Associations Between Migraine, Celiac Disease, Non-Celiac Gluten Sensitivity and Activity of Diamine Oxidase
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
Abstract
Background and pilot study: Recent reports reveal a close relationship between migraine and gastrointestinal disorders (GI), such as celiac disease (CD) and non-celiac gluten sensitivity (NCGS). CD is a genetic autoimmune disorder, which affects the mucosa of the small intestine. Gluten, found in various grains, not only plays a major role in the pathophysiology of CD and NCGS, but also aggravates migraine attacks. Another common food component, which can induce migraine headaches, is histamine. Diamine oxidase (DAO) is an enzyme, which degrades histamine. Reduced activity of DAO means reduced histamine degradation, which can cause histamine build-up and lead to various symptoms, including headaches and migraine. In this paper we propose a hypothesis, that in pathogenesis of migraine, low serum DAO activity is related to CD and NCGS. We also conducted our own pilot study of 44 patients with severe migraine in efforts to evaluate the co-presence of decreased serum DAO activity and celiac disease/NCGS in patients. 44 consecutive migraine patients were divided into 2 groups: decreased DAO activity (group 1; n = 26) and normal DAO activity (group 2; n = 18). All patients were screened for celiac disease. The diagnosis of NCGS was made after exclusion of CD, food allergies and other GI disorders in the presence of gluten sensitivity symptoms. Furthermore, dietary recommendations were given to all participants and their effects were assessed 3 months after the initial evaluation via the MIDAS (Migraine Disability Assessment) questionnaire.
Results and conclusions: Only 1 patient fit the criteria for celiac disease, rendering this result inconclusive. Pathological findings of the remainder of patients were attributed to NCGS (n = 10). 9 of 10 patients with NCGS belonged to the decreased serum DAO activity group (group 1; n = 26), suggesting a strong relationship between reduced serum DAO activity and NCGS. MIDAS questionnaire revealed, that patients with decreased serum DAO activity were more severely impacted by migraine than those with normal DAO activity, and this remained so after our interventions. Dietary adjustments significantly reduced the impact of migraine on patients’ daily activities after 3 months in both groups. We argue, that migraine, celiac disease and NCGS may benefit from treatment with a multidisciplinary approach, involving neurologists, gastroenterologists and dietitians.
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
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
Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls
Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.
Allergy. 2018 Apr;73(4):949-957. doi: 10.1111/all.13361. Epub 2017 Dec 15.
Author information
- 1
- Department of Medicine 1, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
- 2
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Abstract
BACKGROUND:
Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls.
METHODS:
We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated.
RESULTS:
Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance.
CONCLUSIONS:
We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance.
© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
KEYWORDS:
day profile; diamine oxidase activities; food allergy; histamine intolerance; histamine levels
- PMID:
- 29154390
- PMCID:
- PMC5947167
- DOI:
- 10.1111/all.13361
Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia
Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia
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Sci Rep. 2018 Apr 20;8(1):6342. doi: 10.1038/s41598-018-24652-0.
Author information
- 1
- Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria.
- 2
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
- 3
- Department of Obstetrics and Gynaecology, Division of General Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Vienna, Austria.
- 4
- Forensic Toxicology, Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
- 5
- Children’s Cancer Research Institute, Vienna, Austria.
- 6
- Section for Medical Statistics (IMS), Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
- 7
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
- 8
- Gynmed Clinic, Vienna, Austria.
- 9
- Division of Maternal and Fetal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States.
- 10
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. thomas.boehm@meduniwien.ac.at.
- 11
- Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria. juergen.pollheimer@meduniwien.ac.at.
Abstract
Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE).
Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE.
In contrast to published literature, we demonstrate that placenta-associated diamine oxidase(DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels.
Cultures of primary EVTs express and secret large amounts of bioactive DAO.
ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs.
Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels.
This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.
- PMID: 29679053
- PMCID: PMC5910386
- DOI: 10.1038/s41598-018-24652-0
Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population
Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population.
Author information
- 1
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, School of Pharmacy and Food Sciences, University of Barcelona, Avinguda Prat de la Riba, 171; E-08921 Santa Coloma de Gramenet, Spain.
- 2
- IRTA-Food Safety Programme, Institute for Food and Agricultural Research and Technology, Finca Camps i Armet s/n, E-17121 Monells, Spain.
- 3
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, School of Pharmacy and Food Sciences, University of Barcelona, Avinguda Prat de la Riba, 171; E-08921 Santa Coloma de Gramenet, Spain. Electronic address: mcvidal@ub.edu.
Abstract
Tyramine and histamine are the main dietary bioactive amines related to acute adverse health effects. Dry fermented sausages can easily accumulate high levels of these hazards and are frequently consumed in Spain. The present work aims to assess the exposure to tyramine and histamine from the consumption of dry fermented sausages by the Spanish population and to assess the risk to suffer acute health effects from this exposure. A probabilistic estimation of the exposure to these hazards was derived combining probability distributions of these amines in dry fermented sausages (n = 474) and their consumption by the Spanish population. The mean dietary exposure to tyramine and histamine was 6.2 and 1.39 mg/meal, respectively. The risk of suffering hypertensive crisis or histamine intoxication by healthy population due to tyramine or histamine intake, respectively, exclusively from dry fermented sausages, can be considered negligible. For individuals under treatment with MAOI drugs, the probability to surpass the safe threshold dose (6 mg/meal) was estimated as 34%. For patients with histamine intolerance, even the presence of this amine in food is not tolerable and it could be estimated that 7000 individuals per million could be at risk to suffer the related symptoms after consuming dry fermented sausages.
KEYWORDS:
Bioactive amines; Dry fermented sausages; Histamine; Histamine intolerance; Risk assessment; Tyramine
- PMID:
- 27856296
- DOI:
- 10.1016/j.fct.2016.11.011
Migraine: A disorder of metabolism?
Migraine: A disorder of metabolism?
Med Hypotheses. 2016 Dec;97:117-130. doi: 10.1016/j.mehy.2016.10.029. Epub 2016 Nov 2.
Author information
- 1
- University of New England, School of Health, Armidale, NSW 2350, United States. Electronic address: akokavec@une.edu.au.
Abstract
The treatment and prevention of migraine within the last decade has become largely pharmacological. While there is little doubt that the advent of drugs (e.g. triptans) has helped many migraine sufferers to lead a normal life, there is still little knowledge with respect to the factors responsible for precipitating a migraine attack. Evidence from biochemical and behavioural studies from a number of disciplines is integrated to put forward the proposal that migraine is part of a cascade of events, which together act to protect the organism when confronted by a metabolic challenge.
KEYWORDS:
Glucose; Hypoglycemia; Insulin; Insulin resistance; Migraine; Nutrition
- PMID:
- 27876120
- DOI:
- 10.1016/j.mehy.2016.10.029
Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption
Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption.
Author information
- 1
- Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Steyr, Austria; Department of Gastroenterology, General Hospital Steyr, Steyr, Austria; Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
- 2
- Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
- 3
- Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Steyr, Austria.
- 4
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
- 5
- Practice for General Internal Medicine, Bruck an der Mur, Austria; Medical University of Graz, Graz, Austria.
Abstract
The aim of this retrospective study was to analyze the concomitant prevalence rates for lactose malabsorption (LM), fructose malabsorption (FM), and histamine intolerance (HI) in patients with so far unexplained gastrointestinal (GI) symptoms. A total of 439 outpatients, who presented unclear abdominal discomfort, underwent lactose (50 g) and fructose (25 g) hydrogen (H2) breath tests. Additionally, serum diamine oxidase (DAO) measurements were performed. Individuals with low serum DAO activity (<10 U/mL), GI symptoms, and response to histamine-free diet were diagnosed with HI. Of all 439 patients, 341 (77.7%) were found with 7 various GI conditions. In total, 94 (21.4%), 31 (7.1%), and 100 (22.8%) individuals presented LM, FM, or HI only, whereas 116 (26.4%) patients showed an overlap of GI entities investigated here. Interestingly, 89 out of 241 (36.9%) individuals with carbohydrate malabsorption were also diagnosed with HI (LM + HI: 52 [11.8%], FM + HI: 23 [5.2%], and LM + FM + HI 14 [3.2%] individuals). In conclusion different combinations of LM, FM, and HI are present in individuals with unclear abdominal discomfort/pain. In clinical practice we suggest testing for LM, FM, and additional HI in the diagnostic work-up of these patients. Depending on these various diagnoses possible, patients should get an individualized dietary advice.
- PMID:
- 28042564
- PMCID:
- PMC5155086
- DOI:
- 10.1155/2016/4893501
Histamine intolerance and dietary management: A complete review
Histamine intolerance and dietary management: A complete review.
Author information
Abstract
BACKGROUND:
Present in several types of food, bioactive amines are described as organic bases of low molecular weight, which constitute a potential health risk. An awareness of amine levels in foods today is therefore important in relation to food safety and patient care. This review aims to emphasise the need to unify the information on the content of biogenic amines in foods and prevent patients’ misunderstanding.
METHODS:
Selective literature search for relevant publications in PubMed and other scientific data bases combined with further data from the World Wide Web on histamine and other amines content in foods.
RESULTS:
Available reference sources do not reflect a homogeneous consensus, and the variation between foods makes it impossible for dieticians to accurately estimate amines content to correctly advise patients.
CONCLUSIONS:
To achieve the goal of collecting reliable information, all methods and tools used in analytical studies should be standardised and information exposed to patients should be verified.
Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.
KEYWORDS:
Amine; Diamine oxidase; Histamine; Intolerance; Mast cell
- PMID:
- 27590961
- DOI:
- 10.1016/j.aller.2016.04.015