Table 1.
Overview of studies investigating vitamin D serum levels in association with headache.
| Author (Year) | Study Design | Study Group: Type of Headache (Number of Participants) | Study Population Age (Years) | Mean Serum Vitamin D Levels (ng/mL) | Results | Association |
|---|---|---|---|---|---|---|
| Gallelli (2019) [50] | Prospective, single-blind, single-center, control-group | Migraine (n = 95) Control (n = 120) |
Range: 13–54 | 15.4 | Serum vitamin D levels were lower than the normal range in patients with migraines and controls. Mean vitamin D values were significantly higher in the control group compared to the migraine group. |
Associated |
| Patel (2019) [51] | Retrospective, cross-sectional | Migraine (n = 446, 446) | Range: 19–80 | No data | Vitamin D deficiency elevated the odds of major/extreme loss of function. There was higher prevalence and higher odds of migraine among vitamin D deficient patients compared to those with hypocalcemia or no-deficiency. |
Associated |
| Kılıç (2019) [52] | Retrospective study | Migraine (n = 92) | Mean: 12.6 | No data | There was increased migraine frequency, duration, and PedMIDAS scores in those with vitamin D deficiency and insufficiency. Migraine frequency, duration, and PedMIDAS scores were significantly negatively related to serum vitamin D levels. |
Associated |
| Hanci (2019) [53] | Retrospective, observational | Migraine (n = 165) TTH (n = 116) Control (n = 98) |
Range: 5–17 | Migraine: 12.4 ± 7.7 TTH: 13.5 ± 9.9 Control: 13.4 ± 8.8 |
No significant differences in mean vitamin D levels among the three groups | Not associated |
| Hussain (2019) [54] | Case-control | Migraine (n = 40) Control (n = 40) |
32.18 28.8 |
Migraine: 32.11 Control: 41.86 |
Vitamin D levels were significantly lower in those with migraines compared to controls The incidence of aura, allodynia, phonophobia/photophobia, autonomic manifestations, and resistance to medications was increased vitamin D deficient patients with migraines than those with normal vitamin D levels. Serum vitamin D levels were significantly negatively related to the frequency, duration, and severity of migraine headache attacks |
Associated |
| Togha (2018) [55] | Case-control | Migraine (n = 70) Control (n = 70) |
Mean: 37 | Migraine: 30 Control: 43 |
There were more subjects with vitamin D deficiency and insufficiency in the migraine group (53.7%) than the control group (26.1%). Serum vitamin D levels were significantly negatively related to migraine headaches Serum vitamin D levels in those with chronic migraine were not different to those in subjects with episodic migraine Serum vitamin D levels showed no correlation with headache parameters. |
Associated |
| Song (2018) [56] | Retrospective, observational | Migraine (n = 157) | Mean: 37 | 15.9 ± 7.4 | The majority (94.9%) of subjects with migraine had vitamin D insufficiency. Frequent monthly headache was 1.2 times more common in migraine patients with vitamin D deficiency than those without deficiency. |
Associated |
| Donmez (2018) [57] | Retrospective, case-control | Migraine (n = 68) TTH (n = 79) Control (n = 69) |
Mean: 12.2 | Migraine: 17.3 TTH: 16.9 Control: 25.8 |
Serum vitamin D levels were significantly lower in the migraine and TTH groups compared with the control group. | Associated |
| Sohn (2018) [49] | Case-control | CH (n = 28) Migraine (n = 36) Control (n = 36) |
CH: 38.2 Migraine: 35.1 Control: 35.4 |
CH: 14.0 ± 3.9 Migraine: 14.7 ± 5.9 Control: 14.6 ± 7.4 |
The majority (92.8%) of those with CH had vitamin D deficiency. There was no significant difference in vitamin D levels among patients with CH, migraine, or controls. Patients with a headache periodicity during winter to spring showed a trend of lower serum vitamin D levels than those with periodicity during summer to autumn. |
Not associated |
| Rapisarda (2018) [58] | Case-control | CM (n = 100) EM (n = 34) Control (n = 38) |
CM/EM: 41.4 Control: 47.6 |
CM: 12.7 EM: 17.2 Control: 23.0 |
Vitamin D deficiency was severe among headache patients (especially in those with CM) compared to healthy subjects. Vitamin D levels were negatively correlated with the number of days of headache (Pearson’s correlation coefficient: 0.506) |
Associated |
| Farajzadeh (2018) [59] | Case-control | TN (n = 13) Control (n = 13) |
Mean: 53.3 | TN: 22.61 Control: 39.80 |
Vitamin D levels were significantly decreased in patients with TN (before and after microvascular decompression) compared to the control group. | Associated |
| Prakash (2017) [60] | Case-control | Chronic TTH (n = 100) Control (n = 100) |
Chronic TTH: 35.63 Control: 36.86 |
Chronic TTH: 14.7 Control: 27.4 |
Serum vitamin D levels were significantly lower in Chronic TTH patients than in controls. Vitamin D deficiency was more prevalent in patients with Chronic TTH (71%) than controls (25%). Chronic TTH patients with vitamin D deficiency had a higher prevalence of musculoskeletal pain, muscle weakness, muscle and bone tenderness score, associated fatigue, and a more prolonged course. Serum vitamin D levels were positively correlated with the total muscle tenderness score. |
Associated |
| Virtanen (2017) [61] | Cross-sectional | Self-reported frequent headache (n = 250) | Range: 42–60 | 38.3 nmol/L | Serum vitamin D levels were lower in subjects with frequent headaches than other participants. Serum vitamin D levels were inversely associated with frequent headaches. |
Associated |
| Tozzi (2016) [62] | Cross-sectional | MWoA (n = 91) MWA (n = 32) TTH (n = 36) |
Range: 5–18 | No data | Serum vitamin D levels were lower in children with MwoA than those with MWA and THH, albeit not significantly (p = 0.07). | Not associated |
| Iannacchero (2015) [63] | Observational | Migraine (n = 22) | Mean: 45.41 | 13.05 ± 5.70 | Vitamin D levels were similar among those with CM than those with EM Vitamin D levels were not significantly correlated with headache frequency. |
Not associated |
| Buettner (2015) [64] | Cross-sectional | 5938 participants from the National Health and Nutrition Examination | No data | No data | People with serum vitamin D levels >57 nmol/l and use a statin had a lower prevalence of severe headache or migraine. | Associated |
| Prakash (2013) [22] | Observational | Chronic TTH (n = 71) | Mean: 38 | No data | Serum vitamin D levels were significantly associated with headache, musculoskeletal pain, and osteomalacia. Mean vitamin D levels were significantly lower in subjects suffering from daily headache compared to those with intermittent headaches. |
Associated |
| Celikbilek (2014) [65] | Cross-sectional, prospective | Migraine (n = 52) Control (n = 49) |
Migraine: 35.88 Control: 34.24 |
Migraine: 38.08 Control: 48.03 |
Serum vitamin D and VDR levels were significantly lower in migraine patients than controls. Serum VDBP levels were similar between the two groups. Serum vitamin D, VDBP, and VDR levels showed no correlated with headache characteristics. |
Associated |
| Zandifar (2014) [66] | Case-control | Migraine (n = 105) Control (n = 110) |
Migraine: 33.59 Control: 32.46 |
Migraine: 13.55 ± 0.91 Control: 13.19 ± 1.19 |
There was no significant difference in vitamin D levels among between case controls. Severity of headache was not related to vitamin D levels. |
Not associated |
| Mottaghi (2013) [42] | Cross-sectional | Migraine (n = 76) | Mean: 33.1 | 23.3 ± 1.8 | Serum vitamin D were weakly positively associated with headache diary result but not related to migraine severity High serum levels of 25-OH-D3 were related to a higher headache diary result. |
Associated |
| Kjaergaard (2012) [67] | Cross-sectional | 11,614 participants of the sixth survey of the Tromsø study in 2007–2008 | Range: 55–58 | No data | Serum vitamin D levels were inversely associated with non-migraine headache but there was no significant association between migraine and serum vitamin D. | Associated |
| Knutsen (2014) [24] | Cross-sectional | Headache (n = 63) | No data | No data | Mean serum vitamin D levels in patients with headaches were lower than in those suffering from musculoskeletal pain or fatigue. Headache was inversely associated with hypovitaminosis D. |
Associated |
Abbreviations: CH–cluster headache; CM–chronic migraine; EM–episodic migraine; MWA–migraine with aura; MWoA–migraine without aura; PedMIDAS–Pediatric Migraine Disability Assessment; TN–trigeminal neuralgia; TTH–tension type headache; VDBP –vitamin D binding protein; VDR–vitamin D receptor.