Scientific Publications

Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance

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Abstract: Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the KruskalWallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests.

Citation: Schnedl,W.J.; Meier-Allard, N.; Michaelis, S.; Lackner, S.; Enko, D.; Mangge, H.; Holasek, S.J. Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance Breath Test Results. Nutrients 2022, 14, 2026. https://doi.org/10.3390/nu14102026

Wolfgang J. Schnedl 1,* , Nathalie Meier-Allard 2, Simon Michaelis 3 , Sonja Lackner 2 , Dietmar Enko 3,4 , Harald Mangge 4 and Sandra J. Holasek 2
1 Practice for General Internal Medicine, Dr. Theodor Körnerstrasse 19b, 8600 Bruck an der Mur, Austria
2 Division of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, 8010 Graz, Austria; nathalie.allard@medunigraz.at (N.M.-A.); sonja.lackner@medunigraz.at (S.L.); sandra.holasek@medunigraz.at (S.J.H.)
3 Institute of Clinical Chemistry, Laboratory Medicine, Hospital Hochsteiermark, Vordernberger Straße 42, 8700 Leoben, Austria; simon.michaelis@kages.at (S.M.); enko.dietmar@gmx.at (D.E.)
4 Clinical Institute of Medical, Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria; harald.mangge@klinikum-graz.at

• Correspondence: w.schnedl@dr-schnedl.at; Tel.: +43-3612-55833; Fax: +43-3612-55833-22

Intestinal Dysbiosis in Patients with Histamine Intolerance

New study published about microbiota, histamine intolerance and DAO deficiency by the research team of the University of Barcelona (Dr. Mª Carmen Vidal). Adding clinical and scientific evidence every day.

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Abstract: An underlying cause of histamine intolerance is diamine oxidase (DAO) deficiency, which leads to defective homeostasis and a higher systemic absorption of histamine. Impaired DAO activity may have a genetic, pharmacological or pathological origin. A recent proposal also suggests it can arise from an alteration in the gut microbiota, although only one study has explored this hypothesis to date. A greater abundance of histamine-secreting bacteria in the gut could lead to the development of histamine  ntolerance. Thus, the aim of this study was to characterize the composition of the intestinal microbiota of patients with histamine intolerance symptoms and compare it with that of healthy individuals. The study was performed by sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database. Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, in comparison with the healthy individuals, had a significantly lower proportion of Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii, which are bacteria related to gut health. They also had a significantly higher abundance of histaminesecreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis. A greater abundance of histaminogenic bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma and the appearance of adverse effects, even in individuals without DAO deficiency.

Sònia Sánchez-Pérez 1,2,3 , Oriol Comas-Basté 1,2,3 , Adriana Duelo 1,2,3, M. Teresa Veciana-Nogués 1,2,3 ,
Mercedes Berlanga 4 , M. Luz Latorre-Moratalla 1,2,3,† and M. Carmen Vidal-Carou 1,2,3,*,†

1 Department de Nutrició, Ciències de l’Alimentació i Gastronomía, Facultat de Farmàcia i Ciències de l’Alimentació, Campus de l’Alimentació de Torribera, Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain; soniasanchezperez@ub.edu (S.S.-P.); oriolcomas@ub.edu (O.C.-B.); aduelo@ub.edu (A.D.); veciana@ub.edu (M.T.V.-N.); mariluzlatorre@ub.edu (M.L.L.-M.)
2 Institut de Recerca en Nutrició i Seguretat Alimentària (INSA
UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
3 Xarxa d’Innovació Alimentària (XIA), C/Baldiri Reixac 4, 08028 Barcelona, Spain
4 Departament de Biologia, Sanitat i Mediambient, Secció de Microbiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain; mberlanga@ub.edu

• Correspondence: mcvidal@ub.edu
  † These authors contributed equally to this work.

Citation: Sánchez-Pérez, S.; Comas-Basté, O.; Duelo, A.; Veciana-Nogués, M.T.; Berlanga, M.; Latorre-Moratalla, M.L.; Vidal-Carou, M.C. Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients 2022, 14, 1774. https://doi.org/10.3390/nu14091774

Histamine Intolerance—A Kind of Pseudoallergic Reaction

Biomolecules 2022, 12, 454. https://doi.org/10.3390/biom12030454

Ying Zhao 1,2,† , Xiaoyan Zhang 1,2,† , Hengxi Jin 2 , Lu Chen 1,2, Jiang Ji 1,2,* and Zhongwei Zhang 3,*

1 Department of Dermatology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China;
nanjjzhaoying@126.com (Y.Z.); hiohikari@163.com (X.Z.); chenlu1275@163.com (L.C.)
2 Department of Dermatology and Venereology, Suzhou Medical College of Soochow University,
Suzhou 215000, China; jinhengxi1995@163.com
3 Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University,
Nantong 226001, China

*Correspondence: jijiang@suda.edu.cn (J.J.); zhangzwei22@gmail.com (Z.Z.); Tel.: +86-0512-6778-3484 (J.J.)
† These authors contributed equally to this work.

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Abstract:

Histamine intolerance (HIT) is a common disorder associated with impaired histamine metabolism. Notwithstanding, it is often misdiagnosed as other diseases because of its lack of specific clinical manifestations. HIT did not gain traction until the early 21st century. In this review, we will focus on the latest research and elaborate on the clinical manifestations of HIT, including its manifestations in special populations such as atopic dermatitis (AD) and chronic urticaria (CU), as well as the latest understanding of its etiology and pathogenesis. In addition, we will explore the latest treatment strategies for HIT and the treatment of specific cases.

Histamine Intolerance Originates in the Gut

Nutrients 2021, 13, 1262. https://doi.org/10.3390/nu13041262

Wolfgang J. Schnedl 1,* and Dietmar Enko 2

1 General Internal Medicine Practice, Dr. Theodor Körnerstrasse 19b, A-8600 Bruck, Austria
2 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz,
Auenbruggerplatz 15, A-8036 Graz, Austria; enko.dietmar@gmx.at

• Correspondence: w.schnedl@dr-schnedl.at; Tel.: +43-3612-55833; Fax: +43-3612-55833-22

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Abstract:

Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.

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

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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.