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.

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.

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.

Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among the several multi-faced symptoms associated with histamine intolerance, headache is one of the most recognized and disabling consequences. The aim of this study was to determine the prevalence of DAO deficiency in patients with a confirmed migraine diagnosis according to the current International Headache Society (IHS) and in non-migraine subjects. DAO activity was assessed in a total of 198 volunteers recruited at the Headache Unit of the Hospital General de Catalunya, 137 in the migraine group and 61 as a control group. DAO enzyme activity in blood samples was determined by ELISA test. Values below 80 HDU/ml (Histamine Degrading Unit/ml) were considered as DAO deficient. Mean value of DAO activity from migraine population (64.5 ± 33.5 HDU/ml) was significantly lower (p < 0.0001) than that obtained from healthy volunteers (91.9 ± 44.3 HDU/ml). DAO deficiency was more prevalent in migraine patients than in the control group. A high incidence rate of DAO deficiency (87%) was observed in the group of patients with migraine. On the other hand, 44% of non-migranous subjects had levels of DAO activity lower than 80 HDU/ml. Despite the multifactorial aetiology of migraine, these results seem to indicate that this enzymatic deficit could be related to the onset of migraine.

BACKGROUND & AIMS:

Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial.

METHODS:

100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded.

RESULTS:

Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p = 0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme.

CONCLUSIONS:

Migrainous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 h. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 h) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation.

CLINICAL TRIAL REGISTRATION NUMBER:

ISRCTN10091019; www.isrctn.org.

Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.