In our cohort of reproductive aged women, BMI was associated with migraine diagnosis in a linear fashion. After adjusting for confounders we found that obese women (BMI ≥30.0 kg/m2), when compared with normal weight women (BMI 18.5–24.5 kg/m2), were more likely to have had a diagnosis of migraine (OR=1.48; 95%CI 1.12–1.96). Further analyses revealed a linear trend in the prevalence and odds of migraine according to the severity of obesity. Extremely obese women (BMI ≥40.0 kg/m2) had a 2.75-fold higher odds of migraine (95%CI 1.60–4.70) when compared with the reference group. We also found that women diagnosed with migraine as children, were more likely than women without a diagnosis, to gain a substantial amount of weight as adults. Women with a diagnosis of migraine as a child had a 1.67-fold increased odds of gaining ≥10.0 kg since the age of 18 (OR=1.67; 95%CI 1.13–2.47), as compared with non-migraineurs.
Our finding of a cross-sectional association of migraine with obesity is in agreement with previous studies which evaluated the migraine-obesity relationship in predominantly reproductive age populations,5, 18
though not all,20, 21
prior studies on this topic. Ford et al5
reported a positive association between measured BMI and self-reported migraine or severe headache. The authors noted that obese (BMI ≥30 kg/m2
) participants in the 1999–2002 National Health and Nutrition Examination Survey (NHANES), had a significantly higher risk of having headache including migraine (OR=1.37; 95%CI 1.09–1.72) as compared with participants who had normal BMI values (18.5–24.5 kg/m2
Peterlin et al18
in their analysis of 21,783 adult participants NHANES, reported that the relationship between migraine or severe headaches and obesity may vary by age, gender, and adipose tissue distribution. The authors reported that the prevalence of self-reported migraine/severe headache was increased in younger (≤55 years) men and women with obesity (categorized as measure BMI ≥30 kg/m2
), independent of abdominal obesity (waist circumference ≥88 cm for women and ≥102 cm for men). After adjusting for confounders including as age, race and abdominal obesity, the ORs of migraine or severe headache for overall obesity were 1.38 (95%CI 1.1–1.7) for men and 1.20 (95%CI 1.04–1.39) for women <55 years of age. Abdominal obesity was independently associated with increased odds of migraine and severe headache among women (OR=1.26, 95%CI 1.10–1.45), but not men (OR=1.03, 95%CI 0.84–1.27). The authors observed no clear evidence of a positive association between migraine or severe headache with either overall obesity or abdominal obesity among older (>55 years) men and women.
In our present study, we observed particularly higher odds of a life-time prevalence of self-reported physician diagnosed migraine among severely obese and morbidly obese reproductive age women. This observation is also in general agreement with results from a small clinic based study of extremely obese women. There is a very high frequency of migraine noted among the morbidly obese. Horev et al,26
in their clinic-based study of 27 morbidly obese women attending preoperative clinic for laparoscopic gastric banding, noted that 48% reported suffering from severe migraine.
Our findings, and those of others,5, 18
are inconsistent with some published reports.20, 22
found no association between chronic migraine and obesity in their study of 684 peri and post menopausal Swedish women aged 40–74 years (OR=1.1; 95%CI 0.6–1.8). Similarly, Bigal et al,20
in their telephone interview study of 30,215 adults, aged 18–89 years of age, found no evidence suggestive of a positive association between prevalent migraine and obesity based on self-reported BMI. The authors did, however, observe significant associations of body mass index with episodic migraine of high frequency. Compared with the normal weight group (18.5–24.9 kg/m2
), obese (30–34.9 kg/m2
) subjects have a 1.9-foldincreased odds (OR = 1.9; 95%CI 1.9–4.4) and morbidly obese (≥ 35 kg/m2
) subjects have a 5.7-foldincreased odds (OR=5.7; 95%CI 3.6–8.8) of having 10–14 headaches days per month. Attack severity was also associated with BMI; 65% of the morbidly obese (OR=1.9, 95%CI 1.2–2.4) report severe migraine attacks compared to 54% of the normal weight group.
Inconsistent findings across studies may be attributable to methodological differences in obesity and migraine classification and in participant selection. Residual confounding, and sample size may also have contributed to observed inconsistencies across studies. For example, some have argued that the obesity-migraine association may be more consistently observed among migraineurs with concurrent sleep apnea,27
whereas others note that age and gender significantly contributes to a change in disease risk.28
To the best of our knowledge, investigators have not previously evaluated risk of adult weight gain in patients diagnosed with migraine during childhood or early adolescence. However, available evidence from an observational follow-up study of 913 children across seven pediatric headache centers in the US, suggest cross-sectional associations of weight change with the prevalence and severity of headache and migraine.29
For children whom were obese or overweight at the initial visit, BMI change was positively correlated with change in headache frequency at 3 and 6 month follow-up (r
=0.32, p=0.01). Our observations potentially extend the literature by indicating increased odds of adult weight gain among migraineurs diagnosed with the condition prior to age 18 years.
The biological mechanisms underlying observed migraine-obesity and migraine-adult weight gain associations are yet to be fully elucidated. However, investigators have proposed several plausible and compelling hypotheses by which obesity (or severe headache) might lead to the development, worsening and chronification of headache disorders including migraine28, 30, 31
. Plasma concentrations of calcitonin gene-related peptide (CGRP), an important neurobiological mediator,32
are increased in obese versus non-obese women;33
and this has been implicated as one mechanism that accounts for associations of migraine, migrainous symptoms, and appetite with weight gain and obesity.20, 31
An alternative, or perhaps complementary, hypothesis is that the effects of obesity are mediated by a low-grade chronic inflammatory state. Adipose tissue secretes numerous cytokines, and adipocytokines known to influence immune and vascular endothelial functions as well as glucose metabolism in ways that favor chronic inflammation (including neurovascular inflammation), platelet aggregation, endothelial dysfunction and insulin resistance--conditions common to migraine and obesity.28, 34
also speculate that common underlying pathophysiological neuro-endocrine alterations involving the hypothalamus, serotonin and melatonin synthesis and secretion may, in part, explain observations of increased odds of obesity and weight gain in patients with migraine and other primary headache disorders.
The observation that the prevalence of migraine or severe headaches varies with the distribution of adipose tissue, age and gender,18
with increased prevalence among younger men and women with central adiposity, and decreased prevalence in older women with central adiposity have led some investigators to postulate that differences in sex hormones, age, menopausal status, and the site of adipose tissue storage (e.g., peripheral vs. central fat depots) may exert different neuro-endocrinological effects across the life-course and thus may account for inconsistent findings of obesity with migraine, headaches and their clinical course across study populations. Yet other investigators31
hypothesize that migraine may increase adiposity, via eating behaviors. This biologically plausible hypothesis is, in part, supported by our observation of increased odds of weight gain among women who were diagnosed with migraine as children.
While the strengths of this study include the large sample size, and relatively high participation rates, several limitations of our study merit discussion and consideration. First, participants’ migraine status was based on self-reports made during interviews and on medical records review. Similar questions to the ones we used in the current study to ascertain subject’s migraine status have been widely used in epidemiological studies such the Women’s Health Study37
and the National Health and Nutrition Examination Surveys (NHANES);18
and investigators have documented good agreement between migraine classification based on self-reports with information derived from medical records review.37, 38
Nevertheless, we cannot exclude the possibility of that migraine status was under-reported in our study. This concern is particularly important given that underreporting is likely related to participants’ social class, educational status and other socio-demographic characteristics. Studies that systematically use screening and confirmatory diagnostic evaluations will likely attenuate concerns about misclassification of migraine diagnoses in epidemiological studies. We were also unable to differentiate migraineurs on the basis of features such as the frequency and severity of attacks and efficacy and type of therapies used to manage symptoms. Moreover, we did not have information concerning the age of migraine onset. Hence, our use of age of migraine diagnosis can only be viewed as a proxy for migraine onset. Second, errors in reporting of anthropometric characteristics are likely to have occurred.39
Weights reported by participants in other studies, however, have been shown to be valid.40
Troy et al40
reported that women’s self-reported recalled weight at 18 years was highly correlated (r
=0.87) with weight at ages 17–21 abstracted from nursing school records. Third, although we adjusted for several potential confounders, we cannot exclude the possibility of residual confounding due to misclassification of adjusted variables or confounding by other unmeasured variables (e.g., the severity and frequency of migraine and medications used to control symptoms). Lastly, the generalizability of our study may also be limited as our cohort was primarily comprised of Non-Hispanic White and well-educated women. The concordance of our results with those from other studies that have included racially, ethnically and geographically diverse populations, however, serve to attenuate these concerns.
In summary, we found the positive association between pre-gravid body mass index and prevalent migraine. Our data support some earlier observations that the odds of migraine are increased in reproductive-aged women who are obese; and extend the literature to include evidence of adult weight gain among women with a history of pediatric migraine. If confirmed, our findings add to the call for further studies designed to comprehensively evaluate the effects of migraine (and its treatment) on appetite, energy expenditure, and dietary and sleep behaviors. Information from such studies may motivate the development and promotion of public health campaigns that target young adults with migraine, chronic headache and other pain disorders who may be more attuned to making healthful behavioral changes that can positively impact their reproductive outcomes and long-term health.