Recent Research on Non-Immune System Reactions to Foods: Food Intolerances Janice M. Joneja, Ph.D.,...

Recent Research on Non-Immune Recent Research on Non-Immune System Reactions to Foods:System Reactions to Foods:

Food IntolerancesFood Intolerances

Janice M. Joneja, Ph.D., RDJanice M. Joneja, Ph.D., RD

20062006

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Food Allergy and Food Intolerance: Food Allergy and Food Intolerance:

What isWhat is the Difference?the Difference?

Definitions:Definitions:

Food Allergy:Food Allergy:– A response of the immune system involving A response of the immune system involving

antigen consisting of protein or a molecule linked antigen consisting of protein or a molecule linked to a proteinto a protein

Food IntoleranceFood Intolerance– A non-immunologically mediated event, usually A non-immunologically mediated event, usually

triggered by small molecular weight chemical triggered by small molecular weight chemical substances, and biologically active components substances, and biologically active components of foodsof foods

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Characteristics of Food Allergy Characteristics of Food Allergy and Food Intoleranceand Food Intolerance

Food allergy:Food allergy:– Requires a “sensitizing event” that primes the Requires a “sensitizing event” that primes the

immune system for future responseimmune system for future response– Reaction is not dose-dependentReaction is not dose-dependent– Allergic potential is an inherited characteristic (is Allergic potential is an inherited characteristic (is

idiosyncratic)idiosyncratic)

Food IntoleranceFood Intolerance– Does not require “priming”Does not require “priming”– Event is dose-dependentEvent is dose-dependent– Reaction is not always idiosyncraticReaction is not always idiosyncratic

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Examples of Symptoms of Food Examples of Symptoms of Food AllergyAllergy

Urticaria and angioedemaUrticaria and angioedema

Rhinoconjunctivitis and rhinorrheaRhinoconjunctivitis and rhinorrhea

HeadachesHeadaches

Symptoms in the oral cavitySymptoms in the oral cavity

Digestive tract disturbances: abdominal pain, Digestive tract disturbances: abdominal pain, diarrhea, nausea, vomitingdiarrhea, nausea, vomiting

Similar symptoms can be caused by Similar symptoms can be caused by histamine intolerancehistamine intolerance

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Action of Histamine in AllergyAction of Histamine in Allergy

Vasodilation: widening of blood vesselsVasodilation: widening of blood vessels– May cause slight drop in blood pressureMay cause slight drop in blood pressure

– Increase in heart rateIncrease in heart rate

ErythemaErythema– Flushing, reddeningFlushing, reddening

Increased vascular permeabilityIncreased vascular permeability– Fluid moves from blood vessels into tissuesFluid moves from blood vessels into tissues

– Causes swellingCauses swelling

PruritusPruritus– Histamine is the main cause of itchingHistamine is the main cause of itching

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Histamine in Food AllergyHistamine in Food Allergy

Traditionally, allergy is defined as a Traditionally, allergy is defined as a Type I hypersensitivity (IgE-mediated) Type I hypersensitivity (IgE-mediated) reactionreaction

Histamine is the most important Histamine is the most important inflammatory mediator in IgE-mediated inflammatory mediator in IgE-mediated reactionsreactions

Principally released from mast cellsPrincipally released from mast cells

Also released by degranulation of other Also released by degranulation of other granulocytes especially basophilsgranulocytes especially basophils

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Individual Intolerance of Individual Intolerance of HistamineHistamine

Cause is most likely a defect in the Cause is most likely a defect in the catabolism of histaminecatabolism of histamine

In humans, enzymatic inactivation of In humans, enzymatic inactivation of histamine occurs by two pathways:histamine occurs by two pathways:

– Diamine oxidase (DAO)Diamine oxidase (DAO)

– Histamine N-methyl transferase Histamine N-methyl transferase (HMT)(HMT)

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Theory of Histamine ExcessTheory of Histamine Excess

Histamine from dietary sources and Histamine from dietary sources and from the activity of intestinal micro-from the activity of intestinal micro-organisms will normally be catabolized organisms will normally be catabolized before gaining access to circulationbefore gaining access to circulation

If enzyme activity is reduced, histamine If enzyme activity is reduced, histamine will gain access to blood and augment will gain access to blood and augment the level of plasma histamine from the level of plasma histamine from endogenous sourcesendogenous sources

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Histamine-restricted Diet:Histamine-restricted Diet: Case studies - Subject #1 Case studies - Subject #1

Female aged 24 years; cashier and studentFemale aged 24 years; cashier and student

Presenting Sx:Presenting Sx: – Recurrent urticaria on neck, midsection, back, Recurrent urticaria on neck, midsection, back,

arms: Hives occur on various body surfaces arms: Hives occur on various body surfaces several times a week; present for several several times a week; present for several yearsyears

– Dermatographia and pressure urticaria (water Dermatographia and pressure urticaria (water in shower)in shower)

– Frequent headaches: occur almost dailyFrequent headaches: occur almost daily

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Other relevant data:Other relevant data:– Seasonal rhinoconjunctivitisSeasonal rhinoconjunctivitis– ““Borderline asthmatic” (especially in smoky Borderline asthmatic” (especially in smoky

environment)environment)– Skin-test positive to: dust, grasses, trees, Skin-test positive to: dust, grasses, trees,

feathersfeathers– Respiratory tract Sx improved when living in a Respiratory tract Sx improved when living in a

home with hard-wood floorshome with hard-wood floors

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Outcome of histamine-restricted diet:Outcome of histamine-restricted diet:– Urticaria and pruritus completely cleared upUrticaria and pruritus completely cleared up– Patient experienced only one headache Patient experienced only one headache

during the diet trial - following consumption of during the diet trial - following consumption of tomato souptomato soup

– Consumption of Tylenol for control of Consumption of Tylenol for control of headaches reduced from daily to only once headaches reduced from daily to only once (after above episode)(after above episode)

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Female, age 29 years. Case room nurseFemale, age 29 years. Case room nurse

Presenting Sx:Presenting Sx:– UrticariaUrticaria– Frequent diarrhea and vomiting after eating Frequent diarrhea and vomiting after eating

certain meals since childhood, and more certain meals since childhood, and more severely since her latest pregnancyseverely since her latest pregnancy

– Migraine headachesMigraine headaches– ““Panic attacks”Panic attacks”

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Other relevant dataOther relevant data::

– Skin-testing in childhood resulted in “whole arm Skin-testing in childhood resulted in “whole arm swelled to an enormous size”swelled to an enormous size”

– All reactions have worsened since the birth of All reactions have worsened since the birth of her daughter 1 year agoher daughter 1 year ago

– ““Panic attacks” becoming debilitatingPanic attacks” becoming debilitating

Outcome of histamine-restricted dietOutcome of histamine-restricted diet: : – Significant improvement in all symptomsSignificant improvement in all symptoms– Complete remission of symptoms associated Complete remission of symptoms associated

with “panic attack”with “panic attack”

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Indicators of Possible Histamine Indicators of Possible Histamine IntoleranceIntolerance

Skin tests:Skin tests:– ““Mildly positive” to multiple allergensMildly positive” to multiple allergens– Large reaction wheal to histamine controlLarge reaction wheal to histamine control

DermatographiaDermatographia

Unusually sensitive to alcoholic beveragesUnusually sensitive to alcoholic beverages

Sensitive to fermented foods, especially Oriental Sensitive to fermented foods, especially Oriental food, cheese, vinegarfood, cheese, vinegar

Sensitive to benzoate-containing foods, especially Sensitive to benzoate-containing foods, especially cinnamon, green and black teacinnamon, green and black tea

Positive family historyPositive family history

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Level of Histamine Metabolites in UrineLevel of Histamine Metabolites in Urine

Seems to be greatly influenced by:Seems to be greatly influenced by:– Level of histamine in foodLevel of histamine in food– Activity of bacteria in the large bowel (caecum Activity of bacteria in the large bowel (caecum

and colon)and colon)– Possibly activity of bacteria in the vaginaPossibly activity of bacteria in the vagina

These are exogenous sourcesThese are exogenous sources

The level of endogenous histamine may be fairly The level of endogenous histamine may be fairly stable, except when an allergic reaction causes stable, except when an allergic reaction causes increased release of histamineincreased release of histamine

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Exogenous Sources of Exogenous Sources of HistamineHistamine

Amines are produced from amino acids by Amines are produced from amino acids by decarboxylationdecarboxylation

Result from metabolism of animal, plant, and Result from metabolism of animal, plant, and microorganismsmicroorganisms

Are present in most animal and plant foods in Are present in most animal and plant foods in small quantitiessmall quantities

Histamine is produced by decarboxylation of Histamine is produced by decarboxylation of histidinehistidine

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Histidine DecarboxylaseHistidine Decarboxylase

Histidine decarboxylase is produced by a range Histidine decarboxylase is produced by a range of micro-organismsof micro-organisms

These species are used in manufacture of These species are used in manufacture of fermented foods, such as:fermented foods, such as:– CheeseCheese– Fermented sausages (Salami; Bologna; Fermented sausages (Salami; Bologna;

Pepperoni, etc)Pepperoni, etc)– Fermented vegetables (sauerkraut)Fermented vegetables (sauerkraut)– Fermented soy (miso and soy sauce)Fermented soy (miso and soy sauce)

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Other Food Sources of HistamineOther Food Sources of Histamine

Fermented beveragesFermented beverages– WineWine– Beer, ale, lager, etcBeer, ale, lager, etc

Fruits: Fruits: – CitrusCitrus - Stone fruits- Stone fruits - Dates- Dates– BerriesBerries - Pineapple- Pineapple - Currants- Currants

VegetablesVegetables– TomatoTomato - Eggplant- Eggplant - Soy bean- Soy bean– SpinachSpinach - Pumpkin- Pumpkin - Red bean- Red bean– OlivesOlives

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Other Food Sources ofOther Food Sources of Histamine Histamine

Several species of bacteria in the gut of fish and Several species of bacteria in the gut of fish and shellfish produce histidine decarboxylaseshellfish produce histidine decarboxylase– When fish dies bacteria degrade its proteinWhen fish dies bacteria degrade its protein– Bacteria can multiply every 20 minutesBacteria can multiply every 20 minutes– Histamine content of ungutted fish can double Histamine content of ungutted fish can double

every 20 minutesevery 20 minutes

Shellfish are not gutted before consumptionShellfish are not gutted before consumption

Left-over meats may be colonized by histidine Left-over meats may be colonized by histidine decarboxylase-producing bacteriadecarboxylase-producing bacteria

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Other Food Sources of HistamineOther Food Sources of Histamine

Some food additives appear to release Some food additives appear to release histamine:histamine:– Tartrazine and other azo dyesTartrazine and other azo dyes– SulphitesSulphites– BenzoatesBenzoates

Some foods contain natural benzoates:Some foods contain natural benzoates:– CinnamonCinnamon - Tea- Tea - Berries- Berries

Egg white (ovalbumin) has been implicated in Egg white (ovalbumin) has been implicated in histamine release by an unknown mechanismhistamine release by an unknown mechanism

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Histidine decarboxylase and the Histidine decarboxylase and the Resident Micro-floraResident Micro-flora

Many bacterial species that colonize the large Many bacterial species that colonize the large bowel of humans produce histidine bowel of humans produce histidine decarboxylasedecarboxylase

Convert histidine in non-digested food material Convert histidine in non-digested food material to histamineto histamine

This is an additional source of exogenous This is an additional source of exogenous histaminehistamine

If not catabolised by DAO in situ, histamine will If not catabolised by DAO in situ, histamine will enter the blood circulation enter the blood circulation

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Histamine Degrading BacteriaHistamine Degrading Bacteria

Certain species of bacteria produce Certain species of bacteria produce diamine oxidase:diamine oxidase:– Lactobacillus sp.Lactobacillus sp. - Sarcina sp.- Sarcina sp.– Leuconostoc sp.Leuconostoc sp. - E.coli faecium sp.- E.coli faecium sp.

Capable of degrading food sources of Capable of degrading food sources of histaminehistamine

May reduce total histamine loadMay reduce total histamine load

Possible role in probiotics?Possible role in probiotics?

Diet and BehaviourDiet and Behaviour

Current Theories on the Role of Food Current Theories on the Role of Food

in Behavioural Problemsin Behavioural Problems

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Diet and BehaviourDiet and Behaviour

Experts do not agree on whether diet can influence Experts do not agree on whether diet can influence behaviour behaviour

Several different studies in Britain, Canada and U.S.A. Several different studies in Britain, Canada and U.S.A. provide evidence both for and against the theory that provide evidence both for and against the theory that food allergy or food intolerance can cause behaviour food allergy or food intolerance can cause behaviour changeschanges

Adverse effects of food on behaviour suggested to be Adverse effects of food on behaviour suggested to be the result of:the result of:– Physiological manifestation of food intolerance, possibly a Physiological manifestation of food intolerance, possibly a

pharmacological responsepharmacological response– Psychological factors, including suggestion or conditioningPsychological factors, including suggestion or conditioning

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Current Theories on Diet and BehaviourCurrent Theories on Diet and Behaviour

Effect of allergy symptomsEffect of allergy symptoms::

– Child feels ill, miserable, restlessChild feels ill, miserable, restless

– May have difficulty sleepingMay have difficulty sleeping

– Leads to difficulty in concentrationLeads to difficulty in concentration

– Child expresses illness through Child expresses illness through unacceptable behaviourunacceptable behaviour

– Removal of allergen allows childRemoval of allergen allows child

to feel betterto feel better

– Behaviour improvesBehaviour improves

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Effect of Mediators of AllergyEffect of Mediators of Allergy– Some of the chemicals responsible for Some of the chemicals responsible for

allergy cross the blood-brain barrier and allergy cross the blood-brain barrier and stimulate the central nervous systemstimulate the central nervous system

May include histamineMay include histamine

– Removal of the allergen eliminates the Removal of the allergen eliminates the mediatorsmediators

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Chemicals in foods have a direct Chemicals in foods have a direct pharmacological effect pharmacological effect – Natural chemicals:Natural chemicals:

benzoatesbenzoates

salicylatessalicylates

annattoannatto

– Synthetic additives:Synthetic additives: tartrazine and other food dyestartrazine and other food dyes

preservativespreservatives

some flavouringssome flavourings

– Removal eliminates the “drug-like” responseRemoval eliminates the “drug-like” response

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Reasons for Improvement on Restricted DietReasons for Improvement on Restricted Diet

Exclusion of food allergens leads to Exclusion of food allergens leads to remission of allergy symptoms: child feels remission of allergy symptoms: child feels better and behaviour improvesbetter and behaviour improvesRemoval of excess sugar and additives Removal of excess sugar and additives eliminates “junk food” from the child’s diet: eliminates “junk food” from the child’s diet: a more nutritious diet reduces the negative a more nutritious diet reduces the negative behavioural effects of malnutritionbehavioural effects of malnutritionA special diet requires extra care and A special diet requires extra care and attention: a change in family dynamics attention: a change in family dynamics may have a positive effect on the child’s may have a positive effect on the child’s behaviourbehaviour

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Role of Food Additives in Hyperactivity Role of Food Additives in Hyperactivity

Recent study (2004): 227 3-year old Recent study (2004): 227 3-year old children randomly selectedchildren randomly selected

Avoidance of artificial food colourings and Avoidance of artificial food colourings and sodium benzoate (preservative)sodium benzoate (preservative)

Placebo controlled cross-over studyPlacebo controlled cross-over study

Behaviour rated by:Behaviour rated by:– Parental observationParental observation– Research psychologists using validated testsResearch psychologists using validated tests

________________Bateman et al 2004

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Details of Test AdditivesDetails of Test Additives

Mixed fruit juices Mixed fruit juices 300 mL300 mL

Artificial food colourings Artificial food colourings – Sunset yellowSunset yellow 5 mg5 mg– TartrazineTartrazine 5 mg5 mg– CarmoisineCarmoisine 5 mg5 mg– PonceauPonceau 5 mg5 mg

Sodium benzoateSodium benzoate 45 mg45 mg

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Results of Study Results of Study

Based on parental observation:Based on parental observation:– Significant improvement when food additives Significant improvement when food additives

avoidedavoided– Hyperactivity observed when food additives Hyperactivity observed when food additives

consumedconsumed

No difference found between subjects No difference found between subjects based on:based on:– History of allergyHistory of allergy– Hyperactive behaviour prior to studyHyperactive behaviour prior to study

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Conclusions from StudyConclusions from Study

Results suggest:Results suggest:

– Additives have an effect via a Additives have an effect via a pharmacological processpharmacological process

– Possibly due to non-IgE dependent Possibly due to non-IgE dependent histamine releasehistamine release

– All children would benefit from removal All children would benefit from removal of artificial food colourings and of artificial food colourings and benzoates from their dietbenzoates from their diet

Recent Research on Non-Immune System Reactions to Foods: Food Intolerances Janice M. Joneja, Ph.D.,...

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