Voice-over: Welcome to Spotlight on Migraine: The Professional Series hosted
by the Association of Migraine Disorders.
Join us as we dive deeper into migraine topics with guests from the medical field.
This episode includes educational content intended for medical professionals, but may
be useful or interesting for patients as well.
In this episode, registered dietician, Margaret Slavin, reviews dietary patterns that have
been investigated in association with migraine and summarizes current evidence of dietary
interventions for migraine prevention.
This episode is brought to you by our generous sponsors , Amgen and Novartis.
Margaret Slavin: Hi there.
I am Margaret Slavin, and I am here to talk with you about dietary patterns in the context
of migraine prevention.
I am a PhD-trained food scientist specializing in
food composition as well as a registered dietician nutritionist who has taken up the mantle of
research on dietary migraine.
So there have been a spectrum of dietary approaches suggested to improve migraine across various
venues and expertise over the years.
These are the bins that I divide up the different dietary approaches in my own mind, and I've
highlighted here what I most want to talk about today, and that is the overall eating
patterns associated with migraine.
I want to be very deliberate about this.
I am not intending to ignore food triggers or supplements or weight management, but some
of these are being covered by other speakers, and I can only do so much in one presentation.
So I'm focusing on eating patterns today.
And when I submitted these goals originally for the March program, I said that I would
summarize the state of the evidence of dietary interventions.
But, meanwhile, that's already been done for me.
There's a great systematic review that came out of Stanford and is published in Headache,
and with my short time, I'll direct you there with just a few comments here.
I very much appreciated that they broke up their review into a few different categories,
including dietary patterns as observed in the population; triggers arising from within
the diet; and, finally, dietary interventions that have made that leap into controlled trials.
So, briefly, the conclusions probably won't surprise anyone who's been thinking and keeping
up with the data about diet and migraine, in that there is limited high-quality RCT
data on diet patterns or diet triggers.
And there are a few small diet interventions assessed by RCT, but they don't have strong
results.
And my interpretation as a dietician from this is that it's difficult to suggest that
someone change their eating pattern -- which we know is difficult for a whole host of reasons
-- on the basis of limited or weak support.
Then, as a researcher, I think what's most interesting to me is more this bottom piece,
which is that most diet interventions were related to decreases in frequency of migraine
attacks.
And so we know that there is a high placebo effect observed in migraine research outcomes,
and more broadly, in pain research.
And given that it's often difficult to show or to demonstrate that a dietary intervention
moves the needle very far on a health outcome, and especially during a short duration of
some of these trials, it's logical to conclude or at least to be suspicious of some of these
results in that the placebo effect is probably at play and showing up here in some of these
results.
And so then what do we do?
Where do we go?
How do we think about this?
What comes next?
So I'd like to explore this idea with you by looking at dietary interventions as a paradigm
oriented to disease status.
And that's what I've tried to depict here.
And so from this vantage, when we're designing a dietary intervention relative to any particular
disease, we can see that diets realistically can be tailored to do one of two things: either
prevent the disease from happening or manage a disease once it's happened.
And then one you're in a disease or you have a diagnosis, there are steps you can take
from diet in some cases to prevent exacerbation of the disease from advancing further, and
then there are some diet aspects that we might be able to tweak to manage symptoms.
So if we reorient ourselves to the types of study designs that are necessary to inform
interventions for any of these goals, we see that for chronic-disease prevention, really,
the primary means of evidence for chronic-disease prevention, at least in terms of nutrition,
remains longitudinal cohort studies.
There are some limited long-term clinical trials in nutrition, but their very nature
makes them expensive.
And so, frankly, there are relatively few long-term studies with large samples.
And the ones that do exist tend to be toward the more major diseases of public-health concern,
like cardiovascular disease and cancer, for example.
So that's chronic-disease-prevention types of studies.
And when we look at disease management in really either subcategory over here, we get
into the territory of smaller, potentially, randomized controlled trials as well as the
lesser-quality open-label trials or prospective observational trials over here.
And the importance of those long-term prospective epi-studies in nutrition is that they help
us to generate hypotheses for the limited RCTs that we are able to do.
And so we move up the pyramid in terms of quality of evidence as we do this.
Now, prospective cohorts help us to identify which dietary interventions are justified
in testing them out as an independent variable in those full clinical trials.
So here is my interpretation of where we are with dietary migraine interventions based
on the types of evidence that are available for migraine.
And, so, to my knowledge, we have essentially no longitudinal cohort data that would help
us to understand how long-term dietary interventions influence the development of migraine.
We also have limited longitudinal data on migraine after a diagnosis, especially as
it relates to diet, so we really don't have evidence for preventing exacerbation of migraine
through diet either.
What I will say is we do have evidence for the prevention of comorbidities of migraine
through diet and lifestyle, so we have evidence for prevention of cardiovascular disease and
stroke, diabetes, and obesity.
Although it's not explicitly in individuals with migraine, it's potentially low-hanging
fruit as an opportunity for the migraine community.
Then from the perspective of managing symptoms of migraine, this is where most of the trials
have investigated it as a means for migraine management and managing symptoms.
Yet even here there's limited evidence, as was mentioned in the systematic review discussed
earlier.
I divide these sort of arbitrarily into those diet interventions that target prevention
of attacks in general as opposed to those that target specific triggers, which can be
a very narrow aspect of diet.
And so we again are focusing here on kind of this more general approach for broad dietary
pattern to prevent attacks.
This slide spells out in a lot of verbiage what was on the previous slide, so I'll just
highlight a few things.
And one is that without that longitudinal epi-data that I keep mentioning, we're left
to other means to generate hypotheses to justify randomized controlled trials, which, frankly,
can make it a bigger stretch, and therefore it can be harder to find support for this
type of work.
One thing also that I haven't mentioned yet and on that previous slide, because it didn't
really fit, is that there's an increasing amount of cross-sectional data on diet quality
in individuals with migraine.
The one thing I'll emphasize here is to caution against big conclusions with cross-sectional
data, as is usually the custom.
When you see a dietary pattern was associated with migraine odds, for example, we don't
know the directionality of the relationship.
Do migraines cause a change in diet?
Does a diet cause a change in migraine?
It may be possible that neither is true and there happens to be something else in the
data that explains the relationship.
So, again, potentially hypothesis-generating data, but cross-sectional certainly has its
limits here as well.
This slide shows the controlled trials that had beneficial results for migraine and those
that made the cut in the systematic review that I mentioned earlier.
And so the focus on dietary patterns, as we saw in those interventions from the previous
slide, aligns with modern nutrition, this focus on patterns.
We don't eat single nutrients.
We eat meals, we eat snacks, we eat foods, and most of us follow some semblance of a
pattern of eating similar foods over a period of time.
And so the pendulum of modern nutrition is sort of swinging away from our overconfidence
in maybe the eighties and the nineties about the roles of individual nutrients, and we're
going kind of back to what you see on the screen now, in a lot of cases, where it's
all about dietary patterns, which, frankly, can be tricky but possible to quantify.
There are scales, for example, where we can quantify adherence to something like the Mediterranean
diet, as an example of a pattern that's been studied.
This picture -- I quite like -- is from Canada's food guide, and it shows the overall recommended
pattern by food groups, where half the plate is fruits and vegetables, and then the other
half is filled in with whole grains and protein foods.
And in all of these cases in the food groups, they're choosing a variety of foods within
each category -- so not just peas within the vegetable group, but a variety -- and minimizing
processed foods.
So that whole description makes up the pattern there.
So some patterns like this one are based on food groups.
Patterns can take on a number of different forms, food groups.
They can be strictly around macronutrient composition, and they can be even very individualized
as something done with IgG antibody testing to make an individual pattern or some combination
thereof.
Diets investigating macronutrient patterns have been of high interest to date, and the
macronutrients are the energy-contributing nutrients -- your carbs, fats, and proteins.
So this is where it gets interesting in that almost every pattern that's been tested here
seems to have a positive impact, which doesn't seem particularly likely, and they've been
very dramatically different from pattern to pattern.
And one of the reasons I'm suspicious of this -- and until the more recent trials, which
have better designs -- a lot of the trials were not designed to adequately isolate the
effect of the macronutrient modifications they were making.
So to decrease carbs, by necessity in the diet, you're changing something else in the
diet, which means you're either decreasing overall calories, which could have unintended
consequences elsewhere.
Or when you decrease carbs, you're concomitantly increasing one of the other macronutrients
in order to create and isocaloric diet as your control.
So I eye these studies a little suspiciously; but, thankfully, that is changing.
This is a good example of a well-controlled feeding trial in this space.
Now, their inclusion criteria was chronic daily headache, not exclusively migraine,
so they didn't make it into the aforementioned systematic review.
I do mention it here because they worked hard to design meaningful comparison groups.
Individuals were randomly assigned to 12-week interventions and were provided diets that
were either high omega-3 and low omega-6 or just low omega-6 intake.
And their designs were mechanistically driven.
Their intention was to promote omega-3 derivatives with antinociceptive properties in the bodies
while also decreasing omega-6 derivatives with pronociceptive properties.
And they succeeded in showing a difference between groups.
The high-omega-3 groups showed a greater reduction in migraine symptoms and positive influences
elsewhere.
So this was an elegant study to evidence a dietary intervention for reducing migraine
symptoms, so, yes!
But the diet is very far from the typical American diet.
Omega-6 is the predominant fatty acid in our food supply.
It's in high levels in just about any processed food that contains vegetable oil, which there
are many different kinds: sunflower, soybean, canola, corn.
So this team went to great lengths to design their own recipes to achieve this dietary
intervention with low omega-6 and provided food to their participants for 12 weeks.
So for a typical migraine patient to do this at home, to realistically achieve an omega-6
diet is quite difficult to do, and it would require a lot of home cooking after education
even.
To their credit, the team is conducting a follow-up study to assess more practical versions
of the diet, and they're doing it specifically to migraine patients, so I eagerly await those
results.
This brings me to a second example diet, the ketogenic diet, which, of course, limits carbohydrate
intake in an attempt to mimic a fasting state.
Ultimately, while doing this, fat becomes the main dietary source of energy, as we see
depicted over here in the left in the composition of the classic ketogenic diet.
There are some different approaches that vary the composition a little bit while still maintaining
a state of ketosis and making it a little easier to do.
The ketogenic diet has a variety of mechanisms by which it's believed it could influence
the migraine brain.
They're discussed elsewhere but useful for designing studies around this.
And there was a flurry of interest in the 1930s, if you dig back into that literature,
closer to the time when the diet was first investigated for epilepsy, and then not a
whole lot in the intervening years until a recent resurgence.
And I've listed a few citations here for reviews of this current evidence, which are relying
on more recent data, though it's still pretty heavily on prospective open-label studies
and in case series.
Now, there are a few new crossover trials that are becoming available, which is exciting.
And the data has been pretty consistent crossing from those prospective open-label studies
and into this one new crossover trial, with data at least.
And it looks like there might be a "there" there.
There seems to be something beneficial with the ketogenic diet on migraine outcomes.
The trial at the bottom is ongoing, and they are investigating whether it's the ketones
themselves or the lack of carbohydrates that is exerting the influence, so this is also
exciting.
And they're trying to tease out this difference by using dietary supplements of exogenous
ketones.
At this point, the two dietary patterns that are getting traction are doing so in part
because they're building mechanistic insight into their studies.
But it seems that they have more mechanistic insight to build in partially because these
diets are so different from the typical American diet.
And there are biomarkers we can more easily point to.
It's fairly easy to say the diet intervention is producing ketones.
But these are diets that are difficult to follow and would not be attainable for a lot
of people, migraine or not.
So we're currently, in my mind, in this kind of catch-22 situation where we really need
those tightly controlled dietary studies for dietary patterns that are a little more approachable
for the average person before we can strongly recommend a diet to prevent migraine at any
stage.
The problem is it's not as straightforward to connect those mechanistic dots for a diet
that's not as dramatically different from our typical diets.
It's harder to write a sexy proposal for a diet that adheres to the US dietary guidelines,
and yet most people don't adhere to those guidelines.
So, collectively, we need to figure this out.
Studies would likely need to be larger to be powered properly because we wouldn't expect
as dramatic of a difference from a diet that follows the dietary guidelines, for example.
While I'm adding to the dream list here, we might also adjust the outcomes that we target,
not just managing symptoms, but also turning our study designs to be longer-term to be
able to assess any relationship between diet and exacerbation of symptoms over time.
And then, if these work, we need behavioral research to find ways to really support people
with a chronic pain condition to make these dietary changes.
So we have a lot of work to do.
On the optimistic side, in May of this year, the NIH released their first agency-wide strategic
plan for nutrition research, which is centered around precision nutrition.
And it opens up the possibility for answering new nutrition questions with new research
designs in precision nutrition so that maybe we can kind of skirt the old way of doing
things, in that there's that traditional epi-research, and offer up a more direct approach to assessing
dietary patterns in the context of migraine.
And the second and fourth strategic goals I think may be particularly relevant: investigating
the role of dietary patterns and reducing the burden of disease in clinical settings.
So while I can't really recommend a diet for preventing development or exacerbation of
migraine -- though I will mention that there's really no evidence against the current healthy
diet according to the US dietary guidelines, and adherence to that would hopefully prevent
comorbidities of migraine.
We're a little better off when it comes to evidence for preventing migraine attacks or
more generally controlling symptoms.
Unfortunately, it's difficult to recommend either of those two diets I discussed because
of how difficult they are to follow.
But if a patient came in and really wanted to try a ketogenic diet or a high omega-3
omega-6 ratio diet, in my mind there's not a distinct reason not to if they're motivated,
other than the usual contraindications for them.
And lastly, I'm optimistic that we'll find new methodologies in this upcoming era of
precision nutrition that will help us advance the science in this space and hopefully enable
us to expand into studying more approachable dietary patterns as interventions for managing
migraine.
And so, one last time, thank you.