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.

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.

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.

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.

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Objectives Obesity is a major public health concern that increases the risk of many other chronic diseases. Alteration and remodeling of adipose tissue due to obesity affect adipose functions, leading to chronic low-grade inflammation. Additionally, over accumulation of triglycerides in adipocytes can interfere with the endoplasmic reticulum (ER) functions. These functions include ER stress, as a mechanism to address protein misfolding and other cellular processes including autophagy. Previously, fish oil (FO) and tart cherry (TC) were shown to possess anti-inflammatory properties. We hypothesized that while TC and FO individually decrease inflammation, their combinatorial effects will be greater, either synergistic or additive on regulating inflammation and other adipose tissue functions. Methods Four-weeks old, male and female TALLYHO/Jng (TH) and C57BL/6J (B6) mice were fed five different diets including low fat (LF), high fat (HF), and HF supplemented with TC, FO, or TC + FO for 10 weeks. Mice were weighed and adipose tissue was collected and used for gene expression analyses by qRT-PCR. Results Both B6 and TH mice were significantly heavier on HF diets compared to LF with greater extent in TH for both sexes. In B6 males, HF group had higher expression levels of inflammatory markers including Mcp1, Il-6, NF-κB and Il-1b compared to LF group (p &lt; 0.05). Supplementation with TC and TC + FO decreased mRNA levels of Mcp1 compared to HF in B6 male mice (p &lt; 0.05). Furthermore, ER stress markers BIP, CHOP, and SXBP1 were significantly increased in TH males fed HF compared to LF diets (p &lt; 0.01). Similarly, autophagy genes ATG12 and Beclin1 were upregulated in TH male HF group compared with LF group (p &lt; 0.001). Additionally, supplementation with TC + FO reduced both ER stress (CHOP, sXBP1) and autophagy (ATG12) markers compared to HF in TH male mice (p &lt; 0.01). Moreover, Beclin1 mRNA levels were significantly reduced in all supplemented groups compared to HF in B6 male mice (p &lt; 0.05). Conclusions FO and TC individual and combined effects are in part mediated by changes in expression of genes involved in ER stress, autophagy, and inflammatory pathways in adipose tissue. Further experiments are ongoing to determine whether these changes will be translated at the protein level. Funding Sources USDA NIFA AFRI award # 2019-67,017-29,247.