Although the terms food allergy, food sensitivity, and food intolerance are often used interchangeably, they have distinct etiological mechanisms.
What is a food allergy?
Food allergy (FA) is defined as an immune reaction to food proteins. It can be immunoglobulin (Ig) E-mediated, none-IgE-mediated, or mixed. (Lopez et al., 2023; Wong et al., 2021). FA symptoms generally present with acute onset of anaphylaxis, hives, respiratory, cardiovascular, gastrointestinal (GI), or neurological symptoms. However, the onset of non-IgE-mediated or mixed IgE-mediated allergies can take longer to develop (hours to days), manifesting as abdominal discomfort, diarrhea or constipation, vomiting, and colic.
What is food intolerance?
Food intolerance (FI) is a non-immune-mediated reaction to foods associated with challenges in digesting and metabolizing certain compounds or chemicals in foods, additives, and pharmacological agents, such as lactose, histamine, tyramine, MSG, lectins, sulfide, salicylates, etc. This typically occurs if there is a lack of an enzyme required to digest the food compound, such as lactase for breaking down lactose foods and DAO for degrading histamine. FI-induced symptoms are primarily GI-related, including stomach pain, gas cramps or bloating, heartburn, vomiting, and diarrhea. However, some FI, such as histamine intolerance, can trigger a variety of symptoms related to skin, GI, cardiovascular function, mood, and sleep patterns. The onset is relatively quick, making it easy to identify the trigger.
What is food sensitivity?
Food sensitivity (FS) refers to a delayed immunologic reaction to foods. It is an IgA or IgG-mediated hypersensitivity to foods that can induce various symptoms, usually resulting from an imbalanced GI function and the subsequent dysregulated immune system. FS can typically cause a wide range of clinical manifestations related to GI, pulmonary, ocular, skin, systemic symptoms, and joint/muscle/connective tissue. The FS reaction is usually delayed for hours to days, making it challenging to pinpoint the trigger.
Food Allergy (FA) Testing:
There are multiple methods to detect food allergies. The gold standard is the double-blind oral food challenge test. The National Institute of Allergy and Infectious Diseases (NIAID) also allows the use of allergen-specific serum IgE (sIgE) and skin prick testing (SPT) but does not recommend other available tests due to a lack of standardization. Each of these three methods has its pros and cons (Onyimba et al., 2021):
Oral food challenge: This is a provocation test that increases allergen doses while monitoring clinical symptoms. Even though it is the gold standard, it is expensive, inconvenient, and, worse, may lead to severe reactions.
sIgE and SPT: Even though increased sIgE levels or wheal size may correlate with allergy, a positive result may only indicate allergen sensitization but not true FA.
SPT: Allergen is introduced subcutaneously to detect the presence of sIgE bound to mast cells. It has high sensitivity and negative value but low positive predictive value and specificity.
Food Intolerance (FA)/Food Sensitivity (FS) Testing:
Most of the tests on the market to detect FI/FS are IgG antibody testing panels. IgG antibodies develop in response to antigen exposure and play a role in immunologic memory. The controversy of this test method is that there are currently no established reference values, resulting in a wide variability of the testing accuracy, and their clinical significance remains questionable (Wong et al., 2021).
Additionally, the following food panels are also used by some clinicians:
IgG4/IgE is used to assess food tolerance or desensitization rather than sensitivity (Wong et al., 2021). It’s generally designed to confirm an FA further. If the IgG4 level is higher than the IgE antibody level, it suggests that the person has a sufficient immune tolerance and likely won’t develop a reaction regardless of an elevated IgE level. However, the predictive ability of IgG4 remains undefined.
C3d/IgG sensitivity tests both the C3d complement and the IgG antibody to identify FI/FS more accurately. A small retrospective study showed that avoiding C3d/IgG antifood antigens resulted in significant symptom improvement (Clarke et al., n.d.).
MRT testing is a patented non-IgE-mediated FS test to identify FI/FS based on the release of proinflammatory and proalgesic mediators from white cells. However, research evidence is lacking, and I found it unreliable based on my clinical experience.
Elimination Diet (ED):
ED is highly recommended if symptoms are not life-threatening, followed by a food reintroduction. ED can be used for detecting FA, FI, and FS. It generally requires removing common reactive foods and additional suspected food allergens. This method can be therapeutic but may lead to nutrient deficiencies if used long-term (Onyimba et al., 2021).
Jenny Noland, MS, CNS, CNGS, CKNS, LDN, MBA
Functional Nutritionist in Eugene, Oregon
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References:
Clarke, D. P., Burdette, C., Agolli, G., Dorval, B., Gaston, A., & Chesla, S. (n.d.). The Relevance of Using the C3d/Immunoglobulin G Test in Clinical Intervention. Altern Ther Health Med, 21(1), 16–27. Retrieved from: https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=25599429&site=eds-live&scope=site
Lopez, C. M., Yarrarapu, S. N. S., & Mendez, M. D. (2023). Food Allergies. The Digestive System: From Basic Sciences to Clinical Practice, 377–380. https://doi.org/10.1007/978-3-030-98381-9_22 Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK482187/
Onyimba, F., Crowe, S. E., Johnson, S., & Leung, J. (2021). Food Allergies and Intolerances: A Clinical Approach to the Diagnosis and Management of Adverse Reactions to Food. In Clinical Gastroenterology and Hepatology (Vol. 19, Issue 11, pp. 2230-2240.e1). W.B. Saunders. https://doi.org/10.1016/j.cgh.2021.01.025
Wong, K. H., Horwitz, R., & Soffer, G. K. (2021). Immunoglobulin G food testing. Annals of Allergy, Asthma and Immunology, 126(6), 611–612. https://doi.org/10.1016/j.anai.2021.01.022 Retrieved from: https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S1081120621000570&site=eds-live&scope=site