Healthy eating index 2015 might be associated with migraine headaches: Results from a Case-Control study.

Migraine headaches are the most prevalent disabling primary headaches, affecting individuals at an active age. Dietary interventions are considered low-cost and practical approaches to migraine prophylaxis. Hence, the present study aimed to assess the association between adherence to the Healthy Eating Index 2015 (HEI-2015) and migraine headaches. The present case-control study was conducted on 476 newly diagnosed adults with migraine headaches, based on the International Classification of Headache Disorders 3rd edition (ICHDIII criteria(, and 512 healthy controls. Participants' dietary intakes were collected using a validated, 168-item semi-quantitative food frequency questionnaire (FFQ). The association between HEI-2015 and migraine headaches was assessed using logistic regression models. Although the trend was not statistically significant, being in the 4th quantile of the HEI-2015 was associated with about 50% lower odds of migraine headaches in both primary (adjusted for age and gender) (odds ratios (OR): 0.51, 95% confidence intervals (CI): 0.33, 0.78) and fully adjusted models (additionally adjusted for body mass index (BMI) and total calories) (adjusted OR: 0.50, 95%CI: 0.32, 0.77). Intriguingly, the odds of migraine headaches were significantly higher in those in the last quantile of "Total Fruits," which is equal to more than 237 g per 1000 kcal (aOR: 2.96, 95%CI: 1.99, 4.41) and "Whole Fruits," which is equal to more than 233 g per 1000 kcal (aOR: 2.90, 95%CI: 1.94, 4.31). Similarly, higher intakes of "Dairy," which is equal to more than 138 g per 1000 kcal (aOR: 2.66, 95%CI: 1.71, 4.14), and "Total Protein Foods," which is equal to more than 259 g per 1000 kcal (aOR: 2.41, 95%CI: 1.58, 3.70), were associated with higher odds of migraine headaches. The current study revealed an indirect association between HEI-2015 and its components, including "Greens and Beans," "Whole Grains," "Refined Grains," and "Added Sugars" and lower odds of migraine headaches.

The effect of body mass index on the morbidity and outcomes of COVID-19 in Iranian patients with multiple sclerosis.

Background: It seems that patients with multiple sclerosis (MS) are at a higher risk for coronavirus disease 2019 (COVID-19) implications due to being subjected to immunomodulatory or immunosuppressive treatments. Besides, obesity as a risk factor may lead to more adverse consequences. The relationship between obesity and COVID-19 morbidity and outcomes in Iranian patients with MS still remains unclear. Methods: A cross-sectional study was conducted in Sina Hospital, Tehran, Iran. Patients with MS were asked to complete an online questionnaire in the Google Form format. Demographic information, clinical information including MS disease-related factors, COVID-19-related factors, and anthropometric information were recorded. Totally, 492 patients filled the questionnaire during two weeks in November 2021, by the response rate of 21.6%. Body mass index (BMI) was categorized based on the standard classification of the World Health Organization (WHO). The logistic regression was used to examine the risk of morbidity and chi-square test/one-way analysis of variance (ANOVA) was employed to determine the difference regarding severity and symptoms among groups. Results: In the fully adjusted model, the odds ratio (OR) of COVID-19 morbidity in class II obese participants was significantly 5.41 times higher than that in the normal BMI group [OR: 5.41, 95% confidence interval (CI): 1.00-29.09]. COVID-19 severity was significantly different among BMI groups (P = 0.024). Respiratory symptoms (P = 0.05) as well as gastrointestinal (GI) symptoms (P < 0.01) of COVID-19 were more prevalent among class I and class II obese patients compared with overweight, normal weight, and underweight groups. Moreover, no one in the class I and class II obesity groups reported COVID-19 morbidity without any symptoms (P = 0.04). Conclusion: The results of the current study support the view that obesity could play a key role in susceptibility to COVID-19 morbidity and severity of the symptoms in patients with MS. The findings recommended that neurologists pay more attention to patients' BMI during this pandemic.

Fruits and vegetables intake may be associated with a reduced odds of multiple sclerosis: a systematic review and dose-response meta-analysis of observational studies.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated condition of the central nervous system (CNS). Intake of fruits and vegetables high in vitamins, minerals, fiber, and active molecules contributes to the body's overall health, immunity, and physiological function. This study sought to review the literature and investigate the relationship between fruits and vegetables consumption and MS odds. METHODS: In the current systematic review and meta-analysis, a systematic search of original databases from inception to 21 Dec 2022 was conducted based on the PRISMA 2020 statement. Human observational studies examining the association between fruits or vegetables consumption and MS prevalence were included if they reported and provided effect size with 95% confidence intervals (CIs). RESULTS: The systematic review and meta-analysis included eight studies. Random effect model showed the protective effect of fruits (I2 = 81.0%, P for heterogeneity < 0.001; pooled OR = 0.52, 95%CI = 0.27, 0.97, P-value = 0.042) and vegetables consumption (I2 = 73.5%, P for heterogeneity = 0.002; pooled OR = 0.61, 95%CI = 0.38, 1.00, P-value = 0.050) on MS odds. According to a linear dose-response meta-analysis of four case-control studies, an increase of 100 grams of fruits per day reduced the odds of MS by 9% (I2 = 0.0%, P for heterogeneity = 0.77; pooled OR = 0.91, 95%CI = 0.83, 0.99, P-value = 0.021). CONCLUSION: Consumption of fruits and vegetables may be associated with a potential protective effect against MS. However, further confirmation is required through prospective longitudinal studies and randomized clinical trials.

Higher Dietary Acid Load Might Be a Potent Derivative Factor for Multiple Sclerosis: The Results from a Case-Control Study.

This study aimed to investigate the association between dietary acid load (DAL) and multiple sclerosis (MS), through the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. In a hospital-based case-control study of 109 patients with MS and 130 healthy individuals, a validated 168-item semi-quantitative food frequency questionnaire and a logistic regression model were used to evaluate the association between the DAL and MS. After adjusting for age (years), gender (male/female), body mass index (Kg/m2), and total calories (Kcal), the MS odds were 92% lower for those in the highest tertile of total plant-based protein (OR: 0.08, 95%CI: 0.03, 0.23; p-value < 0.001) and about four times higher for those in the highest tertile of the PRAL (OR: 4.16, 95%CI: 1.94, 8.91; p-value < 0.001) and NEAP scores (OR: 3.57, 95%CI: 1.69, 7.53; p-value < 0.001), compared to those in the lowest tertile. After further adjusting for sodium, saturated fatty acid, and fiber intake, the results remained significant for total plant-based protein intake (OR: 0.07, 95%CI: 0.01, 0.38; p-value = 0.002). In conclusion, a higher NEAP or PRAL score may be associated with increased odds of MS, while a higher intake of plant-based protein instead of animal-based protein may be protective.

Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis.

Introduction: Depression, fatigue, and anxiety are three common clinical comorbidities of multiple sclerosis (MS). We investigated the role of physical activity (PA) level and body mass index (BMI) as modifiable lifestyle factors in these three comorbidities. Methods: A cross-sectional study was conducted in the MS specialist clinic of Sina Hospital, Tehran, Iran. Demographic and clinical data were collected. BMI was categorized in accordance with the WHO's standard classification. Physical activity (PA) level and sitting time per day were obtained using the short form of the International Physical Activity Questionnaire (IPAQ-SF). Fatigue, anxiety, and depression scores were measured using the Persian version of the Fatigue Severity Scale (FSS), Beck Anxiety Inventory (BAI), and Beck's Depression Inventory II (BDI-II) questionnaires, respectively. The correlation between the metabolic equivalent of tasks (MET), BMI, and daily sitting hours with depression, anxiety, and fatigue were checked using the linear regression test. The normal BMI group was considered a reference, and the difference in quantitative variables between the reference and the other groups was assessed using an independent sample t-test. Physical activity was classified with tertiles, and the difference in depression, anxiety, and fatigue between the PA groups was evaluated by a one-way ANOVA test. Results: In total, 85 MS patients were recruited for the study. The mean ± SD age of the participants was 39.07 ± 8.84 years, and 72.9% (n: 62) of them were female. The fatigue score was directly correlated with BMI (P: 0.03; r: 0.23) and sitting hours per day (P: 0.01; r: 0.26) and indirectly correlated with PA level (P < 0.01; r: -0.33). Higher depression scores were significantly correlated with elevated daily sitting hours (P: 0.01; r: 0.27). However, the correlation between depression with PA and BMI was not meaningful (p > 0.05). Higher anxiety scores were correlated with BMI (P: 0.01; r: 0.27) and lower PA (P: 0.01; r: -0.26). The correlation between anxiety and sitting hours per day was not significant (p > 0.05). Patients in the type I obesity group had significantly higher depression scores than the normal weight group (23.67 ± 2.30 vs. 14.05 ± 9.12; P: 0.001). Fatigue (32.61 ± 14.18 vs. 52.40 ± 12.42; P: <0.01) and anxiety (14.66 ± 9.68 vs. 27.80 ± 15.48; P: 0.01) scores were significantly greater among participants in the type II obesity group in comparison with the normal weight group. Fatigue (P: 0.01) and anxiety (P: 0.03) scores were significantly different in the three levels of PA, but no significant difference was found in the depression score (P: 0.17). Conclusion: Our data suggest that a physically active lifestyle and being in the normal weight category are possible factors that lead to lower depression, fatigue, and anxiety in patients with MS.

Role of sarcopenia risk in predicting COVID-19 severity and length of hospital stay in older adults: a prospective cohort study.

Sarcopenia is more common in the elderly and causes adverse outcomes with increased morbidity and mortality. This prospective cohort study assessed the association of sarcopenia risk with the severity of COVID-19 at the time of admission and during hospitalisation and the length of hospital stay. Two hundred patients (aged ≥ 60 years) who were hospitalised for COVID-19 were enrolled using consecutive sampling between 29 December 2020 and 20 May 2021. The sarcopenia score of the patients was assessed using the Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls questionnaire. The severity of COVID-19 was determined using the modified National Early Warning Score (m-NEWS) system for 2019 n-CoV-infected patients at admission (T1), day three (T2) and at discharge (T3). Data were analysed using SPSS, version 22 and STATA, version 14. Of the 165 patients included, thirty four (20·6 %) were at risk of sarcopenia. The length of hospital stay was slightly longer in patients with sarcopenia risk, but the difference was not significant (P = 0·600). The adjusted OR of respiratory rate (RR) > 20 /min at T1 for the sarcopenia risk group was 6·7-times higher than that for the non-sarcopenic group (P = 0·002). According to generalised estimating equations, after adjusting for confounding factors, the m-NEWS score was 5·6 units higher in patients at risk of sarcopenia (P < 0·001). Sarcopenia risk could exacerbate COVID-19 severity and increase RR at admission, as well as the need for oxygen therapy at discharge.

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.

The association between dairy intake and migraine odds among pediatrics and adolescents: A case-control study.

OBJECTIVE: Migraine is recognized as a disease with unknown etiology and various pathophysiologic pathways which are not fully understood. Due to the relation between dairy intake and various chronic conditions in children and also the paucity of data on the probable role of dairy intake on pediatrics' odds of having migraine, this study was designed. MATERIALS & METHODS: The present study was a population-based case-control design that was accomplished in a tertiary headache clinic.290 child (aged from7 to 14 years old) was included in this study. A definite diagnosis of migraine was performed by a neurologist; concerning the 2018 international classification of headache disorder 3 (ICHD3) criteria. Also, demographic and anthropometric characteristics were obtained. In addition, the usual dietary intake of participants was evaluated using a validated semi-quantitative food frequency questionnaire (FFQ). RESULTS: Those children in the case group significantly had higher age and BMI means (P.value:0.000). In the second regression model, odds of migraine were 48% (OR: 0.52; 95%CI:0.27-1.00) diminished in the second tertile and 53% (OR:0.47;95%CI:0.24-0.92) in the third tertile of low-fat dairy intake (P-trend:0.03). In the fully adjusted model, the achieved migraine ORs were as followings:0.48 (95% CI:0.240.95) in the second tertile and 0.46 (95% CI:0.21-0.96) in the third tertile (P-trend:0.04), respectively. Children with more high-fat dairy intake also consumed higher amounts of energy, pastries, simple sugar, unhealthy snacks, and hydrogenated oil (P<0.05). CONCLUSION: This study results proposed that a greater amount of low-fat dairy intake may attenuate the odds of having migraine attacks in pediatrics and adolescents who might be at risk of headache, which can be attributed to the micronutrient and also to the bioactive content of these dietary components.

MIND Diet Adherence Might be Associated with a Reduced Odds of Multiple Sclerosis: Results from a Case-Control Study.

INTRODUCTION: The Mediterranean Dietary Approaches to the Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet has been shown to have beneficial neuroprotective effects. The purpose of this research was to evaluate the link between the MIND diet adherence and multiple sclerosis (MS), a degenerative neurological illness. METHODS: In a hospital-based case-control setting, 77 patients with relapsing-remitting multiple sclerosis (RRMS) and 148 healthy individuals were recruited. A validated 168-item semi-quantitative food frequency questionnaire was used to assess participants' dietary intakes and the MIND diet score. A logistic regression model was used to evaluate the association between MIND diet adherence and MS. RESULTS: There was significant difference between RRMS and control groups in the median (Q1-Q3) of age (years, P value < 0.001), body mass index (BMI) (kg/m2, P value < 0.001), and total intake of calories (kcal, P value = 0.032), carbohydrates (g, P value = 0.003), animal-based protein (g, P value = 0.009), and fiber (g, P value = 0.001). Adherence to the MIND diet was associated with a reduced odds of MS [adjusted odds ratio (aOR) = 0.10, 95 percent confidence interval (95% CI) = 0.01-0.88, P for trend = 0.001]. MS odds was significantly lower in the last tertile of green leafy vegetables (aOR = 0.02, 95% CI = 0.00-0.21, P value < 0.001), other vegetables (aOR = 0.17, 95% CI = 0.04-0.73, P value = 0.001), butter and stick margarine (aOR = 0.20, 95% CI = 0.06-0.65, P value = 0.008), and beans (aOR = 0.05, 95% CI = 0.01-0.28, P value < 0.001) consumption. While it was significantly higher in the last tertile of cheese (aOR = 4.45, 95% CI = 1.70-11.6, P value = 0.003), poultry (aOR = 3.95, 95% CI = 1.01-15.5, P value = 0.039), pastries and sweets (aOR = 13.9, 95% CI = 3.04-64.18, P value < 0.001), and fried/fast foods (aOR = 32.8, 95% CI = 5.39-199.3, P value < 0.001). CONCLUSION: The MIND diet and its components, including green leafy vegetables, other vegetables, and beans, seem to decrease the odds of MS; besides butter and stick margarine, the MIND diet's unhealthy components seem to have the same protective effects, while pastries and sweets, cheese, poultry, and fried/fast foods have an inverse effect.

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.

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.

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 ).

Evaluation of Inflammatory State in Migraineurs: A Case-control Study.

Due to inconclusive findings of previous researches, we aimed to evaluate inflammatory state biomarkers in episodic and chronic migraineurs (EM and CM patients) compared to headache-free controls in the current study. Seventy-one migraine patients and 19 age-sex-matched controls were recruited. After obtaining demographic data and recording headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of C-reactive protein (CRP), tumor necrosis factor(TNF)-α and interleukin (IL)-6. Serum levels of IL-6, CRP and TNF-α were significantly higher among subjects with CM than the EM and controls. Further, positive correlations were noted for number of headache days/month and serum IL-6 (r=0.53, p<0.001), CRP (r=0.62, p<0.001), and TNF-α (r=0.58, p<0.001). In sum, according to current findings, a pro-inflammatory state was detected among chronic and episodic migraineurs compared to healthy control, as revealed by augmented concentrations of pro-inflammatory cytokines (e.g. IL6, CRP, and TNF-α). It was also underlined that with increasing levels of inflammatory factors, headaches tended to be more chronic. However, in order to confirm the hypothesis that neuroinflammation plays a role in migraine pain genesis, long-term cohort studies and well-designed experimental and randomized controlled trials are required.

The possible beneficial effects of higher vitamin B6 intake from diet on cognitive function of patients with neuromyelitis optica spectrum disorder.

INTRODUCTION: Given some evidence on the effects of vitamin B6 on cognitive function and the high prevalence of cognitive impairment in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD), we conducted the present study to evaluate the correlation between dietary vitamin B6 intake and cognitive function among NMOSD patients. METHOD: A cross-sectional study was designed on 24 definite NMOSD patients in Sina hospital, Tehran, Iran. A validated 168-item food frequency questionnaire was used to obtain the participants' routine dietary habits. For the cognitive function assessment, Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery was administered. Vitamin B6 intake per day was calculated, and the correlation between vitamin B6 and the results of MACFIMS subtests was examined. RESULTS: The results revealed a positive correlation between dietary vitamin B6 intake and cognitive function in all subtests of MACFIMS. This direct correlation was significant in case of verbal and learning memory according to CVLT-II subtest (p-value:0.02; r:0.45) as well as speed of information processing and working memory according to SDMT subtest (p-value:0.04; r:0.43). The results from linear regression analysis adjusted for carbohydrate intake and disease duration indicated a significant ascending trend for the score of CVLT-II, SDMT, CVLT-II-delayed recall, and Brief Visuospatial Memory Test-Revised (BVMT-R) subtests through the quartiles of vitamin B6 intakes. CONCLUSION: Our finding indicated a positive correlation between higher dietary intake of vitamin B6 and cognitive function of NMOSD patients. Based on high prevalence of cognitive malfunction in NMOSD patients, these results are promising.

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.

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.

A randomized controlled trial investigating the effects of a mediterranean-like diet in patients with multiple sclerosis-associated cognitive impairments and fatigue.

Background: Among multiple sclerosis (MS) related symptoms and complications, fatigue might impact roughly 90% of patients. Decline in cognitive function is one of the other complications that occur in the first years after disease onset. The Mediterranean diet is one of the well-known anti-inflammatory dietary approaches. Therefore, this study aimed to explore the effects of a modified Mediterranean-like diet on cognitive changes and fatigue levels in comparison with a conventional standard diet over a 1-year follow-up. Methods: In the current single-blind randomized controlled trial, 34 MS patients in the Mediterranean- like diet group and 38 patients in the standard healthy diet group were studied for 1 year. The dietary interventions were modified each month by an expert nutritionist. MS-associated fatigue level was evaluated using the Modified Fatigue Impact Scale (MFIS). Cognitive assessment was also performed using Minimal Assessment of Cognitive Function in MS (MACFIMS). Results: Intergroup comparisons demonstrated that after considering confounding variables in ANCOVA, fatigue scores appeared significantly lower in patients who were treated with the Mediterranean-like diet than those in the standard healthy diet group [Mean 95% confidence interval (CI)}: 33.93 (32.97-34.89) and 37.98 (36.99-38.97), respectively; P < 0.001]. However, the intergroup analysis of cognitive status only showed a difference in the mean score of Brief Visuospatial Memory Test-Revised (BVMT-R) subtest of the MACFIMS. The BVMT-R was higher among standard healthy diet patients compared to the Mediterranean-like diet group after the intervention following adjustment for covariates [Mean (95% CI): 23.73 (21.88-25.57) and 20.56 (18.60-22.51), respectively; P = 0.020]. Conclusion: In conclusion, the results of this study highlighted the higher protective effects of the Mediterranean-like diet against MS-related fatigue than the standard healthy diet. However, no significant improvement was observed in the cognitive status of MS patients after a 1-year treatment with the Mediterranean-like diet. More randomized clinical trials with larger sample sizes are needed to elucidate the effects of dietary modifications on MS-associated symptoms and complications.

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.

Body Mass Index and its Association with Migraine Characteristics in Female Patients.

BACKGROUND: Migraine is a debilitating neurological disorder with a high prevalence. This study was conducted to evaluate the relationship between body mass index (BMI) and disability, severity, frequency and duration of headaches in female migraine patients. METHODS: This cross-sectional study was designed to address the characteristics of migraine attacks (duration of each attack, frequency, and severity) and MIDAS (Migraine Disability Assessment) score in female migraineurs. The diagnosis of migraine was based on ICHD-3 beta criteria. Verbal rating scale (VRS) was used for headache severity. Height and weight were measured to calculate the BMI. Mann-Whitney and Kruskal-Wallis tests were used for comparison of means, and analysis of covariance (ANCOVA) test was used for adjustment of the confounding factors. RESULTS: In the current study, 170 female migraine patients with a mean (±SD) age of 34.0 ± 8.0 years were enrolled. There were significant differences between the three groups (18.5 ≤ BMI< 25, 25 ≤ BMI < 30 and 30 ≤ BMI) in terms of headache frequency, duration and severity as well as total MIDAS score (P<0.001). These differences remained significant after adjustment for age. CONCLUSION: This study revealed that migraineurs with higher BMI experienced higher headache frequency, severity and duration as well as higher disability score.

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.