Referring to food intolerances as a phenomenon that occurs when the body doesn’t recognize what it consumes is more of an incomplete thought than a misnomer, given that the definition of intolerance, as it pertains to food is; “abnormal sensitivity or allergy to a food, drug, etc.”. This poses a what came first, the chicken or the egg scenario because the question that arises is whether the “abnormal sensitivity” arose because of the food itself or because of an aberration in the person’s physiology or biochemical pathways that interferes with or impairs their ability to properly digest and assimilate certain food substances. There could simply be an interplay between the two, as there are physiological aberrations that can lead to the development of food intolerances/allergies and there are consequences as a result of modern food processing that also trigger the onset of food intolerances and one may not necessarily cause the other.   

Food intolerance, or hypersensitivity, is an adverse reaction following the ingestion of food and there are distinct pathophysiological differences between food intolerance and food allergy that must be considered because intolerance in not immune-mediated, where as food allergy is, therefore the treatment and management of both conditions is different. As the prevalence of food hypersensitivity increases (15-20% of the world’s population is affected by food intolerance and 1-2% of adults and less than 10% of children are affected by food allergies), it’s become paramount for practitioners and researchers to carefully examine how and why food hypersensitivities occur and form novel strategies to reduce their occurrence (Tuck et al, 2019). Additionally, 50-84% of people with functional gastrointestinal disorders, mainly irritable bowel syndrome, perceive their symptoms being related to food intolerance, and this also raises the importance of mitigating the deleterious effects of food intolerances worldwide (Lomer, 2014). 

Diagnosing food intolerances can be challenging because there are various mechanisms that underpin intolerances, such as pharmacological activity (caffeine, histamine, salicylates, glutamates), enzyme deficiency/transport malfunction (lactose intolerance or lack of glucose transporters in fructose intolerance), and/or non-specific gastrointestinal functioning (visceral hypersensitivity) (Lomer, 2014). In regards, to intolerance, a specific group of carbohydrates, referred to as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), has been implicated in the aetiology of many food intolerances. Keep in mind that FODMAPs themselves may not be the direct cause of the intolerance but instead, irritable bowel syndrome, or its underlying condition, such as small-intestinal-bacterial-overgrowth, can drive the intolerance, due to the fermentation of the short-chain carbohydrates in the small bowel. Symptoms such as bloating, distension, abdominal pain, and excessive flatus all coincide with the fermentable nature of FODMAPs and diarrhoea can be attributed to the osmotic effect of carbohydrates (Barrett & Gibson, 2021). 

Food allergy, on the other hand, occurs when an adaptive immune response that is effective in targeting parasites gets mounted against food proteins and reactivity to proteins in cow’s milk, egg, peanut, shellfish, peanut, soy and wheat account for 85% of all food allergies. Food proteins are taken up by antigen-presenting cells and presented to T-helper cells, which triggers a cytokine release.  Symptoms of a food allergy reaction can occur within minutes of ingesting a culprit food and cause skin, gut, and respiratory manifestations, including abdominal pain, diarrhoea, flushing, itching, swelling, sneezing, amongst others (Turnbull et al, 2014). To elaborate on the underlying mechanisms behind food allergy, wheat allergy, also referred to as coeliac disease, is one of the more publicly known food allergies. Human leukocyte antigens DQ2 and DQ8 present gluten peptides to antigen-specific cells (CD4+ T-lymphocytes) in the intestinal mucosa, which triggers the auto-immune reaction and the release of cytokines (Parzanese et al, 2017).  On the other side of the coin, non-immune mediated reaction to wheat, also known as non-celiac gluten sensitivity, can be triggered by the fructans (a FODMAP) in wheat via the same mechanisms that drive sensitivity to other FODMAPs (Gargano et al, 2021).  

Referring to food intolerances, certain compounds that exert pharmacological effects can induce a reaction when improperly metabolized. Histamine, an endogenously produced (by immune cells in response to injury) compound that is also present in many foods, is a well-known cause of allergy-like symptoms when it isn’t properly metabolized, a condition referred to as histamine intolerance (Shulpekova et al, 2021). The enzymes diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) are responsible for metabolizing histamine but in the case of overproduction (allergies or mastocytosis) or overconsumption (foods/beverages high in histamine/histidine) of histamine, DAO or HMNT production is insufficient to adequately metabolize the excess histamine.

The consequent symptoms resemble those of food allergies, including diarrhea, headache, rhino-conjunctival symptoms, asthma, hypotension, arrhythmia, urticaria (hives), pruritus (itching), and flushing (Smolinska et al, 2013). Other relevant examples of pharmacologically induced reactions are salicylates, which can trigger pro-inflammatory reactions via stimulation of mast cells, and caffeine, which acts as a central nervous system stimulant and can increase gastric juice secretion and colonic motor activity (laxative effect) (Lomer, 2014). 

References

Barrett, J.S. & Gibson, P.R. (2012). Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals? Therapeutic advances in gastroenterology, 5(4), 261-268. https://doi.org/10.1177/1756283X11436241

Gargano, D., Appanna, R., Santonicola, A., De Bartolomeis, F., et al. (2021). Food allergy and intolerance: a narrative review on nutritional concerns. Nutrients, 13(5), 1638. https://doi.org/10.3390/nu13051638

Lomer, M.C.E. (2014). Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance. Alimentary pharmacology and therapeutics, 41(3), 262-275. https://doi.org/10.1111/apt.13041

Parzanese, I., Qehajaj, D., Patrinicola, F., Aralica, M., et al. (2017). Celiac disease: from pathophysiology to treatment. World journal of gastrointestinal pathophysiology, 8(2), 27-38. https://doi.org/10.4291%2Fwjgp.v8.i2.27

Shulpekova, Y.O., Nechaev, V.M., Popova, I.R., Deeva, T.A., et al. (2021). Food intolerance: the role of histamine. Nutrients, 13(9), 3207. https://doi.org/10.3390/nu13093207

Smolinska, S., Jutel, M., Crameri, R. & O’Mahony, L. (2013). Histamine and gut mucosal immune regulation. Allergy (European journal of allergy and clinical immunology), 69(3), 273-281. https://doi.org/10.1111/all.12330

Tuck, C.J, Biesiekierski, J.R., Schmid-Grendelmeier, P. & Pohl, D. (2019). Food intolerances. Nutrients, 11(7), 1684. https://doi.org/10.3390/nu11071684

Turnbull, J.L., Adams, H.N. & Gorard, D.A. (2014). Review article: the diagnosis and management of food allergy and food intolerances. Alimentary pharmacology and therapeutics, 41(1), 3-25. https://doi.org/10.1111/apt.12984