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-1β, 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.

Background: Depression is a serious and burdensome disorder in modern societies, with lifetime prevalence of about 16%. Disturbed immune responses in the gut and immune-privileged sites including the central nervous system might occur subsequent to dysbiosis of gut microbiome. In this study we aimed at assessing the efficacy of 6 weeks synbiotic supplementation in the treatment of moderate depression in a double-blind, placebo-controlled, multi-center, and randomized trial. Methods: A total of 40 adult outpatients, who met the diagnostic and statistical manual of mental disorders fifth edition for moderate depression, were recruited based on the structured interview for DSMV. Recruited patients had a Hamilton rating scale for depression (HAM-D) score of 17 to 23 at baseline. All patients received fluoxetine (20 mg/d) for 4 weeks. Then, either a synbiotic capsule (plus fluoxetine) or placebo (plus fluoxetine) was added to the therapy for 6 weeks. Results: The mean age of the participants in the synbiotic treated group was 34.45 years and it was 35.50 years in the placebo group. Following the adjustment of ANCOVA models for gender, age, and BMI at baseline, there was a greater reduction in HAM-D score in synbiotic treated patients (Mean ± SD =-19.25 ± 1.71) compared to placebo taking group (Mean ± SD =-17.75 ± 2.05; P = 0.024). At the end of the 10th week of the intervention and after applying ANCOVA adjusted for the mentioned variables as well as baseline HAM-D score, it was found that the synbiotic group had a significantly decreased HAM-D score compared to the placebo (3.65 vs. 4.80, P = 0.013). Conclusions: The results of the current study revealed the efficacy of synbiotic as an adjuvant therapy in moderate depression.

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The exact mechanism of the migraine pathophysiology remained unclear. Although there are some reports showing low-grade inflammation in migraineurs, further studies are needed in this field. Thus, we designed a study to evaluate the serum levels of two main proinflammatory markers in migraine patients. In this case-control research, 43 migraine patients (23 chronic and 20 episodic migraineurs) and 40 age-sex-matched headache-free controls were studied. Demographic, dietary, and anthropometric data, headache characteristics, and serum C-reactive proteins (CRP) and tumor necrosis factor-alpha (TNF-α) assessments were collected. The mean ± SD age of the case and control groups were 36.98 ± 9.91 and 34.84 ± 9.75 years respectively. Compared to control subjects, both episodic and chronic migraineurs had significantly higher median levels of TNF-α (0.24, 0.95, and 1.90 pg/ml, respectively; P value < 0.001). Also, we observed a positive association between the TNF-α levels and the odds of having migraine after considering gender, age, body mass index, and dietary intakes of energy, carbohydrate, protein, fat, and mono and poly unsaturated fatty acids in the multivariable regression models (OR = 2.15; 95% CI 1.31-3.52; P value < 0.001). However, no significant association was demonstrated between migraine and serum CRP (OR = 2.91; 95% CI 0.87-9.78; P value = 0.08). These findings supported that inflammatory state could be related to the pathogenesis of migraine and it can thus be suggested that this effect might be beyond migraine progression. Further detailed studies are needed to investigate the importance of these findings in the pathogenesis of migraine 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.

ObjectiveTo assess the efficacy and safety of cinnarizine for the prophylaxis of migraine associated vertigo in the vestibular migraine and migraine with brainstem aura.BackgroundVestibular migraine and migraine with brainstem aura are two principal clinical syndromes that frequently are associated with vertigo. Since cinnarizine is a well-tolerated calcium channel blocker which has acceptable effect on both vertigo and migraine headache, we carried out this study to evaluate the efficacy and safety of this medication in vestibular migraine and also migraine with brainstem aura associated with vertigo.MethodsThis was a retrospective, single-center, open-label, investigation of the effects of cinnarizine on vestibular migraine and migraine with associated with vertigo. We assessed the change in monthly frequency of vertigo and also frequency, duration and intensity of migraine attacks after one, two and three months of cinnarizine administration.ResultsThe mean frequency of vertigo and also the mean frequency, duration and intensity of migraine headaches per month were reduced significantly after three months of cinnarizine therapy (all p < 0.001).ConclusionThis study suggests that cinnarizine is safe and effective in reducing both headache and vertigo aspects of “migraine plus vertigo” among the patients who suffer from either vestibular migraine or migraine with brainstem aura associated with vertigo.

Objective The association between serum vitamin D and migraine is investigated in this research.s Background Although the pathogenesis of migraine headache is not fully understood, the possible role of inflammation and disturbed immune system has been proposed; thus, higher levels of vitamin D might reduce the risk of migraine. However, the results of related studies have been inconclusive. Methods Seventy healthy individuals and 70 age‐ and sex‐matched migraineurs (34 chronic and 36 episodic migraineurs), diagnosed according to the International Headache Society criteria (ICHD‐IIIβ), were recruited. After obtaining baseline data and assessing migraine disability, a 30‐day headache diary was given to the participants. Blood samples were obtained and 25(OH)D serum concentrations were determined using ELISA techniques. Serum 25(OH)D under 20, 20–29, and 30–100 ng/mL were considered deficient, insufficient, and sufficient, respectively. The applied statistical tests for between‐group comparisons include independent‐sample t‐test, chi‐square, and analysis of variance. Multiple regression analysis was also performed to identify the possible risk factors of migraine headache. Results Migraine patients had significantly lower mean (SD) of serum VitD (30 (16) ng/mL) than healthy subjects (43 (19) ng/mL) (P < .001). The number (%) of subjects with VitD deficiency and insufficiency was significantly higher among the migraineurs (36 (53.7%)) than the controls (18 (26.1%)) (P < .0001). A significant negative association between migraine headache and serum VitD was detected in the fully adjusted multiple regression models when comparing the third and the highest serum 25(OH)D quartiles with the lowest (OR = 0.20; 95% CI = 0.05–0.77; OR = 0.17; 95% CI = 0.04–0.64, respectively, P for trend = .009). For each 5 ng/mL increase in serum 25(OH)D, there was a 22% odds decrease in the odds of migraine (OR = 0.78; 95% CI = 0.68–0.90; P = .001). Conclusion We have found that a higher level of serum VitD (between 50 to less than 100 ng/mL) among a sample of the Iranian population is associated with 80–83% lower odds of migraine headache than those with serum 25(OH)D levels below 20 ng/mL. However, there is a need for well‐designed clinical trials to investigate beneficial effects of increased serum 25(OH)D on lower risk of migraine.

Migraine can be accompanied by some gastrointestinal (GI) disorders. In this study, we aimed to investigate the relationship between migraine and tension-type headache (TTH) and different lower and upper GI disorders as well as non-alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study included 1574 overweight and obese participants who were referred to the Obesity Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH was made by an expert neurologist based on the international classification of headache disorders-III β (ICHD III β). GI disorders, including irritable bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology specialist. The overall mean age of participants was 37.44 ± 12.62. A total of 181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects were diagnosed. After adjusting for potential confounders by multivariable regression models, migraine had significant association with IBS (OR = 5.16, 95% CI = 2.07-12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25-6.99, P = 0.000), dyspepsia (OR = 4.12, 95% CI = 2.63-6.45, P = 0.000), and heartburn (OR = 5.03, 95% CI 2.45-10.33, P = 0.000), while the association between migraine and NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98-4.21, P = 0.055). Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29-6.65, P = 0.010) and dyspepsia (OR = 4.06, 95% CI = 2.24-7.34, P = 0.000) was significantly higher in TTH patients than the headache-free group. These findings show an association between GI disorders and primary headaches especially migraine and are, therefore, of value to the management of migraine and TTH. Further studies should investigate the etiology of the relationship between all subtypes of primary headaches and GI disorders.