The effect of probiotic and synbiotic supplementation on appetite-regulating hormones and desire to eat: A systematic review and meta-analysis of clinical trials.

Recent studies have demonstrated the effect of probiotics, prebiotics, and synbiotics on adiponectin and leptin levels; however, those findings remain contested. The present study aimed to explore the impact of probiotics/synbiotics on appetite-regulating hormones and the desire to eat. METHODS: A systematic review was conducted by searching the Medline (PubMed) and Scopus databases from inception to December 2021, using relevant keywords and MeSH terms, and appropriate randomized controlled trials (RCTs) were extracted. The standardized mean differences (SMD) and 95% confidence intervals (95%CIs) were calculated as part of the meta-analysis using a random-effect model to determine the mean effect sizes. Analysis of Galbraith plots and the Cochrane Chi-squared test were conducted to examine heterogeneity. RESULTS: Meta-analysis of data from a total of 26 RCTs (n = 1536) showed a significant decrease in serum/plasma leptin concentration following probiotic/synbiotic supplementation (SMD: -0.38, 95%CI= -0.638, -0.124); P-value= 0.004; I2= 69.4%; P heterogeneity < 0.001). The leptin level decrease from probiotic/synbiotic supplementation was higher in patients with NAFLD than those with overweight/obesity or type 2 diabetes mellitus/ metabolic syndrome/ prediabetes. Probiotic/synbiotic supplementation was associated with a trending increase in adiponectin levels, stronger in patients with type 2 diabetes mellitus, metabolic syndrome, and prediabetes (SMD: 0.25, 95%CI= 0.04, 0.46) µg/mL; P-value= 0.021; I2 = 16.8%; P heterogeneity= 0.30). Additionally, supplementation with probiotic/synbiotic was linked to a slight increase in desire to eat (SMD: 0.34, 95%CI= 0.03, 0.66) P-value = 0.030; I2 = 39.4%; P heterogeneity= 0.16). CONCLUSION: Our meta-analysis indicates a favorable impact of probiotic/synbiotic supplementation on regulating leptin and adiponectin secretion.

Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study.

BACKGROUND: Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population. AIMS: The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality. METHODS: A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported. RESULTS: After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15-20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality. DISCUSSION: The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items. CONCLUSIONS: Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.

The prevalence of headache disorders in children and adolescents in Iran: a schools-based study.

BACKGROUND: While the Global Burden of Disease study reports headache disorders as the third-highest cause of disability worldwide, the headache data in this study largely come from adults. This national study in Iran, the first of its type in the Eastern Mediterranean Region, was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (6-11 years) and adolescents (12-17 years). METHODS: We followed the generic protocol for the global study. In a cross-sectional survey, self-completed structured questionnaires were administered to pupils within their classes in 121 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache. RESULTS: Of 3,357 potential participants, 3,244 (children 1,308 [40.3%], adolescents 1,936 [59.7%]; males 1,531 [47.2%], females 1,713 [52.8%]) satisfactorily completed the questionnaire. Children and males were therefore somewhat under-represented, with a participating proportion of 96.6%. Gender- and age-adjusted 1-year prevalence of any headache was 65.4%, of migraine 25.2%, of tension-type headache 12.7%, of undifferentiated headache 22.1%, of all headache on ≥15 days/month 4.1%, and of probable medication-overuse headache 1.1%. All headache types except undifferentiated headache were more prevalent among adolescents than children; probable medication-overuse headache increased five-fold between childhood and adolescence. CONCLUSIONS: Headache disorders are common in children and adolescents in Iran, with undifferentiated headache accounting for over one third of cases. The increasing prevalence of probable medication-overuse headache with age is concerning. These findings are of importance to health and educational policies in Iran.

Evaluation of cardiometabolic risk markers linked to reduced left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI).

BACKGROUND: It is well established that left ventricular systolic dysfunction (LVSD), as marked by reduced left ventricular ejection fraction (LVEF), notably worsens the prognosis of ST-elevation myocardial infarction (STEMI). However, the link between cardiometabolic risk markers and LVSD seems unclear. This study aimed to investigate the differences in variables affecting reduced LVEF in STEMI patients. METHODS: In the current retrospective study, 200 consecutive STEMI patients were enrolled between April 2016 to January 2017. Analysis of serum parameters, anthropometric evaluation, and echocardiography was performed after admission. The participants were categorized according to LVEF levels as follows: group1 (normal: 50-70%, n = 35), group2 (mildly reduced: 40-49%, n = 48); group3 (moderately reduced: 30-39%, n = 94) and group4 (severely reduced: < 30%, n = 23). Between-group comparisons were made using the Kruskal-Wallis test. RESULTS: Overall, of 200 STEMI patients with a mean age of 62 years, 27%(n = 54) were females. The median of BMI of patients in group4 (31.07 kg/m2) was significantly higher than group3 (26.35 kg/m2), group2 (25.91 kg/m2), and group1 (24.98 kg/m2; P value < 0.0001). Group4 patients showed significantly increased fasting blood sugar (FBS) than groups 1 (212.00, vs. 139.00 mg/dl; P value = 0.040). Patients in groups 1 and 2 exerted significantly elevated triglyceride levels than those in group4 (142.00, 142.50, and 95.00 mg/dl; P value = 0.001). WBC count, neutrophil%, and neutrophil to lymphocyte ratio among those in group1 (10,200/m3, 70.00%, and 2.92, respectively) were significantly lower than group4 (12,900/m3, 83.00%, and 5.47, respectively; P value < 0.05). CONCLUSION: These findings highlight higher BMI, FBS, and leucocyte count linked to LVSD, probably through increasing the inflammation and reducing LVEF levels. More extensive studies are needed to clarify the clinical relevance of these results.

Evaluating the use of novel atherogenicity indices and insulin resistance surrogate markers in predicting the risk of coronary artery disease: a case‒control investigation with comparison to traditional biomarkers.

BACKGROUND: Due to the contribution of coronary artery disease (CAD) to serious cardiovascular events, determining biomarkers that could robustly predict its risk would be of utmost importance. Thus, this research was designed to assess the value of traditional cardio-metabolic indices, and more novel atherogenicity indices and insulin resistance surrogate markers in the identification of individuals at risk of CAD. METHODS: A case‒control survey was conducted, in which 3085 individuals were enrolled. Their clinical and biochemical data were gathered at baseline. The investigated indices included the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), Castelli's risk indices-I, II (CRI-I, CRI-II), and metabolic score for insulin resistance (METS - IR). To examine the relationship between these variables and CAD risk, multiple regression analyses adjusted for potential confounders were conducted. RESULTS: Overall, 774 angiographically confirmed CAD patients (mean age = 54 years) were compared with 3085 controls (mean age = 51 years). Higher triglyceride, total cholesterol and fasting blood sugar levels and lower HDL-C levels were related to an elevated risk of CAD (P-for-trend < 0.001), while the direct association between increased serum LDL-C concentrations and a greater risk of CAD only became apparent when excluding those with diabetes, and statin users. Among novel indices, greater values of the majority of these markers, including AIP, CRI-I, and -II, CHOLINDEX, LCI, and TyG-index, in comparison to the lower values, significantly elevated CAD risk (P-for-trend < 0.001). CONCLUSION: According to the current findings, novel atherogenicity indices and insulin resistance surrogate markers, in particular, AIP, CRI-I and II, CHOLINDEX, LCI, and TyG-index, may be useful in predicting CAD risk.

Review on Headache Related to Dietary Supplements.

PURPOSE OF REVIEW: The lifetime prevalence of headaches is 96%. Approximately 11% of the adult population worldwide has a migraine headache. Migraine is a complex disorder that is more than a simple headache. So far, many underlying mechanisms, i.e. inflammatory, vascular, neurogenic have been hypothesized. In recent years evidences proposed that an energy deficit due to changes in mitochondrial function contributes to migraine pathophysiology as an upstream disorder. Recent insights suggested that the coexistence of sensory-stimuli surplus and energy-reserve shortage activate the trigeminovascular system. Some nutrients are considered as essential elements in mitochondrial bioenergetics and some others are known as natural immuno-modulatory components. Also, evidence showed their beneficial effect in headache prophylaxis and treatment. In present study, we aimed to review the available data in this field. RECENT FINDINGS: Vitamin B group, magnesium, and Coenzyme Q10 (CoQ10) are well-known for their function in mitochondrial energy metabolism. On the other hand, studies support their beneficial role in controlling migraine headache symptoms. For instance, daily intake of 400-milligram riboflavin for 3 months resulted in more than 50% reduction in migraine attacks in more than half of the consumers. According to recent evidence, vitamin D and Omega-3 which are considered as famous immune-modulatory compounds are also reported to be effective in migraine prophylaxis. For example, every 22% reduction in migraine headache occurrence was reported for every 5 ng/ml rise in serum vitamin D. Supplementation with vitamin B group, CoQ10, magnesium, vitamin D and Omega-3 could be considered as an effective, less costly strategy in headache/migraine prophylaxis.

Characteristics and comorbidities of headache in patients over 50 years of age: a cross-sectional study.

BACKGROUND: Although headache is a common complaint in younger individuals, it is one of the most common complaints among persons over the age of 50 and is a significant cause of morbidity. As there are differences in the causes and types of headache, the diagnosis and management of headache in older adults differ from that in younger individuals. METHODS: In this cross-sectional study, 570 patients ≥ 50 years were recruited at a university affiliated tertiary headache center between 2016 and 2019. Demographic data, headache characteristics, and comorbid medical conditions were recorded. The presence of depression was explored using the Beck Depression Inventory. The patients were evaluated using the STOP-BANG scale to determine the risk of obstructive sleep apnea. RESULTS: The mean age of the patients was 57.7 years. Seventy-three percent of the patients had primary headache disorders, with the most prevalent types being migraine, followed by tension-type headache. Secondary headaches were primarily the result of overuse of medication, cervical spine disease, and hypertension. Patients with medication-overuse headache were significantly more likely to suffer from hypothyroidism and gastrointestinal problems such as bleeding/ulcers. Irritable bowel syndrome was also more common in patients with medication-overuse headaches and migraines. The risk for obstructive sleep apnea was intermediate in 45.2% of the patients with hypertension-induced headache, but was lower in the majority of others. There was a high tendency for moderate-to-severe depression in the participants; however, the Beck Depression Inventory scores were significantly higher in medication-overuse headache patients. CONCLUSION: Proper treatment of headache in middle-aged and older adults requires the recognition of secondary causes, comorbid diseases, and drug induced or medication overuse headaches. Special attention should be paid to depression and obstructive sleep apnea in such patients suffering from headache disorders.

Low carbohydrate diet score and odds of neuromyelitis optica spectrum disorder: A case-control study.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating inflammatory disease of The Central nervous system. We aimed to investigate the association between low carbohydrate diet (LCD) and NMOSD odds. Method: Seventy NMOSD patients with definite diagnosis and 164 hospital-based controls were enrolled in this case-control study. Dietary data was obtained using a validated 168-item food frequency questionnaire. To determine the LCD score, participants were stratified into 11 groups according to carbohydrate, protein, fat, animal fat, animal protein, vegetable fat and vegetable protein intakes. Higher intake of protein and fat, and lower intake of carbohydrate received a higher score between 0-10. Macronutrients scores were summed together and LCD scores calculated. The association between LCD scores and likelihood of being assigned to NMOSD group was investigated using multiple regression models. Results: Total LCD scores increased from the median of 21.00 in the first decile to 53.00 in the tenth decile of LCD score. After adjustment for confounding factors including age, gender, BMI, energy intake, cigarette smoking and alcohol consumption, an inverse association was detected between LCD scores and odds of NMOSD. The odds of suffering from NMOSD declined significantly about 78% (OR: 0.22; 95% CI: 0.05-0.87) and 76% (OR: 0.24; 95% CI: 0.06-0.93) in the fifth and sixth deciles of LCD score compared to the first decile. Conclusion: From the obtained results it can be speculated that higher carbohydrate and lower protein and fat intakes may be associate with the increased odds of NMOSD. However, further studies are needed to confirm these results.

The Effects of Probiotics on Inflammation, Endothelial Dysfunction, and Atherosclerosis Progression: A Mechanistic Overview.

INTRODUCTION: The relationship between the intestinal microbiota dysbiosis, inflammation, and cardiovascular disorders (CVDs) has become evident, based on a growing body of literature from animal models and human studies. On the other hand, probiotics are believed to have promising effects on modifying dysbiosis and protecting against CVDs. OBJECTIVE: This narrative review provides an overview of the link between gut microbiota, inflammation, endothelial dysfunction, and atherosclerosis. The influences of probiotic supplementation on biomarkers contributing to these conditions as the primary underlying risk factors for developing CVDs are also discussed. METHODS: An up-to-date review was performed of the available evidence from experimental studies, clinical trials, and meta-analyses, considering their challenges and limitations. It also aimed to provide mechanistic insight into the likely mechanisms of probiotics that could prevent atherosclerosis initiation and progression. RESULTS: Probiotic supplementation seems to be associated with reduced levels of inflammation and oxidative stress biomarkers (C-reactive protein, tumour necrosis factor-α, interleukin (IL)-6, IL-12, and malondialdehyde). Further, these agents might enhance antioxidant factors (IL-10, total antioxidant status, total antioxidant capacity, glutathione, and nitric oxide). Probiotics also appear to improve intestinal barrier integrity, reduce leakage of harmful metabolites (e.g., lipopolysaccharides), inhibit pro-inflammatory signalling pathways, and possibly suppress the formation of trimethylamine/trimethylamine oxide. Probiotics have also been found to enhance endothelial function and halter thrombosis. CONCLUSION: The current clinical evidence underlines belief that probiotics might be associated with reduced levels of inflammation biomarkers. Experimental evidence reports that the beneficial effects of probiotics seem to be mainly imposed by triggering the secretion of short-chain fatty acids and bile acids, in addition to suppressing the NF-κB signalling pathway. However, the current studies are still in their infancy and it is of high priority to design further research on the topic.

Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF, BDNF, VEGF, and PGE2.

BACKGROUND: Several inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls. METHODS: From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index. RESULTS: Serum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850). CONCLUSIONS: Our findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.

The correlation between serum selenium, zinc, and COVID-19 severity: an observational study.

BACKGROUND: Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity. METHODS: Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease. RESULTS: According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (ß = - 0.28, P-value = 0.01 for Se; ß = - 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = - 0.35, P-value = 0.001 for Se; r = - 0.41, P-value < 0.001 for Zn). CONCLUSION: Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.

Rice bran oil could favorably ameliorate atherogenicity and insulin resistance indices among men with coronary artery disease: post hoc analysis of a randomized controlled trial.

BACKGROUND: Despite recent advances in recognizing more reliable indicators to estimate the coronary artery disease (CAD) patients' response to treatment and prognosis, less attention has been paid to evaluating them in clinical trials. Hence, the present research was conducted to study the impact of rice bran oil (RBO) versus sunflower oil (SFO) on various atherogenicity and insulin resistance markers. METHODS: In the present 8-week randomized controlled trial, 40 CAD men with an average age of 56 years were allocated randomly into the intervention or control group to use RBO or SFO (30 g/day) plus a standardized dietary plan. As a further analysis, eight atherosclerosis-related indices were calculated before and after the study. RESULTS: Analysis of covariance test in which potential confounders and baseline levels were considered, indicated that using RBO compared to SFO reduced Castelli's risk index I and II (adjusted means:3.29, 1.52 vs. 4.61, 2.20, respectively), atherogenic coefficient (2.29 vs. 3.61), lipoprotein combine index (6.54 vs. 17.53), and cholesterol index (0.46 vs. 1.20) after the trial (P-value ≤ 0.002). Also, the RBO group yielded significantly lower triglyceride glucose index (8.73 vs. 9.13) (P-value = 0.010). Further, marginally significant amelioration in triglyceride/HDL ratio and atherogenic index of plasma (1.48 and 0.13 vs. 1.86 and 0.24 respectively) were noted (P-value = 0.07). Spearman correlation analysis detected significant positive correlations between alterations in TNF-α serum levels (ng/L) and the majority of evaluated indices (P-value < 0.05). CONCLUSION: Taken together, incorporating 30 g of RBO into the patient's usual diet appeared effective in ameliorating atherogenicity and insulin resistance indicators among men with CAD, probably in relation to its anti-inflammatory properties. TRIAL REGISTRATION: The protocol of the current trial was retrospectively recorded in the Iranian clinical trial registration system (IRCT) with the registration number of IRCT20190313043045N1 (URL: https://en.irct.ir/trial/38346 ; Registration date: 2019-04-27).

Melissa officinalis tea favourably affects the frequency of premature ventricular beats and cardiometabolic profile among patients with premature ventricular contraction: A randomised open-label controlled trial.

BACKGROUND AND AIMS: Premature ventricular contraction (PVC) as one of the most common arrhythmias could worsen the morbidity of cardiovascular events, particularly concurrent with other risk factors. Considering the probable side effects of antiarrhythmic drugs chronic use, prescribing herbal medicines for such conditions is on the rise. Melissa officinalis (MO) is widely identified as an antiarrhythmic and cardioprotective agent but there is limited evidence for its clinical use. This research, thus, aimed to investigate the effects of MO tea among patients with PVCs. METHODS: The present 12-week randomised controlled trial enrolled 60 patients with confirmed diagnosis of moderate to low-grade PVCs. The patients in intervention group received MO teabags (containing 2-g dried leaves/250 mL in hot water) two times/day in addition to lifestyle modification recommendations, while control group only received lifestyle modification recommendations. After collecting the data, blood samples were gathered to explore serum concentrations of glucose and lipid markers. The number of premature ventricular beats and heart rates was determined by 24-hour rhythm Holter monitoring. RESULTS: On average, the patients aged 47 years and approximately 67.8% (n = 40) were women. The ANCOVA adjusted for baseline values and confounders revealed that patients in the MO tea group had significantly lower concentrations of triglyceride (adjusted mean (AM) = 144.75 mg/dL), total cholesterol (AM = 155.35 mg/dL), and fasting blood sugar (AM = 90.85 mg/dL), compared with the controls (AM = 174.27, 171.99, 99.84 mg/dL, respectively (P-value ≤.042). However, the intervention failed to affect LDL-C and HDL-C levels significantly. Significantly reduced frequency of 24-hour premature ventricular beats in the MO tea group (AM = 2142.39) was also noted compared with the controls (AM = 3126.05); (P-value = .017). The 24-hour heartbeats showed only a significant decrease within the intervention group (P-value < .01). CONCLUSION: Together, these results seem to support the higher cardioprotective effects of MO as a medicinal plant than lifestyle modifications alone. Nevertheless, further exploration of this hypothesis is warranted using large-scaled clinical trials.

Enhancement of the electro-activated persulfate process in dye removal using graphene oxide nanoparticle.

This study aimed to improve the speed of the electrochemical process by graphene oxide nanoparticle as a current accelerator in Acid Blue 25 removal from aqueous solutions. To do so, the effect of different parameters including pH, dye concentration, sodium persulfate concentration, the ratio of sodium persulfate to iron (II) sulfate concentration, current density, and the distance between electrodes was investigated on dye removal. Under optimal conditions of pH = 5, dye concentration = 200 mg/L, sodium persulfate concentration = 500 mg/L, iron (II) sulfate concentration = 100 mg/L, current density = 16.67 mA/cm2, and electrode distance = 2 cm, 95% of dye was removed after 60 min in the electro-activated persulfate process; while the modified electro-activated persulfate process achieved 95% dye removal after only 40 min under the same conditions. This system was able to remove 90% of dye after 60 min at a higher concentration (300 mg/L). Also, the modified electro-activated persulfate process obtained the removal of 80% of COD, and 54% of TOC after 180 min in the mentioned conditions, for the dye concentration of 300 mg/L.

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.

Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1ß, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.

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.

The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial.

BACKGROUND: The current study was designed to assess the effect of supplementation with a 14-strain probiotic mixture on episodic and chronic migraine characteristics. METHODS: Forty episodic and 39 chronic migraine patients who completed this randomized double-blind controlled trial received two capsules of multispecies probiotic or placebo. The migraine severity was assessed by visual analog scale (VAS). The number of abortive drugs consumed, migraine days, frequency and duration of attacks were recorded on paper-based headache diaries. Serum tumor necrosis factor alpha (TNF-α) and C- reactive protein (CRP) levels were measured at baseline and the end of the intervention. RESULTS: After a 10-week intervention, among episodic migraineurs the mean frequency of migraine attacks significantly reduced in the probiotic group compare to the placebo group (mean change: -2.64 vs. 0.06; respectively, p < 0.001). A significant reduction was also evident in the migraine severity (mean decrease: -2.14 in the probiotic group and 0.11 in the placebo group; p < 0.001). Episodic migraineurs who received the probiotic also showed significant reduction in abortive drug usage per week (mean change: -0.72; p < 0.001) compare to baseline, while there was no significant changes within the placebo group. In chronic migraine patients, after an 8-week intervention, the mean frequency of migraine attacks significantly reduced in the probiotic compared to the placebo group (mean change: -9.67 vs. -0.22; p ≤ 0.001). In contrast to the placebo, probiotic supplementation significantly decreased the severity (mean changes: -2.69; p ≤ 0.001), duration (mean changes: -0.59; p ≤ 0.034) of attacks and the number of abortive drugs taken per day (mean changes: -1.02; p < 0.001), in chronic migraine patients. We failed to detect any significant differences in the serum levels of inflammatory markers at the end of the study either in chronic or in episodic migraineurs. DISCUSSION: The results of this study showed that the 14-strain probiotic mixture could be an effective and beneficial supplement to improve migraine headache in both chronic and episodic migraineurs. Further research is required to confirm our observations.

An investigation of oxidant/antioxidant balance in patients with migraine: a case-control study.

BACKGROUND: In recent years, the role of neuroinflammation and oxidative stress in migraine pathogenesis has achieved considerable interest; however, to date findings are equivocal. Thus, the objective of this study was to investigate biomarkers of oxidative stress in episodic and chronic migraineurs (EM and CM patients) and controls. METHODS: Forty-four patients with EM, 27 individuals with CM and 19 age-sex-matched controls were enrolled. After collecting data on demographic and headache characteristics, blood samples were collected and analyzed to detect serum levels of oxidative stress biomarkers (malondialdehyde (MDA) and nitric oxide (NO)); total antioxidant capacity using Trolox equivalent antioxidant capacity (TEAC) assay; and antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase-1 (GPx-1)). RESULTS: Serum levels of CAT and SOD were significantly lower in the CM group than the EM group and controls. However, serum GPx-1 levels of the CM patients were slightly higher than the EM patients and controls (P-value≤0.001). CM patients had lower mean TEAC values than EM patients and controls. In addition, serum levels of NO and MDA were significantly elevated among subjects with CM compared to EM and control individuals (P-value≤0.001). Pearson correlation analysis revealed negative correlations between the number of days of having headaches per month and serum concentrations of the two antioxidant enzymes CAT (r = - 0.60, P-value< 0.001) and SOD (r = - 0.50, P-value< 0.001) as well as TEAC values (r = - 0.61, P-value< 0.001); however, there were positive correlations between headache days and serum GPx-1 levels (r = 0.46, P-value< 0.001), NO (r = 0.62, P-value< 0.001), and MDA (r = 0.64, P-value< 0.001). CONCLUSION: Present findings highlighted that chronic migraineurs had lower total non-enzymatic antioxidant capacity and higher oxidative stress than episodic migraineurs and control individuals. Although more studies are needed to confirm these data, applying novel prophylactic medications or dietary supplements with antioxidant properties could be promising in migraine therapy.

Serum Vitamin B12 and Methylmalonic Acid Status in Migraineurs: A Case-Control Study.

BACKGROUND: Although the exact pathophysiological mechanistic pathways that result in the initiation of migraine attacks remain unclear, there are some proposed mechanisms including neurogenic inflammation, trigeminovascular system activation, vascular dysfunction, and augmented release of nitric oxide (NO) and homocysteine (Hcy). Vitamin B12 is thought to be involved in important pathways that seem to be related to the pathogenesis of migraine including scavenging against NO and prevention of hyperhomocysteinemia. Therefore, the aim of the current study was to evaluate the serum vitamin B12 and methylmalonic acid (MMA) status in a group of migraine patients compared to healthy controls. METHODS: After the recruitment of cases and controls, demographic data and migraine characteristics (including the number of headache days, severity of headaches, and duration of each attack in hours) were recorded. Serum vitamin B12 and MMA levels were measured using the enzyme-linked immunosorbent assay technique. RESULTS: Seventy migraine patients and 70 healthy subjects were enrolled in this case control study. The serum levels of B12 were found to be significantly lower in migraine patients than in healthy subjects (512 ± 300 vs 667 ± 351 pg/mL, P = .007); whereas migraineurs had higher levels of MMA than controls (1.39 [0.59,4.01] vs 1.01 [0.49,1.45] µg/dL, P = .027). In the fully adjusted multiple regression model, those in the highest vs the lowest serum B12 quartile had 80% decrease in the odds of having migraine ([OR = 0.20, 95% CI = 0.05-0.73], [P for trend = .008]); while, patients in the highest quartile of MMA had more than 5 times increased risk of having migraine ([OR = 5.44, 95% CI = 1.49-19.87] [P for trend = .002]). There was no association between serum B12 and MMA levels and headache characteristics. CONCLUSION: Taken together, these findings suggest that participants with lower vitamin B12 and higher MMA levels that considered as lower functional activity of B12 had higher odds of migraine.