Vitamin D Deficiency Observed in Patients With Chronic Migraine, Medication Overuse Headache


Findings from an observational study indicate that chronic migraineurs with medication overuse headache may be deficient in vitamin D.

Results of a retrospective observational study indicate an association between chronic migraine (CM)–medication overuse headache (MOH) and vitamin D deficiency, potentially reflecting the anti-inflammatory and tolerogenic properties of vitamin D. Findings were published in Frontiers in Neurology.

Previous studies have showed a link between serum vitamin D levels and migraine. Specifically, the micronutrient “acts as a developmental neuroactive steroid, influencing various functions of the nervous system and neurotransmitters levels,” researchers wrote. It also “regulates serotonin neurotransmission through the genomic regulation of tryptophan hydroxylase 2.”

To explore the level of vitamin D in patients with different kinds of headache, and in relation to pain chronification, the occurrence of chronic extracranial pain (neck, upper and lower back, upper and lower limbs), and allodynia, investigators recruited 80 patients with a diagnosis of primary headache to participate in an observational study.

Between January 2017 and December 2018, patients over the age of 18 and who were not taking vitamin D and/or calcium or multivitamin supplements were enrolled in the study. Each participant presented with episodic migraine (EM) with or without aura, CM, MOH, tension-type headache (TTH), or chronic TTH.

Demographic and medical data were collected in addition to blood samples measuring serum calcifediol (25[OH]D)—the concentration widely considered the most reliable indicator of vitamin D reserve, according to authors. The metric reflects both dietary intake and exposure to ultraviolet (UV) radiation.

In the current analysis, vitamin D status was categorized as insufficient for 25(OH)D values less than 20 ng/ml.

The majority (86.6%) of participants were diagnosed with migraine, with 48% presenting with EM and 52% with CM. “Since CM was complicated by MOH in 91% of the cases, the CM and MOH groups were lumped together in the CM–MOH group,” researchers explained. This subgroup had a mean age of 52 years. The remaining 13.2% of the cohort had episodic TTH; 44.1% of all participants had extracranial pain, and 47.6% suffered from allodynia.

Analyses revealed:

  • Vitamin D deficiency (serum 25[OH]D level <20 ng/ml) was detectable in 46.1% of the patients and occurred more frequently (P = .009) in patients with CM-MOH (62.9%) than in those with EM (25.7%) or TTH (11.4%).
  • Occurrence of extracranial pain and allodynia was higher in the CM-MOH group than in the EM and TTH groups but was not related to the co-occurrence of vitamin D deficiency (Fisher's exact test P = .11 and P = .32, respectively).
  • Season of study enrollment, patient lifestyle, and headache treatment did not affect serum concentrations.

“The mechanisms underpinning migraine chronicity are not fully clarified, but they seem to be connected to a sensitization process acting at a peripheral level first and at a central level afterwards,” authors wrote. Notably, vitamin D is thought to also counteract neuroinflammation.

The retrospective design of the study and its relatively small sample size mark limitations.

“Our results show an association between CM–MOH and vitamin D deficit,” researchers concluded. “We did not find the same relationship between vitamin D deficit and extracranial pain and allodynia, thus suggesting that their pathophysiological mechanism is not exactly the same of pain chronification in CM–MOH.”


Rebecchi V, Gallo D, Cariddi LP, et al. Vitamin D, chronic migraine, and extracranial pain: is there a link? data from an observational study. Front Neurol. Published online May 13, 2021. doi:10.3389/fneur.2021.651750

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