Food Sensitivities: What They Are, When They Matter, and How to Heal: Focus on IBS, Migraines, and Depression – Part 1

Do you have chronic symptoms that come and go, and suspect that something in your diet might be to blame? You’re not alone, as many as 20% of American adults have self-reported food sensitivities, and the number is rising. ¹ But how do we really know if a particular food is giving us trouble? Are food sensitivity tests valid? And, are common, harmless foods really the problem? In this two-part article we’ll look closely at the research on food sensitivities and therapeutic elimination diets, focusing on three common disorders: irritable bowel syndrome, migraines, and depression.

IBS, migraines, and depression are among the most common causes of disability in the United States, ² yet also among the most poorly understood conditions diagnosed today. Conventional medicine often says “it’s all in your head.” While stress can play an important role in all three, the research suggests we should focus more on the second brain – your gut!

What Are Food Sensitivities?

When we talk about food sensitivities, we are typically talking about non-type I hypersensitivity reactions. Hypersensitivity is when the immune system overreacts and causes unnecessary damage or irritation to the body. Type I hypersensitivity is better known as allergy, and also called immediate hypersensitivity because symptoms develop within minutes to hours of exposure and resolve as fast. (Anyone with allergies knows this well!) When you are allergic, you make a class “E” antibody (called “immunoglobulin E,” abbreviated “IgE”) specific for the allergen. Like a key, the allergen “unlocks” the IgE, turning on an allergic response largely driven by the inflammatory mediator histamine and the immune cells that release it, called mast cells.

Non-type I hypersensitivity, however, often doesn’t display symptoms until hours or days after exposure, if at all, and continues to smolder long after. Class “G” antibodies (IgG) are the “locks” opened by specific substances in these reactions. As non-type I symptoms tend to be more varied and less extreme than allergy, there is reason to believe that these reactions may underlie some common chronic disorders. The gut is home to 70% of the immune system, and the diet is a large part of the immune system’s interaction with the outside world, so food sensitivities may have a particularly important role.

Testing for food-specific IgGs may help identify these reactions. Conventional medicine however, and in particular the American Academy of Allergy, Asthma and Immunology (AAAAI), discourages this practice. As the AAAAI outlines in this position statement, IgG testing is not diagnostic of a food allergy or intolerance. They argue that food-specific IgG antibodies, and in particular, IgG4, correlate with exposure to particular foods, and possibly indicate tolerance, not reactivity to them. As noted in Harvard Health Blog and peer-reviewed literature, food sensitivity is fundamentally different from either intolerance or allergy. A food intolerance is a symptomatic response to a specific food, due to difficulty digesting that food. An example is lactose intolerance due to deficiency in lactase enzyme. Indeed, studies show that IgG is a poor indicator of food intolerances, ³ which are better detected on a blinded food challenge, performed by a doctor. Always consult with your doctor before making changes to your diet.

Non-type I hypersensitivity, on the other hand, may not manifest with obvious symptoms, since the reactions can be subtle and delayed. Furthermore, it has also been postulated that increase in intestinal permeability causes larger molecules that would normally stay in the gut to cross into the bloodstream and induce IgG responses. Therefore, heightened IgG response to multiple foods is likely a reflection of increased intestinal permeability, commonly referred to as leaky gut, which is correlated with a number of systemic symptoms and disorders.

The AAAAI states that food-specific IgG may indicate merely “a physiologic response of the immune system to exposure to food.” The research we will discuss in this two-part article will demonstrate that this response of the immune system may have adverse downstream effects and warrants further attention from clinicians and researchers.

In the clinical setting, it is often observed that a standardized elimination diet such as the IFM elimination diet significantly improves symptoms of certain conditions such as autoimmunity, digestive symptoms, migraines and skin conditions such as eczema. Recent studies back up this common practice. In some individuals, however, it is noted that IgG testing-directed elimination diet may yield improved results. Let’s unpack the research on why food sensitivities matter in three common conditions: IBS, migraines, and depression.

Food Sensitivities in IBS

Four clinical studies have found that people with IBS have significantly more food-specific IgG than healthy controls when 14-24 different foods are tested for. ^4–7 While all subgroups of IBS (diarrhea-predominant, constipation-predominant, and mixed) have food sensitivities, IBS-D appears to be the most reactive.

Three foods are the most common offenders in IBS patients: wheat, egg, and soy. Nonetheless, a sizable portion of IBS patients do not react to those top offenders – food sensitivity profiles are highly personal. Three studies also measured allergic IgE to similar foods and found no elevations in IBS, highlighting a specific role for non-type I hypersensitivity. ^5–7

Interestingly, none of these studies found any correlation between total or specific food IgG levels and symptom severity. This suggests a strong role for an underlying mediator, the immune dysfunction that leads to these inappropriate responses in the first place. (More on that later!)

One study of over 500 people found no difference in food-specific IgG’s between controls and individuals with IBS. ⁸ However, this study has a vital flaw: the IBS group was never diagnosed by a gastroenterologist, and instead used an unvalidated, self-administered questionnaire. IBS is a diagnosis of exclusion, alternate causes of gut trouble need to first be eliminated professionally. Without a proper IBS diagnosis, this study was merely comparing IgG levels and gastrointestinal symptoms, which the four previous studies clearly determined do not correlate.

So, research suggests that people with IBS have higher rates of IgG-mediated food sensitivity, though antibody levels are not related to symptom severity.

Food Sensitivities in Depression and Migraine

The connection between food sensitivities and gut health may be intuitive. But, depression and migraine? The clinical research suggests food sensitivities might play a larger role here.

A 2018 study compared IgG levels against 39 common foods in people with major depressive disorder (MDD), IBS, and healthy controls. Sixty four percent of the MDD group had elevated IgG levels to at least one food, compared with 46% of IBS patients, and only 19% of healthy controls. ⁹ Those with depression also had the highest total food-specific IgG, and were more likely than IBS patients or controls to have extremely high levels for individual foods.

Further, a 2019 study compared both IgG and IgE levels to 14 foods in 184 adolescents experiencing their first major depressive episode and age/gender-matched controls. ¹⁰ Unlike in IBS, both IgE and IgG were significantly elevated in depressed adolescents, suggesting that food allergy-type reactions may play a role as well as sensitivities. Nearly 90% of depressed participants were positive for IgG food sensitivities compared with merely 13% of controls. Unlike IBS, dairy hypersensitivity appears common in depression.

Only one study has looked for elevated food IgG levels in people with migraines, but the results are equally striking. Fifty six adult migraine-sufferers were tested for IgG antibodies against 108 different foods, and every single one had hypersensitivities to 6-30 different foods. ¹¹ Among an equal number of age/gender-matched controls 26% had positive levels, and for only 4 foods or less.

So, does that mean the foods you eat may be getting you down? In the next part, we’ll discuss how elimination diets based on high-quality food sensitivity testing may be therapeutic for IBS, migraine, and depression. But, spoiler alert, the story isn’t so simple. That antibody levels correlate poorly with symptom severity, despite clear differences in elevations between patients and controls, suggests food sensitivities may be a casualty in a bigger battle. What causes the immune system to react inappropriately to harmless foods in the first place? IBS, migraine, and depression may have more in common than we think.

Note that it is important to speak to your doctor if you are concerned about food sensitivities or think you may be experiencing symptoms due to food sensitivities. Results of food sensitivity testing need to be interpreted by a qualified healthcare professional who understands the benefits and limitations of this test, who has taken a detailed history of the patient and is able to understand the results and develop a plan in the clinical context of the patient.

To learn more about the benefits of applying targeted elimination diets based on food sensitivity testing, continue reading here.

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Written by Jonah Udall; Select sections of article written by and article reviewed by Dr. Bojana Jankovic Weatherly. Jonah Udall is a nutritionist, herbalist, and functional medicine practitioner in-training, earning his Masters of Science in Human Nutrition and Functional Medicine at the University of Western States. Chronic health challenges taught him the importance of listening deeply, seeking the root causes of dysfunction, celebrating the individual, and finding collaborative paths to vibrant health with nature’s medicines. Jonah is also a professional musician and movement artist, director of New York City-based ECHOensemble, and a certified Deep Listening instructor.

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