1 Research Submissions Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study Mansoureh Togha, MD ; Soodeh Razeghi Jahromi, PhD; Zeinab Ghorbani, PhD; Fahimeh Martami, MSc; Maryam Seifishahpar, MSc Objective.—The association between serum vitamin D and migraine is investigated in this research. 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. Key words: migraine, vitamin D deficiency, vitamin D insufficiency Headache doi: 10.1111/head.13423 © 2018 American Headache Society Published by Wiley Periodicals, Inc. ISSN 0017-8748 Conflict of Interest: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding: This research was supported by a grant (number 95- 02-54-33302) from the Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. From the Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran (M. Togha, S. Razeghi Jahromi, Z. Ghorbani, F. Martami, and M. Seifishahpar); Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran (S. Jahromi, F. Martami, and M. Seifishahpar); School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran (Z. Ghorbani). Address all correspondence to Mansoureh Togha, Professor of Neurology, Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. E-mail: toghae@ tums.ac.ir Accepted for publication July 18, 2018.