Is there any hepatic impact associated with rice bran arabinoxylan compound supplementation? A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). METHODS: In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied. RESULTS: Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value = 0.001, I2 (%) = 29.9; P heterogeneity = 0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170). CONCLUSIONS: In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results. REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYZES: CRD42022361002, registration time: 29/09/2022.

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.

B vitamins and their combination could reduce migraine headaches: A randomized double-blind controlled trial.

Background: The B vitamins can potentially help prevent migraine. This study was designed to examine the effects of supplementation with thiamine (B1), pyridoxine (B6), cobalamin (B12), folic acid (B9), and a combination of these vitamins on women with episodic migraine (EM). Methods: This study was a double-blind, placebo-controlled, randomized, clinical trial conducted on 120 women with EM. The participants were divided into the 6 groups of B1 (n = 20), B6 (n = 20), B12 (n = 20), B9 (n = 20), vitamin B complex (n = 20), and placebo (n = 20). Subjects received 1 capsule daily for 12 weeks. As part of the baseline and post-intervention phases, paper-based headache diaries were used to record the number of abortive drugs consumed and the frequency of headache attacks, and the Migraine Disability Assessment Questionnaire (MIDAS) was used to assess migraine disability. Results: A 16-week study on women with EM revealed that the mean changes in the frequency of headache attacks decreased significantly in all vitamin groups in comparison with the placebo group (P < 0.001). In contrast to the placebo, there was also a significant improvement in the migraine disability score in each vitamin group (P < 0.001). The 12-week supplementation with vitamins B9, B1, B6, B12, and B complex also brought on a significant decrease in the use of abortive drugs compared to the placebo group (P = 0.032). Conclusion: The results of this study showed that B1, B6, B12, and B9, and a combination of these vitamins could be effective as an adjuvant in treatment and prophylaxis of EM. Further large trials with long-term follow-ups will be required to confirm our results.

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).

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.

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.

The effects of rice bran oil on left ventricular systolic function, cardiometabolic risk factors and inflammatory mediators in men with coronary artery disease: a randomized clinical trial.

BACKGROUND/OBJECTIVE: In the current study, we aimed to explore the effects of rice bran oil (RBO) in adjunct to conventional medical therapy on left ventricular ejection fraction (LVEF), cardiometabolic risk factors, and inflammatory mediators in male patients with coronary artery disease (CAD). SUBJECTS/METHODS: The present randomized controlled trial included 40 men diagnosed with CAD (mean age = 55.76 years) who were randomly allocated into two groups to receive either 30 grams per day of RBO (intervention group) or sunflower oil (control group) plus a standard diet for eight weeks. At the initial visit, demographic and anthropometric data and blood samples were collected. LVEF levels and serum concentrations of lipid profile, glucose, uric acid, hs-CRP, and TNF-α were investigated. RESULTS: A total of 37 participants completed the study (n = 18 in the intervention group, n = 19 in the control group). Analysis of covariance (ANCOVA) adjusted for baseline values, age and body mass index revealed that RBO significantly improved LVEF (51.34%) and reduced triglyceride (125.01 mg dl-1), blood sugar (110.4 mg dl-1), total cholesterol (123.01 mg dl-1) and low density lipoprotein (56.88 mg dl-1) levels compared to sunflower oil ((45.56%), (155.93 mg dl-1), (128.94 mg dl-1), (163.93 mg dl-1) and (83.79 mg dl-1), respectively) following a 8-week trial (P-values < 0.05). Additionally, the test demonstrated that RBO consuming patients had significantly lower levels of serum uric acid (4.60 mg dl-1), TNF-α (6.99 ng L-1) and hs-CRP (2.11 mg L-1) compared to the control group ((5.92 mg dl-1), (15.23 ng L-1), (4.47 mg L-1), respectively) (P-value < 0.05). However, no significant changes were found regarding weight, blood pressure or serum HDL levels throughout the trial. CONCLUSION: Consumption of 30 grams per day RBO within a standard diet could be considered an effective non-pharmacological approach in improving LVEF, cardiometabolic risk factors, and inflammatory state in CAD. However, future trials are recommended for more clarification.

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

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

The effects of regular consumption of green or black tea beverage on blood pressure in those with elevated blood pressure or hypertension: A systematic review and meta-analysis.

OBJECTIVE: As a popular beverage, there has been much interest in studying the effects of tea intake on hypertension (HTN), a particular risk factor for cardiovascular disorders (CVDs). We have thus aimed to isolate the randomized controlled trials investigating the efficacy of black or green tea as a beverage in subjects with elevated blood pressure (BP), or HTN. METHODS: PubMed, Scopus, Web of Science, and ProQuest dissertations and theses databases were searched from February 1, 1995, up to July 20, 2019, to identify relevant studies. RESULTS: The search strategy generated 1119 trials, of which finally five trials fulfilled the criteria for being included in the current study. Three out of 5 articles showed a low risk of bias. According to nine measurements derived from 5 trials on 408 individuals, it was found that regular tea intake resulted in the reduction in SBP (weighted mean difference (WMD): -4.81 mmHg, 95 %CI: -8.40 to -1.58, P = .004) and DBP (WMD:-1.98 mmHg, 95 %CI: -3.77 to -0.20, P = .029); however, excluding the most heterogeneous trials showed that regular tea intake might reduce SBP and DBP by about -3.53 and -0.99 mmHg, respectively. Based on meta-regression findings, we found the longer the duration of tea intake (≥3months), the higher the decrease in both SBP and DBP. Categorized studies, according to the tea type, revealed that the hypotensive effects of green tea were more pronounced compared to black tea. None of the studies reported any side effects. CONCLUSION: These results suggest the positive effects of regular tea intake on BP in subjects with elevated BP or HTN. Hence, it may be applicable to physicians, health care providers, and particularly HTN 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.

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.

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.

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.

Association of diet and headache.

The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.

Vitamin D in migraine headache: a comprehensive review on literature.

INTRODUCTION: As a primary headache, migraine has been established as the first leading disability cause worldwide in the subjects who aged less than 50 years. A variety of dietary supplements have been introduced for migraine complementary treatment. As an anti-inflammatory and antioxidant agent, vitamin D is one of these agents which has been of interest in recent years. Although higher prevalence of vitamin D deficiency/insufficiency has been highlighted among migraineurs compared to controls, there is not any consensus in prescribing vitamin D in clinical practice. Therefore, in the current review, in addition to observational and case-control studies, we also included clinical trials concerning the effects of vitamin D supplementation on migraine/headache. METHODS: Based on a PubMed/MEDLINE and ScienceDirect database search, this review study includes published articles up to June 2019 concerning the association between migraine/headache and vitamin D status or supplementation. RESULTS: The percentage of subjects with vitamin D deficiency and insufficiency among migraineurs and headache patients has been reported to vary between 45 and 100%. In a number of studies, vitamin D level was negatively correlated with frequency of headaches. The present findings show that supplementation with this vitamin in a dose of 1000-4000 IU/d could reduce the frequency of attacks in migraineurs. CONCLUSION: It seems a high proportion of migraine patients might suffer from vitamin D deficiency/insufficiency. Further, the current evidence shows that in addition to routine drug therapy, vitamin D administration might reduce the frequency of attacks in migraineurs. However, these results have yet to be confirmed.

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.

Dietary supplementation in patients with alcoholic liver disease: a review on current evidence.

BACKGROUND: Alcoholic liver disease (ALD) is one of the main causes of liver disease worldwide. Although the pathogenesis of ALD has not yet been well elucidated, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species play a pivotal role in the clinical and pathological spectrum of the disease. This review summarizes the existing evidences on dietary supplements considered to have antioxidant, and/or anti-inflammatory properties, and their role in the management of ALD and the proposed mechanisms. DATA SOURCES: The present study reviewed all studies published in PubMed, ScienceDirect and Scopus, from 1959 to 2015, indicating the role of different dietary supplementation in attenuation of many pathophysiological processes involved in development and progression of ALD. Full-texts of citations were used except for those that were published in languages other than English. RESULTS: Significant progress has been made to understand the key events and molecular players for the onset and progression of ALD from both experimental and clinical studies; however, there is no successful treatment currently available. The present review discussed the role of a variety of dietary supplements (e.g. vitamin A, carotenoids, vitamins B3, C and E, in addition to antioxidants and anti-inflammatory agents) in treating ALD. It has been shown that supplementation with some carotenoids, vitamin B3, vitamin C, silymarin, curcumin, probiotics, zinc, S-adenosylmethionine and garlic may have potential beneficial effects in animal models of ALD; however, the number of clinical studies is very limited. In addition, supplementation should be accompanied with alcohol cessation. CONCLUSIONS: Since oxidative stress and inflammation are involved in the pathogenesis of ALD, dietary supplements that can modulate these pathologies could be useful in the treatment of ALD. In addition to alcohol cessation, these supplements have shown beneficial effects on animal models of ALD. Clinical trials are needed to validate the beneficiary role of these supplements in patients with ALD.