The role of homeopathic treatment in histamine intolerance ...

1 The role of homeopathic treatment in histamine intolerance due to diamine oxydase deficiencyDr. Mariana Carmen ZapucioiuDr. Gabriela MihaelaIonROMANIAAUTHORS: DR. CARMEN ZAPUCIOIU, CLINICAL RESEARCH DIRECTOR PresenterDR. ION GABRIELA, CLINICAL RESEARCH DIRECTOR DR. MIRELA PAVELESCUC opyright CEDH France -All rights reserved, including reproduction and translation rightsAllergic diseases are among the most frequent immunological disorders. Allergies are becoming more common Asthma = 10% Bronchial asthma = the most common chronic childhood diseaseCopyright CEDH France -All rights reserved, including reproduction and translation rightsHistamineHistamine is a biogenic amine. It is found in animal tissues, plants, bacteria, and venoms. In humans, histamine is located in the lungs, skin and gastrointestinal mucosa. -Formula:C5H9N3-Melting point: C-Molecular g/mol-Boiling C-2-(1H-imidazole-4-yl) ethanamineSoluble in:waterCopyright CEDH France -All rights reserved, including reproduction and translation rightsDiscovered in 1910 by Dale and in 1932 as a mediator of anaphylactic reactions.

2 Biogenic amine is synthesized under the control of pyridoxal phosphatase and L histidine phosphatase from Histidine, with vitamins B6 and C as co-factors. It is synthesized by: mast cells, basophils, platelets, histamino-gene neurons, and entero-chromatophile is stored in intracellular vesicles and released upon CEDH France -All rights reserved, including reproduction and translation rightsThe metabolism of histamine histamine and histamine intolerance Laura Maintz and Natalija Novak American Journal of Clinical Nutrition, 2007 Copyright CEDH France -All rights reserved, including reproduction and translation rightsDiamine oxidaseDiamine oxidase (DAO) or histaminase is the main enzyme involved in the degradation of ingested DAO activity can cause symptoms mimicking an allergic reaction to food and drugs that influence the amount of histamine in the CEDH France -All rights reserved, including reproduction and translation rightsHistamine intoleranceHistamine intolerance the result of an imbalance between histamine levels and histamine degradation capacity.

3 About 1% of the population is affected by histamine intolerance (HIT) and 80% of patients are middle-aged (Missbicher A. Georg Thieme Vertag 2004).Clinical symptoms resembling food allergies or other causes of food intolerance (sulphites, lactase deficiency, etc.) make it difficult to identify and diagnose histamine intolerance . This is not an IgE-mediated disease, so specific IgE serum and skin tests are negative. Copyright CEDH France -All rights reserved, including reproduction and translation rightsHistamine exerts its effects by binding to 4 types of target cell receptors (H1, H2, H3, H4), causing: Muscle fiber contraction Vasodilation Increased vascular permeability Mucus secretionHistamineCopyright CEDH France -All rights reserved, including reproduction and translation rightsEffects of histamine on plasma concentrationHistamine clinical effectng/ml 0 1 Reference1 2 Gastric acid secretion, heart rate 3 5 Tachycardia, migraine, flush, hives, pruritus6 8 Blood pressure7 12 Bronchospasm100 Cardiac arrestHistamine and histamine intolerance 1, 2, 3 Laura Maintz and Natalija Novak, American Journal of Clinical Nutrition, CEDH France -All rights reserved, including reproduction and translation rightsTypeIII AllergiesFood allergiesIntolerancePseudo-allergyType I AllergiesCommon symptomsCopyright CEDH France -All rights reserved, including reproduction and translation causes due to enzymatic deficiency of MTHFR, DAO, MAO, HNMT blocking methylation or producing histamine .

4 Deficiencies: B12, folate, B6, B2, B1, Zn, Cu, C, nutrients: Histidine, protein in excess in : long-term use of antibiotics, antacids, intolerancehas multiple causesCopyright CEDH France -All rights reserved, including reproduction and translation rights6. Stress, anxiety, lack of sleep 7. Hormonal deficiency 8. Excess estrogen hormones 9. Lifestyle with excess alcohol 10. Diet high in fermented foods, fish, or citrus 11. Environmental factors: pollen, house intolerancehas multiple causesCopyright CEDH France -All rights reserved, including reproduction and translation rightsHISTAMINE INTOLERANCEby MAO -requires vitamin B2 and ironHNMT -requires SAM as a cofactor DAO -requires vitamin B6 and copper Methylation by HNMTHNMT = histamine N-methyltransferase SAM = S adenosine methionineOxidative deaminationby DAOMAO = mono amine oxidase HNMT histamine N-methyltransferase [ Homo sapiens(human) ] Gene ID: 3176, updated 4 Oct 2015 Copyright CEDH France -All rights reserved, including reproduction and translation rightsSummary of histamine -mediated symptoms.

5 Adapted with permission from Maintz L et al. Dtsch Artzebl 2006; 103:A3477 -83 Copyright CEDH France -All rights reserved, including reproduction and translation rightsLaboratory tests for DAO:Synevo Sanador Ixia Diamine oxidase activity ( histamine intolerance )Serum / REA (radioextraction)DAO serum activity14-33 IU/mL: normal enzyme activity < 3 IU/mL: marked reduced enzyme activity (possible genetic deficiency) 3-10 IU/mL: reduced enzyme activity 10-14 IU/mL: borderline enzyme activity; It is possible to record clinical symptoms when the body is loaded with histamine , fluoride allergies or a high- histamine diet (latent deficiency);Copyright CEDH France -All rights reserved, including reproduction and translation rights-Allergic bronchial asthma-Non-allergic bronchial asthma -Recurrent Wheezing -Children aged 0-18 years-Both sexes-DAO determination Criteriafor inclusion in the studyCopyright CEDH France -All rights reserved, including reproduction and translation rights-Determination of eosinophil cationic protein = EPC-Respiratory allergen panel -Food allergen panel-Imupro Test -Specific IgE-Eosinophilia -Allergy skin tests, spirometry, FeNOdetermination Criteriafor inclusion in the studyCopyright CEDH France -All rights reserved.

6 Including reproduction and translation rightsHigh EPC level = delayed allergic reaction of 6-24 hours = influx of eosinophils into the region EPC -better reflects the allergic inflammatory process than total IgE EPC -is correlated with the severity of allergic disease Copyright CEDH France -All rights reserved, including reproduction and translation rightsCopyright CEDH France -All rights reserved, including reproduction and translation rights-Age > 18 years -Absence of DAO determination -Other diseases than those mentioned in the criteria for inclusion Studyexclusion criteriaCopyright CEDH France -All rights reserved, including reproduction and translation rights= medical history = satisfaction questionnaire on disease progressfor patients and family members= clinical examination = successive determinations of DAO, Eosinophils, total IgE, EPCat: -Time 0 = diagnosis -1 month after start of homeopathic treatment -3 months after start of treatment -6 months after start of treatment -After 1 yearStudyprotocolCopyright CEDH France -All rights reserved, including reproduction and translation rightsCopyright CEDH France -All rights reserved, including reproduction and translation rightsDAO -has been tested on -375 patients-Study period: 1 Jan 2013 1 Aug 2015-moderate and severe DAO deficiency -45 patients = 12%-Slight DAO deficiency -52 patients = CEDH France -All rights reserved, including reproduction and translation rightsSex distribution for moderate and severe DAO deficiency:-Girls = 27 cases = 60% -Boys = 18 cases = 40%Copyright CEDH France -All rights reserved, including reproduction and translation rightsAge group distribution for moderate and severe DAO deficiency.

7 -0-1 year = 0 cases = 0%-1-3 years = 3 cases = years = 33 cases = years = 6 cases = 14 years = 3 cases = Age3-7 years Copyright CEDH France -All rights reserved, including reproduction and translation rightsDAO values for studied patientsDAO No OF CASES% <3 Severely reduced enzyme activity, possible genetic mutation413 10 Moderately reduced enzyme 14 Enzyme activity borderline, mild > 14 Normal value 278 CEDH France -All rights reserved, including reproduction and translation rightsEnvironmental distribution for moderate to severe DAO deficiency: -URBAN: 36 cases -broader area-RURAL: 9 cases Copyright CEDH France -All rights reserved, including reproduction and translation rightsSYMPTOMS CASES %RED EYES SENSATION IN THE THROAT of symptoms for moderate and severe DAO deficiency Copyright CEDH France -All rights reserved, including reproduction and translation rightsClinical diagnosis of moderate and severe DAO deficiencyCLINICAL DIAGNOSISNoOF CASES%ALLERGIC BRONCHIAL BRONCHIAL WHEEZING CEDH France -All rights reserved, including reproduction and translation rightsTreatment used in moderate and severe DAO deficiency -All patients received diet instructions for the DAO test + allergy testing (skin, panels, specific IgE, Imupro test).

8 -21 patients received allopathic treatment . -24 patients received allopathic + homeopathic treatment . Copyright CEDH France -All rights reserved, including reproduction and translation rightsThe homeopathic treatment was represented by: -Histaminum -for all patients for:-1 month -15 CH -5 granules/day-7/7 -3 months -15 CH -5 granules/day-3/7-6 months -15 CH -5 granules/day-2/7 -12 months -30 CH -5 granules/day-1/7-Constitutional type remedies -Blatta orientalis, house dust and mites -for people allergic to dust -pollen allergy. -Influenzinum + Aviaire + Oscillococcinum -prophylactic during the cold CEDH France -All rights reserved, including reproduction and translation rightsResults O1 month3 months6 months12 monthsDAO -for patients treated with homeopathic + allopathic treatment Reduced Identical to Time 0 Increase by1-2 IUIncrease by2-3 IU 60% = normal or borderline DAO values Clinical course of patients treated with homeopathic + allopathic treatment Disease symptoms 10% improvement 50% improvement 60% improvement 80% improvementDAO for patients receiving allopathic treatment onlyReducedIdentical to Time 0 Identical to or less than at Time 0 Increase by 1-2 IU 30% cases = normal or borderline values Clinical course of patients receiving only allopathic treatmentDisease symptoms 5% improvement 20% improvement30% improvement40% improvementEvaluation of clinical progress is based on clinical examination and the subjective assessment is made by the patient and CEDH France -All rights reserved.

9 Including reproduction and translation rightsPatients with borderline DAO values -who have received treatment with: -Diet + -Allopathic treatment +- homeopathic treatment 100% -clinical and para-clinical improvement Copyright CEDH France -All rights reserved, including reproduction and translation rightsChanges in other parameters: Eosinophil cationic protein = EPC = shows a pattern similar to DAO. Eosinophils are reduced significantly after 3 months of treatment , in both types of treatment . Total IgE -is improved by 20% both in patients with joint treatment and in those with conventional treatment . Specific IgE does not change during the first year of treatment in the case of the allopathic treatment , and improves by 20% in the case of the joint allopathic + homeopathic CEDH France -All rights reserved, including reproduction and translation rightsCurrent pharmacological understandingCOMPLEMENTARY ALTERNATIVE MEDICINE CONVENTIONAL MEDICINE homeopathic SCIENCEDERIVATIVES OF MINERALS OF ANIMALSOF PLANTSMOLECULAR BIOLOGYNEUROPEPTIDES CYTOKINE HORMONESGROWTH FACTORS Dipartimento Scientifico Guna CEDH France -All rights reserved, including reproduction and translation rightsCurrent treatments should apply to pathophysiological mechanisms and integrate.

10 MOLECULAR BIOLOGY HOMEOPATHYPSYCHO -NEURO -ENDOCRINO -IMMUNOLOGYC opyright CEDH France -All rights reserved, including reproduction and translation rightsCopyright CEDH France -All rights reserved, including reproduction and translation rightsCopyright CEDH France -All rights reserved, including reproduction and translation rightsIn conclusion Up until now: Histaminum hidrocloricum is a form of histamine used as a homeopathic remedy in the treatment of insect bites, food allergies, pollen allergies, and nasal congestion. Remedy for bronchitis, stomach, muscle and joint pain. There are no references in the literature regarding the changing para-clinical parameters for DAO, EPC, and eosinophils during homeopathic treatment with Histaminum. Our contribution: This is the first study to include such an approach, based on para-clinical investigations. Copyright CEDH France -All rights reserved, including reproduction and translation rightsIn conclusion, homeopathic treatment combined with allopathic treatment for histamine intolerance has shown that: histamine intolerance due to diamine oxidase deficiency in asthmatic symptoms in children can benefit from this treatment with very good results from both clinical and para-clinical perspectives.