Low serum diamine oxidase (DAO) activity levels in patients with migraine

Abstract

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.

Histamine Intolerance: The Current State of the Art

“…Klockler et al found no differences in plasma DAO activity between men and women, although the number of individuals considered was scarce (n = 28) [ 93 ]. Likewise, the study performed by Izquierdo et al reported similar percentages of DAO deficiency in migraine-suffering women (83%) and men (90%) [ 66 ]. On the contrary, García-Martín et al did describe differences in plasma DAO activity by gender, with the prevalence of this enzyme deficiency being higher in women [ 94 ].…”

“…As mentioned in previous sections, the main barrier against exogenous histamine in the intestines is the DAO enzyme, which prevents its passage into the systemic circulation [ 10 , 13 , 65 ]. Numerous clinical studies have provided data on the prevalence of low plasma DAO levels in individuals showing symptoms of histamine intolerance, mainly headaches and gastrointestinal or dermatological disorders [ 66 ]. Although certain studies have limitations, either in the design or number of participants, the majority point to an association between symptoms and DAO deficiency, establishing a general trend that supports the key role of DAO in the etiology of these disorders.…”

“…In parallel, the authors described a significant increase in DAO activity after patients followed a low-histamine diet for four weeks, along with a remission or reduction in frequency of headaches in almost 90% of individuals. More recently, Izquierdo et al studied the prevalence of DAO deficit in 137 patients diagnosed with a confirmed migraine diagnosis and in a control group of 61 nonmigraine individuals [ 66 ]. In this study, a high prevalence of DAO deficiency was observed in the migraine group (87%) and with a mean DAO activity significantly lower in comparison with that obtained from control volunteers.…”

Human Copper-Containing Amine Oxidases in Drug Design and Development

“…hDAO has a central role in histamine intolerance, which is caused by histamine-rich food, alcohol, or drugs that release histamine or inhibit hDAO and, thus, leads to an excess of histamine and symptoms similar to an allergic reaction in the patients [26]. hDAO deficiency has been described in patients with atopic eczema, chronic urticaria, chronic abdominal pain or inflammatory bowel disease, migraines, and asthma [94][95][96][97][98][99]. Histamine also induces contractions and spontaneous abortions when injected into pregnant animals [28,[100][101][102].…”

“…Inhibition of DAO can also increase the risk of developing intestinal carcinoma, indicating that prolonged use of drugs inhibiting DAO may elevate the cancer risk [111,112]. The patients of atopic eczema, chronic urticaria, chronic abdominal pain or inflammatory bowel disease, migraines, and asthma [94][95][96][97][98][99] that have hDAO deficiency, as well as pregnant women, form high-risk groups for severe ADRs if treated with drugs causing histamine release or drugs having an off-target and activity-blocking effect on hDAO. Currently, aminoguanidine, berenil, pentamidine, and metformin have been indicated to have off-target, activity-blocking effects on hDAO, but many more drugs are expected to show similar behavior, thereby potentially causing severe ADRs [13,27,113].…”