Low Vitamin D Linked to Increased Headache Risk

Deborah Brauser

January 19, 2017

More research is adding to the literature of a link between vitamin D deficiency and headaches, at least for men living in colder climates.

Data from 2600 middle-aged men from Finland who participated in the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study showed that those with the lowest levels of serum 25-hydroxyvitamin D (25[OH]D) were more than twice as likely to report having chronic headaches as those who had the highest vitamin D levels.

"This increased risk was only seen in the lowest quartile. But it was surprisingly strong for the men with very low vitamin D status," lead author Jyrki K. Virtanen, PhD, adjunct professor in nutritional epidemiology at the University of Eastern Finland in Kuopio, told Medscape Medical News.

Dr Jyrki K. Virtanen

In addition, reports of chronic headache were significantly more frequent in months other than the summer months (June through September).

The findings were published online January 3 in Scientific Reports.

Past Results "Inconclusive"

The investigators note that although past studies have examined the link between vitamin D and headaches, the results have been "inconclusive" because many included small sample populations.

Dr Virtanen said that the investigative team was also interested in examining these associations in a population from Finland, "where there's quite low exposure to vitamin D from the sun most of the year."

So they examined a cohort of 2601 participants in the population-based, all-men KIHD study. All were aged 42 to 60 years at baseline, which was between 1984 and 1989.

"When the KIHD study originally started, men here in this part of Finland had the highest prevalence of heart disease in the world, and it was looking at risk factors for cardiovascular disease," said Dr Virtanen, when asked why only men were included.

"But of course other data on other risk factors were collected, such as on headache," he added.

During the baseline examinations, questionnaires asked the participants to report headache status during the previous 12 months. "Frequent headache" was defined as a daily or weekly occurrence — and was reported by 9.6% of the full group.

Also at baseline, fasting venous blood samples were collected during morning hours and 25(OH)D concentrations were measured.

Interestingly, the mean concentration of serum 25(OH)D for the study group was 43.4 nmol/L, which is below the 50-nmol/L threshold generally considered to be a marker of vitamin D deficiency. In fact, 67.9% of the group had levels that were less than 50 nmol/L. Only 6.9% had concentrations of 75 nmol/L or greater.

All participants were split into four subgroups based on their level of serum 25(OH)D. The group with the lowest level had a concentration of less than 28.9 nmol/L and those with a concentration greater than 55.0 nmol/L were placed into the highest level group (n = 650 in each group).

The two middle groups had concentrations of 28.9 to 40.1 nmol/L (n = 650) or 40.2 to 55.0 nmol/L (n = 651).

The lowest concentration group members "were more likely to be younger, have lower leisure-time physical activity, lower income, and lower self-reported health" (all, P for trend < .02), report the investigators. This group was also more likely to smoke (P < .001).

Significantly Increased Headache Odds

After adjustment for factors such as age and date of blood draw, the average 25(OH)D concentration was significantly lower for the study participants who did vs those who did not report frequent headaches (38.3 vs 43.9 nmol/L, respectively; P < .001).

In addition, fully adjusted analysis showed that the odds for frequent headache were 113% greater in the lowest vs highest concentration groups (odds ratio, 2.13; 95% confidence interval, 1.42 - 3.18; P < .001).

Finally, 7.2% of the men who had blood drawn during high ultraviolet B (UVB)-exposure months reported frequent headache vs 10.4% of the men who had draws in other months (P = .02).

The investigators note that study limitations include that the outcomes were self-reported and they had no information on headache type, only a small percentage of the participants had very high serum 25(OH)D levels, and the cross-sectional design of the study itself prevented them from evaluating the direction of the associations found.

"For example, those who suffer from frequent headaches may be less likely to spend time outdoors and would thus be less exposed to the UVB light," write the researchers.

"However, this may not be that relevant in Finland and in other regions where UVB exposure is strong enough for vitamin D formation in the skin only during few months of the year," they add.

Another limitation cited was that it only included middle-aged men. When asked whether the results are generalizable, Dr Virtanen said, "Yes to other populations. But to women, I'm not sure. That's one of the drawbacks in this particular study."

The researchers note that while their findings suggest a link between vitamin D deficiency and risk for chronic headache, large trials are needed to assess whether long-term use of vitamin D supplementation can actually convey benefit.

"A Number of Open Questions"

Mark W. Green, MD, professor of neurology, anesthesiology, and rehabilitation medicine and director of headache and pain medicine at the Icahn School of Medicine at Mt Sinai, New York City, noted to Medscape Medical News that, while interesting, it's important to not credit the study too much in terms of treatment implications.

Dr Mark W. Green

"The identified association does not mean causation. And this was a men's study, when there's a 3-to-1 female-to-men ratio in migraine," commented Dr Green, who was not involved with this research.

That said, "this information isn't that new as we've seen these associations before. It's more confirmatory of what we already thought."

Dr Green commented that past studies have given mixed results when examining whether supplementing vitamin D "does anything for headaches" and reiterated that the current findings are association, not causation.

"Whenever we do a migraine study, one of the things you have to keep in mind is that migraine is a phenotype. And it's probably due to [many] different genotypes which we've not fully identified," he said.

"There are a number of open questions: Where does this lead us? Does vitamin D supplementation help? And does it help in women? Does a certain level of [nmol/L] predict improvement? Suppose you have a normal level: is more better? We don't know that either," Dr Green pointed out.

"So we're far from saying that we should test this in everyone and if it's low we should treat it, at least in terms of migraine."

Researchers conducting the on-going Finnish Vitamin D (FIND) trial are hoping to answer some of these questions. The 5-year University of Eastern Finland randomized clinical trial includes 2500 participants, half of whom are women, who are taking 40 or 80 μg of a vitamin D supplement daily or matching placebo. FIND is then assessing the treatment's effect on various conditions, including those involving pain.

Dr Virtanen reported that the study is scheduled to end in the spring of 2018, with first results to be released soon after.

Dr Virtanen, seven of the eight study authors, and Dr Green have disclosed no relevant financial relationships. The remaining study author was supported by a research grant from the Academy of Finland.

Sci Rep. Published online January 3, 2017. Full text

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