Asociación entre Migraña, Celiaquía, Sensibilidad al Gluten no celíaca y Actividad de la Diamino Oxidasa
K Griauzdaitė1, K Maselis2, A Žvirblienė1, A Vaitkus1, D Jančiauskas1, I Banaitytė-Baleišienė1, L Kupčinskas1, D Rastenytė1
Medical Hypotheses Volume 142, September 2020, 109738
https://doi.org/10.1016/j.mehy.2020.109738
Resumen
Antecedentes y estudio piloto: Informes recientes revelan una estrecha relación entre la migraña y los trastornos gastrointestinales (GI), como la enfermedad celíaca (EC) y la sensibilidad al gluten no celíaca (NCGS). La EC es un trastorno genético autoinmune, que afecta la mucosa del intestino delgado. El gluten, que se encuentra en varios cereales, no solo juega un papel importante en la fisiopatología de EC y NCGS, sino que también agrava los ataques de migraña. Otro componente alimenticio común, que puede inducir migrañas, es la histamina. La diamino oxidasa (DAO) es una enzima que degrada la histamina. La actividad reducida de DAO significa una degradación reducida de la histamina, que puede causar la acumulación de histamina y provocar diversos síntomas, incluidos dolores de cabeza y migraña. En este artículo proponemos una hipótesis, que en la patogénesis de la migraña, la baja actividad de DAO en suero está relacionada con EC y NCGS. También realizamos nuestro propio estudio piloto de 44 pacientes con migraña severa en un esfuerzo por evaluar la presencia conjunta de disminución de la actividad sérica de DAO y la enfermedad celíaca / NCGS en pacientes. Se dividieron 44 pacientes de migraña consecutivos en 2 grupos: actividad DAO disminuida (grupo 1; n = 26) y actividad DAO normal (grupo 2; n = 18). Todos los pacientes fueron examinados para detectar enfermedad celíaca. El diagnóstico de NCGS se realizó después de la exclusión de EC, alergias alimentarias y otros trastornos gastrointestinales en presencia de síntomas de sensibilidad al gluten. Además, se dieron recomendaciones dietéticas a todos los participantes y sus efectos se evaluaron 3 meses después de la evaluación inicial a través del cuestionario MIDAS (Evaluación de la discapacidad de la migraña).
Resultados y conclusiones: Solo 1 paciente cumple los criterios para la enfermedad celíaca, lo que hace que este resultado no sea concluyente. Los hallazgos patológicos del resto de pacientes se atribuyeron a NCGS (n = 10). 9 de 10 pacientes con NCGS pertenecían al grupo de actividad de DAO en suero disminuido (grupo 1; n = 26), lo que sugiere una fuerte relación entre la actividad de DAO en suero reducida y NCGS. El cuestionario MIDAS reveló que los pacientes con disminución de la actividad sérica de DAO se vieron más afectados por la migraña que aquellos con actividad normal de DAO, y esto siguió siendo así después de nuestras intervenciones. Los ajustes dietéticos redujeron significativamente el impacto de la migraña en las actividades diarias de los pacientes después de 3 meses en ambos grupos. Argumentamos que la migraña, la enfermedad celíaca y el NCGS pueden beneficiarse del tratamiento con un enfoque multidisciplinario, que involucra neurólogos, gastroenterólogos y dietistas.
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Sukhvinder Kaura,⁎, Arif Alib, Yaser Siahbalaeic, Uzair Ahmadc, Fazila Nargisc, A.K. Pandeyd,
Balkirat Singhe
a UGC-PDF, Gene Expression Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
b UGC-BSR-FF, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
c Department of Biosciences, Jamia Millia Islamia, New Delhi, India
d Head, Department of Physiology, ESIC Medical College & Hospital, Faridabad, India
e NC Medical College & Hospital, Panipat, India
A B S T R A C T
Background: Migraine is a common neurovascular disorder affected by various levels of neurotransmitters. Low histamine metabolism is also related with pathophysiology of migraine. As diamine oxidase (DAO) gene variants are linked with higher levels of histamine in migraine patients, we investigated the possible relationship of two variants rs2052129 and rs10156191of this gene with migraine risk in North Indian population.
Methods: A case-control study for 250 migraine patients and 250 matched healthy controls was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: We found statistically significant differences in allelic frequencies of rs2052129 (p = .009, OR = 1.462; 95% CI: 1.098–1.947) and rs10156191 (p = .019, OR = 1.430; 95% CI: 1.060–1.928) variants in DAO gene. For rs1015691, we were able to show statistically significant association at all genotypic, dominant and allelic levels in both MA (for T allele, p = .020; OR = 1.662, 95% CI: 1.083–2.551) as well as in female subgroup (for T allele, p = .025, OR = 1.460; 95% CI: 1.049–2.033). But no such significant association was found in clinical sub grouping of migraine in rs2052129 as p > .05. However in gender analysis, protective effect of T allele in male migraine patients for rs2052129 (OR < 1) was found.
Conclusions: Our findings clearly indicated that female patient with rs10156191T allele and in MA subgroup showed an increased risk for migraine. Our data also indicated that rs2052129T variant showed a significant role in migraine susceptibility of this population.
Impaired resolution of wheals in the skin prick test and low diamine oxidase blood level in allergic patients
Aneta Wagner1, Krzysztof Buczyłko2, Hanna Zielińska-Bliźniewska1, Waldemar Wagner3
1Allergology and Respiratory Rehabilitation Department, Medical University of Lodz, Lodz, Poland
2NZOZ Allergology Center, Lodz, Poland
3Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland
Adv Dermatol Allergol 2019; XXXVI (5): 538–543
DOI: https://doi.org/10.5114/ada.2019.89504
Abstract
Introduction: Histamine is the major mediator of IgE- and non-IgE-mediated allergic reactions upon allergen or
hapten contact. Reduced histamine degradation capacity was associated with atopic eczema as well as with nonimmunological
histamine intolerance. Higher blood serum histamine level concomitant with decreased intestinal
diamine oxidase activity were observed in patients with food allergy.
Aim: To evaluate the relationship between patients’ blood diamine oxidase (DAO) activity/histamine status and
their reactivity to time-resolved histamine skin prick test in respect to vulnerability to allergic diseases.
Material and methods: Fifty-three patients were examined with skin prick tests (SPT) and patch tests for suspected
presence of either IgE- or non-IgE-mediated allergy. All individuals were skin prick tested with histamine and the
resolution of the wheal was monitored for 50 min. Blood DAO activity and histamine concentration were measured
with a radio-extraction radioimmunoassay.
Results: Time-resolved histamine skin prick testing revealed presence of wheals which were 35% larger in diameter
in 47% of examined subjects at 20 min of the test. These patients exhibited significantly compromised time-course
wheal resolution (wheal ≥ 3 mm at 50 min) compared to a group of patients with the normal-rate of wheal resolution
(wheal = 0 mm at 50 min). Within a group of subjects exhibiting impaired wheal resolution, 61% of patients
were diagnosed allergic compared to 50% in a group of patients with a normal rate of wheal resolution. Finally,
allergic patients were characterized by a significantly lower DAO activity and higher histamine content compared
to healthy subjects.
Conclusions: The results of this study indicate that patients with IgE- or non-IgE-mediated allergy are likely to
have low DAO blood activity and may concomitantly suffer from histamine intolerance. Furthermore, our results
suggest that allergic patients are more likely to develop an excessive SPT reaction. Our results emphasize caution
in interpretation of the SPT results in allergic patients with diagnosed histamine intolerance or histamine/DAO
activity imbalance.
Migraines appear more likely to be caused by histamine rather than ethanol
Migraines appear more likely to be caused by histamine rather than ethanol.
Eur J Neurol. 2019 May 20. doi: 10.1111/ene.14003. [Epub ahead of print]
1General Internal Medicine Practice, Dr. Theodor Körnerstrasse 19b, 8600, Bruck, Austria.2Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Auenbruggerplatz 36, 8036, Graz, Austria.
Abstract
We read with interest the manuscript by Onderwater et al. that reported on alcoholic beverages as a trigger factor for migraines [1]. Although, epidemiological studies have found a correlation between alcohol intake and headaches, a specific pathophysiologic mechanism of this headache remains unidentified [2]. Particularly red wine was documented as the most common trigger for migraines in this evaluated population [1]. Most commonly found biogenic amines in wine – histamine, tyramine, phenylethylamine, putrescine, cadaverine, spermidine, serotonin, tryptamine, agmatine – and, flavonoids have suspected relevance for migraines and this implies that ethanol seems not to be the main culprit for the headaches [2]. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Alcohol; Diamine oxidase; Headache; Histamine intolerance; MigrainePMID: 31106460 DOI: 10.1111/ene.14003
Liberación masiva de la enzima diamina oxidasa que degrada la histamina durante la anafilaxia grave en pacientes con mastocitosis
Thomas Boehm, 1 Birgit Reiter, 2 Robin Ristl, 3 Karin Petroczi, 1 Wolfgang Sperr, 4 Thomas Stimpfl, 2 Peter Valent, 4 and Bernd Jilma 1
Allergy. 2019 Mar; 74(3): 583–593.
Published online 2019 Jan 1. doi: 10.1111/all.13663 PMCID: PMC6590243 PMID: 30418682
Resumen
Antecedentes
La actividad histaminolítica mediada por la diamina oxidasa (DAO) está presente en el plasma después de la inducción de anafilaxia severa en ratas, cobayas y conejos. La heparina liberada durante la desgranulación de mastocitos en el tracto gastrointestinal podría liberar DAO de los sitios de almacenamiento sensibles a la heparina. La liberación de DAO durante la anafilaxia no se ha demostrado en humanos.
Métodos
Las concentraciones plasmáticas de DAO, triptasa e histamina de cuatro eventos graves de anafilaxia se determinaron en múltiples puntos de tiempo en serie en dos pacientes con mastocitosis sistémica. Las tasas de degradación de histamina se midieron en muestras de anafilaxia y en suero y plasma durante el embarazo con concentraciones de DAO comparables.
Resultados
Las concentraciones medias de DAO (132 ng / ml) y triptasa (304 ng / ml) aumentaron 187 y 4.0 veces, respectivamente, por encima de los valores iniciales (DAO 0.7 ng / ml, triptasa 76 ng / ml) durante la anafilaxia severa. En condiciones sin anafilaxia, las concentraciones de DAO no se elevaron en 29 pacientes con mastocitosis en comparación con voluntarios sanos y no hubo correlación entre los niveles de DAO y triptasa en pacientes con mastocitosis. La tasa de degradación de la histamina de la DAO en plasma de pacientes con mastocitosis durante la anafilaxia se ve gravemente comprometida en comparación con la DAO de muestras de embarazo.
Conclusión
Durante la anafilaxia grave en pacientes con mastocitosis, es probable que se libere DAO de los sitios de almacenamiento gastrointestinal sensibles a la heparina. Las concentraciones medidas pueden degradar la histamina, pero la actividad DAO se ve comprometida en comparación con las muestras de embarazo. Para mediciones precisas de histamina durante la anafilaxia, la inhibición de DAO es esencial para inhibir una mayor degradación de histamina después de la extracción de sangre. La determinación de los niveles de antígeno DAO podría ser de valor clínico para mejorar el diagnóstico de activación de mastocitos.
Serum levels of histamine and diamine oxidase in multiple sclerosis
Serum levels of histamine and diamine oxidase in multiple sclerosis
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Am J Clin Exp Immunol 2018;7(6):100-105 www.ajcei.us /ISSN:2164-7712/AJCEI0086352
Aryan Rafiee Zadeh1, Masih Falahatian1, Fereshteh Alsahebfosoul2
1School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; 2Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract:
Background:
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system, mostly affecting young adults. Diamine oxidase is an enzyme essential for histamine production. Histamine which is produced mostly by mast cells can have effects on different aspects of immune system via its different histamine receptors (H1R, H2R, H3R and H4R). The crucial role of diamine oxidase and histamine in immune balance has been documented in different studies and experiments both on MS patients and on experimental allergic encephalomyelitis (EAE). In this regard, we aimed to measure the level of histamine and diamine oxidase in the serum of MS patients.
Methods:
A total number of 50 relapsing-remitting MS (RRMS) patients and 41 age and sex matched controls were enrolled in this study. Assessments of serum levels of histamine and diamine oxidase enzyme were performed using enzyme-linked immune sorbent assay (ELISA). Results: The serum levels of histamine and diamine oxidase in RRMS patients were lower than healthy controls (P-value = 0.00, for both).
Conclusion:
Our research team found significant low levels of histamine and diamine oxidase in RRMS patients; however the pathogenesis of this issue was unclear.
Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets?
Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets?
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Foods 2018, 7(12), 205.
Autors information:
Abstract
Low-histamine diets are currently used to reduce symptoms of histamine intolerance, a disorder in histamine homeostasis that increases plasma levels, mainly due to reduced diamine-oxidase (DAO) activity. These diets exclude foods, many of them of plant origin, which patients associate with the onset of the symptomatology. This study aimed to review the existing data on histamine and other biogenic amine contents in nonfermented plant-origin foods, as well as on their origin and evolution during the storage or culinary process. The only plant-origin products with significant levels of histamine were eggplant, spinach, tomato, and avocado, each showing a great variability in content. Putrescine has been found in practically all plant-origin foods, probably due to its physiological origin. The high contents of putrescine in certain products could also be related to the triggering of the symptomatology by enzymatic competition with histamine. Additionally, high spermidine contents found in some foods should also be taken into account in these diets, because it can also be metabolized by DAO, albeit with a lower affinity. It is recommended to consume plant-origin foods that are boiled or are of maximum freshness to reduce biogenic amine intake.
Cite this article:
Sánchez-Pérez, S.; Comas-Basté, O.; Rabell-González, J.; Veciana-Nogués, M.T.; Latorre-Moratalla, M.L.; Vidal-Carou, M.C. Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets? Foods 2018, 7, 205.
DOI: https://doi.org/10.3390/foods7120205
Microbial patterns in patients with histamine intolerance
Microbial patterns in patients with histamine intolerance.
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J Physiol Pharmacol. 2018 Aug;69(4). doi: 10.26402/jpp.2018.4.09. Epub 2018 Dec 9.
Author information
- 1
- First Department of Medicine, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany.
- 2
- Second Department of Medicine, Thuringia-Clinic Saalfeld, Saalfeld/Saale, Germany.
- 3
- First Department of Medicine, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany.
- 4
- First Department of Medicine, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany. yurdaguel.zopf@uk-erlangen.de.
Abstract
Histamine intolerance represents a controversially discussed disorder. Besides an impaired degradation of orally supplied histamine due to diamine oxidase (DAO) deficiency, a deranged gut flora may also contribute to elevated histamine levels. Our aim was to determine the intestinal bacterial composition in patients with proven histamine intolerance in comparison to other food intolerances and healthy controls. A total of 64 participants were included in the study, encompassing 8 patients with histamine intolerance (HIT), 25 with food hypersensitivity (FH), 21 with food allergy and 10 healthy controls (HC). All participants underwent blood testing for total and food-specific immunoglobulin E, plasma histamine and DAO serum activity. Stool samples were used to analyze stool histamine and zonulin levels and bacterial composition by 16s rRNA sequencing. No significant differences in stool histamine levels were observed, but HIT patients showed elevated levels of stool zonulin. Microbiota analysis revealed increased levels of Proteobacteria (5.4%) and a significantly reduced alpha-diversity in the HIT group (P = 0.019). On family level, HC showed a significantly higher abundance of Bifidobacteriaceae compared to other study groups (P = 0.005), with lowest levels in the HIT group (P = 0.036). Also significantly reduced abundances of the genera Butyricimonas (P = 0.026) and Hespellia (P = 0.025) were observed in the HIT patients, whereas Roseburia were significantly elevated (P = 0.021). We concluded that the altered occurrence of Proteobacteria and Bifidobacteriaceae, reduced alpha-diversity as well as elevated stool zonulin levels suggest a dysbiosis and intestinal barrier dysfunction in histamine intolerant patients, which in turn may play an important role in driving disease pathogenesis.
- PMID:
- 30552302
- DOI:
- 10.26402/jpp.2018.4.09
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
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Abstract
A functional mini protein can be developed by miniaturising its size. The minimisation technique provides an excellent model system for studying native enzymes, especially in creating an alternative novel biocatalyst. Miniaturised proteins may have enhanced stability, a crucial characteristic for large-scale production and industrial applications. In this study, a huge enzyme molecule, known as diamine oxidase (DAO, comprising 700 amino acids), was selected to undergo the process.
Methods
Results
Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance
Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance.
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Eur J Clin Nutr. 2018 Jul 18. doi: 10.1038/s41430-018-0260-5. [Epub ahead of print]
Author information
- 1
- Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, A-8010, Graz, Austria.
- 2
- Institute of Laboratory Medicine, General Hospital Steyr, Sierninger Straße 170, A-4400, Steyr, Austria.
- 3
- Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, A-8036, Graz, Austria.
- 4
- Practice for General Internal Medicine, Dr. Theodor Körnerstrasse 19b, A-8600, Bruck, Austria. w.schnedl@dr-schnedl.at.
Abstract
Diagnosis of histamine intolerance (HIT) has been based on low serum diamine oxidase (DAO) values, functional gastrointestinal disorders and improvement of symptoms with a histamine-reduced diet (HRD). In a retrospective analysis of outpatients’ charts we identified 101 patients with HIT. After a median of 13 months, a questionnaire was distributed to the patients so that they could be classified into four diet-compliance groups. Calculated with all 101 patients we found an increase of serum DAO values due to a HRD. In the 63 patients that completed the questionnaire, we found that 50 patients had improvement of symptoms or no continuing symptoms. A significant increase of serum DAO levels was found in the patients with strict and occasional diet compliance. Therefore, we demonstrate that a HRD is not only improving symptoms in HIT, but is causing an increase in serum DAO values that correlates with the degree of diet compliance.
- PMID:
- 30022117
- DOI:
- 10.1038/s41430-018-0260-5