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June 2011

INNOVATING

in BIOFUNCTIONALISM

June 2011

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June 2011

About Migraine

About Histamine

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June 2011

About Migraine

Migraine is more than a simple headache. It’s 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

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June 2011

Society doesn’t give importance that MIGRAINE deserve, associating it with a

simple headache, and resignation arises. However, it’s 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

About Migraine - Much more than a simple headache

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June 2011

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

Learning from Migraine sufferers

About Migraine – A desperate research

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June 2011

. 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.

About Migraine – Prevalence and Market

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June 2011

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.

About Histamine

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June 2011

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.    

Ingested histamine is broken down significantly more slowly and accumulates within the body. The body then reacts to the accumulated histamine with side effects, the most incapacitant is the migraine.  

CH2-COOH

NN-CH3

Àc.N-metilimidazol acètic

H+

CO2

Histidina descarboxilasa

CH2-CH-NH2-COOH

CH2-CH2-NH2

NNH

DAO HMT

Histamine

CH2-CHO

NNH

CH2-COOH

NN-Ribosa

CH2-CHO

NNH

ADH

Àc. Imidazolacètic

Ribòsit Ac. Imidazolacètic

N-imidazol acetilaldehid CH2-CH2-NH2

NN-CH3

N-metilhistamina

N-metilimidazol acetaldehidCH2-CHO

NN-CH3

DAO

ADH

About Histamine - What is histaminosis?

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June 2011

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

About Histamine – DAO vs Symptoms

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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

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June 2011

substrate inhibtion

0

100

200

300

400

500

600

700

1 10 100 1000am ine concentration [µM]

lum

ine

sce

nce

sig

na

l [rl

u]

histamine

putrescine

cadaverine

spermidine

spermine

High concentrations of biogenic amines saturates DAO activity

About Histamine – Inhibition of DAO

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June 2011

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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).

About Histamine - Degradation

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June 2011

Small Intestine

Receptors

DAO

Histamine

Putrescine

Cadaverine

Tyramine

Serotonine

Biog

enic

Am

ines

Degradation products are easily metabolised

Enzyme Deficiency

MIGRAINE AND OTHER

SYMPTOMS

About Histamine – DAO deficiency

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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

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 .

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

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June 2011

41,2%

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

Migraine sufferers with other symptoms of histamine

DAO activity value in migraine sufferers

33,8%

41,2%

20,0%5%

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)

46% 48,2%

5.2%

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June 2011

1.- Déficit de DAO como posible desencadenante de migraña. Estudio Migradao. Mayo de 2010, Jornada Internacional de Sensibilización sobre la Migraña. Congreso de los Diputados de España1.C. Vidal, Catedrática de Nutrición y Bromatología de la Universidad de Barcelona, 2.F. Titus, Miembro de Honor de la Sociedad Española de Neurología, 3. Asociación Española de Pacientes con Cefalea (AEPAC), 4.- Dpt. Epidemiología del Colegio de Farmacéuticos 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 NutritionLaura 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 ImmunologyLaura 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, Birkhäuser Verlag, Basel/Switzerland 2009H.G. Schwelberger, 1 Molecular Biology Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Austria.

Scientific background

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June 2011

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. Neurosciencies- Cagliari (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. 18/08Prof. Manuel Rodriguez Pazos & Prof. Manuel Romacho Romero. Schhol of Medicine. Autonomous University of Barcelona University Hospital Valle Hebrón.

Scientific background (2)

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June 2011

Thak you for your attention