Food sensitivity tests: what do they measure, and what do the allergy societies say?

Food sensitivity tests have become a common product aimed at athletes. A home kit contains a lancet, a card for a finger-prick blood sample and a return envelope, and a few days later the athlete receives a report that grades around 100 foods as low, medium or high and recommends removing the "high" foods from the diet, often followed by a retest a few weeks later. The claims are that the test identifies food allergies, intolerances or "sensitivities", explains symptoms such as bloating and fatigue, and improves recovery and performance. Companies also approach athletes and teams directly. This blog replaces a shorter piece we wrote in 2020 and now we have updated it. A companion blog (coming soon) now explains what to do when the report arrives. Here we will look in more detail at four questions. What do these tests actually measure? What can, and cannot, be concluded from a result? What about the other tests that are sold for the same purpose? And what do the professional allergy and immunology organisations say about them?

What do food sensitivity tests actually measure?

Almost all food sensitivity tests measure immunoglobulin G (IgG), and sometimes specifically the subclass IgG4, against a panel of foods. Immunoglobulins, also called antibodies, are proteins produced by immune cells called B lymphocytes, and they exist in five classes: IgA, IgD, IgE, IgG and IgM. Each class has a different role in defending the body against pathogens, toxins and other foreign material. IgG is the most abundant antibody in the blood. It is produced when the immune system encounters foreign proteins (antigens), and when it binds to them it acts as a signal for other immune cells to remove them.

After a meal, small amounts of intact or partially digested food protein pass from the gut into the blood and lymph. These proteins act as antigens, but they very rarely cause allergic reactions, because they are removed quickly with the help of IgG. The presence of IgG against a food is therefore evidence of two things: the person has eaten that food, usually repeatedly, and the immune system has dealt with it in the normal way. A task force of the European Academy of Allergy and Clinical Immunology (EAACI) concluded that food-specific IgG4 indicates repeated exposure and immunological tolerance, linked to the activity of regulatory T cells, and should not be regarded as a factor that causes hypersensitivity (1).

What can be concluded from the result?

Food allergy is mediated by a different antibody, immunoglobulin E (IgE). Food-specific IgE is bound to mast cells and basophils, and when the food protein binds to it these cells release histamine and other mediators within minutes. This produces the typical allergic reaction, from hives and swelling of the lips to breathing problems and anaphylaxis. IgG does not take part in this pathway: there is no convincing evidence that IgG4 releases histamine in humans, and there are no controlled studies showing that food-specific IgG4 has diagnostic value for food allergy (1).

A high IgG against a food therefore does not indicate an allergy or an intolerance. Of course, it does contain information: it shows which foods the athlete eats regularly. This is why the foods flagged on a report are almost always the athlete's staples, such as milk, eggs or wheat. The opposite conclusion is also wrong. A person with a genuine IgE-mediated food allergy may not have raised IgG against that food, and could be wrongly advised to reintroduce a food that can cause a life-threatening reaction (2).

A high IgG against a food shows which foods the athlete eats regularly, not which foods cause problems.

The word "sensitivity" on the report adds to the confusion. It has no agreed clinical definition, so it cannot be shown to be absent. An athlete who feels better after removing foods takes this as confirmation that the test worked, although symptoms can improve after any change in diet, for reasons that have nothing to do with IgG.

What about other tests sold for the same purpose?

IgG panels are not the only tests offered to identify problem foods. A review of unproven tests for adverse reactions to foods listed six types (3): measurement of changes in white blood cell volume after incubation with foods (cytotoxic tests), serum IgG or IgG4 against foods, intradermal provocation and neutralisation with food extracts, hair analysis, electrodermal testing, and applied kinesiology, in which muscle strength is tested while the person holds a food. The review concluded that in some cases the laboratory method may be valid but no study shows a correlation with disease, that in other cases blinded controlled studies have shown a lack of reproducibility and no correlation with disease, and that most of these tests lack biological plausibility (3).

A simple rule follows from this. Genuine allergy testing narrows down a question that comes from the athlete's history. A test that returns a long list of foods to avoid, without a history and without a food challenge, is not a diagnostic test.

What do allergy societies say about IgG testing?

This is not an area of immunology with two defensible positions. The EAACI task force concluded in 2008 that testing IgG4 against foods is irrelevant for the diagnosis of food allergy or intolerance and should not be performed in case of food-related complaints (1). The American Academy of Allergy, Asthma and Immunology (AAAAI) formally supported this position in 2010 (4). In the same year, the expert panel guidelines sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID) recommended against a list of non-standardised tests for the evaluation of food allergy, including food-specific IgG4 and cytotoxicity assays (5).

The Canadian Society of Allergy and Clinical Immunology (CSACI) went further in 2012 (2). It strongly discouraged food-specific IgG testing for identifying or predicting adverse reactions to food, and described its concerns in some detail: the tests were being sold directly to consumers through a national pharmacy chain, promotional material had been placed in physicians' waiting rooms without their knowledge or consent, a test typically cost 400 to 700 Canadian dollars, and the results could lead to unnecessary dietary restrictions and to the risk of reintroducing a food to which a person is genuinely allergic.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) guideline on food allergy recommends not using the vega test, applied kinesiology or hair analysis, and not using serum-specific IgG testing, in the diagnosis of food allergy (6). The guideline covers children and young people under 19, but the same reasoning applies to adults. Most recently, a position paper of the World Allergy Organization (WAO) described testing for IgE sensitisation as the cornerstone of allergy diagnosis and discussed unproven, non-validated tests separately (7).

The European, American, Canadian and UK allergy organisations have all concluded that IgG food testing should not be used for diagnosis.

What does work?

The WAO position paper stresses one principle that applies to every allergy test, including the valid ones: sensitisation is not the same as allergy (7). A positive skin prick test or a raised specific IgE shows that the immune system recognises a food protein, but a food allergy is only diagnosed when that finding matches a history of symptoms that occur reproducibly after eating the food. Allergy diagnosis therefore starts with a detailed history and uses skin prick tests or specific IgE to test a specific suspicion, with a supervised food challenge as the reference standard (5). This is also why broad screening panels are poor practice even when the assay is valid: the more foods tested, the more positives without clinical relevance, and each of these risks an unnecessary exclusion. A practical pathway for athletes with symptoms is described in our companion blog (coming soon).

Practical takeaways

• Food sensitivity tests measure IgG or IgG4 against foods. A raised value shows that a food has been eaten regularly and is tolerated by the immune system. It does not indicate allergy or intolerance.

• Food allergy is mediated by IgE, not IgG, so a low IgG also gives no reassurance to an athlete who may be genuinely allergic to a food.

• Cytotoxic tests, hair analysis, electrodermal testing, applied kinesiology and provocation-neutralisation testing have no demonstrated diagnostic value either.

• The EAACI, AAAAI, NIAID expert panel, CSACI and NICE all advise against food-specific IgG testing for diagnosis, and the WAO identifies IgE-based testing, combined with the clinical history, as the basis of allergy diagnosis.

• Athletes should not use these tests: they are a waste of money and can cause harm through unnecessary exclusion of foods. Suspected allergy needs a medical assessment.

References

1. Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy 63(7) 793-796, 2008.

2. Carr S, Chan E, Lavine E, Moote W. CSACI position statement on the testing of food-specific IgG. Allergy Asthma Clin Immunol 8(1) 12, 2012.

3. Kelso JM. Unproven diagnostic tests for adverse reactions to foods. J Allergy Clin Immunol Pract 6(2) 362-365, 2018.

4. Bock SA. AAAAI support of the EAACI Position Paper on IgG4. J Allergy Clin Immunol 125(6) 1410, 2010.

5. Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FER, Teach SJ, Yawn BP, Schwaninger JM. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol 126(6) 1105-1118, 2010.

6. National Institute for Health and Care Excellence. Food allergy in under 19s: assessment and diagnosis. Clinical guideline CG116, 2011.

7. Ansotegui IJ, Melioli G, Canonica GW, Caraballo L, Villa E, Ebisawa M, Passalacqua G, Savi E, Ebo D, Gómez RM, Luengo Sánchez O, Oppenheimer JJ, Jensen-Jarolim E, Fischer DA, Haahtela T, Antila M, Bousquet JJ, Cardona V, Chiang WC, Demoly PM, DuBuske LM, Ferrer Puga M, Gerth van Wijk R, González Díaz SN, Gonzalez-Estrada A, Jares E, Kalpaklioğlu AF, Kase Tanno L, Kowalski ML, Ledford DK, Monge Ortega OP, Morais Almeida M, Pfaar O, Poulsen LK, Pawankar R, Renz HE, Romano AG, Rosário Filho NA, Rosenwasser L, Sánchez Borges MA, Scala E, Senna GE, Sisul JC, Tang MLK, Thong BY, Valenta R, Wood RA, Zuberbier T. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. World Allergy Organ J 13(2) 100080, 2020.