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In the Clinic – Headache: Is the Correlation between Low Vitamin D Level and Chronic Tension-Type Headache Clinically Meaningful?

Hurley, Dan

doi: 10.1097/01.NT.0000525667.82023.93
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In a case control trial, researchers found that vitamin D deficiency led to an increased risk for chronic tension-type headache. But independent experts said a phase 3 randomized trial is needed to assess outcomes.

A case-control study has found a strong correlation between low blood levels of vitamin D and increased risk of chronic tension-type headache. But with compelling evidence from randomized trials lacking, the study has done little to quell the debate over the vitamin's clinical significance.

Researchers from Smt. B.K. Shah Medical Institute & Research Centre in Vadodara, India, tested the serum 25-hydroxyvitamin D of 100 consecutive adults who came to its headache clinic and fulfilled the International Classification of Headache Disorders-3b criteria for chronic tension-type headache (CTTH). They compared those findings to 100 matched healthy controls.

The mean serum 25-hydroxyvitamin D level was about half as high in CTTH patients as in the controls (14.7, + 8.5 ng/mL vs 27.4 +10.2 ng/ mL, p<0.001). Prevalence of vitamin D deficiency, below 20 ng/mL, was 71 percent in CTTH patients compared to 25 percent in controls (p<0.001).



CTTH patients also had a significantly high prevalence of musculoskeletal pain (79 percent vs. 57 percent, p<0.001) and muscle weakness (29 percent vs. 10 percent, p=0.0011).

“We know that vitamin D deficiency causes generalized pain, muscle and bone tenderness, muscle weakness and fatigue by involving both muscle and bones,” said the first author of the paper published in July in the journal Headache, Sanjay Prakash, DM, professor of neurology at the medical institute.

“Pericranial muscles and bones of the skull are not different from the muscles and bones of other parts of the body. Therefore, we speculate that vitamin D deficiency may cause headache and pericranial tenderness by involving skull and pericranial muscles.”

Neurologists who specialize in headache said the study was well designed, but emphasized that it does not settle the question of whether treatment with vitamin D can improve outcomes for people with headaches, which only a phase 3 randomized trial can do. They also expressed surprise, and some puzzlement, that so many patients with chronic tension-type headaches could be found at a single institution, something they would not expect to see in the United States.

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Jennifer Bickel, MD, FAAN, chief of the headache section in the division of neurology at Children's Mercy Kansas City and associate professor of pediatrics at the University of Missouri, Kansas City, said the new study is keeping the scientific dialogue going on whether vitamin D might be an effective clinical treatment for at least some cases of headache or migraine.

But, she added, “Ultimately we're going to need a large-scale vitamin D intervention study to look for outcomes.”

She said she was surprised that Dr. Prakash's group collected 100 chronic tension-type headache patients, particularly given that those with a confirmed diagnosis of migraine were excluded.

“The vast majority of patients we see with chronic daily headache have migraine,” she said.

Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, where he directs the Dartmouth Headache Center, shared Dr. Bickel's ambivalence about the role of vitamin D in headache generally.

“I think we don't know its significance,” he said. “I see a lot of patients who have had their vitamin D blood levels drawn and who have been taking supplements as a result. But I don't prescribe it, and I haven't started routinely testing people.”

What's needed, he said, is for the promising results from the simvastatin-vitamin D trial to be replicated in a larger, phase 3, multifactorial trial in which the two agents are given separately and combined, and for those three arms to be compared to placebo.

Rami Burstein, PhD, professor of anesthesia and neuroscience at Harvard Medical School, hopes to conduct that trial. Of the case-control paper by Dr. Prakash, he said, “Correlation is not the same as causation. It makes sense that low vitamin D levels would be associated with a higher incidence of muscle tenderness and tension-type headaches. But just because it makes sense doesn't mean it's true.”

In the meanwhile, he said, “For me to recommend combining simvastatin with vitamin D would be irresponsible. We have only a phase 2 trial, and that's not enough for physicians to go ahead and start prescribing it.”

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•. Prakash S, Rathore C, Makwana P, et al Vitamin D deficiency in patients with chronic tension-type headache: A case-control study Headache 2017;57(7):1096–1108. Epub 2017 May 3.
    •. Prakash S, Makwana P, Rathore C, et al Vitamin D deficiency mimicking chronic tension-type headache in children BMJ Case Rep 2016; pii: bcr 2015213833.
      •. Virtanen JK, Giniatullin R, Mäntyselkä P, et al Low serum 25-hydroxyvitamin D is associated with higher risk of frequent headache in middle-aged and older men Sci Rep 2017; 7: 39697.
        •. Buettner C, Nir RR, Bertisch SM, et al Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial Ann Neurol 2015; 78(6):970–981.
          © 2017 American Academy of Neurology