Informatii

Stiintifice

Informatii stiintifice despre intoleranta la histamine si DAOSiN®

Clasificarea reactiilor adverse la alimente

Reactii adverse la alimente

Toxice

Non toxice

Fara mediere imunologica Mediate immunologic

(Intoleranta alimentara) (alergie alimentara)

Enzimatice
Malabsorbtie Nedefinite IgE mediate Non IgE mediate
e.x : intoleranta la histamina

Modificata dupa recomandarile EAACI (European Academy of Allergy and Clinical Immunology)

Alergie vs. Intoleranta

Alergie Intoleranta

Prim contact, sensibilizare, producere Ac-IgE Fara sensibilizare (simptomele pot apare oricand)

Cantitati mici de allergen declanseaza simptomele Intensitatea simptomelor este dependenta de cantitatea de alimente ingerata

Simptomele se instaleaza rapid Exista timp de latenta pana la instalarea simptomelor

Manifestari clinice specifice Simptome alergy-like

Diagnostic: detectarea Ac-IgE ( teste sanguine, tegumentare) Se testeaza deficite enzimatice

Informatii stiintifice despre intoleranta la histamine si DAOSiN®

 Prevalenta

Afectiune Procent din populatia generala

Intoleranta la lactoza 10-30%

Malabsorbtia fructozei 5-7%

Alergie alimentara 3-5%

Intoleranta la histamina 2%

Boala celiaca 0.5%

Intoleranta la fructoza (ereditara) <0.1%

Clasificare sistematica

Intolerante prin deficit enzimatic Alte intolerante

Intoleranta la lactoza (lactaza) Boala celiaca

Intoleranta la histamina (DAO) Malabsorbtia fructozei

Intoleranta ereditara la fructoza (Aldolaza B)

Informatii stiintifice despre intoleranta la histamine si DAOSiN®

Cauzele intolerantei la histamina

Dezechilibru intre cantitatea de histamina si nivelul de DiAminOxidaza (DAO)

Deficit Genetic Aport crescut de histamina Inhibitori exogeni

Reducerea activitatii DAO

Intoleranta la Histamina (HIT)

Organismul este mai sensibil la actiunea histaminei exogene h

Mecanismul de declansare a simptomelor

receptori simptome

deficit enzimatic

histamina

putresceina
amine biogene

catabolism
cadaverina DAO absorbtie facila a compusilor
tyramina

serotonina

intestin subtire

Informatii stiintifice despre intoleranta la histamine si DAOSiN®

 Simptome frecvente

Intoleranta la histamina – sumar al simptomelor care pot apare dupa consumul de alimente bogate in histamina

• Simptome gastro intestinale (ex: dureri gastrice, flatulenta, diaree)

• Dureri de cap, migrena
• Prurit, edem palpebral, urticarie
• Rinoree
• Dismenoree
• Obstructie bronsica, fenomene astmatiforme
• Tachicardie, extra sistole, hipotonia, oboseala cronica

Histamina

NH2 Surse Metabolizare CH2 CH2 NH2

N
CH2 C COOH CH2 CH2 NH2 Histamine

N N
H e)
in
st as am
am st
Histidine Hi N Hi in
decarboxilaza (D N
H
AO, e- -m
se et
N N da an
H H in ltr
am oxi hy as
L-Histidina Histamina Di
CH2 COOH
er
CH2 CH2 NH2

N sf e
N
Imidazole acetic acid N-Methylhistamine

Phosphoribosyltransf
erase
• Decarboxilarea histidinei N N
• Survine in mod obisnuit in organisme vegetale si animale H DAO; MAO B H
• Survine in procesele naturale de
CH2 COOH
fermentatie/putrefactie/maturare a alimentelor CH3
N
Imidazole acetic acid ribosid CH2 COOH

N
N-Methylimidazole acetic acid

N
H

N
H
Ribose

CH3

Intestin subtire SNC

Informatii stiintifice despre intoleranta la histamine si DAOSiN®

DiAminOxidaza

• DiAminOxidaza (DAO) EC 1.4.3.6

• DAO este responsabila de degradarea aminelor biogene ingerate odata cu alimentele
(histamine exogena)
• DAO actioneaza in intestinul subtire si protejeaza organismul de excesul de
histamine exogena
• DAO se gaseste in cantitati mari la nivel renal si placentar Vicinal disulfide bridge
• Alcoolul inhiba activitatea DAO
Active-site
entrance

Efectele histaminei

H1 H1/2 H2 H3 H4
Permeabilitate endoteliala
Secretie de mucus

Neurotransmitter
SMC constrictie

hematopoesis
nociceptive nerves
Vasodilatatie

Tachycardia

Estrogen

Regulation
Arrhytmia

Gastric Acid
cAMP
Stimulation

cGMP
release
secretion

Aparat cardiovascular Tract Respirator Uter Tegument Tract digestiv SNC Maduva osoasa Leucocite

Anafilaxie Congestie nazala, Dismenoree Prurit Dureri gastrice Vertij Degranulare Mastocitara
Hipotonie stranut Flush Crampe Cefalee
Hipotensiune Bronchoconstrictie- dispnee Urticarie Meteorism Greturi, Varsaturi
Vertigo Diaree Tulburari de ritm circadian
Aritmie Contributie in termoreglare
Locomotie, invatare,
memorie

Maintz et al; Dtsch Aeztbl.

2006; Am J Clin Nutr 2007

Informatii stiintifice despre intoleranta la histamina si DAOSiN®

Alimente bogate in (Hist)amina
• Vin rosu, vin spumant, sampanie
• Ciocolata
•

! !
Branzeturi maturate, afumate Pizza este o posibila bomba cu histamina, continand aproape toate alimentele
• Varza murata bogate hin histamina: branza,salami, ton conservat, sunca afumata, rosii, drojdie,
• Ton carne tocata si probabil un pahar de vin sau de bere ca bautura de insotire !
• Mezeluri si preparate din carne
• Rosii, ketchup

Eliberatori de histamina
• Capsuni
• Citrice
• Kiwi
• Banane
• Ciocolata
• Peste si fructe de mare
• Stress

Medicamente care inhiba DAO

Substanta activa Utilizare
Acemitacin agent antireumatic
Acetilcisteine (ACC, NAC) expectorant

Acriflavine antiseptic
Ambroxol expectorant

Aminophiline tratamentul astmului bronsic

Amitriptilina antidepresiv
Quinidine aritmii cardiace

Chloroquina agent antireumatic, tratamentul malariei

Cimetidina H2 Antagonist, tratamentul ulcerului

Clavulanic acid antibiotic

D-Cycloserine antibiotic

Diazepam tranchilizant
Dihidralazina vasodilator
Furosemid diuretic
Haloperidol antipsihotic
Isoniazid antibiotic,tratamentul tuberculozei

Metamizole analgezic
Metoclopramide Diopamin antagonist, tratamentul greturilor si varsaturilor

Neomicin antibiotic
Pancuronium mio relaxant

Propafenone tratamentul afectiunilor cardiovasculare

Teofilina bronhodilatator

Verapamil tratamentul afectiunilor cardiovasculare

Informatii stiintifice despre intoleranta la histamina si DAOSiN®

Diagnostic
• Anamneza – Simptome, legatura intre simptome si alimente, jurnal de dieta
• Testari alergologice (dozari IgE)
• Determinarea activitatii DAO in ser/plasma
• Testari pentru alte intolerante – lactoza, fructoza and gluten
• Dieta cu eliminarea anumitor produse din alimentatie

Solutii posibile
• Dieta cu alimente sarace in histamina
• Evitarea ingerarii de amine biogene si a eliberatorilor de histamina
• Aport exogen de DAO patentat (Patent No: AT411688)

Sugestii
• De evitat alimentele care nu sunt tolerate
• De evitat dietele cu deficite de nutrienti
• De citit continutul produselor alimentare – atentie la conservanti
• Nu consumati alimente care au fost pastrate timp indelungat

Schema functionala
cefalee, migrena,
vertigo

iritatii
ale mucoasei nazale

tahicardie,
hipertensiune

Astm,
Dificultati respiratorii

Metabolismul normal al Intoleranta la simptome gastro Solutia:

intestinale
histaminei histamina

sistem circulator sistem circulator Sistem circulator

intestin subtire intestin subtire intestine subtire

DAO rash, eczeme, prurit DAO

catabolismul histaminei Catabolismul histaminei

histamina histamina histamina

Stare fiziologica Problema Solutia

Daca DAO este deficitara histamine nu DAOSiN® suplineste deficitul enzimatic.

DiA mineOxidaza ( DAO)
poate fi degradata. Histamina este degradata
degradeaza histamina ingerat a in intestinul subtire Surplusul de histamina trece in circulatia sanguina via
mucoasa intestinala producand simptome variate.

Informatii stiintifice despre intoleranta la histamina si DAOSiN®

Surse de informare
Histamine intolerance:
Pfisterer M., Mayer I.: Histamin-Intoleranz – aktueller Stand der Technik von Diagnose und
Therapie; EHK (2008)
Maintz L., Novak N.: Histamine and histamine intolerance; AM J Clin Nutr (2007)
Missbichler A., Pfister M.: Biogene Amine und Histamin – Genuss oder Verdruss?; Ernähr
Aktuell (2007)
Maintz L., Bieber T., Novak N.: Die verschiedenen Gesichter der Histamin-Intoleranz –
Konsequenzen für die Praxis; Ärzteblatt (2006)
Jarisch R.: Histamin-Intoleranz: Ein oft übersehenes Problem; Arzt & Praxis (2005)
Fructose malabsorption:
Born P.: Carbohydrate malabsorption in patients with non-specific abdominal complaints; World J Gastroenterol
(2007)
Gibson P. R., Newnham E., Barrett J. S., Shepard S. J., Muir J.G.: Review article: fructose malabsorption and the
bigger picture; Aliment Pharmacol Ther (2006)
Sheperd S. J., Gibson P. R.: Fructose Malabsorption and Symptoms of Irritable Bowel Syndrome: Guidelines for
Effective Dietary Management; J Am Diet Assoc (2006)
Drozdowski L. A., Thomson A. B. R.: Intestinal Sugar Transport; World J Gastroenterol (2006)
Skoog S. M., Bharucha A. E.: Dietary Fructose and Gastrointestinal Symptoms: A Review; Am J Gastroenterol
(2004)
Ledochowski M., Widner B., Fuchs D.: Fruktosemalabsorption; J Ernährungsmed (2000)
Lactose intolerance:
Bhatnagar S., Aggarwal R.: Lactose intolerance; BMJ (2007)
Hryman M. B.: Lactose Intolerance in Infants, Children and Adolescents; Pediatrics (2006)
Montalto M., Curigliano V., Santoro L., Vastola M., Cammarota G., Manna R., Gasbarrini A., Gasbarrini G.: Management and
treatment of lactose malabsorption; World J Gastroenterol (2006)
Celiac disease:
Dubois P. C., van Heel D. A.: Translational Mini-Review Series on the Immunogenetics of Gut Disease: Immunogenetics of coeliac disease; Clin Exp
Immunol (2008)
Kagnoff M.: Celiac disease: pathogenesis of a model immunogenetic disease; J Clin Invest (2007)
Van Heel D. A., West J.: Recent advanced in coeliac disease; Gut (2006)
Howdle P. D.: Gliadin, glutenen or both? The search for the Holy Grail in coeliac disease; Eur J Gastroenterol Hepatol (2006)
Hischenhuber C., Crevel R., Jarry B., Mäkis M., Moneret-Vautrin D. A., Romano A., Troncone R., Ward R.: Review article: safe amounts of gluten f or
patients with wheat allergy or coeliac disease; Aliment Pharmacol Ther (2005)