Dr. Fawzia abo aliProf. of internal medicine & immunology

Ain shams faculty of medicine

Food Allergy and Food Intolerance:Food Allergy and Food Intolerance:What is the Difference?

Food Allergy:

– A response of the immune system involvingantigen consisting of protein or a moleculelinked to a protein

Food Intolerance

– A non immunologically mediated event,usually triggered by small molecular weightchemical substances, and biologically activecomponents of foods

Histamine in Food Allergy

Histamine: is a physiologic protein, only

active for a short time, released by mast

cells & other granulocytes.

The main function of histamines is to protect

the body against invaders such as allergens,

bacteria and viruses. Histamines also

promote wakefulness and alertness.

Histamine & food Intolerance

Histamine is a biologically active derivative of an

amino acid (histidine)via histidine decarboxylase

(HDC)

Is present in many foods and beverages

High doses are toxic to all humans : levels of >2.7

mg/kg body weight cause“histamine poisoning”

Individual tolerance determines reactivity to small

quantities.

Individual Intolerance of Histamine

Cause is most likely a defect in the catabolism of

histamine.

In humans, enzymatic inactivation of histamine

occurs by two pathways:

– Exogenous histamine is metabolised predominantly via oxidative deamination by DAO

– Endogenous histamine is metabolised more via ring N-methylation by histamine N-methyltransferase

Mechanism of Histamine Sensitivity

Symptoms develop when:

• Excessive amounts of histamine exceed the enzymes’ capacity to break it down

• There is a lowered enzyme capacity for histamine breakdown

• Drugs inhibit enzyme action (e.g. isoniazid)

Theory of Histamine Excess

1.Histamine from dietary sources and from the

activity of intestinal microorganisms will

normally be catabolized before gaining access

to circulation.

2. If enzyme activity is reduced, histamine will

gain access to blood and augment the level of

plasma histamine from endogenous sources.

Symptoms of Histamine Excess

Symptoms of Histamine Excess♥ Pruritis (skin, eyes, ears, nose)♥ Urticaria♥ Angioedema♥ Hypotension♥ Tachycardia♥ “Panic attack”♥ Chest pain♥ Nasal congestion♥ wheezes♥ Headache♥ Fatigue, confusion, irritability♥ Abdominal pain

Sources of Histamine in Foods

1. Histidine can be decarboxylated to histamine (histidine decarboxylase )by intestinal bacteria

– May develop in fish [especially tuna and mackerel that have been improperly processed and refrigerated.

– In shellfish, where intestine is not removed

2. Histamine is produced by microbial action in manufacture of foods such as cheese, wine, beers, vinegar, yeast extract.

Sources of Histamine in Foods

3. Some foods contain high levels of histamine naturally, especially spinach and eggplant

4. Plant foods may produce histamine during the ripening process, e.g. tomato

5. Some foods may release histamine by a non-immunologically mediated mechanism which is presently unknown. Such foods include:

• Egg white • Strawberry• Alcohol (ethanol)• Citrus fruits

Other Food Sources of Histamine

Some food additives appear to releasehistamine:– Tartrazine and other azo dyes– Sulphites– Benzoates

Egg white (ovalbumin) has been implicated in

histamine release by an unknown mechanism

Inhibitors of DAO and HMT

Drugs that inhibit enzymes involved in histaminebreakdown result in histamine excess:– HMT inhibitors: Antimalarial drugs Anticancer drugs (pyrimidine analogs)– DAO inhibitors: Copper-chelating agents . Carbonyl group reagents (aminoguanidine)

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Signs of Possible Histamine Intolerance

1.Skin tests:– “Mildly positive” to multiple allergens– Large reaction wheal to histamine control2.Unusually sensitive to alcoholic beverages3.Sensitive to fermented foods, cheese&vinegar4.Sensitive to benzoate-containing food.5.Dermatographia6. Indicators of reduced histamine metabolism:– Elevated plasma histamine (>2 ng/ml)– Reduced DAO activity (<0.7 nkat/L)7.Normal serum IgE.8.Positive family history

Histamine poisoning

Histamine poisoning results from the consumption of foods, typically certain types of fish and cheeses, that contain unusually high levels of histamine. Spoiled fish of the families, Scombridae (e.g. tuna, mackerel, bonito), termed, “scombroid fish poisoning”, cheeses especially Swiss cheese, can be implicated in histamine poisoning.

The symptoms of histamine poisoning include :

1.nausea, vomiting, diarrhea,2.oral burning sensation or peppery taste,3. hives, itching, red rash, and hypotension. 4.The onset of the symptoms usually occurs

within a few minutes after ingestion of the implicated food, and the duration of symptoms ranges from a few hours to 24 h.

5.Antihistamines can be used effectively to treat this intoxication.

Management of Histamine Intolerance

Management of Histamine Intolerance

1. Avoidance of foods that:

1. Contain high levels of histamine naturally:Tomato SpinachEggplant Histamine-rich fruits

2. Contain histamine as a consequence of manufacture:Fermented foods and beverages

Cheese – Alcoholic beveragesVinegars – Fermented sausages

3. Contain histamine as a result of microbial activity :Non-gutted fish,Shellfish

4. Release histamine:Benzoates,Tartrazine .

2. Histamine Degrading Bacteria

Certain species of bacteria produce diamine oxidase:

– Lactobacillus sp. - Sarcina sp. Capable of degrading food sources of

histamine- May reduce total histamine load- Possible role in probiotics?

Histame is the first product worldwide that regulates histamine levels that can cause food intolerance by replenishing the body’s digestive enzyme Diamine oxidase, or DAO. Histame is not effective with immune system-based food allergies