Do you get headaches often? Do they interfere with your life? Repeated headaches and migraines have a significant effect on quality-of-life and productivity at the personal level. Collectively migraines and other associated symptoms cost the US economy over ten billion dollars per year [1], with an estimated 10% to 15% of the population, mostly women, suffering from repeated migraines [2]. If you’ve ever tried to see a doctor about repeated migraines, you’ll know that the condition is poorly understood. Medications are available, but prevention is another matter entirely since it is extremely difficult to determine the primary underlying causes in any given individual. Stress levels, hormones, sleep patterns, and even the weather are listed as culprits [3]. Obviously, all of these factors can be extremely difficult, if not impossible, to control without making major life-style changes [3]. On the other hand, specific food triggers are rarely mentioned, despite the fact that 50% of migraine sufferers avoid specific foods [2]. Arguably, eliminating a few foods from your diet could potentially be much easier to manage, but scientists are only just beginning to find concrete evidence for the role of food in migraines, and as a result the approach is not standard practice with most doctors.

In fact, in western medicine, dietary migraine triggers are a controversial topic. A few foods like wine and aged cheese are known to contain specific chemical components that can trigger blood vessel dilation or constriction, and these foods commonly trigger headaches in many individuals who don’t otherwise suffer from migraines. Foods high in fat can also trigger headaches [4], but, to many migraine sufferers, supposedly healthy foods such as wheat (gluten), dairy and bananas, are also problems. However, there is currently no accepted consensus among scientists on how so many innocuous foods could induce migraines.

Scientists have long wondered whether some form of food allergy could be the root of the problem. These and other negative reactions to food, such as lactose intolerance, are not uncommon. Approximately 20% of the population in industrialized nations is affected by some form of food intolerance, and 1-4% of adults have food allergies [5]. Traditional food allergies are, in many cases, hard to miss. Onset of the allergic reaction is quite rapid after a food allergen exposure, which can even occur through skin contact. The reaction usually affects the airways, the skin, or the cardiovascular system, and in severe cases, it can cause anaphylaxis and death.  These immediate reactions involve recognition of the allergen by an IgE antibody, subsequent activation of the immune system, and inflammation. In fact, in allergy tests, doctors specifically look for elevated levels of IgE antibodies in response to a supposed allergen [8]. On the other hand, consistent reactions to food that involve migraines or some general digestive problems, are not usually diagnosed as being allergic reactions and are often considered psychosomatic, or are labeled as Irritable Bowel Syndrome (IBS) when the symptoms are mostly related to digestion [6]. IBS, like repeated migraines, is a health condition that is defined by a set of symptoms as opposed to an understood root cause, and interestingly, IBS sufferers are statistically more likely to suffer from migraines too [7].

However, research is providing increasing evidence that there can be immune responses to food that don’t work through the same mechanisms as standard allergies, and therefore don’t have the same symptoms, and don’t get picked up by standard allergy tests. Scientists are now discovering that immune responses can also be initiated in predisposed individuals when improperly digested food allergens pass through the intestinal lining along with properly digested nutrients. The intestinal immune system, which is geared towards recognizing ingested bacteria, can start to recognize these food fragments too. The onset of symptoms is delayed, ranging from anywhere between 1-120 hours, which is why it can be extremely difficult for anyone with distressing symptoms to realize that a specific food is triggering them. On top of that, if the primary problem is headaches and not a gastrointestinal problem, it isn’t obvious that a food could be triggering them. It is important to note, however, that while symptoms such as migraines, chronic fatigue, and behavioral changes are considered to be potential manifestations of this type of reaction to food, it has yet to be firmly established [5].

Figure 1:  Left: In healthy individuals with normal mucosal barrier (intestinal lining) function, nutrients, bacteria, and other ingested chemicals do not gain access to the tissue surrounding the gut. Right: in genetically predisposed individuals, the barrier is permeable to some fragments of undigested food. When high levels of a food component gain access to the tissue surrounding the gut, the immune system is locally activated and develops antibodies to recognize that food. The tissue gets inflamed, and other symptoms ensue. Adapted from [5].

Our current ability to clinically test for this type of allergy is seriously limited. While the allergen recognition mechanism can involve IgE antibodies, which many tests can detect, clinical studies suggest that these are produced locally in the intestines, and therefore don’t reach detectable levels in the serum or the skin. Instead, the few available diagnostic tests look for the presence of food-specific IgG antibodies in the patient’s blood. IgG antibodies don’t trigger allergic reactions like IgE antibodies do; they are only indicators that the immune system might be recognizing the food. Their presence is actually linked to helping the immune system tolerate the food. Thus, as the presence of IgG antibodies is only an indirect indicator that the immune system might be activated, and the link is not fully understood, the validity of these diagnostic tests is questioned [9]. In addition, when tested for IgG production in response to a variety of foods, individuals without any noticeable symptoms may test positive to a few foods, but the average number of foods is less than in individuals who do have negative reactions to foods [10]. However, it is also hard to know for sure whether food intolerances always cause noticeable symptoms. In any case, the absence of IgG antibodies should signify no immune recognition of the food whatsoever.

Despite the lack of well-established diagnostic tests, and solid mechanistic data to support the link between migraines and food intolerance, some studies have shown that migraine symptoms are alleviated when test subjects avoid the foods to which they have developed IgG antibodies [7,10]. In these studies, researchers first checked the test subjects’ blood for the presence of food-specific IgG antibodies to over one hundred foods. Based on the results of these initial blood tests, the subjects were given an elimination diet, in which all the foods towards which they had IgG antibodies were removed, and a challenge diet, which encouraged the consumption of these same foods. The subjects were then asked to record the number, duration, and intensity of migraines that they had during each diet phase. In order to rule out the placebo effect, the subjects were not told which diet was the elimination diet, and which one was the challenge diet. With this approach, Carlos Arroyave Hernandez and his colleagues found that migraine sufferers had a significant reduction in the frequency and intensity of their migraines on the elimination diet compared to their regular diet or their challenge diet [10]. A second study by a different group looked at patients who suffered both from migraines and IBS, and also found that symptoms from both disorders were alleviated with the elimination diet [7]. While this data might sound quite conclusive, there is some question about whether researchers tested enough people to fully validate the results; a similar study did not get the same positive effect [3]. More research will have to be done, but the inherent difficulty with all these studies is that the test subjects are in charge of their diets. While the researchers did ask the subjects to keep food diaries, they did not know whether they were accurate, and they had no way of fully determining the level of compliance.

So what’s the take-home message? Migraine-causing reactions to food are not fully understood from a scientific perspective, and are hard to test for conclusively. Self-diagnosis is also difficult since the symptoms of food intolerance can take up to a few days to appear. It can be very hard to pinpoint the problem without actually looking for it, particularly since foods such as wheat and dairy, which many North Americans eat on a daily basis, are also some of the most common foods to which people are intolerant. Researchers and doctors are only just beginning to look at food intolerance seriously. A better understanding of this phenomenon may someday lead to increased public awareness, more reliable diagnostic tests, and even improved treatments for migraines and many other ailments.

Amy Sutton is a PhD candidate in the Harvard University department of Chemistry and Chemical Biology.

References

[1] Jenkins, Brian and Tepper, Stewart J. “Neurostimulation for Primary Headache Disorders: Part 2.” Medscape, 2011. http://www.medscape.com/viewarticle/751727_7. April 12, 2013.

[2] Reddy, Sumathi. “Why That Banana or Onion Might Feel Like Three Martinis.” The Wall Street Journal, December 15, 2012. http://online.wsj.com/article/SB10001424127887324677204578185404253745608.html. April 12, 2013.

[3] Mitchell, N. et al. “Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches.” Nutrition Journal, 10:85, 2011. http://www.nutritionj.com/content/10/1/85.

[4] “Headache Sufferers’ Diet.” National Headache Foundation. http://www.headaches.org/content/headache-sufferers-diet. April 12, 2013.

[5] Bischoff, Stephen and Crowe, Sheila E. “Gastrointestinal Food Allergy: New Insights into Pathophysiology and Clinical Perspectives.” Gastroenterology. April 2005. http://www.sciencedirect.com/science/article/pii/S0016508504014052. April 12, 2013.

[6] Beck, Melinda. “New Guide to Who Really Shouldn’t Eat Gluten.” The Wall Street Journal. February 7, 2012. http://online.wsj.com/article/SB10001424052970204136404577206891526292590.html. April 12, 2013.

[7] Aydinlar, Elif Elgaz et al. “IgG-Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome.” Headache. March 2013. http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2012.02296.x/abstract. 12th April 2013.

[8] “Allergy Basics”. WebMD. http://www.webmd.com/allergies/guide/allergy-basics. April 12, 2013.

[9] Miller, Sheryl B. “IgG Food Allergy Testing by ELISA/EIA – What Do They Really Tell Us?” Townsend Letter for Doctors and Patients. http://www.tldp.com/issue/174/IgG%20Food%20Allergy.html. April 12, 2013.

[10] Arroyave Hernandez, Carlos M. et al. “Food allergy mediated by IgG antibodies associated with migraine in adults.” Revista Alergia México. September 2007. http://www.ncbi.nlm.nih.gov/pubmed/?term=Food+allergy+mediated+by+IgG+antibodies+associated+with+migraine+in+adults. April 12, 2013.

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