What is food intolerance, and how does it differ from food allergy?
Food intolerances are not IgE-mediated, i.e. they are not allergic hypersensitivity reactions, which most commonly cause symptoms in the intestinal tract (abdominal pain, bloating, diarrhoea). In contrast, food allergies are typically IgE-mediated, rapid immune responses that can have serious, even anaphylactic consequences.
- Coeliac disease and other food intolerances
Coeliac disease
Coeliac disease is a chronic autoimmune disease that develops in genetically predisposed individuals after consuming gluten, causing inflammation of the small intestine mucosa, atrophy of the intestinal villi, and malabsorption of nutrients. Symptoms may include classic diarrhoea, weight loss and growth retardation, but may also take the form of iron deficiency anaemia, osteoporosis, neurological or skin symptoms, or may be completely asymptomatic. Diagnosis is made through serological tests, genetic tests, and small intestine biopsy, always on a gluten-containing diet. The only effective treatment is a strict, lifelong gluten-free diet, which eliminates symptoms, restores the intestinal wall, and prevents long-term complications.
Other important food intolerances
- Intolerance to proteins in food: If the continuity of the intestinal wall cells is disrupted (e.g. due to infection, inflammation or autoimmune processes), undigested food proteins can also enter the bloodstream. The immune system detects the foreign substance and may produce antibodies. IgG class 1-3 antibodies present in the blood represent the direct blood reaction, but similar processes also occur in the mucous membranes (IgA antibodies) and on the skin (IgE antibodies). IgG4 class antibodies may be signs of abnormal reactions that have developed on their own, or they may weaken the effect of IgE antibodies, mitigating the tissue-damaging effect.
- Lactose intolerance – due to a lack of the lactase enzyme, milk sugar is not broken down, resulting in bloating and diarrhoea.
- Fructose malabsorption – impaired fructose absorption causes similar symptoms.
- Sensitivity to FODMAP nutrients (fermentable oligo-, di-, monosaccharides and polyols) – their fermentation in the colon can cause symptoms, especially in irritable bowel syndrome (IBS). A low-FODMAP diet provides symptom relief for many patients in the short term; the long-term effects and consequences on the microbiome are still under investigation.
- Histamine intolerance — overproduction of histamine, excessive histamine intake, problems with the appropriate breakdown pathways, including a deficiency or malfunction of the diamine oxidase enzyme. It does not constitute a separate clinical picture, but its symptoms may be similar to mild allergic reactions, skin reactions, gastrointestinal complaints, and respiratory, cardiovascular and cardiovascular symptoms. The problem caused by excessive amounts of histamine in the body should not be confused with poisoning/allergic reactions caused by other biogenic amines, which enter the body from the same foods, as histamine is also an important messenger molecule in the immune system, playing a role in immune response and inflammation.
The relationship between food intolerances and Lyme disease
The direct relationship between the above-mentioned intolerances and Lyme disease has either not been studied or has not yet been substantiated by data in the literature.
However, a generally higher prevalence of food intolerance has been confirmed in Lyme disease, but these studies do not specify the type of intolerance involved.
Protein intolerance: Patients with Lyme disease may develop autoimmune inflammation of the intestinal tract and intestinal infections, but unique dysbiotic changes have also been found in the intestinal flora of patients who have undergone Lyme treatment. All of these can alter the permeability of the intestinal wall, which can lead to intolerance to dietary proteins. Detailed measurement of intolerance (IgG 1-3, IgG4, IgA, IgE) and selective elimination of reactive proteins may alleviate existing symptoms.
Coeliac disease was not found to be statistically more common in Lyme patients, nor were HLA-DQ heterodimers, considered a lifelong factor in coeliac disease, more common. Nevertheless, Borrelia burgdorferi OspA or other proteins have been linked on numerous occasions to the development of T-cell-mediated immune responses and to a defect in the foreign-self recognition system, which is also responsible for the development of coeliac disease.
Lactose intolerance is also not directly related to Lyme disease. The body cannot break down lactose entering the intestinal tract due to a lack of enzymes, so it is utilised by the microflora present in the intestine. If the intestinal flora changes as a result of inflammation, possibly caused by Lyme disease, or as a result of taking antibiotics, the symptoms may worsen. However, it should not be confused with the fact that avoiding dairy products, which is recommended by some doctors treating Lyme disease, may even alleviate gastrointestinal symptoms, as food intolerance to milk proteins (e.g. A1 beta-casein) may also be part of the clinical picture.
Fructose malabsorption is not related to Lyme disease, but it should be monitored as it can affect the microflora of the small intestine.
A low FODMAP diet is included in many Lyme doctors’ protocols, and a reduction in gastrointestinal symptoms has been reported.
According to many Lyme doctors, small intestinal bacterial overgrowth (SIBO) is a concomitant of Lyme disease, which may be a consequence of Lyme disease or its co-infections: Lyme disease can cause inflammation not only in the gut, but also spasms, slowed bowel movements and irregular movements in the parasympathetic nervous system associated with the gut, thus promoting the development of dysbiosis in the small intestine. However, according to one study, a higher prevalence of SIBO could not be confirmed in the population suffering from tick-borne diseases, but it was found that members of the population had more than three digestive symptoms.
Any of the above digestive syndromes may be associated with or may be a cause of Lyme disease and its co-infections, so it is recommended to investigate them in cases of gastrointestinal symptoms. Elimination diets can further alleviate the patient’s symptoms.
Histamine and Lyme disease
Lyme disease and its co-infections are associated with a state of chronic inflammation in the body. An infection that the immune system is unable to completely eliminate can trigger a number of undesirable reactions. Although no detailed clinical research has been conducted on the relationship between histamine levels and Lyme disease, chronic infection may be one of the main causes of mast cell activation syndrome (MCAS). In MCAS, mast cells release histamine and cytokines.
Reducing histamine levels, limiting histamine intake (low-histamine diet), and avoiding foods and substances that increase histamine production can reduce the “histamine” symptoms of patients suffering from Lyme disease and its co-infections.
- α-gal syndrome (alpha-gal syndrome, AGS).
Food intolerance is generally not an IgE-mediated process, whereas food allergy is based on an IgE-mediated reaction. Alpha-gal syndrome (AGS) develops after a tick bite and is a delayed allergy to the α-gal carbohydrate found in mammals: symptoms appear several hours after consumption, often in the form of gastrointestinal symptoms. For this reason, it is often mistakenly considered a food intolerance, although it can be confirmed by specific IgE testing and may extend not only to meat but also to dairy products or gelatin.
The link between Lyme disease and AGS is primarily ecological: the same ticks (e.g. Ixodes ricinus in Europe) can spread Borrelia infection and cause α-gal sensitisation. In addition, α-gal is found in tick saliva proteins, and according to some reviews, α-gal structures may also be present on the surface of tick-borne pathogens (e.g. Borrelia burgdorferi). Studies investigating the causes of AGS have not examined the presence of Borrelia burgdorferi in the blood of AGS patients, but based on existing data, the scientific consensus is that AGS may not be a consequence of Lyme infection, but rather of tick exposure.
In a German study, α-gal sensitisation was more common among patients with Lyme borreliosis than among controls, while it was highest in the group with multiple tick bites, suggesting that the number of bites is likely to be the decisive risk factor.
Diagnosis is based on a detailed medical history (delayed reaction after eating red meat) and a positive blood test (alpha-gal IgE >0.1 IU/mL). Traditional skin tests are unreliable, although intradermal or “prick-prick” tests with cooked meat can supplement the diagnostic process. Differential diagnosis is important: for example, beef reactivity is not the same as milk protein allergy, so testing for milk protein components (casein, whey protein) may also be necessary.
The basis of AGS treatment is allergen avoidance:
- complete prohibition of meat (beef, pork, lamb, game, offal),
- in certain cases, avoidance of dairy products, gelatin and carrageenan,
- attention to “hidden” ingredients (e.g. “natural flavourings”, additives of animal origin).
In everyday life, it is challenging that many foods and medicines may contain ingredients of mammalian origin (e.g. gelatin capsules, heparin, bioprosthetic heart valves). For this reason, dietary support for patients is recommended.
Medicinal supplements may be necessary:
- antihistamines (e.g. long-acting agents for preventive purposes),
- cromolyn solution for gastrointestinal symptoms,
- adrenaline autoinjectors due to the risk of severe reactions,
- rarely, omalizumab or other adjunctive therapies.
Alpha-gal IgE levels may decrease over time if the patient does not suffer another tick bite, and some people regain tolerance to red meat years later. However, the course of the disease is highly individual, and relapse can occur at any time.
- Chronic intestinal pseudo-obstruction
Chronic intestinal pseudo-obstruction is often considered idiopathic, which can also mimic food intolerance. The condition is associated with poor quality of life and high morbidity, and treatment options are often unsatisfactory. A literature article describes the case of a 66-year-old woman who developed chronic intestinal pseudo-obstruction with back and abdominal pain, urinary retention and severe constipation. The patient lived in an area where Lyme disease is endemic and was bitten by Ixodes ticks. Anti-Borrelia IgM and IgG intrathecal reactions and lymphocytosis were found in the cerebrospinal fluid, which was consistent with chronic neurological complications of Lyme disease, as the symptoms had persisted for more than six months.
Following antibiotic treatment, the patient’s gastrointestinal function was restored and the pain was significantly alleviated. Lyme neuroborreliosis (LNB) often leads to paralysis and can affect the autonomic nervous system. Three cases have been previously described in which acute LNB caused intestinal pseudo-obstruction. However, this is the first reported case in which chronic Lyme neuroborreliosis caused pseudo-obstruction.
LNB should be considered in all patients who develop intestinal pseudo-obstruction.
In summary, food intolerances are generally not IgE-mediated processes, whereas food allergies (such as α-gal syndrome) are the result of allergic immune reactions.
Significantly higher levels of food intolerances were found in the Lyme disease population, and it was also confirmed that people suffering from tick-borne diseases had more than three types of gastrointestinal symptoms.
Lyme disease may be associated with intestinal inflammation or dysbiosis, making patients more susceptible to food intolerances.
There is currently no proven direct causal relationship between Lyme disease and food intolerances, although α-gal allergy associated with tick bites and certain rare cases of Lyme neuroborreliosis with gastrointestinal symptoms may be linked to or resemble food intolerance. According to the literature, Lyme disease does not cause food intolerance on its own and may be indirectly linked to coeliac disease through molecular mimicry, but there is currently insufficient data available in the literature on this subject.
The diagnosis and treatment of food intolerance, or elimination diets, are definitely part of modern Lyme disease treatment protocols, as they can lead to symptom relief. Further information on food intolerance testing is also available in Hungarian: Food sensitivity testing – Nutritest.eu
Sources:
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0926-1
https://www.tandfonline.com/doi/full/10.1080/1744666X.2020.1782745
https://www.gastrojournal.org/article/S0016-5085(21)00324-3/fulltext
https://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm14118
(C) Lyme Borreliosis Foundation
