MANAGEMENT AND THERAPY Relationship between severity of migraine and vitamin D deficiency: a case-control study Laura Rapisarda 1 & Maria Rosaria Mazza 1 & Federico Tosto 1 & Antonio Gambardella 1 & Francesco Bono 1 & Alessia Sarica 2 # Springer-Verlag Italia S.r.l., part of Springer Nature 2018 It is well recognized that vitamin D deficiency is involved in a number of neurological disorders. In the last years, several studies gave evidence of the relationship between chronic pain and vitamin D deficiency. Recently, a few studies investigated on the association between vitamin D deficiency and migraine [1]. However, if the serum vitamin D levels correlate with severity of migraine remains uncertain. The aim of this study was to investigate if the severity of vitamin D deficiency correlates with the frequency of head- aches in migraine patients. In this prospective study, we en- rolled 171 consecutive headache sufferers who attended the Institute of Neurology in Catanzaro from 2014 to 2017. We selected those patients with a primary headache (migraine or tension-type headache) diagnosed according to IHS diagnos- tic criteria, excluding subjects with trigeminal autonomic cephalalgias, patients already receiving a vitamin D supple- ment. Therefore, we excluded 37 patients as they did not re- spect our inclusion criteria or dropped out. We included 134 headache sufferers (22 men, 112 women; mean age: 41.4 ± 12.8 years) and 38 healthy controls (16 men, 22 women; mean age 47.6 ± 13.6 years). Each patient underwent a careful neu- rological evaluation. The frequency of headache was mea- sured using a monthly headache diary recorded for 3 months by the headache sufferers; pain and disability were assessed with a 0–10 visual analogue scale (VAS) and Migraine Disability Assessment (MIDAS) questionnaire; allodynia was estimated through the validated 12-item allodynia symptom check lists (ASC-12) administered during an head- ache attack; depression and anxiety were assessed with Beck Depression Inventory-II (BDI-II) and Hamilton Anxiety Rating Scale (HARS). It has also been evaluated the presence of medical overuse. All participants underwent a venous blood sampling for 25-hydroxyvitamin D. It has been considered sufficient for 25-hydroxyvitamin D levels higher than 30 ng/ ml; insufficient for 25-hydroxyvitamin D values between 20 and 30 ng/ml; and deficient for 25-hydroxyvitamin D levels lower than 20 ng/ml. According to headache monthly frequen- cy, we grouped our patients into two groups: group 1 included 100 patients (16 males, 84 females; mean age 41.4 ± 13.5 years) with chronic migraine (patients with more than 15 headache days monthly); group 2 included 34 patients (6 males, 28 females; mean age 39.8 ± 11.9 years) with episodic migraine (patients with less than 15 headache days monthly). Statistical analysis was performed using the Statistical Package for Social Science software (SPSS, v20.0, Chicago, IL, USA) for Macintosh. First, we demonstrated that headache sufferers had a se- vere vitamin D deficiency compared to the healthy subjects, mainly in group 1. Indeed, there was a significant difference among groups: serum 25-hydroxyvitamin D mean values were 12.7 ± 5.1 in the first group, 17.2 ± 4.0 in the second group, and 23.0 ± 6.4 in the healthy control group (p < 0.001). Nevertheless, a moderate insufficiency was re- vealed even in the control group, which is consistent with epidemiological data that give evidence that vitamin D in- sufficiency is not an unusual finding at our latitude. Moreover, comparing the two groups of headache sufferers, chronic migraneurs had a higher percentage of medication overuse (61 and 15% respectively, p < 0.001) and higher disability (MIDAS score: 36.5 ± 17.2 and 9.6 ± 7 respec- tively, p < 0.001). No statistically relevant differences were reported among the other clinical parameters. Then it has been evaluated if headache frequency might be directly related to serum 25-hydroxyvitamin D levels. Our data gave evidence that there is a linear negative relationship * Francesco Bono f.bono@unicz.it 1 Headache Center, Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Viale Europa, 88100 Catanzaro, Italy 2 Neuroscience Research Center, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy Neurological Sciences (2018) 39 (Suppl 1):S167–S168 https://doi.org/10.1007/s10072-018-3384-4