Dr.

Fawzia abo ali

Prof. of internal medicine & immunology
Ain shams faculty of medicine
 Food Allergy and Food
Intolerance:
What is the Difference?
Food Allergy: Food Intolerance

– A non immunologically
– A response of the mediated event,
immune system usually triggered by small
involving molecular weight
antigen consisting of chemical substances, and
biologically active
protein or a molecule
components of foods
linked to a protein
 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
1. 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 release

histamine:
– 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

histamine
breakdown 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 control
2. Unusually sensitive to alcoholic beverages
3. Sensitive to fermented foods, cheese&vinegar
4. Sensitive to benzoate-containing food.
5. Dermatographia
6. 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 Intoleranc
 Management of Histamine
Intolerance
1. Avoidance of foods that:

1. Contain high levels of histamine naturally:

Tomato • Spinach
Eggplant • Histamine-rich fruits
1. Contain histamine as a consequence of
manufacture:
Fermented foods and beverages
Cheese – Alcoholic beverages
Vinegars – Fermented sausages
1. Contain histamine as a result of microbial
activity :Non-gutted fish,Shellfish
2. 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-