Isolated and Joint Effects of Stress & Fasting on Headache
A recent study published in Headache: The Journal of Head and Face Pain, “Stress and Fasting for Inducing Migraine Attacks: A Randomized 2 × 2 Factorial Crossover Trial,” led by Timothy T. Houle, PhD, evaluates the independent and joint effect of two commonly cited migraine headache triggers on the likelihood of headache onset in those with migraine.
To study both stress and fasting, researchers used an efficient factorial crossover design, assigning stress as the control condition and randomizing fasting across two study visits in a controlled laboratory environment. Headache onset was defined as the acute onset of at least a moderate intensity headache within a 6-hour time frame, allowing for temporal alignment with the hypothesized effects from the experimental manipulations. The findings revealed that fasting alone was associated with a small but noticeable increase in the chance of headache onset, while stress alone had a decreased chance.
Notably, those exposed to only stress experienced a sharp increase in headache onset eight to twelve hours later. “And that lines up with what Richard Lipton and his team has called the letdown headache,” said Dr. Houle. “The letdown phenomena lasted 12 to 24 hours. That was a little longer than I thought. It was surprising.”
Most importantly, the data showed that the combination of both exposures led to a greater likelihood of acute headache onset, and with earlier presentation. “If you got stress by itself, you didn't get an attack until later, but if you had stress and fasting, well, then you had an attack closer to the real time. It happened earlier and more often. So we concluded that stress and fasting may interact to increase your risk of having an attack,” explained Dr. Houle.
Watch the full interview with Dr. Houle:
Incidentally, fewer headaches were observed across the whole study, despite participants reporting a higher frequency ahead of the study. “I still don't know what to make of that, but the attacks we did observe seemed to be associated with certain combinations of things and that's what we really chose to focus on in the paper,” added Dr. Houle.
Headache publishes original clinical and basic research on head and face pain, aiming to advance understanding and care of headache medicine. This study contributes to a growing body of research aimed at understanding the causes of headache among individuals with migraine and helping clinicians develop management strategies that consider how multiple triggers work together.
The confluence of triggers and the letdown headache associated with stress underscores the importance of building stress resilience. Dr. Houle encourages providers to recommend behavioral approaches and stress management techniques to their patients to help protect against the effects of stress. Additionally, he suggests individuals with migraine should pay close attention to periods of stress, which may cause them to miss a meal, potentially increasing the chance of headache.
The study also reveals a major challenge in understanding migraine triggers: variable control. “There's so many things that we think or people have hypothesized that might cause attacks,” said Dr. Houle. “The weather, mood, too much water, not enough water, certain foods, exercise. So if you're doing a study where you want to isolate the effect of these others, you want to make sure you can try to control those other ones as much as possible. And that's really hard to do. For example, in our study, we couldn't control weather. So we tried to control the amount of stress they had and their fasting and we just let everything else vary.”
Looking ahead, Dr. Houle and colleagues are continuing to enroll participants into the larger forecasting study in which this factorial study was embedded. The forecasting study aims to predict when individuals will experience an attack in the future with modeling.
This research shines a light on the difficulties of identifying a singular cause for migraine attacks and the potential combined effect of multiple triggers. Coupled with larger studies and further research on other triggers, these observations can help clinicians and patients develop strategies for reducing headache attacks.
Read the Full Transcript
Dr. Rashmi Halker Singh:
I'm Rashmi Halker Singh. I'm the deputy editor of Headache. It's my pleasure to be joined today by Dr. Tim Houle, who's one of the authors of a recent publication entitled Stress and Fasting for Inducing Migraine Attacks. Today we're discussing this paper that talks about how stress and fasting, two commonly reported migraine triggers, may interact to influence migraine. Welcome, Dr. Houle is so excited to talk to you about this recent work.
Dr. Tim Houle:
Thank you very much. It's good to be here.
Dr. Rashmi Halker Singh:
So first of all, what inspired you to study stress and fasting together rather than separately?
Dr. Tim Houle:
Good question. It's widely believed that stress causes headache attacks. A lot of individuals with migraine believe that's true. It's also pretty common to believe that fasting or missing meals or maybe not eating enough food might also cause attacks. But what's less well known is if the two of those factors combine to produce risk that's maybe beyond either one by themselves. And so we were trying to figure that out in this study.
Dr. Rashmi Halker Singh:
So you used something called a two by two factorial crossover design. Can you briefly explain what that is and what that allowed you to test?
Dr. Tim Houle:
Absolutely. So, if you're trying to study two things at the same time, a factorial design can be a good idea. Basically what you do is you can randomize one or more of the levels of one of the factors and then you randomize one or more or the others too. We randomized fasting. So at each visit, when someone came into the laboratory, they either were randomized to be fasting or not. And so if they fasted the first visit, then the second visit they crossed over and they were not. That's the crossover, they do the other. We were worried about the stress condition, so we didn't randomize that. Everybody did the control condition, which would be no stress, on the first visit, and then they crossed over to the stress condition on the second visit. So fully randomized fasting with a set order of stress.
And what this allowed us to do was to look at the combinations of those things without having to study four or five times as many people as it might've taken if everybody got a recondition. So this allows you to use an efficient design within persons so that you can actually take a look to see what the effect of the combinations are or each one by themselves without having to study a lot more people.
Dr. Rashmi Halker Singh:
That sounds so straightforward the way you explain that. But as we both know, it can be very challenging to study migraine triggers. Can you explain that a little bit and speak to that point?
Dr. Tim Houle:
Yeah, I think migraine triggers are one of the hardest things to study in the whole headache world. We're not even really sure what causes headaches anyway. And I don't think we believe they are just caused randomly, so something causes them. But what that is is hard to put your hands around. So people have more or less headaches. So person one might have a lot of headaches and person two might have very few, but they both report different sets of beliefs about what might cause their attacks. So when you study something like this, you want to expose people to the things that you think or that they think might cause attacks. That can be stressful in itself or threatening because a lot of times people avoid the things that they think cause their attacks. So it's tricky because you have to expose someone to something that they may not want to be exposed to because they avoid them.
That's one issue. The other is there's so many things that we think or people have hypothesized that might cause attacks. So the weather, mood, too much water, not enough water, certain foods, exercise. You and I both have read it. There's a lot of things that we think might cause headaches. So if you're doing a study where you want to isolate the effect of these others, you want to make sure you can try to control those other ones as much as possible. And that's really hard to do because there's all these other factors.
So for example, in our study, we couldn't control weather. We just had the weather as it did, varied on any given day, whatever the weather was, we just rolled with it, if that makes sense. So we tried to control the amount of stress they had and their fasting and we just let everything else vary. And so that'll make it a little noisier than if we were to control other things, but we just didn't think we could. I hope that answers your question.
Dr. Rashmi Halker Singh:
Absolutely. And I think it's very relevant and applicable to the real world. So what did you find? What were your main results?
Dr. Tim Houle:
We found a couple things that I want to tell you about. First of all, we didn't observe many headaches in the laboratory. So we brought people in and we observed them for about eight hours during the day. And remember, they were either fasting or not and they had either been stressed out or not. And I'll tell you about the stress in a second if you want to hear more about that. But what surprised us was that we only observed 16 or 18 headache attacks across the whole study. When we asked people ahead of time their headache frequency, they reported much higher headache frequency than that. So we expected more attacks in the laboratory than we actually observed, which is interesting. I still don't know what to make of that, but the attacks we did observe seemed to be associated with certain combinations of things and that's what we really chose to focus on in the paper.
For example, fasting by itself. So fasting without stress was associated with a small increase in the chances that someone would get an attack. It was a small increase, not a large one, but enough to make us take notice of it.
The opposite, so stress without fasting, was associated with a decrease in the amount of headaches, the chance of having a headache, which I think was interesting. So during the lab visit, they were less likely to get an attack if we stressed them out. Now, after the lab visit was over, these individuals had a sharp increase in the amount of attacks in the next eight to 12 hours. And that lines up with what Richard Lipton and his team has called the letdown headache. So you get a dose of stress right away and then after the stress subsides, well, then your risk goes up. So that's how we interpreted that.
But the most important finding we thought was the combination of the two. So if you fasted and had this stress, then the probability of getting in a headache attack increased even more. It wasn't a profound amount, but it was more than either one by themselves and it roughly happened earlier. So if you got stress by itself, you didn't get an attack until later, but if you had stress and fasting, well, then you had an attack closer to the real time. So it happened earlier and more often. So we concluded that stress and fasting may interact to increase your risk of having an attack.
Dr. Rashmi Halker Singh:
I think all of that's very fascinating. Some of that resonates with things that I see in my clinical practice. For example, the letdown headache phenomena is something that patients commonly share with me. I'm curious though, did any of this surprise you? And was any of this unexpected to what you thought you might see when you went in to do this work?
Dr. Tim Houle:
Yeah, I think we thought in the beginning that stress would increase attacks in the laboratory. So the fact that it decreased stress in the laboratory toward the letdown, it did surprise us. I don't know why. I knew about the letdown phenomena, but I thought that we'd see those attacks in the laboratory. After the stressor, we had individuals relax. And so we thought that the six hours after the stressor would be enough time for the attack to occur, but it looks like, so this was surprising, the letdown phenomena lasted 12 to 24 hours. That was a little longer than I thought. It was surprising.
Dr. Rashmi Halker Singh:
So how should the clinician seeing patients interpret your work and how should I counsel my patients the next time I see somebody in clinic who talks about triggers or diet or stress or even anything else that's related to the things that you found?
Dr. Tim Houle:
Great question. And I think that's a tough one too because obviously you can't control stress. Stress will happen to you. As a matter of fact, if you're a healthy adult or even a healthy child, you're going to get stress. It's the nature of life. So the stress is going to come at you regardless if you're ready for it or not.
So that's why I think the behavioral approaches are really good here because let's say exercise or physical conditioning, there seems to be some evidence that that can protect you against the effects of stress and so too can stress management techniques like deep breathing or muscle relaxation or problem solving, all the great things that psychologists do to help patients or individuals manage their headaches. Protecting against stress or having skills or tools to protect yourself from stress I think is a really nice thing. I think that's one of the things I'd recommend is if you haven't seen that or if you don't recommend that as a provider, maybe it's worth thinking about.
From the fasting point of view, it's a little easier. I think skipping meals seems like it's a bad idea and I think most people would know that, but obviously I think the two might go hand in hand because if you're really stressed out, it might make it more probable for someone to miss a meal because they're dealing with something or they're coping in some way. So I think the idea is that when you need to eat the most is when you might be least likely to do so because you're undergoing some stress. So knowing that would be important.
And my last thought on what providers could say to patients would be the idea of multiple triggers together. I think this study does shine a nice light on the idea that it's really hard to figure out one single thing that causes an attack. And this study supports that multiple things might come together to increase someone's risk for an attack — and we only studied two things.
There could be a lot of things that combine together, and I think helping our individuals who we see with migraine understand the fact that eliminating one single thing from their life may not be the cure. It just may not. It's probably not. It could be a bad idea because by eliminating certain things, you might make it more likely that you experience those things or you actually get attacks. So that's what I was hoping providers would learn from our study.
Dr. Rashmi Halker Singh:
They're excellent points. So what's the next step? What do you do next to build on the findings that you've gained from this work?
Dr. Tim Houle:
Yeah, thanks for asking. This was a laboratory study that was embedded in a large forecasting study. So what we're trying to do is predict when someone's going to get an attack in the future. So we follow people over time and we have them closely monitor mood, stress, sleep, all kinds of stuff. And we have these models that make a prediction about when they might experience an attack or the probability that they're going to have an attack. So these data nicely support some of the variables in our model, which we had identified. So now we've learned some things about that that we can put into those models. So we are currently enrolling for that study now, where we've got one year left on this study. We've going to try to enroll 320 people. We've already enrolled, I think about 240, so we're going to keep going, which is exciting.
So the next step is to try to use this information to predict when someone gets an attack.
Dr. Rashmi Halker Singh:
That sounds fascinating. I look forward to seeing what you find from that and how we can use that data to help our patients.
Dr. Tim Houle:
Well, thanks. Yeah, we're excited to do the work.
Dr. Rashmi Halker Singh:
Well, thanks so much for speaking with me today and we look forward to more work from you and your colleagues.
Dr. Tim Houle:
Thank you, Dr. Halker Singh. Appreciate it.