TRANSCRIPT:

Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease.

This episode is brought to you by our generous sponsors, Amgen and BioDelivery Sciences. 

Can regular aerobic exercise and physical activity impact migraine? Dr. Megan Irby explains what we know about the relationship between migraine and exercise, how it might help, and what we still need to learn.

Dr. Megan Irby: Hi there. Today we’ll be talking about migraine and its relationship with exercise and whether or not engaging in physical activity and aerobic exercise can yield a benefit. 

We know already that engaging in aerobic exercise — and that’s exercise that increases your rate of respiration and your heart rate — we know that that kind of activity can prevent or reduce symptoms of many different chronic diseases and medical conditions. Aerobic exercise may then seem like a very well-established therapeutic avenue for reducing migraine burden, and there are many different organizations that recommend exercise for improving migraine outcomes, like the American Academy of Neurology, the American Headache Society, and many, many more. 

But while there is some empirical support or scientific data to base this recommendation on, there’s still very little that we know about how exercise might confer that benefit to folks who have migraine. We lack the answers to some of the most fundamental questions about this relationship between aerobic exercise and migraine, like who might benefit? What dose of exercise is needed to see a benefit? Does migraine occur as a function of exercise, and if it does, how can that be prevented? What types of intensities are optimal? Is it effective as a treatment all by itself? Are there benefits of aerobic exercise that work in synergy with other behavioral or pharmacologic interventions? And what are the real mechanisms that underlie that potential benefit of aerobic exercise in migraine? 

So my colleagues recently conducted a systematic review that looked at headache interventions incorporating aerobic exercise. And there were about nine different studies at the time that this was done, and they found that aerobic exercise can yield at least a modest benefit for migraineurs. Virtually all of those nine studies reported reductions in headache frequency and intensity. Seven of nine studies reported improvements in at least one secondary outcome, being health-related quality of life, disability related to headache, and depressive symptoms as well. And no study reported any worsening of migraine.

Despite these apparent consistencies, though, it’s really a challenge to draw conclusions about how well exercise works as an intervention all on its own. And the reason it’s so hard to do that is because many of the studies that have already been done have looked at exercise as one component of multicomponent migraine interventions. So it might’ve been exercise plus a nutrition and a weight loss intervention, or exercise plus a pharmacologic agent, for example. So we don’t know the unique benefits of exercise for reducing migraine burden.

Earlier reviewers have been similarly critical of the literature related to headache and exercise and report the recommendation for exercise as a migraine treatment is really only deserving of a grade B or C, where A would be the best possible recommendation. So there’s still much more that we need to know. And part of the reason that these interventions have only gotten a grade B or a C is because there are very few randomized controlled trials. And when you’re not doing randomized controlled trials, it’s hard to isolate the benefit of exercise for migraine.

Despite these methodological limitations, the evidence that we do have with exercise as a primary intervention for headache reveals that the mean or average reduction in headache frequency is about 40 percent after 8, 10, or 12 weeks of engaging in physical activity. And that suggests that exercise as a sole intervention may yield benefits for folks who experience migraine and might also be a good adjuvant to behavioral and pharmacological interventions as well. 

Fortunately, there are a number of valuable insights that we can glean from one of the better trials that has been done at this point. So, in this trial by Varkey et al., it was a three-group randomized controlled trial that compared aerobic exercise with the drug topiramate and with another group of folks who were in relaxation training. And all three interventions were beneficial and equivalent with respect to their primary outcome variable, which was the number of headache attacks that somebody experienced in a week. 

Adverse events were not reported in the aerobic-exercise group or in the relaxation-training group but did occur in about a third of patients who were in the topiramate arm of the study. The study attrition rates, or the rate at which people were dropping out of the study, were fairly low for exercise, at about 16 percent; even lower in the relaxation-training group, at 13 percent; but were considerably higher amongst those who were in the topiramate group, at 32 percent. As you might imagine, the folks who were in the aerobic exercise group also enhanced their maximal oxygen intake, so they were able to take in more oxygen and utilize it more effectively. 

And while we find considerable value in this type of trial, we agree with others that these results are only really generalizable to folks who had the same number of headache days per month as those that were in the trial. And, in this particular trial, the folks who were participating only had about two to eight migraine days per month. 

Even in the absence of definitive research, a prescription of aerobic exercise may be well-advised for migraineurs because we already know so many of the other benefits of physical activity. And exercise also is beneficial in the management of so many other conditions that frequently exist alongside of migraine, so obesity, hypertension or high blood pressure, dyslipidemia, sleep apnea, depression, anxiety. So if we know exercise can be beneficial for any of those other issues, perhaps exercise can also confer a benefit to folks who have migraine. But it is useful, though, to look at other research and see what we can learn from other areas. 

So if we’re looking at the depression literature, for example, we can learn a lot about how exercise might influence migraine. There’s now a number of empirical studies that have boasted the antidepressive effects of exercise, with significant improvements in depressive symptoms that are equal to or even better than the use of antidepressant drugs. And though antidepressants may facilitate more rapid therapeutic responses, engaging in an aerobic-exercise program with the appropriate frequency, intensity, and duration might be just as effective for reducing depression in adults. 

So, adequate doses — when I say that, I mean 45 to 60 minutes of regular exercise on most days of the week at a level that’s considered to be moderate or vigorous. And that kind of exercise prescription has found to be useful for folks who are experiencing depression. And since depression is so highly linked with migraine, there’s a good chance that exercise will have a similar effect on migraine as it does with folks who are experiencing depression. 

So this body of literature can also be helpful for trying to tease out the potential mechanisms that link exercise and migraine improvement, as the antidepressive effect of exercise could be happening through the same kind of biological and psychological mechanisms, and certain antidepressant medications have shown success in reducing migraine frequency and severity. Studies thus far have shown that the therapeutic effect of aerobic activity on depression could occur through enhanced endorphin levels and neurotransmitter function, improved hormone regulation, decreased inflammation, and, just like antidepressants, it could also occur through increased serotonergic activation and neurogenesis. 

So these changes happening in the brain that we see in exercise and depression studies could also be happening in exercise and migraine. Improvements in self-efficacy and self-esteem also are associated with improvements in symptoms of depression and in migraine. So as it pertains to migraine, the progress documented over the last 30 years or so in the exercise and depression literature provides a really good model for determining effective guidelines for exercise as a migraine therapy. 

In addition to that, an exercise intervention might be well-suited for migraineurs, given their tendency towards inactivity and the reported association between low physical activity and greater migraine frequency. So folks who have migraine are less likely to engage in physical activity. Unfortunately, the evidence that we have really does not shed any light on whether migraine contributes to low levels of physical activity or vice versa. And there is conflicting evidence on whether migraine is a barrier to exercise participation. 

So, though we know engagement in regular exercise routinely is recommended as a means for managing and preventing migraine, the empirical support for this recommendation is really less than definitive, and we have a very weak understanding of the relationship between aerobic exercise and migraine, as well as the parameters for exercise regimens.

So, assuming that aerobic exercise is confirmed for its value for folks who have migraine, then a clear articulation of the mechanisms and pathways through which these benefits occur would prove invaluable for informing implementation of exercise therapies for migraine. And given that migraine is both a neurovascular and neuroinflammatory disorder, these inflammatory and neurovascular pathways are obvious candidates for studying the mechanisms through which exercise influences migraine.

So a big question here is, Does exercise trigger migraine? And this is a reasonable question, given that exacerbation of headache by physical activity is a defining diagnostic feature of migraine, according to the ICHD criteria. And these criteria list exacerbation of headache episodes by physical activity as a cardinal feature of migraine but not necessarily as a trigger of headache. In contrast with migraine, the physical-activity exercise serves as a trigger for primary exercise headache — that’s ICHD criteria 4.2 — but some migraineurs do believe that exercise triggers their migraine.

And that’s confirmed in some retrospective studies as well that show that between 22 percent and 38 percent of patients report a lifetime history of at least one exercise-triggered migraine attack, but we believe that these data have been influenced by recall bias. And that’s what we’re learning from a lot of these intervention trials that don’t support the assertion that exercise-induced headache applies to the typical migraineur. 

So in published trials that are looking forward at examining aerobic exercise as a treatment for migraine, there have been very few reports of exercise-induced headache. So in the Varkey study I talked about earlier, they reported a 0.1 percent incidence of migraine occurring in proximity to exercise — and that was in one trial — and reported no adverse headache events in a later trial. 

In future investigations, it would be prudent to track and report the incidence of migraine and where it occurs in proximity to exercise, but, interestingly, although exacerbation of headache by physical activity is incorporated into those ICHD criteria for migraine, a recent study by a colleague Dale Bond found no association between objectively measured daily physical activity and how often physical activity was cited as an exacerbating factor in migraine attacks. And this was over the course of a month. 

So, contrary to popular belief, physical activity might not actually be triggering or exacerbating migraine. There might be some other things that are going on here. For instance, a lot of folks who are not used to exercising might go out without warming up and getting their bodies ready. They might not be well hydrated, and they might be exercising in an environment that’s not very good for them physically. And, in doing so, they might be setting themself up for a headache, not because of the exercise that they’re engaging in, but because of lack of preparation around hydration and getting the body ready and warmed up for activity. 

So, back to focusing on mechanisms and markers. Perhaps the most common mechanistic conceptualization implies that aerobic exercise confers a benefit on migraine through exercise-induced enhancements and aerobic fitness. This conceptualization is intentionally broad, as the benefits of increased aerobic fitness could be occurring by any number of cardiopulmonary, inflammatory, and neurovascular processes. As a neurovascular and neuroinflammatory disorder, the physiology of migraine overlaps with the physiology of aerobic exercise in many different ways. 

Beyond these biological pathways, improvements in aerobic fitness and migraine could be occurring through these overlapping changes in social cognitive factors, like those self-efficacy beliefs that I mentioned. So, in reality, there are a number of different specific mechanisms and pathways that potentially could be operational in the relationship between exercise and migraine improvement. And these mechanistic pathways could be parallel and perhaps even synergistic, where they’re working together. 

So what do these mechanisms and markers look like? So, relying on some previous literature, we were able to identify mechanisms common to both exercise and migraine. There are additional biological pathways potentially linking aerobic exercise and migraine as well. So this list here is not necessarily comprehensive but presents instead a number of candidates that we should be exploring, as they may have an impact in that relationship between exercise and migraine.

So for each mechanism or a marker that’s listed here, we also have different examples and supporting evidence that they are affected by exercise and they also link to migraine. And these processes are known, based on the exercise literature, to be operational in exercise physiology and, based on the headache literature, to be operational in migraine pathophysiology. Any one or more of these mechanisms or markers operating independently, synergistically, or even antagonistically against one another may play a role in that link between aerobic exercise and migraine improvement.

So if we were to take all of this information and put it into a model for exploring these questions further, it might look something like this. So this is just a starting point here, and the true value of this process will only be realized once we develop an understanding of how these different various factors interrelate with one another. In other words, we need to possess a clearly articulated and ultimately validated conceptual model that shows the relationship between aerobic exercise and migraine and all of the different inner working parts in between.

So, conceivably, every single item that was listed on that previous slide could be incorporated into a single working model that could guide future research initiatives and priorities. And while this is valuable, a model like this would be highly complex. So, in this figure, we present kind of a model of what a conceptual model should look like and, principally, for the purposes of illustrating the types of models that can be built and how the various factors might interact with one another. 

So to do something that’s a bit more testable, here’s a smaller model. So even though that larger one is useful as a heuristic to help kind of guide our understanding of the relationship between exercise and migraine, it doesn’t really lend itself to be tested because it’s so big. In a more simplified or disaggregated model like this one, though it’s less complete, it’s more testable. It shows a simplified conceptual model that incorporates just a few components from that more complex model and just a couple of different pathways here.

So, to quickly summarize here, there’s not a whole lot of evidence from which we can base a recommendation for exercise related to migraine, but there is a wealth of evidence showing that exercise works on the same kind of factors that are also linked with migraine pathways. So even though we don’t have that good evidence to tell you exactly how much exercise you might need or what type and what dose and all of these other questions, we know that working towards a more active lifestyle likely does benefit migraine health.

So rather than telling folks to just go out and start exercising an hour every day or work towards running a marathon, instead we would say take baby steps towards decreasing sedentary activity. Take it one day at a time and start adding activity into your daily routine while also tracking and keeping an eye on your migraine and headache activity and see if there’s any connections there that you’re able to pull together in that relationship between exercise and migraine.

And also understand that the benefit of exercise for migraine is not one that’s going to accrue overnight. Typically, we see benefits occurring physiologically in our bodies after about the 12-week point. So engaging in exercise on most days of the week and decreasing your sedentary activity level for 12 weeks, you should start to see a benefit at least in some part of your body at that point by the end of 12 weeks. 

All right, that’s all I have for you today. Thank you.

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Voice-over: Thank you for tuning in to Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.