The Pivotal Role of Histamine in the Symptoms of Food Intolerance Janice M. Joneja, Ph Ph.D. .D. Janice M. Joneja,
Histamine in Food Allergy � Traditionally, allergy is defined as a Type I Traditionally, allergy is defined as a Type I � hypersensitivity (IgE- -mediated) reaction mediated) reaction hypersensitivity (IgE � Histamine is the most important inflammatory Histamine is the most important inflammatory � mediator in IgE- -mediated reactions mediated reactions mediator in IgE � Principally released from mast cells Principally released from mast cells � � Also released by degranulation of other Also released by degranulation of other � granulocytes especially basophils granulocytes especially basophils 2
Histamine in Non-IgE-mediated Reactions � IgG IgG- -mediated reactions also release mediated reactions also release � histamine histamine – Food Food- -specific antibody specific antibody- -antigen complex formed antigen complex formed – – Activates complement cascade Activates complement cascade – – Production of Production of anaphylatoxins anaphylatoxins (C3a; C5a) (C3a; C5a) – – Action of Action of anaphylatoxins anaphylatoxins on mast cells releases on mast cells releases – histamine and other inflammatory mediators and other inflammatory mediators histamine � Reaction is delayed in onset (up to 8 hours) Reaction is delayed in onset (up to 8 hours) � compared to IgE- -mediated immediate mediated immediate compared to IgE reaction reaction 3
Action of Histamine in Allergy � Vasodilation Vasodilation: widening of blood vessels : widening of blood vessels � – May cause slight drop in blood pressure May cause slight drop in blood pressure – – Increase in heart rate – Increase in heart rate � Erythema Erythema � – Flushing, reddening Flushing, reddening – � Increased vascular permeability Increased vascular permeability � – Fluid moves from blood vessels into tissues Fluid moves from blood vessels into tissues – – Causes swelling Causes swelling – � Pruritus Pruritus � – Histamine is the main cause of itching Histamine is the main cause of itching – 4
Examples of Symptoms of Food Allergy � Urticaria and angioedema Urticaria and angioedema � � Rhinoconjunctivitis Rhinoconjunctivitis and and rhinorrhea rhinorrhea � � Headaches Headaches � � Symptoms in the oral cavity Symptoms in the oral cavity � � Digestive tract disturbances: abdominal pain, Digestive tract disturbances: abdominal pain, � diarrhea, nausea, vomiting diarrhea, nausea, vomiting � Similar symptoms can be caused by Similar symptoms can be caused by � histamine intolerance histamine intolerance 5
Food Allergy and Food Intolerance: What is 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 antigen consisting of protein or a molecule linked to a protein linked to a protein � Food Intolerance Food Intolerance � – A non A non- -immunologically mediated event, immunologically mediated event, – usually triggered by small molecular weight usually triggered by small molecular weight chemical substances, and biologically active chemical substances, and biologically active components of foods components of foods 6
Characteristics of Food Allergy and Food Intolerance � Food allergy: Food allergy: � – Requires a “ Requires a “sensitizing sensitizing event” that primes the event” that primes the – immune system for future response immune system for future response – Reaction is not dose Reaction is not dose- -dependent dependent – – Allergic potential is an inherited characteristic Allergic potential is an inherited characteristic – (is idiosyncratic) (is idiosyncratic) � Food Intolerance Food Intolerance � – Does not require “priming” Does not require “priming” – – Event is dose Event is dose- -dependent dependent – – Reaction is not always idiosyncratic Reaction is not always idiosyncratic – 7
Histamine Intolerance � Histamine is a biologically active Histamine is a biologically active � derivative of an amino acid (histidine) derivative of an amino acid (histidine) � Is present in many foods and beverages Is present in many foods and beverages � � High doses are toxic to all humans: High doses are toxic to all humans: � levels of >2.7 mg/kg body weight cause levels of >2.7 mg/kg body weight cause “histamine poisoning” “histamine poisoning” � Individual tolerance determines Individual tolerance determines � reactivity to small quantities reactivity to small quantities 8
Individual Intolerance of Histamine � Cause is most likely a defect in the Cause is most likely a defect in the � catabolism of histamine catabolism 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 Histamine N- -methyl transferase (HMT) methyl transferase (HMT) – 9
Theory 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 catabolized organisms will normally be before gaining access to circulation before 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 sources endogenous sources 10
Histamine-restricted Diet: Case studies - Subject #1 � Female aged 24 years; cashier and student Female aged 24 years; cashier and student � � Presenting Presenting Sx Sx: : � – Recurrent Recurrent urticaria urticaria on neck, midsection, on neck, midsection, – back, arms: Hives occur on various body back, arms: Hives occur on various body surfaces several times a week; present for surfaces several times a week; present for several years several years – Dermatographia Dermatographia and pressure and pressure urticaria urticaria – (water in shower) (water in shower) – Frequent headaches: occur almost daily Frequent headaches: occur almost daily – 11
Histamine-restricted Diet: Case studies - Subject #1 � Other relevant data: Other relevant data: � – Seasonal Seasonal rhinoconjunctivitis rhinoconjunctivitis – – “Borderline asthmatic” (especially in smoky “Borderline asthmatic” (especially in smoky – environment) environment) – Skin Skin- -test positive to: dust, grasses, trees, test positive to: dust, grasses, trees, – feathers feathers – Respiratory tract Respiratory tract Sx Sx improved when living improved when living – in a home with hard- -wood floors wood floors in a home with hard 12
Histamine-restricted Diet: Case studies - Subject #1 � Outcome of histamine Outcome of histamine- -restricted diet: restricted diet: � – Urticaria Urticaria and and pruritus pruritus completely cleared completely cleared – up up – Patient experienced only one headache Patient experienced only one headache – during the diet trial - - following consumption following consumption during the diet trial of tomato soup of tomato 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) 13
Histamine-restricted Diet: Case studies - Subject #2 � Female, age 29 years. Case room nurse Female, age 29 years. Case room nurse � � Presenting Presenting Sx Sx: : � – Urticaria Urticaria – – Frequent Frequent diarrhea diarrhea and vomiting after eating and vomiting after eating – certain meals since childhood, and more certain meals since childhood, and more severely since her latest pregnancy severely since her latest pregnancy – Migraine headaches Migraine headaches – – “Panic attacks” “Panic attacks” – 14
Histamine-restricted Diet: Case studies - Subject #2 � Other relevant data Other relevant data : : � – Skin Skin- -testing in childhood resulted in “whole testing in childhood resulted in “whole – arm swelled to an enormous size” arm 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 ago her daughter 1 year ago – “Panic attacks” becoming debilitating “Panic attacks” becoming debilitating – � Outcome of histamine Outcome of histamine- -restricted diet restricted diet : : � – Significant improvement in all symptoms Significant improvement in all symptoms – – Complete remission of symptoms associated Complete remission of symptoms associated – with “panic attack” with “panic attack” 15
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