Low Levels of Vitamin D may be associated with Migraine

A recent study conducted by researchers in JIPMER has shown that Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. 

The exact mechanisms contributing to the pathophysiology of migraine are elusive. Recent evidence supports the role of underlying neurogenic inflammation activating meningeal nociceptors and vascular smooth muscle dysfunction. Vitamin D modulates brain-derived reactive oxygen species production, regulates calcium signaling in the brain, and also stimulates neurotrophic factor production. Hypovitaminosis D is associated with lower serum magnesium levels, which is also associated with migraine attacks.Diverse neurological diseases, such as fibromyalgia and depression, which are associated with vitamin D deficiency, are often closely associated with migraine. There is also growing evidence regarding the role of endothelial dysfunction in the pathophysiology of migraine implying that migraine is attributed to vascular smooth muscle dysfunction with which vitamin D deficiency is often associated.

In the last few years, several studies have exhibited the relationship between chronic pain and vitamin D deficiency. In this meta-analysis published in Neurology India, the autthors aimed to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms.

They found a significantly lower level of serum 25-hydroxy vitamin D in the migraineurs as compared to that in the nonmigraineurs. Vitamin D deficiency was also found in a study involving patients with chronic tension-type headache. They also found that hypovitaminosis D was significantly associated with migraine. 

They further found that vitamin D supplementation resulted in a statistically significant reduction in migraine frequency as compared to placebo. The probable explanation of this finding is due to a favorable change in the cytokine milieu after vitamin D supplementation resulting in reduced inflammation and pain. Vitamin D, via its active metabolite 1,25-dihydroxy vitamin D, is known to modify the sensitivity of nociception through a reduction in nitric oxide generation and its interactions with calcitonin gene-related peptide, thereby reducing the headache frequency in the migraineurs.  Vitamin D deficiency is known to be associated with interleukin-1, interleukin-6, tumor necrosis factor-α, and nitric oxide production. These results support the idea of utilizing the anti-inflammatory effects of vitamin D in inflammatory diseases, such as migraine as a primary drug or as an adjunct therapy with other drugs.

However, the study found that vitamin D intervention did not produce any beneficial effects on the duration and severity of migraine as compared to placebo. Hence, although vitamin D supplementation was found to be effective in reducing the frequency of migraine attacks, it appears not to have any beneficial effects once a migraine attack occurs, thereby suggesting a prophylactic rather than a therapeutic role. 

Reference: 

Das S, Roy A, Behera SK, Selvarajan S, Kamalanathan S, Sahoo JP, Nair N S. Effects of Vitamin D on Migraine: A Meta-Analysis. Neurol India 2023;71:655-61 DOI: 10.4103/0028-3886.383862