| Translations may contain older or less information than the German original page! Chronical form of histamine intolerance (type HNMT)
The description of this particular form of this medical condition is based on the author's theoretical deliberations, interpretations and model predictions and is supported by a growing number of individual case reports. This is primarily an hypothesis and not established scientific data. |
Summary:
Two degradation pathways for histamine
There are two main pathways for histamine degradation in the human body. One of these is via diamine oxidase (DAO), the other via histamine N-methyltransferase (HNMT). Histamine intolerance is often defined as a diminished DAO activity. This ignores the fact that an impairment of histamine N-methyltransferase (HNMT) can also lead to an intolerance of histamine.
Two types of HIT: the acute and the chronic forms
Because of the different roles played by the two histamine-degrading enzymes (DAO, HNMT), the existence of two different types of histamine intolerance with differing symptoms can be predicted: an acute form (type DAO) and a chronic form (type HNMT).
Job division between DAO and HNMT: Who works where?
DAO is an excretory enzyme which is mainly excreted by the cells of the intestinal mucus membrane and already acts outside the body cells to degrade the histamine in the food pulp in order to prevent too large a quantity entering the body. HNMT, on the other hand, is a cytosolic enzyme within the body cells, especially the liver (detoxification organ), instrumental in degradation of histamine.
Hybrid forms
Several genetic variables (polymorphisms) of both enzymes are known, not all of which have the same degree of deactivation. This means that hybrid forms between type DAO and type HNMT are possible and the degree to which each enzyme is affected can vary. Which of the two enzymes is affected and to what degree influences the symptomatology in terms of chronology, intensity and type of symptoms.
Chronology: comparison of the acute and chronic types
In the DAO type (acute case) the histamine level rises sharply but then also declines rapidly. In the HNMT type the histamine level does not rise remarkably after a single meal, compared to healthy subjects. Because of lack of degrading capacity, however, it only declines slowly. At the next meal the new dose of histamine is added to the remaining level of histamine and thus rises from day to day until, after several days, an equilibrium concentration is reached where degradation/excretion and intake are in balance.
Symptoms in the chronic type (HNMT)
The acute and the chronic forms of histamine intolerance not only differ in terms of intensity and chronology. The types of symptoms that can occur also differ in part. This is explained by the differing distribution of the enzymes in the different organs, tissue structures and cell types: most cells produce DAO as well as HNMT. However, the quantity varies considerably according to organ or cell type. In the central nervous system, the bronchial mucous membrane and in the skin HNMT is the main degradation channel. When HNMT is functionally impaired it is thus these organs, the brain in particular, which tends to be particularly badly affected. In the acute form, on the other hand, the spasmodic occurrence of stomach and intestinal symptoms and heart and circulatory symptoms tend to dominate.
Diagnosis
A diagnosis is much more difficult for the doctor in the case of chronic histamine intolerance as opposed to the acute type. It is more obvious here than in the case of acute HIT that the illness can best be diagnosed with the cooperation of the patient, in so far as, following thorough instruction, they try out the histamine elimination diet while keeping a nutritional diary. The role of the doctor is primarily limited to eliminating other illnesses and to making the patient aware of a possible HIT. But it remains, however, absolutely central that the doctor is aware of this possibility and talks to the patient about it, because otherwise patients hardly stand a chance of discovering what is plaguing them on their own.
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Many thanks to www.histamineintolerance.org.uk for the translation of this page.
ReferencesHint: The "back"-button of your browser takes you back to the previous position. | Aktories 2008 | Klaus Aktories, Wolfgang Forth, Ulrich Förstermann, Franz Hofmann: "Allgemeine und spezielle Pharmakologie und Toxikologie". Elsevier, Urban & Fischer, 2008. 1189 Seiten. | | Bielenberg 2005 | Bielenberg, Jens: "Korrelate einer schadstoffinduzierten Veränderung des Histaminstoffwechsels? Die Allergie-Hypothese". Österreichische Apotheker-Zeitung ÖAZ Aktuell (Ausgabe 15/2005), Hauptartikel 15/2005. Anschrift des Autors: Apotheker Jens Bielenberg, Raphael-Apotheke, D-25364 Westerhorn, Bahnhofstr. 53
http://www3.apoverlag.at/pdf/files/OAZ/OAZ-2005/OAZ-2005-15.pdf
http://www.zaen.org/download/artikel/2005_11_aefn_bielenberg.pdf
(Sehr interessanter Artikel über mögliche Ursachen von Allergien, Störfaktoren im Histaminstoffwechsel, Abbaumechanismen von Histamin, Ascorbate (Vitamin C), Umweltschadstoffe, Schilddrüsenerkrankungen, mit Kommentar von Prof. Jarisch) | | Brown et al. 1959 | Brown, Donald D.; Tomchick, Robert; Axelrod, Julius: "The Distribution and Properties of a Histamine-methylating Enzyme". The Journal of Biological Chemistry, 234, 2948-2950. 1. November 1959.
http://www.jbc.org/content/234/11/2948.long
(Erstnachweis der Histamin-N-Methyltransferase bereits im Jahre 1959 publiziert!) | | García-Martín et al. 2009 | García-Martín E, Ayuso P, Martínez C, Blanca M, Agúndez JA: "Histamine pharmacogenomics". Pharmacogenomics. 2009 May;10(5):867-83.
http://www.ncbi.nlm.nih.gov/pubmed/19450133
(Übersicht über die Gendefekte (Polymorphismen) im Histaminstoffwechsel und damit verbundene Erkrankungen.) | | Jarisch 2004 | Jarisch, Reinhart: "Histamin-Intoleranz, Histamin-Intoleranz und Seekrankheit", Thieme-Verlag, 2. Auflage, 2004. ISBN 3-13-105382-8 | | Kennedy et al. 2008 | Kennedy, Mary Jayne et al. 2008: "Association of the Histamine N-methyltransferase C314T (Thr105Ile) Polymorphism with Atopic Dermatitis in Caucasian Children." Pharmacotherapy. 2008 December ; 28(12): 1495–1501. doi:10.1592/phco.28.12.1495.
www.ncbi.nlm.nih.gov/pmc/articles/PMC2642612/pdf/nihms88562.pdf/?tool=pmcentrez | | Kitanaka et al. 2002 | Kitanaka, Junichi et al. 2002: "Expression of diamine oxidase (histaminase) in guinea-pig tissues." European Journal of Pharmacology, Volume 437, Issue 3, 22 February 2002, Pages 179-185.
http://dx.doi.org/10.1016/S0014-2999(02)01302-X | | Knies 2005 | Knies, Konstanze: "Untersuchungen zur Histaminkonzentration im Plasma als Stressindikator bei Hunden". Inaugural Dissertation aus dem Institut für Tierschutz, Verhaltenskunde und Tierhygiene der tierärztlichen Fakultät der Ludwigs-Maximilians-Universität München, 2005
http://edoc.ub.uni-muenchen.de/3960/ | | Ogasawara et al. 2006 | Masahito Ogasawara, Kohei Yamauchi, Yoh-ichi Satoh, Ryoichi Yamaji, Kenichi Inui, Johan W. Jonker, Alfred H. Schinkel and Kazutaka Maeyama: "Recent Advances in Molecular Pharmacology of the Histamine Systems: Organic Cation Transporters as a Histamine Transporter and Histamine Metabolism". Journal of Pharmacological Sciences, Vol. 101 (2006), No. 1 pp.24-30.
http://www.jstage.jst.go.jp/article/jphs/101/1/101_24/_article
(Beschreibung von Transportmechanismen, die erklären, wie Histamin ins Innere der Zellen gelangen kann, obwohl es die Zellmembran nicht ohne weiteres passieren kann. Abbau von HNMT erfolgt im Cytoplasma durch HNMT, besonders in Bronchien, Nieren, Hirn.) | | Preuss et al. 1998 | Preuss CV, Wood TC, Szumlanski CL, Raftogianis RB, Otterness DM, Girard B, Scott MC, Weinshilboum RM: "Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity". Molecular Pharmacology April 1, 1998 vol. 53 no. 4 708-717.
http://molpharm.aspetjournals.org/content/53/4/708.long
(Verschiedene Genvarianten der Histamin-N-Methyltransferase mit unterschiedlicher Enzymaktivität) | | PharmGKB | Pharmacogenomics Knowlege Base: "HNMT, histamine N-methyltransferase". Online-Datenbank
http://www.pharmgkb.org/do/serve?objId=PA190#tabview=tab4
(Das Gen wird mit folgenden Krankheiten in Verbindung gebracht: Asthma, Hypersensitivität, Neoplasie (=Schwellung bei Entzündung, z.B. Ödem), saisonale allergische Rhinitis. Zudem ist eine unüberprüfte Liste mit Publikationen verfügbar, die das Gen im Zusammenhang mit weiteren Krankheiten nennen.) | | Schwartz et al. 1991 | Schwartz J.-C., Arrang J.-M., Garbarg M., Pollard H. & Ruat M. 1991: "Histaminergic transmission in the mammalian brain." Physiol. Rev. 71, 1–51.
www.ncbi.nlm.nih.gov/pubmed/1846044?dopt=Abstract | | Walther 2007 | Walther, D.J.: "Protein-Monoaminylierung: Neu erkannte Funktionen monoaminerger Hormone", Jahrbuch 2007, Max-Planck-Institut für molekulare Genetik.
www.mpg.de/463476/forschungsSchwerpunkt1 | | |
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