01 migradao

Evaluation
DAO-deficiency
patients
migraine.
Carmen Vidal1, Feliu Titus2 y Rafael Guayta-Escolies3
1
Professor of Nutrition and Bromatology at University of Barcelona, Barcelona (Spain); Member of honour in the Spanish Society of Neorology, Madrid (Spain) and Scientific assessor in the Spanish Association of Patients with Headache (AEPAC), Valencia (Spain); Assessor in the Department of Clinical projects at the Pharmacists Association of Barcelona, Barcelona (Spain). Correspondence address: Tel: +34 935 533 692; Fax: +34 934 176 099. E-mail: [email protected] Presented: 24 may 2010 Abstract
Objective: To determine the proportion of patients diagnosed with migraine that present DAO-deficiency
regarding the observed deficit in non-migrainous population.
Hypothesis: Migrainous patients present lower DAO concentrations than healthy subjects. Therefore, this
deficiency may be the cause of histamine intolerance and represents a physiopathological factor of the studied
neurological entity. That being the case, an etiologic treatment approach could be hypothesized based on the
administration of DAO in patients with this deficiency.
Design of the trial: A descriptive observational cross-sectional prospective study with a control group without
masking or randomisation.
Sample population: The target population are volunteer subjects suffering migraine, members of the Spanish
Association of Patients with Headache that meet the diagnostic criteria accepted by the International Headache
Society (IHS). The healthy controls are chosen among volunteers of their microsocial environment.
Key words: Histamine, diamine Oxidase (DAO), migraine, food histaminosis.
Introduction
5-HT(IB/ID) has occurred in parallel with Sumatriptan and the successive generations of Migraine is a complex neurological disease, recurrent and incapacitating. It is suspected a genetic origin, but its etiopathogeny remains The prophylaxis of migraine contemplates frequently with these agonists, calcium channel blockers and beta-adrenoceptor antagonists. Despite this progress, and due to its complex electrophysiological, molecular and genetic approaches constitute a setting of findings that underdiagnosed and sometimes undertreated. The last studies about the treatment focus the need to find new approaches that insist on the Headache is often unilateral, pulsating and nausea and vomiting. Headache is the major and One of the most significant is histamine. This most important clinical sign of migraine. substance has a selective affinity to H3 recipient and may have an inhibitory effect of the Most of the therapeutic approaches for the acute interfacing with the vascular recipients. In the This biogenic amine is in different concentrations of many food of the daily diet. In healthy people, (ergotamine, dihydroergotamine, etc.). In the last 20 years, the advent of agonist recipients oxidases, but certain people presenting a lower activity of these Presented in the International Awareness Day for migraine at the Spanish Parliament, coinciding with the Spanish presidency of the European Union; 24th may 2010. All rights reserved @ To request permission, please email to [email protected] oxidases may have a higher risk of histaminic Hypothesis: Migrainous patients present lower
toxicity. Histamine intolerance, involved in DAO concentrations than healthy subjects. Therefore, this deficiency could be the cause of inflammatory nature, including migraine, is the result of an imbalance between accumulation neurological entity. That being the case, an Histamine is essentially metabolized by two hypothesized based on the administration of ways, methylation and desamination. In the last way, acts the enzyme diamine oxidase (DAO) or the histaminase, followed by a conjugation of observational cross-sectional prospective study ribose to form the riboside of the imidazole acid. DAO is the enzyme with higher involvement in the metabolization of the ingested histamine. It is accepted therefore that a decrease in the Material and methods:
histamine degradation related to a decrease in DAO activity may be the cause of an excess of 1.- Target population. The target population are
histamine that would increase the risk of volunteer subjects suffering migraine, members suffering different clinical pictures that mimic an of the Spanish Association of Patients with allergic-type reaction: diarrhea, conjunctivitis, Headache that meet the diagnostic criteria rhinitis, asthma, low blood pressure, arrhythmia, accepted by the International Headache Society hives, flushing, itching and headache among (IHS). The healthy controls are chosen among volunteers of their microsocial environment. The intake of alcohol or food rich in histamine 2.- Sample volume. Among an unknown
that increases the histamine concentration or the proportion of migrainous subjects presenting blockage of DAO activity could trigger the above histamine intolerance due to DAO-deficiency, it was chosen the most unfavourable proportion p=0,05. For a unilateral hypothesis with an alpha error of 0,05, a power of the trial of 0,9 and with decreasing the intake of alcohol or food rich in the aim of detecting intergroup differences of histamine or by favouring the action of oxidases. 10%, volunteer patients were recluted during a month, until the sample of 164 patients was Probably, its existence could be underestimated symptommatology associated with histamine 3.- Sampling technique. The patients fulfilling
intolerance. Despite the fact that existing the inclusion criteria defined in the trial, were evidences in the literature are not conclusive, selected by a simple non-random sampling experts recommend to develop experimental among those volunteer subjects that apply for studies to determine the presence of histamine participating in the trial through the recruitment intolerance in patients with this clinical picture. page of the Spanish Association of Patients with Headache. Likewise, non-migrainous patients in In recent times, unverified information suggests the control group, were selected among those a genetic role, not in the genesis of migraine, but subjects that, voluntarily, wanted to be included in the deficiency of oxidases. In such a way that in the control group and were members of the what could be transmitted was the histamine microsocial environment of the patients. intolerance condition linked to the deficiency of Both contingents were assigned by the research team without randomization or masking to the Objective: To determine the proportion of
patients diagnosed with migraine that present DAO-deficiency regarding the observed deficit in non-migrainous population. Presented in the International Awareness Day for migraine at the Spanish Parliament, coinciding with the Spanish presidency of the European Union; 24th may 2010. All rights reserved @ To request permission, please email to [email protected] 4.- Sample size: The total sample size was 164
1.- The average age for patients with migraine is patients distributed in two groups, of 82 patients 37,98 years with a standard deviation of +/- 12,46 each; group 1 (migrainous) and group 2 (non- years. The mode is established between 32 and migrainous) , without stratification by age, sex, or 46 years. The age range varies between 17 and 5.- Recruitment period. Patients were recruited
2.- The 65% of the studied patients present a between the 8th and 26th of February, until the diagnostic time of 10 years or more. The 85% of the patients have an accurate diagnosis made 6.- Description: The trial expected to determine
the level of DAO activity in the subjects 3.- The average intensity perceived by the patients, measured with a validated visual determination with validated ELISA procedure analogue scale, was 7,7 (minimum value 0, and the use of a test with acceptable predictive maximum value 10) with a standard deviation of value and a defined cut-off point. The trial was +/- 1,58. The mode was 8. The 38.8% of the developed by properly trained personnel and patients presented this value. It should be using accurately calibrated devices in Sabater- emphasised that 12 (15%) of them suffered a pain Tabella Análisis S.A. laboratory, that owns the described as unbearable (maximum store of 10) appropriate accreditation to carry out the trial. Both groups of patients underwent a blood 4.- The average obtained for the value of DAO activity in migrainous patients was 45,87 with a 7.- Materials:
The obtained range varies between 20,9 and 155. 3.- A number of 164 analytical tests to determine The 48,8% of patients present values compatible with a much reduced DAO activity, the 47% 5.- Documentation to inform about the inclusion values compatible with reduced DAO activity and participating in the trial to the Spanish Data 5.- The 50% of patients presented an average of 8.- Trial duration: The fieldwork for the trial took
place during February 2010. The analytical part 6.- The 95% of migrainous patients underwent of the trial was finished in 2 months after the end symptoms related to non-migrainous pathology compatible with histamine intolerance when eating certain food or after drinking alcohol. Rule values and evaluation criteria
The 41,3% of patients underwent 3 or 4 of these DAO < 40 HDU/ml
The proportion contrast and the comparison of DAO 40 - 80 HDU/ml
averages carried out in the migrainous group regarding the control group, show the next results: DAO > 80 HDU/ml
a. Despite the average value of DAO activity for both groups is situated in the category of reduced activity, the comparison of the said average value, is lower in the intervention group (45,88) than in It has been developed a descriptive analysis of the characteristics of the population being studied Presented in the International Awareness Day for migraine at the Spanish Parliament, coinciding with the Spanish presidency of the European Union; 24th may 2010. All rights reserved @ To request permission, please email to [email protected] the control group (56,37), with a difference Moreover, the proportion of subjects with much between averages of -10,49 (IC 95% 3,58:- reduced activity values is higher in the 17,41). The difference observed is statistically b. Bringing together the categories of reduced DAO activity (very low and low) the average The results answered affirmatively to the value obtained for DAO activity is lower among question targeted in the research, so it can be
the migrainous group (41,73) than in the control stated that DAO activity is significantly lower
group (48,73), with an observed difference migrainous
patients
regarding
between averages of -6,99 ( IC 95% -2,988:- controls.
11,008). The difference observed is statistically It should be noted, that this difference could be undervalued, being some of the control subjects c.- Among those with a reduced DAO activity, members of the microsocial environment of the there is in the migrainous group, a higher cases or having kinship relationships. If it is proportion of patients (52%) with a very low DAO assumed a genetic etiology of the studied activity (<40), regarding the controls (29%). This enzyme deficiency, controls could present this is, therefore, a significant difference (p=0.004). deficiency in higher proportion than general population despite not appearing as neurological If this proportion is observed by bringing together the categories of reduced activity (>40 y <80) and normal activity (>80) regarding a very low There is a higher risk of suffering migraine in activity (<40), the difference gains even more subjects that have a much reduced DAO activity statistical significance (p=0.001), because the (<40) or reduced (>40 y <80) regarding those relative "weight" of very low activity, has a higher subjects with a normal activity (>80). The excess of risk is all the higher the smaller the DAO d. The odds (excess of risk ratio) that a patient with a much reduced indicative value of DAO Bibliography
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