What are the differences between Food Intolerance, Food Allergy and Food Hypersensitivity?

In fact, intolerance, allergy and hypersensitivity to food are all adverse reactions.

For a long time, the scientific community could not agree on the classification of adverse reactions to food. The most widely recognized classification is that of European Academy of Allergology and Clinical Immunology presented hereunder. This classification is based on physiopathological mechanisms and is very easy to understand (see figure I) (1).

This classification distinguishes between two categories of adverse reactions to food: toxic and non-toxic.
adverse food reaction

Fig. 1: Diagram representing the classification of different adverse reactions to food.

Toxic Adverse Reactions to Food (ARF)

Toxic ARFs result from the consumption, in a sufficient amount, of compounds that are toxic to the human body. Such compounds are found in food itself (for example, during the consumption of Amanita phalloides containing phalloidin and -amanitin) or following the transformation of food (for example, canned foods contaminated by Clostridium botulinum anaerobic bacteria; or by lead).

Non-toxic Adverse Reactions to Food (ARF)

Non-toxic ARFs are dependent upon and individual’s genetic characteristics. Non-toxic adverse reactions to food are subdivided into two categories: on the first part, food allergies resulting from an individual’s immunology and, on the second part, intolerances to food that do not involve the immune system.

Intolerance to food
Intolerance to food is caused by an enzymatic deficiency. Such deficiency may be partial or total, or caused by an overabundance of substrates to catabolize.
1. Enzymatic Deficiencies
  1. Congenital Enzymatic Deficiencies. Such Enzymatic Deficiencies include:
    1. Phenylketonuria
    2. Galactosemia
    3. Favism
    4. Disulfiram-like reaction following the consumption of alcohol or certain medication
  2. Non-Congenital Enzymatic Deficiencies or Lactose Intolerance
    Lactose intolerance occurring after weaning is caused by the intestinal epithelium’s gradual discontinuation of an enzyme synthesis (lactase) which catalyzes the breakdown of lactose www.sanslactose.com
2. Pseudo or False Allergies
  1. Excessive intakes of vasoactives biogenic amines found in food such as:
    1. Intolerance to histamine only occurs when too much histamine is absorbed or when it can not be broken down. In such cases, histamine will cause allergic and pseudo-allergic reactions.
      Intolerance to histamine is caused by a (temporary) deficiency or inhibition of the diamine oxidase (DAO), a body’s own enzyme that metabolizes histamine.
      Intolerance to histamine can also result from the ingestion of histamino-libérateurs foods (such as eggs, chocolate, strawberries or certain food additives).
    2. Biogenic amines can also be synthesized by intestinal flora (for example: putrescine, cadavérine), or found in fruits (for example: spermidine in grapefruit).
  2. Reactions causing other, often obscure, mechanisms to intervene, such as interference with the metabolism of acide arachidonique (e.g.: azoic dyes) or with neurotransmission (e.g.: réaction vagale aux métabisulfites ou glutaminergique dans le Chinese restaurant syndrome).
Food allergies
Food allergies (also referred to as hypersensitivity) are immunological reactions. Reactions due to hypersensitivity entail undesirable reactions of the immune system. Such reactions bring about tissue lesions [lesions tissulaires] and may sometimes be deadly. There are four main types of hypersensitive reactions according to which biological mechanism is involved (2). Each type involves molécules effectrices and typical clinical manifestations
1. Type I Hypersensitivity
  Type I hypersensitivity involves IgE antibodies, of which the Fc attaches to mastocytes or basophiles receptors. This attachment triggers the dégranulation of mastocytes or basophiles which releases des médiateurs pharmacologiquement actifs (example histamine) thereby causing la contraction des muscles lisses et d’une vasodilatation. Clinical manifestations of Type I hypersensitive reactions include anaphylaxie (eventually leading to death), atopie and asthma.
2. Type II Hypersensitivity
  Type II hypersensitivity appears when IgG or IgM antibodies react with déterminants antigéniques présents à la surface des cellules. This leads to a lesion or a deadly lyse of the cell by the facteurs du complément ou par la cytotoxicité cellulaire dépendante d’un anticorps (ADCC). Clinical manifestations of this type of hypersensitive reactions include hémolytique auto immune anaemia (for example in the case of the incorrect transfusion of incompatible blood), thrombocytopenia, érythroblastose fœtale, or Goodpasture Syndrome.
3. Type III Hypersensitivity
  Type III hypersensitivity stems from the formation of immune complexes, involving IgG antibodies, followed by the activation of facteurs du complement. Such activation of the complément releases molécules effectrices which causes a localized vasodilatation and an attraction of neutrophiles by chimiotactisme. An immune complex deposit at the antigen entry site may cause an Arthus reaction with localized release of enzymes lytiques by the accumulated neutrophiles. Generalized Type III reactions occur when lors de la précipitation des complexes immuns circulants. Clinical manifestations of this type of reaction which varies in accordance with the immune complexes deposit site are: serum sickness-like illnesses (such as nephrites, skin lesions, arthritis, vasculitis), the Arthus reaction or systemic érythémateux lupus. Immuns complexes deposit sites can include small blood vessels, articulations or glomérules. Clinical reactions may take hours, days, or even weeks before arising.
4. Type IV Hypersensitivity
  Type IV hypersensitivity involves cell-mediated immunity ular médiation of the immune system together with the activation, by the antigen, of sensitized T4 cells which, in turn, release cytokines. The release of cytokines activates macrophages which cause localized tissulaires lesions. Clinical manifestations of this type of hypersensitivity include: contact dermatitis, chronic rejection of transplants, multiple sclerosis and the Mantoux test.
Autoimmune Diseases
In certain cases, food allergens may cause autoimmune diseases. Such is the case, amongst others, of certain cow’s-milk proteins (3) that cause Type I diabetes mellitus or gluten that causes celiac disease.Autoimmune illnesses result from an overactive immune response of the body against substances or tissues normally present in the body.Several factors, together with a genetic predisposition to the presence of foreign antigens, have quite possibly led to the existence of auto-immune illnesses.

It would appear that women are more commonly afflicted with auto-immune illnesses. Although evidence exists regarding a connection correlation between hormone levels and the severity of certain auto-immune illnesses, the reasons explaining this situation remain unknown.

The aforementioned illnesses include: auto-immune thyroiditis, rheumatoid arthritis, Type I diabetes mellitus, ankylosing spondylitis, celiac disease, Goujerot-Sjögren Syndrome, myasthenia, etc.

Conclusion

Adverse reactions to food constitute clinical realities. Their frequency and severity increase with human progress. Over time, more and more biological tests have been established for identification purposes and for the greater good of patients patient well-being. Once detected, there exists and infallible treatment: food eviction. Unfortunately, such treatment is difficult to implement.

Ch. Linard, PhD, DEPD, CSPQ
Biochimiste clinique

References:

(1) Bruijnzeel-Koomen C, Ortolani C, Aas K, Bindslev-Jensen C, Bjorksten B, Moneret-Vautrin D et al. Adverse reactions to food. European Academy of Allergology and Clinical Immunology Subcommittee. Allergy 1995; 50: 623- 3

(2) PGH Gell, RRA Coombs, eds. Aspects cliniques de l’immunologie. 1re éd. Oxford, Angleterre: Blackwell; 1963.

(3) Melnik BC. Milk–the promoter of chronic Western diseases. Med Hypotheses. 2009 Jun;72(6):631-9..