Food Hypersensitivity: Allergy vs Intolerance
Before answering the question "are food intolerance tests accurate?", one must first consider where does the widespread interest in such tests stem from.
The concept of 'food intolerance' or 'food sensitivity' is often offered as a (purportedly scientific) basis for someone to get a test that highlights their reactions to food, and then to modify their diet accordingly.
Interestingly, despite the actual incidence rates of medically diagnosed food allergy remaining consistent at around 2-3% of the population, the prevalence of adults who believe they have a food allergy is up to 25%. With a resulting increase in the numbers of adults self-diagnosing with a food allergy, without obtaining a medical diagnosis.
Food hypersensitivity (i.e. adverse reactions to food) may be classified as a 'food allergy' or 'food intolerance', depending on the physiological mechanisms involved in the reactions. In the popular conversation, it is not uncommon to see 'food intolerance' and 'food allergy' used interchangeably, however, they are fundamentally different. The primary differentiation is between:
- Food Allergy: Reactions mediated by the immune system
- Food Intolerance: Reactions not mediated by the immune system
Food allergy can be further sub-classified as:
- IgE food allergy - Reactions that are mediated by Immunoglobulin-E, which is a type of antibody produced by the immune system in response to an allergen
- Non-IgE allergy - Reactions mediated by other immune cell pathways (non-IgE allergy)
Food intolerance, which is independent of the immune system, may be sub-classified as:
- Reactions mediated by enzymatic pathways - e.g., lactose intolerance
- Pharmacological reactions - e.g., urticaria from alcohol ("alcohol flush")
While food allergies are not dose-dependent and may be triggered with even trace exposure to an allergen (e.g., anaphylactic response to nuts) food intolerance is often dose-dependent (e.g., gastrointestinal motility from caffeine).
It is important to bear in mind the prevalence of self-diagnosis in this area, and we stress that if you are experiencing recurring symptoms with reactions to food, to please consult your doctor for a referral to a gastrointestinal dietitian.
What is a "Food Intolerance Test"?
It is important to bear in mind that the increased self-diagnosis has occurred in the context of a recent surge in popularity of expensive "food intolerance" tests, which purport to examine tolerance to hundreds of foods. They claim to identify food intolerances that cause or contribute to any constellation of conditions: Chronic Fatigue Syndrome, Irritable Bowel Syndrome (IBS), headache, hyperactivity, congestion and sinus problems, arthritis, and almost any mental symptom.
These tests are marketed specifically as food intolerance tests, not allergy tests, and this Sigma Statement will focus on the utility and validity of these tests from the scientific evidence.
In this regard, "food intolerance test" refers to blood tests for another antibody, Immunoglobulin-G (IgG). The IgG antibody is the most abundant antibody in the body, constituting up to 75% of total circulating antibodies, and has a high circulation in the blood. Elevated IgG reflects exposure to a compound (i.e., "maturation" of the antibody response), a point of significance that will be revisited below. IgG antibodies also exhibit an exceptionally long half-life of up to 22 to 96 days, which is also relevant when considering the clinical validity and utility of IgG 'food intolerance' tests.
So are food intolerance tests accurate then?
Are Food Intolerance Tests Accurate?
In considering the utility of any measurement instrument, in this case a diagnostic test, an important concept is validation. In other words:
- Does the test reliably measure the particular marker it intends to?
- Does the marker accurately predict the health status of the subject?
- Is the test specific and precise?
- Are the results reproducible in different lab settings?
Upon examination of the scientific evidence for IgG antibody testing for food intolerance, it appears that none of the criteria for validity of this assay are present.
There is no standardized methodology for IgG testing. Different laboratory methods may not yield comparable results, even if they are reported in the same units or classes, and there appears to variable quality controls (the method for ensuring that lab analyses return results within specified limits of precision, and are consistent). IgG tests also lack specificity, and are unable to identity IgG subclasses which may be directed against foods.
A troubling fact from the perspective of validity is that no study published on the purported utility of IgG-antibody testing has published any details regarding validation of the assay. They may state what classifications were used for IgG levels, and what lab provided the test, and describe how the assay was carried out, but that is often the extent of the detail in the methods section. One study which cited evidence for the details of the IgG test, in fact cited a study carried out in dogs.
A further point, which provides the final nail in the coffin for any purported validity to IgG testing for food intolerances, relates to the fact that elevated IgG reflects exposure to a compound.
Tolerance to food is acquired through immune cells, known as iTreg cells. These iTreg cells migrate to the intestinal lining, where they are involved in the suppression of allergic responses to food allergens, the suppression of IgE, and inducing the production of IgG. So properly interpreted, elevated IgG does not even reflect intolerance to food, but the very opposite: it is associated with immune tolerance for food allergens.
Elevated IgG doesn't reflect intolerance to a food, but rather it reflects exposure to the food (or compound in that food). Therefore, a test result of elevated IgG may simply indicate you've eaten that food, and not that you are intolerant to it. In fact elevated IgG is associated with immune tolerance, not intolerance.
Thus, IgG testing lacks any specificity to food intolerance, and does not measure any clinically valid marker. More evidence for this relationship between elevated IgG and immune tolerance is the fact that, in IgE-mediated food allergy, IgG antibodies are typically low, not high. Some research has proposed that IgG testing may be used alongside IgE food allergy testing, however, as a diagnostic tool IgG testing in this circumstance does not add any information and is superfluous.
If this is the case, then what should we make of published studies that suggest a benefit to IgG testing?
Studies Suggesting a Benefit to IgG Testing
One of the issues with studies using IgG food testing to determine food intolerance is that the studies often look at subjects with irritable bowle syndrome (IBS).
Consider the oft-cited study from Atkinson et al. In this study, patients with IBS took an IgG antibody test. Then one group eliminated foods identified by the test, while the other 'sham diet' control group eliminated the same number of foods, but not foods identified by the IgG test. However, if one scrutinizes the foods eliminated by the group using the IgG test results, one sees that foods like wheat, barley, corn, beans, and nuts, were excluded. Many of these foods would be eliminated in cases where a low-FODMAP diet was implemented clinically (the low-FODMAP diet is an evidence-based intervention used in dietetics with IBS patients. For more, see this episode). So to conclude this group saw an improvement in symptoms as a consequence of an accurate identification of suspect foods by an IgG antibody test is an erroneous conclusion; as the reduction in several FODMAP-containing foods would be expected to yield an improvement in symptoms.
Similar issues arise in other research, for example in relation to migraine. One intervention used an IgG test to guide an elimination diet. After the elimination diet, patients experienced a reduction in headache days and migraine attacks. However, such results simply show that elimation of a wide variety of foods/food groups, led to sympomt reduction. This is not of itself retrospective validation of IgG testing, which is in effect what studies like this try to suggest.
In addition, large population research shows wide variance between the exposure to a food and actual symptoms correlating with elevated IgG. IgG levels are also elevated in otherwise symptom-free, healthy individuals. Again, this reflects that the elevation in IgG in fact represents immunological tolerance, and may simply be a reflection of recent exposure to a food.
Overall, the studies that purport to demonstrate validity follow the same sequence:
- They use baseline IgG tests to then direct a subsequent elimination diet
- Such a diet eliminates foods people with self-reported food reactions may commonly respond to. For example: FODMAPs, gluten, dairy, tree nuts, etc.
- Then they report symptom improvement.
This is post hoc fallacy, not scientific validity.
To quote the conclusion of the European Academy of Allergy and Clinical Immunology (EAACI) Task Force report:
"Food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food related complaints."
In conclusion, there is no evidence supporting the use of IgG as a valid measure of food intolerance.
Summary of Key Points
- The number of self-diagnosed food intolerance has increased in recent years, but in the absence of any increase in the population prevalence of diagnosed food allergy.
- Food hypersensitivity may be sub-classified as food allergy or food intolerance.
- Food allergy are reactions mediated by the immune system, and can be divided between IgE-mediated and non-IgE-mediated allergic reactions.
- Food intolerance is independent of the immune system, and can be divided between enzymatic reactions and pharmacological reactions.
- So-called 'food intolerance tests' have become commercially successful, and present a veneer of scientific legitimacy.
- However, there is no evidence that testing for IgG antibodies reflects a food intolerance.
- Elevated IgG in fact reflects immune tolerance to foods.
- No study has published any details regarding validation of the IgG test for identifying intolerance to foods.
- The existing studies are confounded by post-hoc bias and reverse causality, and are typified by participants with conditions associated with food sensitivities, who then eliminate a wide range of foods and potentially show some symptom improvement.
- These studies should not be taken as retrospective validation of the IgG test, in circumstances where the test itself meets no criteria for laboratory or clinical utility and validity
Statement Primary Author: Alan Flanagan
Alan is the Research Communication Officer at Sigma Nutrition. Alan is currently pursuing his PhD in nutrition at the University of Surrey, UK, with a research focus in chrononutrition. Alan previuosly completed a Masters in Nutritional Medicine at the same institution.