CONCLUSION: The serum levels of omentin, chemerin, TNF-α, and some micronutrient intakes were not significantly different between smokers and non-smokers. Further population studies are needed to clarify this subject.

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.

Effect of probiotic supplementation on migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials.

Objective: The prevalence of migraine is higher in patients with gastrointestinal disorders. Possible underlying mechanisms could be increased intestinal permeability and systemic inflammation. Probiotics may reduce gut permeability as well as inflammation, and therefore may improve the clinical features of migraine. This systematic review and meta-analysis aimed to evaluate the impact of probiotic supplementation on the frequency and severity of migraine attacks.Methods: A systematic review of the literature was conducted using ISI Web of Science, PubMed/Medline, Scopus, Cochrane Library, EMBASE, Google Scholar, Magiran.com and Sid.ir to identify eligible studies published up to October 2019. A meta-analysis of eligible trials was performed using the random-effects model to estimate pooled effect size.Results: Three randomized controlled trials with 179 patients (probiotic group = 94, placebo group = 85) were included. Probiotic supplementation had no significant effect on frequency (weighted mean difference (WMD) = -2.54 attacks/month, 95%CI: -5.31-0.22, p = 0.071) and severity of migraine attacks (WMD = -1.23 visual analog scale (VAS) score, 95%CI = -3.37-0.92, p = 0.262) with significant heterogeneity among the studies (I2 = 98%, p < 0.001).Conclusions: A pooled analysis of available randomized controlled clinical trials showed that probiotic supplementation had no significant effect on the frequency and severity of episodic migraine attacks.

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 ).

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 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.

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.

The Effect of Nano-Curcumin Supplementation on Pentraxin 3 Gene Expression and Serum Level in Migraine Patients.

BACKGROUND: This study was designed to investigate the effect of nano-curcumin supplementation on pentraxin 3 (PTX3) gene exp ression and serum level in migraine patients. METHODS: The present study, performed as a clinical trial, included 38 episodic migraine patients in two groups that received either nano-curcumin or placebo over a two-month period. At the start and the end of the study, PTX3 gene expression and serum levels were measured. RESULTS: After two months of treatment, PTX3 gene expression and serum levels were both significantly less in the nano-curcumin than in the placebo group (P= 0.01 and P< 0.001, respectively). No significant gene expression differences were found between the two groups. CONCLUSION: Curcumin may have a potential inhibitory effect on PTX3 gene expression and serum levels in migraine disease and can be considered as an efficient therapy in migraine management.

Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats. / Quercetina Melhora o Perfil Lipídico e Apolipoproteico em Ratos Tratados com Glicocorticóides em Altas Doses.

Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.).

Quercetina Melhora o Perfil Lipídico e Apolipoproteico em Ratos Tratados com Glicocorticóides em Altas Doses / Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats

Resumo Fundamento Os glicocorticóides (GCs) são amplamente prescritos para o tratamento de numerosos distúrbios clínicos devido às suas propriedades anti-inflamatórias e imunomoduladoras, e um dos efeitos indesejáveis mais comuns desses medicamentos é a dislipidemia. Objetivo Avaliar o efeito da quercetina, um flavonoide derivado de plantas, no perfil lipídico de ratos tratados com glicocorticóides em altas doses. Métodos Um total de 32 ratos Sprague-Dawley foram distribuídos aleatoriamente entre quatro grupos (8 ratos por grupo) e tratados por 6 semanas com uma das seguintes opções : (i) solução salina normal; (ii) 40 mg/kg de succinato sódico de metilprednisolona (MP); (iii) MP + 50 mg/kg de quercetina; (iv) MP + 150 mg/kg de quercetina. O MP foi injetado por via subcutânea e a quercetina foi administrada por gavagem oral 3 dias por semana. No final do estudo, o perfil lipídico dos animais foi medido através de kits enzimáticos. Os dados foram analisados e a significância estatística foi estabelecida em p <0,05. Resultados Os níveis séricos médios de colesterol total (CT), triglicerídeos (TG) e LDL aumentaram drasticamente em animais tratados com GC em comparação com o grupo controle. Ambas as doses de quercetina (50 e 150 mg/kg) melhoraram o CT (43% e 45%), LDL (56% e 56%) e TG (46% e 55%, respectivamente). A razão Apo B/A1 diminuiu mais de 20% após a ingestão de Anti-Inflamatory Agents. Conclusões Esses dados sugerem que a ingestão de quercetina Quercetin; induzida por glicocorticóides. (Arq Bras Cardiol. 2020; 115(1):102-108)

Abstract Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.)

Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies.

PURPOSE: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection. METHODS: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done. RESULTS: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (≥65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality. CONCLUSIONS: Older age (≥65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.

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.