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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
Allergic diseases are among the most frequent
immunological disorders.

Allergies are becoming more common

Asthma = 10%
Bronchial asthma = the most common chronic
childhood disease

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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
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Histamine

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.

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The metabolism of Histamine

Histamine and histamine intolerance – Laura Maintz and Natalija Novak


American Journal of Clinical Nutrition, 2007
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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.

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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.
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Histamine

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

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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.
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Food allergies

Type I Allergies Type III Allergies

Intolerance
Pseudo-allergy

Common symptoms

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Histamine intolerance has multiple causes

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.

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Histamine intolerance has multiple causes

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.

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DAO - requires
HNMT - requires vitamin B6 and
SAM as a cofactor copper
Methylation by HNMT

HNMT = histamine N-
methyltransferase
SAM = S adenosine
methionine by MAO - requires
vitamin B2 and iron
Oxidative deamination

by DAO
MAO = mono amine oxidase

HNMT histamine N-methyltransferase [ Homo sapiens


(human) ]
Gene ID: 3176, updated 4 Oct 2015
HISTAMINE INTOLERANCE
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Summary of histamine-mediated symptoms. Adapted with permission from Maintz L et al. Dtsch Artzebl 2006; 103:A3477 - 83
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Diamine oxidase activity
(histamine intolerance) 14-33 IU/mL: normal enzyme
Serum / REA (radioextraction) activity
< 3 IU/mL: marked reduced enzyme
DAO serum activity 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);

Laboratory tests for DAO:


Synevo
Sanador
Ixia
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Criteria for inclusion in the study

- Allergic bronchial asthma


- Non-allergic bronchial asthma
- Recurrent Wheezing
- Children aged 0-18 years
- Both sexes
- DAO determination

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Criteria for inclusion in the study

- Determination of eosinophil cationic protein


= EPC
- Respiratory allergen panel
- Food allergen panel
- Imupro Test
- Specific IgE
- Eosinophilia
- Allergy skin tests, spirometry, FeNO
determination
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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

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Study exclusion criteria

- Age > 18 years


- Absence of DAO determination
- Other diseases than those mentioned
in the criteria for inclusion

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Study protocol
= 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
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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%

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Sex distribution for moderate
and severe DAO deficiency:

- Girls = 27 cases = 60%


- Boys = 18 cases = 40%

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Age group distribution for moderate and
severe DAO deficiency:

Age
- 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%
3-7 years

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DAO values for studied patients
DAO No OF CASES %

<3 Severely reduced 4 1


enzyme activity,
possible genetic
mutation

3 – 10 Moderately reduced 41 10.9


enzyme activity

10 – 14 Enzyme activity 52 13.8


borderline, mild
impairment

> 14 Normal value 278 74.1


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Environmental distribution for moderate to
severe DAO deficiency:

- URBAN: 36 cases - broader area


- RURAL: 9 cases

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Distribution of symptoms for moderate and
severe DAO deficiency
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 37 82.2

THROAT

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Clinical diagnosis of moderate and severe
DAO deficiency
CLINICAL No OF CASES %
DIAGNOSIS

ALLERGIC 23 51.1
BRONCHIAL
ASTHMA

NON-ALLERGIC 17 37.7
BRONCHIAL
ASTHMA

RECURRENT 5 11.1
WHEEZING
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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.

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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.
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Results
O 1 month 3 months 6 months 12 months
DAO - for patients Reduced Identical to Time Increase by Increase by 60% = normal
treated with 0 1-2 IU 2-3 IU or borderline
homeopathic + DAO values
allopathic
treatment
Clinical course of Disease 10% improvement 50% improvement 60% 80%
patients treated symptoms improvement improvement
with homeopathic +
allopathic treatment

DAO for patients Reduced Identical to Time Identical to or less Increase by 1-2 30% cases =
receiving allopathic 0 than at Time 0 IU normal or
treatment only borderline values

Clinical course of patients Disease 5% improvement 20% improvement 30% improvement 40% improvement
receiving only allopathic symptoms
treatment

Evaluation of clinical progress is based on clinical examination and the subjective


assessment is made by the patient and family.
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Patients with borderline DAO values - who have
received treatment with:

- Diet
+
- Allopathic treatment
+
- Homeopathic treatment

100% - clinical and para-clinical improvement


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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.
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Current pharmacological understanding

COMPLEMENTARY ALTERNATIVE MEDICINE CONVENTIONAL MEDICINE

HOMEOPATHIC SCIENCE MOLECULAR BIOLOGY

DERIVATIVES OF MINERALS NEUROPEPTIDES


OF ANIMALS CYTOKINE
OF PLANTS HORMONES
GROWTH FACTORS

© Dipartimento Scientifico Guna S.p


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Current treatments should apply to pathophysiological
mechanisms and integrate:

HOMEOPATHY

MOLECULAR
BIOLOGY
PSYCHO - NEURO -
ENDOCRINO -
IMMUNOLOGY

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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.
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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.
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