Low serum 25-hydroxyvitamin D levels in migraine are not related to headache frequency: A case-control study in patients with high-frequency/chronic migraine

Background: Serum 25-hydroxyvitamin D (25[OH]D) concentrations have been shown to be low in patients with migraine, but results are controversial regarding the current role of vitamin D in migraine severity. Using a case-control design, we aimed to evaluate serum 25(OH)D levels in a group of females with high-frequency episodic migraine/chronic migraine (HF/CM) and analyze its association with headache frequency and serum calcitonin gene-related peptide (CGRP) levels. Methods: Serum 25(OH)D levels were measured in 97 females with HF/CM (age 48.9 +/- 9.4 years) and 146 healthy females (47.4 +/- 8.1 years). Participants taking vitamin D supplements were excluded. Serum concentrations of 25(OH)D were determined by electrochemiluminescence (Roche, Germany), and CGRP levels were measured by enzyme-linked immunosorbent assay (Abbexa, UK). Results: Mean 25(OH)D levels in females with HF/CM (median [interquartile range] 19.0 [13.0-24.5] ng/mL) were below the values considered for insufficiency or deficiency and significantly lower than controls (25.0 [19-29.8] ng/mL; p < 0.0001). Fifty (51.5%) patients with HF/CM had levels below 20 ng/mL. There was no significant association between vitamin D levels and monthly headache days (Spearman's rank correlation coefficient [rho]: -0.086; p = 0.404) or with serum alpha (rho: 0.114; p = 0.267) and beta-CGRP (rho: 0.113; p = 0.276) levels. Serum 25(OH)D levels in females with HF/CM with a minimum daily sunlight exposure were significantly higher than those without (23.0 [15.0-26.0] ng/mL vs. 14.0 [10.0-20.0] ng/mL; p < 0.001). Females with HF/CM who performed exercise had higher, albeit not significant, plasma 25(OH)D levels than those who did not (21.0 [15.5-28.0] ng/mL vs. 16.5 [12.0-24.0] ng/mL; p = 0.059). Conclusions: Serum concentrations of 25(OH)D were low in many patients with HF/CM. Because there was no correlation with migraine frequency or serum CGRP levels, this deficiency seems to be a direct consequence of the migraine impact. Our data do not support either a relationship of 25(OH)D levels with migraine severity or the use of vitamin D supplements as a specific migraine treatment, although further studies are needed.