June 2011

June 2011

INNOVATING in BIOFUNCTIONALISM

June 2011

About Migraine About Histamine

June 2011

About Migraine
Migraine is more than a simple headache. Its an illness. The prevalence of the migraine pathology, according to credible sources such as the World Health Organization (WHO), International Headache Society (HIS) and the European Headache Alliance (EHS), is approximately 16% of the general population (more than 1 billion people). Of these, 75% are women between the ages of 15-65 65% of MIGRAINE sufferers feel abandoned by health institutions

June 2011

About Migraine - Much more than a simple headache

Society doesnt give importance that MIGRAINE deserve, associating it with a simple headache, and resignation arises.
However, its an illness that affects the family, social and economic life of those who suffer. It significantly alters sufferers lifes within and beyond the work sphere and greatly affects their quality of life.

Source: International Headache Society 4

June 2011

About Migraine A desperate research

In desperation, resigned Migraine Sufferers look for solutions on their own, and the doctors are who learn from them...

Learning from Migraine sufferers

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June 2011

About Migraine Prevalence and Market

. These billion people anxious for pain relief are the primary target market for Migracalm and Migratest. According to studies by the University of Barcelona and DR Healthcare, at least 50% of migraine sufferers have a serious deficit of DAO. This half billion people are the target market for Migrasin. Up till now, all the therapeutic arsenal has been based on pharmacological treatment proven to be inefficient and dangerous due to the fact that excess medication provokes the cronification of the illness and provides little relief. For this reason the new biofunctional protocol is a unique opportunity.
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June 2011

About Histamine

Histamine, a molecule present in all living creatures and in food, is a vital substance for the body. It is present in all food products but in different proportions. Thus, histamine is necessary for life. However, histamine can accumulate excessively and have negative effects. On the other hand, it is also naturally present in many food products. Consumption of such food is harmless, as the histamine they contain can be quickly broken down and processed by the enzyme DiAminoOxidase (DAO), which occurs in the body.

June 2011

About Histamine - What is histaminosis?

Food histaminosis is quite simply an imbalance of histamine and the enzyme DAO in the body. The deficiency of DAO activity means that the body is not in the position to breakdown ingested histamine quickly enough.
N-imidazol acetilaldehid
DAO N H N NCH3 DAO CH2-CH-NH2-COOH

Histidina descarboxilasa

H+ CO2

Histamine

CH2-CH2-NH2 HMT

N-metilhistamina
CH2-CH2-NH2 N

Ingested histamine is N broken down significantly N H more slowly and ADH accumulates within the c. Imidazolactic CH -CHO body. The body then N reacts to the accumulated N H histamine with side Ribsit Ac. Imidazolactic effects, the most CH -COOH incapacitant is the N Nmigraine. Ribosa
2 2

CH2-CHO

N-metilimidazol acetaldehid
CH2-CHO N

NCH3 ADH

c.N-metilimidazol actic
CH2-COOH NCH3 N

June 2011

About Histamine DAO vs Symptoms

M. Pfisterer, C. Wennemer, K. Fiedler, A. Missbichler. Diagnose and Treatment of Histamin intolerance, 9 XXVI FAACI Congress. Gteborg. Sweden. 2007

June 2011

About Histamine Biogenic amines in food

pH optimum is betwen 5 and 6 The lower the temperature, the slower the production of amines
Silla Santos M.H Int J. Food Microbiol 29 (1996) 213-231 10

June 2011

About Histamine Inhibition of DAO

High concentrations of biogenic amines saturates DAO activity

substrate inhibtion
700 600 histamine putrescine cadaverine spermidine spermine

luminescence signal [rlu]

500 400 300 200 100 0 1

am ine11 concentration [M]

10

100

1000

June 2011

About Histamine - Degradation

1 Pellet encapsulate DAO degrades approx. 40 ng / ml (39.2 2.3) Histamine. The increases of the in taking of DAO, results in a linear increase in the degradation of histamine (R2 = 0.995 and R2 = 0.985).

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June 2011

About Histamine DAO deficiency

Receptors
MIGRAINE AND OTHER SYMPTOMS

Enzyme Deficiency

Biogenic Amines

Histamine
Putrescine Cadaverine Tyramine Serotonin e

DAO

Degradation products are easily metabolised

Small Intestine

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June 2011

Too much histamine ingested through Eating too much food containing histamine

Too little DAO Ingesting substances that block DAO

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June 2011

About Histamine - What can happen if we make a diet low in histamine?

Histamine is formed from histidine. From a nutritional perspective, histidine is considered one of the nine essential amino acids. Eggs, cheese, milk, beef, chicken, pork, bacon, venison, fish, beef, cod, soy protein, banana, mustard seeds, seaweed, cottonseed meal, sesame seeds sunflower seeds, and yeast are examples of foods that contain a relatively high amount of histidine

It is not a good idea to solve the problem of histamine only by reducing the consumption of histidine. HISTIDINE is involved in much more than the production of histamine. To give just one example, histidine is essential for the stabilization of the oxygen binds to hemoglobin in iron ions. In other words without HISTIDINE , the red blood cells would not be able to carry oxygen to the tissues in the body .
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June 2011

Clinical Study Barcelona University, 2010

DiAmine Oxidasa deficit in Migraine sufferers 48,8% of migraine sufferers, presented values of very low DAO activity, and 46% had values of reduced activity. 95% of migraine sufferers also experience other symptoms related to histaminosis. The average value obtained for DAO activity is lower among the group of migraine sufferers, with a significant difference observed (p = 0.001) Migraine sufferers with other symptoms of histamine
33,8% 5% 41,2% 41,2% 20,0% 46%

DAO activity value in migraine sufferers

5.2% 48,2%

Whitout other symptoms

1 or 2 symptoms

3 or 4 symptoms

5 or 6 symptoms

DAO very low < 40 HDU/ml

DAO low 40-80 HDU/ml

DAO normal > 80 HDU/ml

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June 2011

Scientific background
1.- Dficit de DAO como posible desencadenante de migraa. Estudio Migradao. Mayo de 2010, Jornada Internacional de Sensibilizacin sobre la Migraa. Congreso de los Diputados de Espaa 1.C. Vidal, Catedrtica de Nutricin y Bromatologa de la Universidad de Barcelona, 2.F. Titus, Miembro de Honor de la Sociedad Espaola de Neurologa, 3. Asociacin Espaola de Pacientes con Cefalea (AEPAC), 4.- Dpt. Epidemiologa del Colegio de Farmacuticos de Barcelona. 2.- Supplementation of enteric coated Diamine Oxidase improves intestinal degradation of food-born biogenic amines in case of histamine intolerance.2010 - March, 6th Annual Conference of the ENA in Vienna. A. Missbichler1, I. Mayer1, C. Pongracz2, F. Gabor3 and P. Komericki 1 Sciotec Diagnostic Technologies, Tulln, Austria. 2 Dept. of Nutritional Sciences, University of Vienna, Austria 3 Dept. of Pharmaceutical echnology & Biopharmaceutics, University of Vienna, Austria 4 Dept. of environmental Dermatology, Medical University of Graz, Austria. 3.- Histamine and histamine intolerance. 2007 - The American Journal of Clinical Nutrition Laura Maintz1 and Natalija Novak1, 1 Department of Dermatology and Allergology, University of Bonn, Germany. 4.- Effects of histamine and diamine oxidase activities on pregnancy: a critical review. 2008 - May 22, European Society of Human Reproduction and Embryology. Laura Maintz1, Verena Schwarzer2, Thomas Bieber1, Katrin van der Ven2 and Natalija Novak, 1 Department of Dermatology and Allergology, University of Bonn, Germany., 2 Department of Obstetrics and Gynaecology, University of Bonn, Germany 5.- Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema. 2005 - November 29, The Journal of Allergy and Clinical Immunology Laura Maintz, MDa - Said Benfadala, Jean-Pierre Allam, MDa Tobias Hagemann, MDa Rolf Fimmers, PhDb and Natalija Novak, MDa Bonn, Germany. a The Department of Dermatology, University of Bonn. b The Department of Medical Biometry, Informatics and Epidemiology, University of Bonn. 6.- Histamine intolerance: a metabolic disease? 2009 - December 12, Birkhuser Verlag, Basel/Switzerland 2009 H.G. Schwelberger, 1 Molecular Biology Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Austria. 17

June 2011

Scientific background (2)

7.- Effectiveness of a prolonged compression of scalp arteries on migraine attacks. June 2006 -Journal of Neurology. Volume 253, number 6 Prof. Carlo Cianchetti & Prof. Jousef Hmaidan. University dpt. NeuroscienciesCagliari (Italy) 8.- Compression of Superficial Temporal Arteries by a Handmade Device: A Simple Way to Block or attenuate Migraine Attacks in Children and Adolescents. June 2009 Journal Child Neurology, Volume 25, pp 67-70. Prof. Giussepina Ledda. University dpt. Neuroseciencies Cagriari (Italy) 9.- Treatment of migraine attacks by compression of temporal superficial arteries using a device. April 2009 -Journal of Neurology. Medical Science Monitor New York CR 185-8 Prof. Carlo Cianchetti, Prof. Tiziana Pisano, Prof. Elisabeth Cianchetti & Prof. Giussepina Ledda University dpt. Neurosciencies Cagliari (Italy) 10.-Legal-medical and neurological assessment of its informative distribution as a medical device used to relieve migraines. May 2008 - Autonomous University of Barcelona-Valle Hebron University Hospital. Ref. 18/08 Prof. Manuel Rodriguez Pazos & Prof. Manuel Romacho Romero. Schhol of Medicine. Autonomous University of Barcelona University Hospital Valle Hebrn.

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June 2011

Thak you for your attention

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