Both Overweight and Underweight Linked to Migraine

Deborah Brauser

April 21, 2017

Although past research has shown that obesity is associated with an increased risk for migraine, a new meta-analysis suggests that being underweight is also a significant risk factor.

After reviewing studies with a total of almost 300,000 adult participants, the investigators found that those who had a body mass index (BMI) of 30 or higher had a 27% higher risk for migraines than those who were at a normal weight.

In addition, the individuals who were underweight (BMI < 18.5) had a 13% higher risk.

Dr B. Lee Peterlin

The results, which "substantiate and validate" that both excessive and too-low body weight are migraine risk factors, "were not surprising to our team," principal investigator, B. Lee Peterlin, DO, associate professor of neurology and director of headache research at Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.

"Much like too much or too little thyroid hormone can cause disease, too much or too little adipose tissue can cause problems," said Dr Peterlin.

The findings were published online April 12 in Neurology.

Pooled Analysis

The researchers examined 12 studies that were published in peer-reviewed journals and had a cumulative number of 288,981 participants who were at least 18 years of age at baseline.

In both the age- and sex-adjusted models and the multivariate models, the pooled odds ratios (ORs) for migraine were significantly greater for patients who were obese or underweight compared with those who had a normal weight. But only the first model showed a significant association for those who were only overweight (BMI of 25 to 29.9).

Table. Obese, Overweight, and Underweight vs Normal Weight for Migraine Risk

Weight Status

OR (95% Confidence Interval)

P Value



  Age-, sex-adjusted model

1.27 (1.16 - 1.37)


  Multivariate model

1.21 (1.08 - 1.34)




  Age-, sex-adjusted model

1.08 (1.04 - 1.12)


  Multivariate model

1.01 (0.96 - 1.07)




  Age-, sex-adjusted model

1.13 (1.02 - 1.24)


  Multivariate model

1.12 (1.03 - 1.21)


aSignificant association.


"As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital" for both patients and clinicians, said Dr Peterlin in a release. "More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine."

The investigators note that although mechanisms for these associations aren't yet fully known, fatty tissue is likely involved.

"Since the mid-1990s, adipose tissue has been increasingly viewed as an endocrine organ that actively secretes a wide range of bioactive signalling molecules that have autocrine, paracrine, and endocrine functions," they write.

"With changes in body composition (increases and decreases), the production and secretion of these molecules from adipocytes changes."

However, they add that medication use, comorbidities, and changes in physical activity level could also be contributors.

Still, Dr Peterlin reported that the researchers are looking into differences in volumes and ratios of deep-to-superficial adipose tissue depots in individuals with and without migraine.

"We are also focusing on how to use targeted obesity-related proteins and lipids as potential [diagnostic] biomarkers…and as therapeutic agents for treatments," she said.

"A New Twist"

Approached for comment, J.D. Bartleson, MD, professor of neurology at Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News that although a lot of the data in the current study "covers old ground," the finding that risk for migraine was 13% if a person was underweight "was sort of a new twist."

Dr J.D. Bartleson

"A lot of times, people speculate about biochemical abnormalities and hormonal things even in the central nervous system, such as: what makes for obesity and are there metabolic and inflammatory changes that then cause more headaches?" he said.

"But now, if a person is on the other side of the fence and is underweight, how do you explain them having more migraines? It calls into question some of these metabolic factors that may be from being overweight."

Dr Bartleson, who was not involved with the research, also noted that the investigators write that it might be important to lower the weight in those who are obese in order to lower the risk for migraine. "Fair enough, but they don't mention that other people should maybe gain weight. That's unproven right now."

When asked what he thought the overall take-home message is, he reiterated the researchers' finding that being significantly overweight could have an adverse effect on headaches, "although we don't understand why that's the case."

"I wonder if it might be an inherited tendency," speculated Dr Bartleson. "Maybe what we're seeing is that the gene for migraine goes with the gene for being overweight and also for the gene for being underweight. So it could be interesting to do a genetic analysis."

Dr Peterlin has received funding through a grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, serves on the editorial board for Neurology, and is an associate editor for Headache. Disclosures for the coauthors are in the paper. Dr Bartleson has disclosed no relevant financial relationships.

Neurology. Published online April 12, 2017. Abstract

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