Obesity Linked Even to Infrequent Episodic Migraine

Pauline Anderson

September 12, 2013

Obesity raises the risk not only of chronic migraine but also of episodic migraine (EM), even relatively infrequent ones, new research suggests.

The relationship appears strongest among white women younger than age 50 years.

The research suggests that doctors shouldn't wait until patients with migraine have more frequent or chronic migraines to counsel them on the risk for obesity, said lead author B. Lee Peterlin, DO, associate professor, neurology, and director, headache research, Johns Hopkins University School of Medicine, Baltimore, Maryland.

"Obesity is associated with episodic migraine even of low frequencies," said Dr. Peterlin. "Healthy lifestyle behaviors, including healthy exercise and diet regimens, should be recommended as soon as possible. Additionally, clinicians should consider their patient's current weight and the potential impact of migraine medications on their weight before starting migraine preventative therapy."

The study is published online September 11 in Neurology.

Body Mass Index

For this analysis, researchers used the National Comorbidity Survey Replication (NCS-R), a 2-part nationally representative face-to-face household survey of English-speaking US residents aged 18 years and older.

Investigators categorized individuals who reported never experiencing headaches in the past as nonheadache controls. Those who reported having headaches in the past 12 months provided more detailed questions about such things as headache duration, severity, frequency, and presence of nausea and vomiting and of photophobia or phonophobia.

Participants who reported 168 or fewer headache days per year were categorized as having episodic headaches. Those with 108 or fewer headache days per year were categorized as lower-frequency EM and those with 60 or fewer as very-low-frequency EM.

Dr. B. Lee Peterlin

Participants self-reported their height in inches and weight in pounds, for calculation into body mass index (BMI) values (kg/m2). A BMI less than 18.5 was considered underweight, 18.5 to 24.9 as normal weight, 25.0 to 29.9 as overweight, and 30.0 or greater as obese.

The analysis included 3862 participants (average age, 46.6 years) who represented both white and black races. Of these, 188 fulfilled criteria for EM; the mean headache frequency was 40.8 headache days per year. Just over 43% reported visual aura.

After adjustments for age, sex, race, poverty, smoking, diabetes, and depression, the risk for EM was 81% greater in those who were obese than in those of normal weight (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.27 - 2.57; P = .001).

Similar findings were shown for the less frequent EM subgroups (low-frequency EM: OR, 1.83 [95% CI, 1.26 - 2.65]; very-low-frequency EM: OR, 1.89 [95% CI, 1.29 - 2.78]) compared with those of normal weight.

"The most important point of this study is that obese individuals had an increased risk of episodic migraine of any frequency — including low-frequency EM," Dr. Peterlin told Medscape Medical News. "While the risk of EM in general was increased by 81% in those with obesity, the risk of lower-frequency episodic migraine was increased by 83% to 89% in those with obesity."

Increasing Inflammation

There was a significant trend of increasing odds of EM with increasing obesity, the mechanisms for which may be related to inflammation. "All fat cells, whether they're in normal-weight, overweight, or obese subjects, can secrete proteins that change the overall state of inflammation in the body," said Dr. Peterlin. "As you gain weight, these fat cells function differently and move increasingly towards a proinflammatory state."

Age, race, and sex factored into the increased odds of EM in the obese compared with normal-weight participants. In those who were younger than 50 years, the OR was 1.86 (95% CI, 1.20 - 2.89; P = .006); in whites, the OR was 2.06 (95% CI, 1.41 - 3.01; P = .0002); and in women, the OR was 1.95 (95% CI, 1.38 - 2.76; P = .0002).

Although the reason the migraine-obesity relationship subsides with age isn't known, Dr. Peterlin noted that the risk for migraine itself is strongest in those of reproductive age (18 to 49 years), irrespective of obesity, and that migraine prevalence substantially declines after menopause and with older age, irrespective of obesity.

"The decline in disease risk associated with obesity with advancing age is not unexpected," she said. "Overall morbidity and mortality of obesity as well as the cardiovascular risks associated with obesity, which are increased in reproductive age individuals, have been shown to be attenuated or even inversely associated with obesity in older age."

The stronger relationship between EM and obesity in women might have something to do with differences in the quantity and function of fat cells. Dr. Peterlin noted that obesity is more common in women than men and that women's adipose tissue is distributed differently at different ages. "After puberty, women have more total adipose tissue and more subcutaneous adipose tissue than men. After menopause, women have an increase in visceral adipose tissue and an adipose tissue distribution more like men."

She also pointed out that fat cells in the subcutaneous and visceral depots function differently in women than in men and secrete different proteins and hormones.

Migraine alone also exhibits sex differences. Before puberty, migraine is about as common in boys as in girls, but it is 2 to 3 times more common in women than men of reproductive age, said Dr. Peterlin.

Previous studies that failed to find a relationship between obesity and EM included mostly or only patients of peri- and postreproductive age or used control groups that included participants with other headache disorders and nonactive migraine, said Dr. Peterlin.

Overlapping Mechanisms

Shared overlapping pathophysiologic mechanisms may contribute to the relationship between migraine and obesity, said Dr. Peterlin. "For example, the hypothalamus is activated in acute migraine attacks and regulates the drive to feed or not feed. Additionally, fat cells secrete several proinflammatory proteins which have also been shown to be increased in migraineurs during acute migraine attacks."

Certain lifestyle and behavioral factors may add to this association, said Dr. Peterlin. "Migraineurs may have lower activity levels than those without migraine due to pain, and they may take more medications which impact or cause weight gain."

It's not clear whether having migraine predates obesity status. "A longitudinal study following those without any headache disorder at baseline and monitoring obesity status and development — or nondevelopment — of migraine over time would be needed to determine this," she said.

But it does look like patients with EM who lose weight may have fewer headaches. Dr. Peterlin pointed to recent research that suggests bariatric surgery may be part of an effective migraine prevention treatment strategy.

One study that evaluated 24 morbidly obese male and female patients with EM reported a mean reduction in headache frequency from about 4 to 2 headache days per month 6 months after bariatric surgery. Another study of 23 morbidly obese patients with EM undergoing the same surgery found that the median monthly headache frequency declined from 4 to 2 headache days at 3 months and to 1 headache day per month at 6 months.

Dr. Peterlin referred to other research that links aerobic exercise with reduction in headache attack frequency, although it's difficult to sort out whether it's the exercise or resulting weight loss that lessens the number of headaches.

She added that no substantial data support a specific diet for overweight and obese migraineurs, although this is an area of current research.

As with previous studies, the current analysis did not find a link between obesity and the subgroup of patients with EM who have aura.

Because obesity is now linked to EM, doctors might want to reconsider pharmacologic therapy for these patients. Dr. Peterlin said amitriptyline, nortriptyline, valproic acid, and, to a lesser extent, propranolol are among the migraine prophylactic medications that can induce weight gain. Agents that are more likely to be weight neutral or be associated with weight loss include protriptyline, timolol, candesartan, and topiramate.

Some Controversy

Asked to comment, Ana Recober, MD, assistant professor, neurology, University of Iowa, Des Moines, and director of the Headache Clinic, said the study authors asked relevant questions and conducted a well-designed study that is important partly because, while the association between obesity and chronic migraine is well established, "there is still some controversy regarding the association between episodic migraine and obesity."

One of the strengths of the study relative to other population-based studies is that migraineurs without active headaches were excluded from the control group, Dr. Recober told Medscape Medical News.

She pointed out that the study results suggest that the risk of episodic migraine is increased only in obese women and not in obese men. As well, the study revealed a significant association between episodic migraine and obesity even in the subgroup of migraineurs with 5 or fewer days with headache per month, she said.

Dr. Recober thought it was noteworthy that study participants were initially screened by being asked whether they had ever experienced "frequent or severe headaches," so the participants with infrequent episodic migraines included in the study were most likely those with more severe attacks.

"It will be important to determine whether the association between obesity and episodic migraine is also present in subjects with milder pain," said Dr. Recober. "In fact, this could shed some light on our understanding of how obesity may influence migraine pathophysiology."

Another consideration, she added, is that the sample of black participants was not large enough to draw definitive conclusions. "Future studies would ideally include Asians and other races because the associations between BMI, body fat distribution, and percentage of body fat differ across populations," she said.

Dr. Peterlin receives investigator-initiated research support from GSK and Luitpold Pharmaceuticals for studies unrelated to the current manuscript; receives royalties from Oxford University Press, funding by National Institutes of Health-National Institute of Neurological Disorders and Stroke and Landenberger Foundation grants for a study unrelated to the current manuscript; and serves as an associate editor for the journals Headache and BMC Neurology.

Neurology. Published online September 11, 2013. Abstract

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