The role of homeopathic treatment in
histamine intolerance due to diamine
oxydase deficiency
Dr. Mariana Carmen Zapucioiu
Dr. Gabriela Mihaela Ion
ROMANIA
AUTHORS:
DR. CARMEN ZAPUCIOIU, CLINICAL RESEARCH
DIRECTOR
Presenter
DR. ION GABRIELA, CLINICAL RESEARCH DIRECTOR
DR. MIRELA PAVELESCU
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Allergic diseases are among the most frequent immunological disorders.
Allergies are becoming more common
Asthma = 10%
Bronchial asthma = the most common chronic childhood disease
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Histamine
Histamine 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: 83.5°C
- Molecular mass: 111.15 g/mol
- Boiling point: 209.5°C
- 2-(1H-imidazole-4-yl) ethanamine
Soluble in: water
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Discovered in 1910 by Dale and Laidlaw.
Identified in 1932 as a mediator of anaphylactic reactions.
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 cells.
It is stored in intracellular vesicles and released upon
stimulation.
Histamine
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
The 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 rights
Diamine oxidase
Diamine oxidase (DAO) or histaminase is the main
enzyme involved in the degradation of ingested
histamine.
Reduced DAO activity can cause symptoms
mimicking an allergic reaction to food and drugs that
influence the amount of histamine in the body.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Histamine intolerance
Histamine intolerance the result of an imbalance between
histamine levels and histamine degradation capacity.
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 rights
Histamine 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 secretion
Histamine
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Effects of histamine on plasma concentration
Histamine clinical effect
ng/ml
0–1 Reference
1–2 Gastric acid secretion, heart rate
3–5 Tachycardia, migraine, flush, hives, pruritus
6–8 Blood pressure
7–12 Bronchospasm
100 Cardiac arrest
Histamine and histamine intolerance 1, 2, 3
Laura Maintz and Natalija Novak, American Journal of Clinical Nutrition,
2007.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Type III Allergies
Food allergies
Intolerance
Pseudo-allergy
Type I Allergies
Common symptoms
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
1.Genetic causes due to enzymatic deficiency of MTHFR,
DAO, MAO, HNMT PEMT.
2.Pathogens blocking methylation or producing histamine.
3. Nutritional deficiencies: B12, folate, B6, B2, B1, Zn, Cu, C,
methionine.
4. Excess nutrients: Histidine, protein in excess in general.
5. Medications: long-term use of antibiotics, antacids,
antihistamines.
Histamine intolerance has multiple causes
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
6. 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 dust.
Histamine intolerance has multiple causes
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
HISTAMINE INTOLERANCE
by MAO - requires vitamin B2 and iron
HNMT - requires SAM as a cofactor
DAO - requires vitamin B6 and
copper
Methylation by HNMT
HNMT = histamine N-
methyltransferase
SAM = S adenosine
methionine
Oxidative deamination
by DAO
MAO = 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 rights
Summary of histamine-mediated symptoms. Adapted with permission from Maintz L et al. Dtsch Artzebl 2006; 103:A3477 - 83
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Laboratory tests for DAO:
Synevo
Sanador
Ixia
Diamine oxidase activity
(histamine intolerance)
Serum / REA (radioextraction)
DAO serum activity
14-33 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, e.g. 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
Criteria for inclusion in the study
Copyright® 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, FeNO
determination
Criteria for inclusion in the study
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
High 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 rights
Copyright® 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
Study exclusion criteria
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
= medical history
= satisfaction questionnaire on disease progress
for patients and family members
= clinical examination
= successive determinations of DAO, Eosinophils,
total IgE, EPC at :
- Time 0 = diagnosis
- 1 month after start of homeopathic treatment
- 3 months after start of treatment
- 6 months after start of treatment
- After 1 year
Study protocol
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
DAO - 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 = 13.8%
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Sex 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 rights
Age group distribution for moderate and
severe DAO deficiency:
- 0-1 year = 0 cases = 0%
- 1-3 years = 3 cases = 6.66%
- 3-7 years = 33 cases = 73.33%
- 7-14 years = 6 cases = 13.32%
- Over 14 years = 3 cases = 6.66%
Age
3-7 years
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
DAO values for studied patientsDAO No OF CASES %
<3 Severely reduced
enzyme activity,
possible genetic
mutation
4 1
3 – 10 Moderately reduced
enzyme activity
41 10.9
10 – 14 Enzyme activity
borderline, mild
impairment
52 13.8
> 14 Normal value 278 74.1
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Environmental 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 rights
SYMPTOMS CASES %
RED EYES 25 55.5
NASAL OBSTRUCTION 30 66.6
SKIN RASHES 24 53.3
WHEEZING 28 62.2
SNEEZING 22 48.8
RUNNY NOSE 26 57.7
COUGH 45 100
ITCHING SENSATION IN THE
THROAT
37 82.2
Distribution of symptoms for moderate and
severe DAO deficiency
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Clinical diagnosis of moderate and severe
DAO deficiencyCLINICAL
DIAGNOSIS
No OF CASES %
ALLERGIC
BRONCHIAL
ASTHMA
23 51.1
NON-ALLERGIC
BRONCHIAL
ASTHMA
17 37.7
RECURRENT
WHEEZING
5 11.1
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Treatment used in moderate and severe
DAO deficiency
- All patients received diet instructions for the DAO test +
allergy testing (skin, panels, specific IgE, Imupro test).
- 21 patients received allopathic treatment.
- 24 patients received allopathic + homeopathic treatment.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
The 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
mites.
- Pollen - pollen allergy.
- Influenzinum + Aviaire + Oscillococcinum - prophylactic during the
cold season.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Results O 1 month 3 months 6 months 12 months
DAO - for patients
treated with
homeopathic +
allopathic
treatment
Reduced Identical to Time
0
Increase by
1-2 IU
Increase by
2-3 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%
improvement
DAO for patients
receiving allopathic
treatment only
Reduced Identical 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
treatment
Disease
symptoms
5% improvement 20% improvement 30% improvement 40% improvement
Evaluation of clinical progress is based on clinical examination and the subjective
assessment is made by the patient and family.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Patients 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 rights
Changes 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 treatment.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Current pharmacological understanding
COMPLEMENTARY ALTERNATIVE MEDICINE CONVENTIONAL MEDICINE
HOMEOPATHIC SCIENCE
DERIVATIVES OF MINERALS
OF ANIMALS
OF PLANTS
MOLECULAR BIOLOGY
NEUROPEPTIDES
CYTOKINE
HORMONES
GROWTH FACTORS
© Dipartimento Scientifico Guna S.p
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Current treatments should apply to pathophysiological
mechanisms and integrate:
MOLECULAR
BIOLOGY
HOMEOPATHY
PSYCHO - NEURO -
ENDOCRINO -
IMMUNOLOGY
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
Copyright® CEDH France - All rights reserved, including reproduction and translation rights
In 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 rights
In 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.
• Specific IgE and total IgE are marginally influenced by treatment with Histaminum.
• The EPC corresponds to the patient's progress and DAO values.
• Clinical symptoms improve before para-clinical symptoms.
Copyright® CEDH France - All rights reserved, including reproduction and translation rights