The effect of selenium supplementation on oxidative stress, clinical symptoms and mental health status in patients with migraine: a study protocol for a double-blinded randomized clinical trial.

BACKGROUND: Despite a number of recommended strategies, effective treatment of migraine remains elusive. Given the role of oxidative stress in the pathogenesis of migraine, selenium, as an antioxidant nutrient, may have a beneficial effect on migraine outcomes. However, no study has explored the effects of selenium supplementation on migraine symptoms, oxidative stress biomarkers, and mental health. Therefore, this randomized, double-blinded, placebo-controlled clinical trial aims to examine the effects of selenium supplementation among migraine patients. METHODS: Seventy-two migraine patients will receive either 200 µg/day selenium supplement (n = 36) or placebo (n = 36) for 12 weeks in a randomized, double-blinded, placebo-controlled study. The severity, frequency, and duration of headaches, mental health indices including depression, anxiety, and distress, and quality of life, as well as biomarkers of oxidative stress such as nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS), will be measured at the baseline and end of the study. The intention-to-treat (ITT) approach will be used to estimate missing values. One-way analysis of covariance (ANCOVA) will be performed to detect the effect of selenium supplementation on outcome variables. DISCUSSION: Oxidative stress is recognized as a key contributor to migraine pathogenesis. Selenium is an essential trace element with antioxidant properties, capable of crossing the blood-brain barrier (BBB), holding promise to alleviate the oxidative stress and neurotoxicity. Thus, selenium may beneficially affect clinical symptoms and oxidative stress as well as the quality of life in migraine patients. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials ( https://www.irct.ir/ ) on 27 May 2023 with the code number IRCT20121216011763N60.

Is oral consumption of dates (Phoenix dactylifera L. fruit) in the peripartum period effective and safe integrative care to facilitate childbirth and improve perinatal outcomes: a comprehensive revised systematic review and dose-response meta-analysis.

BACKGROUND: Recent reviews have reported inconclusive results regarding the usefulness of consuming dates (Phoenix dactylifera L. fruit) in the peripartum period. Hence, this updated systematic review with meta-analysis sought to investigate the efficacy and safety of this integrated intervention in facilitating childbirth and improving perinatal outcomes. METHODS: Eight data sources were searched comprehensively from their inception until April 30, 2023. Parallel-group randomized and non-randomized controlled trials published in any language were included if conducted during peripartum (i.e., third trimester of pregnancy, late pregnancy, labor, or postpartum) to assess standard care plus oral consumption of dates versus standard care alone or combined with other alternative interventions. The Cochrane Collaboration's Risk of Bias (RoB) assessment tools and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were employed to evaluate the potential RoB and the overall quality of the evidence, respectively. Sufficient data were pooled by a random-effect approach utilizing Stata software. RESULTS: Of 2,460 records in the initial search, 48 studies reported in 55 publications were included. Data were insufficient for meta-analysis regarding fetal, neonatal, or infant outcomes; nonetheless, most outcomes were not substantially different between dates consumer and standard care groups. However, meta-analyses revealed that dates consumption in late pregnancy significantly shortened the length of gestation and labor, except for the second labor stage; declined the need for labor induction; accelerated spontaneity of delivery; raised cervical dilatation (CD) upon admission, Bishop score, and frequency of spontaneous vaginal delivery. The dates intake in labor also significantly reduced labor duration, except for the third labor stage, and increased CD two hours post-intervention. Moreover, the intervention during postpartum significantly boosted the breast milk quantity and reduced post-delivery hemorrhage. Likewise, dates supplementation in the third trimester of pregnancy significantly increased maternal hemoglobin levels. The overall evidence quality was also unacceptable, and RoB was high in most studies. Furthermore, the intervention's safety was recorded only in four trials. CONCLUSION: More well-designed investigations are required to robustly support consuming dates during peripartum as effective and safe integrated care. TRIAL REGISTRATION: PROSPERO Registration No: CRD42023399626.

Effects of marine-derived n-3 PUFA supplementation on soluble adhesion molecules: A systematic review and dose-response meta-analysis of randomized controlled trials.

Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: -1.26, 95% CI: -1.88 to -0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: -1.76, 95%CI: -3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: -0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: -2.67, 95%CI: -5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

Adjuvant pomegranate juice intake improves the inflammatory status of hospitalized COVID-19 patients: A randomized and placebo-controlled trial.

BACKGROUND: This study aimed to evaluate the effect of pomegranate juice intake on the inflammatory status and complete blood count in hospitalized Covid-19 patients. METHODS: This randomized, double-blinded placebo-controlled trial included 48 patients with two parallel arms. In addition to the standard care provided at the hospital, the patients consumed 500 mL of whole pomegranate juice (PJ) daily or a placebo for 14 days. Inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR)) and complete blood count were determined at baseline and after the 14 days of intervention. RESULTS: At the end of the intervention, a significant decreased was observed in primary outcomes [mean difference (95 %CI)] including IL-6 [5.24(0.87-9.61)], CRP [23.19(11.93-34.44)] and ESR [10.52(1.54-19.50)] in the PJ group vs. before the intervention. In addition, significant changes were also observed in the some of the secondary outcomes, including neutrophils, lymphocytes, platelets, platelets-to-lymphocyte(PLR) and neutrophils-to-lymphocyte (NLR) ratios (p < 0.05) in the PJ group compared to before the intervention. At the end of the intervention period, the mean change of IL-6 [- 7.09(-12.21 to - 1.96)], white blood cells [- 3.09(- 6.14 to - 0.05)], neutrophils [- 9.12(-18.08 to -0.15)], lymphocyte [7.05(0.17-13.92)], platelets [- 94.54(- 139.33 to - 49.75)], PLR [- 15.99(- 29.31 to - 2.67)], blood oxygen saturation [1.75(0.13-3.37)] and MCV [0.31(- 0.25 to 0.88)] levels were significantly different between groups while no difference was observed between the two groups in other blood indices. CONCLUSION: Our results suggest that pomegranate juice intake might slightly improve the inflammatory status and CBC outcomes of COVID-19 patients and it may be beneficial.

Effect of vitamin E intake on glycemic control and insulin resistance in diabetic patients: an updated systematic review and meta-analysis of randomized controlled trials.

Since a 2014 meta-analysis, several randomized controlled trials (RCTs) evaluating the effect of vitamin E intake on glycemic indices and insulin resistance in adults with diabetes have reached inconsistent conclusions. Therefore, we updated the previous meta-analysis to summarize the current evidence in this regard. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to identify relevant studies published up to September 30, 2021, using relevant keywords. Random-effects models were used to obtain overall mean difference (MD) comparing vitamin E intake with a control group. In total, 38 RCTs with a total sample size of 2171 diabetic patients (1110 in vitamin E groups and 1061 in control groups) were included. Combining the results from 28 RCTs on fasting blood glucose, 32 RCTs on HbA1c, 13 RCTs on fasting insulin, and 9 studies on homeostatic model assessment for insulin resistance (HOMA-IR) showed a summary MD of -3.35 mg/dL (95% CI: -8.10 to 1.40, P = 0.16), -0.21% (95% CI: -0.33 to -0.09, P = 0.001), -1.05 µIU/mL (95% CI: -1.53 to -0.58, P < 0.001), and -0.44 (95% CI: -0.82 to -0.05, P = 0.02), respectively. This indicates a significant lowering effect of vitamin E on HbA1c, fasting insulin and HOMA-IR, while no significant effect on fasting blood glucose in diabetic patients. However, in subgroup analyses, we found that vitamin E intake significantly reduced fasting blood glucose in studies with an intervention duration of < 10 weeks. In conclusion, vitamin E intake has a beneficial role in improving HbA1c and insulin resistance in a population with diabetes. Moreover, short-term interventions with vitamin E have resulted in lower fasting blood glucose in these patients. This meta-analysis was registered in PROSPERO with code CRD42022343118.

Opium Use and Cancer Risk: A Comprehensive Systematic Review and Meta-Analysis of Observational Studies.

Background: Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results: In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60-4.79, P ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions: Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.

Effect of supplementation with Chlorella vulgaris on lipid profile in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

OBJECTIVE: To summarize available findings on the effect of Chlorella vulgaris supplementation on lipid profile in adults. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: This study followed 2020 PRISMA guideline. We performed a systematic search in the online databases to identify relevant articles and then, extracted required data from each paper for the meta-analysis. Random-effects models were used to obtain overall mean difference (MD) comparing Chlorella vulgaris supplementation with a control group. MAIN OUTCOME MEASURES: Blood lipids including triglyceride (TG), total cholesterol (TC), LDL-C, and HDL-C. RESULTS: In total, 10 RCTs with a total sample size of 539 adults (264 in the Chlorella vulgaris group and 275 in the control group) were included. Of the 10 RCTs, four had a low risk of bias for all aspects of the Cochrane risk of bias tool. Also, only two studies determined the chlorella content, purity, potency, and contamination of the supplements used in the intervention. Combining results from these studies showed a summary MD of -2.11 mg/dL (95% CI: -7.28 to 3.06) for TG, -7.47 mg/dL (95% CI: -12.98 to -1.96) for TC, -7.71 mg/dL (95% CI: -14.05 to -1.37) for LDL-C, and -0.45 mg/dL (95% CI: -0.67 to 1.57) for HDL-C, indicating a beneficial effect of Chlorella vulgaris supplementation on TC and LDL-C levels. Based on the dose-response analysis, the reducing effect of Chlorella vulgaris supplementation on LDL-C levels was seen at the dosages between zero and 1500 mg/d (P for non-linearity= 0.01), whereas in higher amounts, this effect was not significant. CONCLUSION: We found that Chlorella vulgaris supplementation had a beneficial effect on TC and LDL-C levels with no significant effect on TG and HDL-C levels.

Effects of Melatonin and Propolis Supplementation on Inflammation, Oxidative Stress, and Clinical Outcomes in Patients with Primary Pneumosepsis: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVE: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. MATERIALS AND METHODS: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. RESULTS: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07). CONCLUSION: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.

Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.

Total, dietary, and supplemental calcium intake and risk of all-cause cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the association between calcium intake and mortality risk. Therefore, this study aimed to summarize available findings on the associations of total, dietary and supplemental calcium intake with all-cause, CVD, and cancer mortality. We searched PubMed, Scopus, Embase, and ISI Web of Knowledge until February 2020 to identify eligible publications. Random-effects models were used to calculate pooled effect sizes (ESs) and 95% confidence intervals (CIs) for highest versus lowest categories of calcium intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between calcium intake and mortality. 36 publications were included in this systematic review and 35 in the meta-analysis. During the follow-up periods ranging from 4.2 to 28 years, the total number of deaths from all causes was 163,657 (83703 from CVD and 83929 from cancer). Total calcium intake was associated with a lower risk of CVD mortality (Pooled ES for highest v lowest category: 0.91; 95% CI: 0.83-0.99, I2=68.1%, P < 0.001). Dietary calcium intake was associated with a lower risk of all-cause mortality (Pooled ES for highest v lowest category: 0.95; 95% CI: 0.92-0.99, I2=62.1%, P < 0.001). Supplemental calcium intake was not significantly associated with risk of all-cause, CVD and cancer mortality. In the dose-response analysis, there was evidence of nonlinear association between calcium intake and risk of all-cause, CVD, and cancer mortality. In conclusion, a non-linear association between calcium intake with all-cause, CVD, and cancer mortality risk was observed in this meta-analysis. Moderate intake of total (1000-1800), dietary (600-1200), and supplemental calcium (600-1200) was inversely significantly associated with mortality risk but higher calcium intake was not associated with a lower risk of mortality.

Green tea intake and its effect on laboratory parameters and disease symptoms in hospitalised patients with Covid 19: a structured protocol for a randomized controlled trial.

OBJECTIVES: The current randomized controlled trial (RCT) will be conducted to assess the effect of green tea intake on disease symptoms and laboratory parameters including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count (CBC) in patients with mild-to-moderate Covid-19 infection. TRIAL DESIGN: Randomized, double-blinded, parallel (1:1 ratio) clinical trial exploratory study PARTICIPANTS: We will recruit patients with COVID-19 infection admitted to Yasuj Shahid Jalil Hospital in Yasuj City, Kohgiluyeh and Boyer-Ahmad Province, Iran. Participants' inclusion criteria are as follows: Inclusion Criteria Patients aged ≥18 years COVID-19 diagnosis according to real-time polymerase chain reaction (RT-PCR) Exclusion Criteria Pregnancy or lactation Disseminated intravascular coagulation or any other types of coagulopathy Severe congestive kidney failure Having a history of participating in a clinical trial during the last 30 days INTERVENTION AND COMPARATOR: Intervention: Two capsules containing 450 mg green tea extract along with routine treatment for COVID-19 patients in the intervention group. Two capsules containing placebo plus routine treatment for patients with COVID-19 infection. Capsules will be taken twice a day, after lunch and dinner, for 14 days. MAIN OUTCOMES: Changes in disease symptoms and laboratory parameters including CRP, ESR, and CBC after 14 days of the intervention compared to control group. RANDOMISATION: Eligible patients will be randomly assigned into the intervention or control group in a 1:1 ratio. Randomization will be performed based on 8 permuted blocks with block sizes of 10, and patients in the intervention and control groups will be matched according to sex and age categories. Randomization will be done using computer-generated random numbers ( Randomization.com ) BLINDING (MASKING): The appearance of placebo and green tea capsules will be similar in terms of shape and color, and they will be packed in the same bags that will be prepared by the company. Also, the researcher and all participants will not be aware of the divisions until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total sample was determined based on CRP MCID in which high CRP levels were considered >2.6 mg/L. Accordingly, a total sample size of 37 patients for each intervention group was required. TRIAL STATUS: The protocol is Version 1.0, on June 5, 2021. Recruitment will start on July 11, 2021, which is anticipated to be completed by September 21, 2021. TRIAL REGISTRATION: IRCT20150711023153N3 ( https://www.irct.ir/trial/55948 ) retrospectively registered on June 4, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting was eliminated; this Letter serves as a summary of the key elements of the full protocol.

Effects of curcuminoids on inflammatory and oxidative stress biomarkers and clinical outcomes in critically ill patients: A randomized double-blind placebo-controlled trial.

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.

Total, Dietary, and Supplemental Magnesium Intakes and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

A meta-analysis of prospective studies was conducted to examine the association of total, supplemental, and dietary magnesium intakes with risk of all-cause, cancer, and cardiovascular disease (CVD) mortality and identify the dose-response relations involved in these association. We performed a systematic search of PubMed, Scopus, Google Scholar, and ISI Web of Knowledge up to April 2020. Prospective cohort studies that reported risk estimates for the association between total, supplemental, and dietary magnesium intakes and risk of mortality were included. Random effects models were used. Nineteen publication with a total of 1,168,756 participants were included in the current meta-analysis. In total, 52,378 deaths from all causes, 23,478 from CVD, and 11,408 from cancer were identified during the follow-up period of 3.5 to 32 years. Dietary magnesium intake was associated with a lower risk of all-cause [pooled effect size (ES): 0.87; 95% CI: 0.79, 0.97; P = 0.009; I2 = 70.7%; P < 0.001] and cancer mortality (pooled ES: 0.80; 95% CI: 0.67, 0.97; P = 0.023; I2 = 55.7%; P = 0.027), but not with CVD mortality (pooled ES: 0.93; 95% CI: 0.82, 1.07; P = 0.313; I2 = 72.3%; P < 0.001). For supplemental and total magnesium intakes, we did not find any significant associations with risks of all-cause, CVD, and cancer mortality. However, linear dose-response meta-analysis indicated that each additional intake of 100 mg/d of dietary magnesium was associated with a 6% and 5% reduced risk of all-cause and cancer mortality, respectively. In conclusion, higher intake of dietary magnesium was associated with a reduced risk of all-cause and cancer mortality, but not CVD mortality. Supplemental and total magnesium intakes were not associated with the risk of all-cause, CVD, and cancer mortality. These findings indicate that consumption of magnesium from dietary sources may be beneficial in reducing all-cause and cancer mortality and thus have practical importance for public health.

Breakfast consumption is inversely associated with primary headaches in university students: The MEPHASOUS study.

OBJECTIVE: This study was conducted to examine the association between breakfast consumption pattern and primary headaches in a large population of university students. METHODS: This cross-sectional study was done on the MEPHASOUS dataset that contained the information of 83,677 university students, aged ≥18 years, from 28 provinces of Iran. Dietary intakes and breakfast consumption pattern were assessed using a validated self-administered dietary habits questionnaire. Primary headaches were determined according to the International Classification of Headache Disorders-3 (ICHD-3) criteria. Binary logistic regression in different adjusted models was used to assess the association between breakfast consumption and primary headaches. RESULTS: The mean age of participants was 21.50 ± 4.01. Primary headaches were prevalent among 9% of university students. A significant inverse association was seen between breakfast consumption and odds of primary headaches [odds ratio (OR): 0.57, 95 % confidence interval (CI): 0.51-0.62]. This association remained significant even after taking potential confounders into account; such that students who consumed breakfast frequently had 26 % lower odds of primary headaches compared with those who consumed it <1 day/week (OR: 0.74, 95 % CI: 0.65-0.85). Moreover, such a significant inverse association was observed in female students (OR: 0.54, 95 % CI: 0.49-0.61) as well as those with BMI < 25 kg/m2 (OR: 0.68, 95 % CI: 0.58-0.79). However, it became non-significant in male students and those with overweight or obesity. CONCLUSION: We found that frequent breakfast consumption is associated with a decreased odds of primary headaches in female students and those with BMI < 25 kg/m2. Further prospective studies are needed to confirm our findings.

Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis.

The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.

The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials.

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (- 0.52, 95% CI - 0.80, - 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose-response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.

BACKGROUND: Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine. METHODS: This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial. RESULTS: Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates. CONCLUSION: Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required. TRIAL REGISTRATION CODE: IRCT20121216011763N23 at www.irct.ir .

The effects of green coffee extract supplementation on glycemic indices and lipid profile in adults: a systematic review and dose-response meta-analysis of clinical trials.

BACKGROUND: The role of coffee consumption in the risk of cardiovascular diseases has been debated for many years. The current study aimed to summarize earlier evidence on the effects of green coffee extract (GCE) supplementation on glycemic indices and lipid profile. METHODS: We searched available online databases for relevant clinical trials published up to October 2019. All clinical trials investigating the effect of GCE supplementation, compared with a control group, on fasting blood glucose (FBG), serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were included. Overall, 14 clinical trials with a total sample size of 766 participants were included in the current meta-analysis. RESULTS: We found a significant reducing effect of GCE supplementation on FBG (weighted mean difference (WMD): -2.35, 95% CI: - 3.78, - 0.92 mg/dL, P = 0.001) and serum insulin (WMD: -0.63, 95% CI: - 1.11, - 0.15 µU/L, P = 0.01). With regard to lipid profile, we observed a significant reduction only in serum levels of TC following GCE supplementation in the overall meta-analysis (WMD: -4.51, 95% CI: - 8.39, - 0.64, P = 0.02). However, subgroup analysis showed a significant reduction in serum TG in studies enrolled both genders. Also, such a significant reduction was seen in serum levels of LDL and HDL when the analyses confined to studies with intervention duration of ≥8 weeks and those included female subjects. In the non-linear dose-response analyses, we found that the effects of chlorogenic acid (CGA) dosage, the main polyphenol in GCE, on FBG, TG and HDL were in the non-linear fashions. CONCLUSION: In conclusion, we found that GCE supplementation improved FBG and serum levels of insulin and TC. Also, there was a significant improvement in other markers of lipid profile in some subgroups of clinical trials.

Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: a randomized double-blind placebo-controlled trial.

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.