Food Sensitivities On The Rise

According to the Center for Disease Control, food allergies in the US rose more than 50% between 1997 and 2011. This increase can serve as a useful proxy for the growing collective inflammatory response to modern franken-foods. 

While the high incidence of food allergy is alarming and deserves thoughtful consideration, non-allergic responses go mostly unacknowledged in the medical community and may pose an even larger danger to public health due to their subtle and insidious nature. Unchecked, these reactions create a constant inflammatory environment in the body over time, providing an ideal breeding ground for chronic illness and dysfunction. 

Food sensitivities have been widely acknowledged in literature as a legitimate medical issue, yet most of the medical community still reacts to complaints of the afflicted with a suspicious side-eye. This may, in part, be due to no medical-grade lab test established to reliably measure when a sensitivity is present. So, despite the very real symptoms that are experienced, somehow many doctors put the patients who bring up these issues into the ‘psychological’ category, dismissing them as hypochondriacs without providing any real answers or treatment. 

This gap in the market has resulted in a handful of food sensitivity testing options that have appeared out of the woodwork in recent years, professing to wield life-changing technology that will distill all of your dietary questions into an easy to read report that’s full-proof… because science. But many conventional circles decry these tests as being scientifically invalid, and, to an extent, I would agree. However, it’s useful to draw the distinction between testing methods that have been studied and debunked, versus testing methods that are relatively light on literature. 

To get to the heart of the matter, let’s start with the basics.

What is a food sensitivity?

Food sensitivities are immune-mediated responses to the ingestion of specific foods that result in symptom onset. 

Immune-mediated hypersensitivity reactions to food or other substances can take 4 different forms (discussed below). Meanwhile, food reactions that are not mediated by the immune system at all are considered ‘intolerances’, and instead result from improper digestion. 

Types of Food Reactions

Intolerances result when the body does not possess the digestive secretions necessary to properly break down and digest a certain food compound. The undigested particles cause stress as they move through the GI tract, and often result in digestive issues. An example of this is lactose intolerance. Those who suffer from this malady do not possess the digestive enzyme lactase, which means the lactose sugar molecules in dairy fail to get broken down and cause inflammation in the intestines. This is both because of the physical burden of the compound’s size and because the compounds can feed microbes which may exacerbate any imbalances that are present. 

Other common examples of food intolerances include fibers such as FODMAPS (Fructo-Oligo-Di-Mono-And-Poly-Saccharides) or high fat foods for those who have had their gallbladders removed and have a shortage of bile. Key point: these reactions to food are due to the body’s inability to digest them, not because an immune response is happening. Accordingly, this type of food reaction is not detected in food sensitivity testing.

The 4 food reactions that are immune-mediated begin with the immune system designating all compounds that enter the body as either safe or not-safe. Substances deemed not-safe are tagged for destruction via our powerful internal weaponry and can be termed generally as antigens. Problems arise when harmless foods get tagged as antigens, working to elicit an inappropriate inflammatory cascade in the body whenever that food is ingested. 

Food Allergies or Type 1 Sensitivities, are immediately triggered within 15 to 30 minutes of exposure to a given food. The humoral immune system produces IgE antibodies that recognize the food, and call in Mast Cells whenever the substance is detected in the body. These Mast Cells secrete large amounts of inflammatory chemicals such as histamine and can produce life-threatening symptoms i.e. asthma, anaphylaxis, or even death if left untreated. 

 Usually, a person needs no help determining which foods they are allergic to as the symptom onset is so acute and immediate. This makes testing for this kind of reaction clinically irrelevant.  

Cytoxic or Type 2 Sensitivities also involve the humoral immune system. IgM and IgG antibodies are formed to a food antigen that is closely associated with a cell membrane. They then trigger the body’s Complement System to kill the cell. This may create a cross-reaction with the body’s similar internal chemical structures which results in autoimmunity. Symptoms typically onset minutes to hours after exposure and are associated with diseases such as hemolytic anemia, rheumatic heart disease, Grave’s disease, and Myasthenia gravis. 

 Immune Complex or Type 3 Sensitivities occur within hours to days of exposure. The humoral immune system forms IgM and IgG antibody complexes that are bound with the food antigen. These complexes are a way of signaling to the body’s elimination pathways that ‘there is garbage here that needs to be taken out’. Typically, macrophages from the liver and spleen are responsible for clearing this debris. If elimination pathways are not functioning properly or there is liver congestion, the body may eventually tag these uncleared complexes as antigens and resort to storing them in connective tissue. There, the body subjects the complexes to its inflammation processes in an effort to destroy them. This type of sensitivity is associated with Rheumatic diseases like Systemic Lupus Erythematosus and Rheumatoid Arthritis. 

Delayed Reaction or Type 4 Sensitivities occur at least 48-72 hours after exposure to the antigen. Unlike other types of sensitivities, these reactions do not involve antibodies or the humoral immune system and instead are mediated entirely by T-Cells. Conditions associated with these reactions include Celiac, Hashimoto’s, Crohn’s, MS, and non-celiac gluten sensitivities. 

Food Sensitivity Testing

Pinpointing sensitivities of all types can usually be accomplished with carefully constructed elimination diets, though this process can be time, energy, and resource intensive. 

Enter the appeal of an accurate Food Sensitivity lab test that, with the prick of a needle, could reveal all of your problem foods back to you in a few business days. Wouldn’t that be nice? 

Unfortunately, many testing options currently on the market are based on flawed or debunked methodology, whose advice can actually work to worsen your problems rather than improve them.

 However, not all tests are the same.

The first crucial thing to understand about food sensitivity testing is that we can’t lump all of them together.

Allergy Tests 

Diagnosis of Type 1 Allergy Sensitivity has historically used Oral Challenging methods to quantify and confirm the existence of food allergies in individuals experiencing adverse symptoms. This method involves the participant being served an allergen-free elemental diet over the course of a few days to establish a new symptom baseline. Then, incremental doses of the suspected food substance are administered under medical supervision, and the participant is observed for symptom onset. These tests can be performed blind (with placebo) or openly (no placebo).

Oral Challenging tests are considered the Gold Standard in the medical community for food allergies because of their accuracy. However, the time, energy, and resources required to administer a test make it very impractical given the current healthcare model, where the average doctor-patient visit lasts 17.4 minutes and costs $300-600. If a willing practitioner agrees to devote a few days to organizing and administering the test, participants may find the process to be stressful, as known problem foods need to be consumed and the accompanying negative symptoms experienced for validation. The moral implications of making people suffer through the diagnosis process just to confirm what they already know are murky, to say the least. 

Blood test options for Type 1 reactions include the radioallergosorbent test (RAST) and enzyme-linked immunosorbent assay (ELISA) tests, which both measure IgE and IgG concentrations. The accuracy of these tests is controversial and can often yield false positives [1].

Types 2 and 3: IgG

Chances are that if you’ve come across Food Sensitivity Testing the IgG method is what you’ve encountered. 

Immunoglobulin G (IgG) is an antibody in the immune system, which can be involved in pathogen or invader detection. Tests such as the ELISA, Viome, EverlyWell, and others take samples of a person’s blood and look at the serum IgG concentrations associated with each food on a given list. The logic, according to these tests, is that the more IgG associated with a given food, the more inflammatory that food is for that individual. 

This seems straight forward, right? It would make sense, if the role of IgG were directly associated with an inflammatory response. However, the literature says that this is, unfortunately, not the case [1-5]. The reality is that IgG antibodies are involved in many different immunological pathways – some of which are inflammatory, and some of which are not [6-7]. What’s more, as we know from our discussion of hypersensitivity types, IgG is completely uninvolved in Delayed Type 4 sensitivities. 

IgG antibodies account for approximately 75% of all antibodies in the human body. Conveniently omitted from many of the promotional literature for these testing companies? IgG is associated with virtually every single food that we ingest [8]. We don’t know the exact role that it is playing – but some research suggests that IgG is actually protective; high concentrations may prevent IgE allergic responses from forming [9]. It’s safe to conclude, then, that we don’t want to be using this marker as a metric for symptom aggravation, if it actually can play a role in mitigating inflammation and negative symptoms.

Let’s say this test were, in fact, scientifically viable and producing accurate and helpful results for people. A few other problems:

• The test requires the consumption of any tested foods within 2 weeks of taking the test even if a known sensitivity, burdening the participant with the fallout.

• IgG antibodies are involved in two of the three types of non-allergic Food Sensitivities, and are not the only antibody pathway for either. Therefore, the test provides incomplete information for Type 2 and 3 Sensitivities and completely omits Type 4.

• These tests are expensive! Typically one of these analyses will run you up at least a grand.

So, if these IgG tests are more or less quackery – why do some people report positive results when they follow the dietary advice put forward by these companies?

While I can’t speak specifically to this, I do have a theory. Presumably, the people taking this test suffer from some kind of food sensitivity and these foods are likely still in their diet since they’re experiencing negative symptoms. Because IgG tests basically just tag whatever you’ve eaten most recently, if you follow the advice to cut those items out of your diet you would experience relief. You’ve cut out everything, including the problem foods. However, whether you needed to cut everything from the test out, and whether you are sensitive to other foods you didn’t happen to eat prior to the test are still big unknowns.

Given the state of the literature on these tests, I can’t advocate its utility. I recommend saving your money and opting for support in constructing a proper elimination diet, or opting for the option below.

Types 2, 3, and 4: MRT Testing

Mediator Release Testing (MRT) is a newer and much less studied method of sensitivity testing that is my preferred test. It can be considered a newer and more sophisticated iteration of ALCAT testing.

How it works

The key to understanding food sensitivities lies in the inflammation a given food induces in the body. While inflammation is immune mediated, there are countless pathways that the immune system can engage in that will result in this response. For this reason, focusing on any early actors in inflammation cascades, such as immunoglobulins (IgG), presents difficulties as we don’t actually know if they are triggering inflammation in the end. Likewise, there may be other pathways that are occurring that result in inflammation which don’t involve immunoglobulins.

To be clear: inflammation as an endpoint is not correlated closely with immunoglobulin activity [4-5].

When we think of inflammation what we should think of is the majestic White Blood Cell (WBC) – of which there are many different types: Neutrophils, Eosinophils, Basophils, etc. These WBCs are the actors responsible for inflammation via their release of Mediators. Mediators are toxic chemicals that are used to destroy pathogens and invaders.

Mediators, then, are the endpoint, the direct cause of inflammation, and include over 100 different chemicals such as cytokines and histamine. 

The MRT test measures and quantifies the release of the mediators, which is directly correlated to inflammation. Because there are over 100 different mediators, instead of measuring for any specific mediator, the MRT test instead measures the literal release of mediators by WBCs. 

The idea is simple: in a given blood sample, WBCs are solids immersed in the liquid matrix of the blood. These WBC solids contain within them liquid inflammatory mediator chemicals. When the solid WBCs release these mediators, they and their solid mass shrink in size while the chemical mediators enter and bolster the extracellular liquid. Therefore, if we measure the ratio change in solid to liquid before and after exposure, we can detect whether or not an inflammatory response has occurred [10].

A Silly Analogy

Think of 3 filled water balloons floating in a kiddie pool. Say there are 6 square feet of water in the kiddie pool and each water balloon takes up 1 square foot of volume. The ratio of solid to liquid then is 3:6 - 3 square feet of solid balloon to 6 square feet of liquid water. 

Suddenly, an unfastened safety pin is thrown in the pool and empties the contents of 1 water balloon, transferring 1 square foot of volume from solid balloon to liquid water. The new ratio of solids to liquid is then 2:7 - the remaining 2 square feet of solid balloons to the new 7 square feet of liquid water. The safety pin is akin to eating a bite of cheese if you are sensitive to dairy, where the dairy serves as a trigger for an inflammatory response. Likewise, if you toss a fastened safety pin in the pool, nothing happens, the ratio would remain 3:6 – this can be likened to eating safe or non-reactive foods. 

So we start with a normal baseline blood sample where, presumably, the mediators are still within the WBCs. The blood sample is then exposed to 1 of the 170 foods tested for on the MRT, and the ratio is measured again. If the ratio has changed in a statistically significant manner this means the WBCs have expelled their mediator contents and have shrunk in size, while the mediators have entered the extracellular matrix and have bolstered the volume of the liquid. We can then make inference about the food at hand and its reactivity for the individual.

MRT Advantages 

• The measurement of endpoints, the mediators, rather than intermediary agents of inflammation ensures that you are getting a much more accurate picture of the foods that cause inflammation. This also means that it accounts for all 3 types of non-allergic food sensitivities

• This response is measured after the compound is manually exposed to the blood sample, so it does not require the test-taker to eat any known problem foods to get an accurate read. A person may have never eaten a food in their life, but will still get an accurate read on their sensitivity to it.

• The results are presented on a gradient that dictates how sensitive you are to a given food which is useful for making clinical decisions on diet.

• At roughly $350 it is one of the most economical functional lab tests out there.

As I mentioned earlier, this is a relatively new technology and there is limited peer-reviewed data on its efficacy. However, the limited literature available on the test is encouraging. The MRT has a 94.5% sensitivity rate and 91.7% specificity rate according to in-house studies presented by Oxford BioMedical. Finally, according to these studies, the reproducibility rate is consistently over 90% via split sampling [11]. 

MRT Caveats

When I finally did my MRT food sensitivity testing, I had already gone through the AIP protocol and had identified the vast majority of the food sensitivities that came back on the MRT. This, in part, was what impressed me so much with the test – the results mirrored my own observations incredibly closely. However, I was at a point in my healing journey where I had already engaged in significant gut healing and was feeling great, even with the inclusion of some of these foods. This brings me to my first caveat about the test:

1)    Everyone will come up positively for something. 

The test is processed and results are scaled according to the spectrum of reactivity for each individual. This is great because some individuals release very few mediators but are especially sensitive to those mediators, and some people release many mediators and don’t meaningfully respond to them. For everyone, results are presented as a percentage of your most reactive food (this food showed 100% reactivity, and this food showed 20%, etc.). This means that even those who are relatively healthy and not necessarily suffering from any overt food sensitivities will show test results that come back with reactive foods. Whether or not those foods are above the threshold of causing symptoms in the body is undefined.

For this reason, I don’t recommend this test for those who are simply looking at maintaining or optimizing their health. Rather, this should be used in a targeted way for people who are actively experiencing negative symptoms, who know they have multiple food sensitivities and want help identifying what those are.

Ironically, doing this test when you are not reacting to foods in your diet and avoiding the flagged items can be detrimental. Eating a smaller number of foods dramatically increases your likelihood of developing new sensitivities.

2)    A Lack of data.

While the data available on the test is cause for optimism, there is very little literature available compared to most lab tests. The lab has a plausible scientific mechanism and has rave anecdotal reviews in clinical practice, but you need to assess whether or not you are comfortable using something that is not backed by a robust amount of work.

3)    LEAP recommendations aren’t reliable.

 The test comes with a set of recommendations called Lifestyle Eating and Performance (LEAP), which is a diet program designed by the test company with the aim to address your food sensitivities. I can’t stand by these recommendations and recommend you work with a skilled practitioner to guide you in your test interpretation to get optimal utility and results from this test.

Who is the MRT for? 

• You are reacting to lots of different foods and don’t know where to start for safe foods

• You feel overwhelmed by an elimination diet or don’t want to limit yourself to the extent that something like the AIP requires

• You’ve tried lots of elimination diets and haven’t come up with any major answers – you want to see a clear snapshot of what’s happening in your body

• You don’t want to spend a lot of time doing elimination diets, you want targeted answers now

   

A perfect marriage: the MRT and GI-MAP

As I have discussed elsewhere, food sensitivities have everything to do with the structural integrity of your gut, and by extension, the robustness of your digestive function. This means that sensitivities are often dynamic, and present moving thresholds that change over time.

This is especially true when we pair the MRT with the GI-MAP – an advanced stool test that gives us a snapshot of microbial populations, efficacy of digestive secretions, and inflammatory markers. Addressing dysbiotic activity revealed by the GI-MAP, augmenting secretion shortages, and quelling inflammation in the intestinal lining is often instrumental in moving food sensitivity thresholds. This movement doesn’t mean the initial readings provided by the MRT were inaccurate or false, it simply means that the primary driver of the sensitivity has been addressed in some way. Likewise, trying to address food sensitivities without actively introducing gut-healing agents will likely prove fruitless as the gut will remain permeable. 

Leaky gut won’t heal if you aren’t addressing underlying drivers of pathogen presence, poor digestive function, or dysbiosis. 

Dysbiosis won’t resolve without omitting food sensitivities and increasing digestive function.

REFERENCES

1)    Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol. 2016;12(4):389–403. doi:10.1586/1744666X.2016.1124761

2)    Testing for IgG4 against foods is not recommended as a diagnostic tool: European Academy of Allergy and Clinical Immunology (EAACI) Task Force Report, 2008.

3)    The American Academy of Allergy, Asthma, & Immunology (AAAAI) supports the EAACI’s position against IgG testing, 2010

4)    The Canadian Society of Allergy and Clinical Immunology (CSACI) strongly discourages the practice of food-specific IgG testing for the purpose of identifying or predicting adverse reactions to food, 2012

5)    The Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance. Jenkins M, Vickers A.  Clinical and Experimental Allergy 1998; 28; 1526-1529. PMID: 10024224

6)    IgG Food Allergy Testing by ELISA/EIA What Do They Really Tell Us? by Sheryl B. Miller, MT (ASCP), PhD, Clinical Laboratory Director , Bastyr University Natural Health Clinic

7)    Nakagawa, T., The role of IgG subclass antibodies in the clinical response to immunotherapy in allergic disease. Clin Exp. Allergy 1991; 21:289-96.

8)    Measurement of Specific and Nonspecific IgG4 levels as Diagnostic and Prognostic Tests for Clinical Allergy. Position Statement 28, 1996 America Academy of Allergy, Asthma and Clinical Immunology.

9)    Carr S, Chan E, Lavine E, et al. CSACI position statement on the testing of food-specific IgG. Allergy Asthma Clin Immunol. 2012;8(1):12.

10) Avilahti EM, Rantanen V, Lin JS, et al. Early recovery from cow’s milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow’s milk epitopes. J Allergy Clin Immunol. 2010;125(6):1315-1321.

11) Pasula, Mark J.;  The Patented MRT (MRT ); A Comprehensive Blood Test for Inflammation Caused by Food and Food-Chemical Sensitivities. Townsend Letter, January 2014

12) Pediatryczny, 1997, Supplement 1, 61-65 MRT TEST - NEW GENERATION OF TESTS FOR FOOD HYPERSENSITIVITY IN CHILDREN AND ADULTS Kaczmarski Maciej, Pasula Mark, Sawicka Ewa, Werpachowska Irena. III Children Clinic, University of Bialystok Medical School. Oxford Biomedical Technologies, Inc.