The association between migraine and obesity: Empty calories?

Epidemiological studies have identified a number of conditions that are comorbid with migraine (1,2). Failure to classify and analyze comorbid diseases can create misleading medical statistics. Comorbidity can alter the clinical course of patients by affecting the time of detection, prognosis, therapeutic selection and post-therapeutic outcomes (3). Few putative migraine comorbidities have caused so much debate and confusion as the one with obesity, which is curious, considering that plausible mechanisms to justify the association have been better defined than for many of the other well-accepted comorbidities (4,5). It is my personal opinion that the confusion is partially justified by the fact that several relevant and seemingly overlapping questions about this specific association have been proposed, including: (i) Are episodic migraine and obesity comorbid? (ii) Are frequent migraine headaches and obesity comorbid? (iii) If so, is the association specific to migraine, or is the association seen for any headache (or pain)? (iv) Is obesity not only associated with, but a risk factor for, migraine or frequent migraine headaches? (v) Alternatively, are migraine or chronic migraine risk factors for incident obesity? These are indeed very different research questions, often presented in a confusing framework with misleading conclusions. In the current issue of Cephalalgia, Winter and colleagues analyzed data from the Women’s Health Study (WHS) to examine whether having migraine is a risk factor for becoming overweight or obese (6). Although focusing on one of these questions, this very robust study offers us an opportunity to comment on the others as well. The study by Winter et al. is unique for many reasons. The WHS enrolled nearly 40,000 women aged 45 years or older at study entry. They were meticulously followed for more than a decade. Furthermore, being a clinical trial designed to test the benefits and risks of low-dose aspirin and vitamin E in the prevention of cardiovascular disease and cancer (7), exposures of interest (e.g. nutrition, exercise, health status) were collected more meticulously than in most other migraine cohorts. The sample size, quality of information and longitudinal nature of the study were matched by very sophisticated and elaborate statistical analyses, with robust adjustments. Three limitations are worth mentioning. First, migraine and body weight were self-reported. Self-report of migraine seems to have good correlation with gold-standard diagnosis as reported by the authors. Self-reported weight is of little concern, because biased information would most likely equally affect those with migraines and those without migraine. Second, the mean age of patients with migraine at the start of the study was 56 years. Third, headache frequency was categorized in less than monthly, monthly, weekly, and daily time periods, and the last two categories were pooled together, therefore lumping participants with 4 to 30 headache days per month in a single category. The authors analyzed participants (with or without migraine) with normal weight at study entry. After almost 13 years of follow-up, 49.3% became overweight and only 3.8% became obese. Findings were strikingly similar comparing participants with migraine and controls, leading the authors to conclude that migraine is not a risk factor for becoming overweight or obese. The authors also failed to identify an association between frequent headaches and incident overweight or obesity.