Low-histamine Diet Research Articles

Measurement of diamine oxidase (DAO) during low-histamine or ordinary diet in patients with histamine intolerance

Background/ObjectivesQuantification of diamine oxidase (DAO) concentrations in serum has been proposed as an adjunctive diagnostic modality for the evaluation of histamine intolerance (HIT). Limited empirical data exist concerning the influence of dietary patterns on DAO levels.Subjects/MethodsIn the context of a prospective study employing a crossover design, 18 individuals diagnosed with HIT were randomized to initiate either a low histamine diet (LHD) or a conventional mixed diet (MXD). Serum DAO concentrations were measured at the commencement of the study and following each dietary phase. A control group underwent analogous DAO assessments without imposition of dietary constraints.ResultsDuring the time when a diet restricted in histamine was implemented, noticeable differences in changes in DAO levels did not become apparent when compared to the changes observed during the mixed (MXD) phase. Specifically, among the group, 10 of the 18 patients exhibited elevated DAO values subsequent to the LHD regimen, while the remaining eight displayed either reduced or unchanging DAO levels. The prevalence of elevated DAO levels in the LHD group did not differ significantly from that observed in the control group during the MXD phase. Additionally, during the LHD phase, patients reported a significant reduction in gastrointestinal and cutaneous symptoms.ConclusionsThis prospective investigation underscores the enduring utility of a histamine-restricted diet, coupled with structured dietary reintroduction, as an efficacious diagnostic approach for individuals presenting with suspected food-related histamine hypersensitivity. Notably, the measurement of DAO levels appears to furnish only a limited capacity to discern dietary-induced fluctuations. Notwithstanding, the dynamics of DAO alteration do not appear to exhibit a discernible association with specific dietary patterns, a finding consistent across both patient and control groups.

ELEVATED HISTAMINE LEVELS WITH NORMAL TRYPTASE IN ANAPHYLAXIS

<h3>Introduction</h3> The most commonly described pathway of anaphylaxis involves IgE mediated mast cell activation. Here we present three patients with elevated histamine, normal tryptase, and normal IgE. These findings suggest a non-mast-cell mediated pathway of anaphylaxis. All patients were placed on a low-histamine diet (LHD) following their anaphylaxis episodes with subsequent decrease in histamine and resolution of anaphylactic episodes. <h3>Cases Description</h3> The first patient was a 25-year-old male who presented to the emergency department with a histamine level of 6.0 (ng/mL). The patient experienced a second anaphylaxis episode a week later. Repeat histamine was 6.5. The patient was placed on a LHD, and follow-up testing demonstrated histamine of 1.6. The second patient was a 51-year-old male who presented to the emergency department for anaphylaxis. Laboratory studies after the event found histamine of 13.2, and the patient was subsequently placed on a LHD. Follow-up testing demonstrated histamine of 5.8. The third patient was a 33-year-old female that developed anaphylaxis after a patch test. Laboratory studies revealed histamine of >28.6. The patient was instructed to start a LHD. Subsequent testing demonstrated histamine of 10.8. <h3>Discussion</h3> Persistent elevation of histamine levels in the absence of elevated tryptase or IgE suggests a non-mast-cell mediated pathway of histamine release. Further studies should be performed in similar cases examining the potential of LHD as a treatment for anaphylaxis with elevated histamine and normal tryptase as LHD resulted in a decrease in histamine level and resolution of anaphylactic episodes.

CHRONIC SPONTANEOUS URTICARIA, LOW HISTAMINE DIET AS A TREATMENT

<h3>Introduction</h3> Chronic Spontaneous Urticaria (CSU) is defined as urticaria that persists longer than six weeks. It was previously known as Chronic Idiopathic Urticaria. The current mainstay treatments for CSU include antihistamines and immunomodulators. The exact pathogenesis of CSU remains unclear. Here, we discuss two patients treated for CSU who demonstrated persistently elevated histamine levels with normal tryptase suggesting a non-mast-cell-mediated histamine elevation. Both were responsive to low-Histamine diet (LHD) as a primary treatment. <h3>Case Description</h3> A 50-year-old male presented for CSU. The patient was placed on intramuscular and oral corticosteroids for his symptoms with minimal relief. Laboratory studies revealed an elevated histamine level of 5.1 ng/mL and a normal tryptase level of 7.1 mcg/L. The patient was placed on LHD and subsequently reported complete resolution of CSU. 38-year-old male presented for a pruritic skin rash diagnosed as CSU. The patient was previously placed on antihistamines and steroid cream. Laboratory studies revealed multiple elevated histamine levels greater than 6.0 ng/mL and normal tryptase levels of 6.5 and 7.7 mcg/L. The patient was placed on LHD with satisfactory resolution of symptoms. <h3>Discussion</h3> Persistently elevated histamine levels may contribute to CSU in a subgroup of patients who may be experiencing symptoms due to a non-mast-cell-mediated histamine elevation. Further research is needed to evaluate LHD as a primary treatment for CSU articulately in the presence of persistently elevated histamine.

The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study.

Restrictive diets for the treatment of different gastrointestinal disorders are reported to change the composition of intestinal microbiota. Recently, it has been proposed that individuals with histamine intolerance suffer from intestinal dysbiosis, having an overabundance of histamine-secreting bacteria, but how it is still unknown this state is affected by the usual dietary treatment of histamine intolerance [i.e., low-histamine diet and the supplementation with diamine oxidase (DAO) enzyme]. Thus, a preliminary study was carried out aiming to evaluate the potential changes on the composition of the intestinal microbiota in a group of five women diagnosed with histamine intolerance undergoing 9 months of the dietary treatment of histamine intolerance. After sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database, we observed a reduction in certain histamine-secreting bacteria, including the genera Proteus and Raoultella and the specie Proteus mirabilis. Moreover, it was also observed an increase in Roseburia spp., a bacterial group frequently related to gut health. These changes could help to explain the clinical improvement experienced by histamine intolerant women underwent a dietary treatment.

Simple and Reliable Determination of the Histamine Content of Selected Greek Vegetables and Related Products in the Frame of “Low Histamine Diet”

The determination of histamine in Greek foods that should potentially be avoided during a “low histamine diet” is reported herein. Cation exchange chromatography combined to selective post column derivatization proved to be an excellent tool for this type of analysis as well, offering accurate results following minimal sample preparation. Tomato-, eggplant- and spinach-related products have been successfully analyzed and were all found to contain histamine. Higher amounts were quantified in eggplants, eggplant salads and spinach in the range of 15.4–34.2 mg kg−1 and lower in fresh tomatoes and related products (0.8–10.6 mg kg−1). The method is capable of determining as low as 0.5 mg kg−1 histamine without matrix effects, with percent recoveries ranging between 87 and 112% (tomatoes and related products), 95 and 119% (eggplants and related products) and 90 and 106% (fresh and frozen spinach).

Histamine intolerance (HIT)

Histamine intolerance (HIT) is food intolerance of non-immunological origin, and it results from an imbalance between the consumption of histamine with food and the organism ability to metabolize it. The patients with HIT were found to have a significantly reduced concentration of histamine-degrading enzymes, diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). Factors which have been identified that are conducive to histamine intolerance are: genetic factors, dysbacteriosis, chronic diseases – especially allergic and intestinal diseases, chronic infections, mastocytosis and some drug use. Clinical symptoms of histamine excess may affect various organs and systems - the most common are skin symptoms (pruritis, erythema) nausea, vomiting, abdominal pain, diarrhea, headaches and sometimes severe reactions with shortness of breath, arrhythmias, blood pressure drop, and even cardiac arrest. Diagnostic methods in HIT utilize determination of serum DAO, determination of histamine metabolites in urine, measurement of the histamine wheal in the 50th minute of the skin prick test (SPT), gastroscopy with intestinal biopsy, diagnostic and therapeutic test, oral histamine-challenge test and genetic tests. The mainstay of histamine intolerance treatment if a low-histamine diet. Patients should avoid products belonging to the three groups of food: containing large amounts of histamine, histamine liberators, and products inhibiting the activity of DAO. Additionally, supplements containing DAO and antihistamines can be used.

Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3–10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3–10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33–60%) when compared to patients with low DAO (40%, IQR = 20–60%; p = 0.045) or high DAO (33%, IQR = 0–50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

Predictors of Response to Oral Medications and Low-Histamine Diet in Patients with Chronic Urticaria.

Background Chronic urticaria (CU) is comprised of diverse phenotypes, and thus, a shift towards a precision medical approach is warranted in its management. Methods This study enrolled 78 patients with CU. Serum erythrocyte sedimentation rate, hemoglobin, hematocrit, eosinophil count, IgE, antinuclear antibody (ANA), and serum diamine oxidase (DAO) levels of the patients were measured and were compared according to the patient's response to second-generation antihistamines (sgAH), corticosteroids, leukotriene receptor antagonist (LTRA), H2 blockers, and low-histamine diet. Results Age- and sex-adjusted logistic regression analysis showed that patients with duration of CU > 3 years (adjusted odd ratio [aOR] = 4.39) and a DAO level < 10 U/mL (aOR = 3.90) were significantly associated with a good sgAH response. Age > 50 years (aOR = 0.02), duration of chronic urticaria > 3 years (aOR =0.06), and an ANA titer ≥ 1 : 80 (aOR = 0.03) were significantly and inversely associated with corticosteroid response. A low-histamine diet response was significantly associated with LTRA response (aOR = 67.29). In addition, a DAO level < 5.4 U/mL (aOR = 71.95) was significantly associated with H2 blocker response. Furthermore, concomitant angioedema (aOR = 10.56), multiple food triggers (aOR = 11.69), and a DAO level < 5.4 U/mL (aOR = 3.78) were significantly associated with a low-histamine diet response. Conversely, dermatographic urticaria and a hematocrit level < 36% were significantly and inversely associated with low-histamine diet response. Conclusions Several promising biomarkers were identified in this study to predict the efficacy of chronic urticaria treatment. DAO could be a novel biomarker for predicting the efficacy not only of dietary intervention but also for antagonists of H1 and H2 receptors.

Dietary strategies for chronic spontaneous urticaria: an evidence-based review.

Although the relationship between diet and chronic spontaneous urticaria (CSU) remains elusive, several patients seek dietary modifications as they are easy and cost-effective. Adequate patient education and counseling are crucial as modified diets may be beneficial for a subset of antihistamine refractory CSU patients, and no modality currently exists to identify these patients. Elimination of food items based exclusively on patient history may lead to unnecessary restrictions in most cases resulting in nutritional deficiencies and impaired quality of life. Several dietary strategies have been tried till date with varying rates of success and evidence. This review highlights the various dietary strategies along with their levels of evidence, which may help the treating dermatologists and physicians to counsel CSU patients and make evidence-based treatment decisions. There is grade A recommendation for the elimination of food additives (artificial pseudoallergens), personalized diets, vitamin D supplementation, Diamine oxidase supplementation and probiotics (in children), grade B recommendation for dietary elimination of red meat, fish and their products, natural pseudoallergens (fruits, vegetables, and spices), and low-histamine diet, while dietary elimination of gluten (with concomitant celiac disease) has grade C recommendation. Notably, elimination diets should be continued for at least 3 consecutive weeks to assess their effectiveness.

Role of nutritional supplements in selected dermatological disorders: A review.

While a plethora of literature continues to be published on the role of nutritional agents both in lay press and indexed journals, the data is not on a firm footing and leaves the dermatologist in a quandry and the patient confused. The various agents include vitamins, minerals, amino acids, antioxidants, diets & gluten. A proper knowledge of the role of nutritional supplements in dermatological diseases can be a useful tool in advising the patients and in certain cases ameliorating the disorder. Literature review of last 15 years was made using the terms "diet in dermatology," "nutrition and skin," "nutritional supplements in dermatology," "nutritional agents and acne," "nutritional agents and alopecia," and "nutritional agents and psoriasis." While there are multiple publications on the use of nutritional supplements for amelioration of skin diseases, most of them are based on either associations or in vitro studies, but very few transcend the rigors of a clinical trial or the holey grail of a double-blinded randomized controlled trial. There seem to be some evidence in acne, psoriasis, telogen effluvium, urticaria & vitiligo. Coeliac disease and dermatitis herpetiformis have a strong link with diet. Rosacea has a strong link with certain foods, but the other disorders like melasma, aphthous stomatitis do not have any scientifically validated association with diet. Our updated review examines the role of nutritional supplements and antioxidants in various dermatological disorders. We have found that there are varying levels of evidence with notable associations of low glycemic diet & acne, fish oil & weight loss with psoriasis, fish oils & probiotics with atopic dermatitis & vitamins & botanical extracts with vitiligo. The evidence for diet and nutrition in bullous disorders and photoageing is scarce. The role of low histamine diet in urticaria is useful in select cases of episodic urticaria. Rosacea is triggered by hot and spicy food . Apart from gluten and Dermatitis Herpetiformis, no diet can be considered disease modifying in our reveiw. The lack of comparison of nutritional or dietary modiffication with conventional validated agents, makes the data difficult to translate in real world patient management.

Histamine Intolerance-The More We Know the Less We Know. A Review.

The intake of food may be an initiator of adverse reactions. Food intolerance is an abnormal non-immunological response of the organism to the ingestion of food or its components in a dosage normally tolerated. Despite the fact that food intolerance is spread throughout the world, its diagnosing is still difficult. Histamine intolerance (HIT) is the term for that type of food intolerance which includes a set of undesirable reactions as a result of accumulated or ingested histamine. Manifestations may be caused by various pathophysiological mechanisms or a combination of them. The problem with a “diagnosis” of HIT is precisely the inconstancy and variety of the manifestations in the same individual following similar stimuli. The diagnosing of HIT therefore requires a complex time-demanding multidisciplinary approach, including the systematic elimination of disorders with a similar manifestation of symptoms. Among therapeutic approaches, the gold standard is a low-histamine diet. A good response to such a diet is considered to be confirmation of HIT. Alongside the dietary measures, DAO supplementation supporting the degradation of ingested histamine may be considered as subsidiary treatment for individuals with intestinal DAO deficiency. If antihistamines are indicated, the treatment should be conscious and time-limited, while 2nd or 3rd generation of H1 antihistamines should take precedence.

Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content?

A low-histamine diet is currently the most advised strategy to prevent the symptomatology of histamine intolerance. Conceptually, these diets should be founded on the exclusion of histamine-containing foods, although a certain disparity is found within the list of excluded foods in accordance with the different low-histamine diets available in the literature. This study aimed to critically review low-histamine diets reported in the scientific literature, according to the histamine and other biogenic amine contents of the excluded foods. A total of ten scientific studies that provided specific recommendations on the foods that must be avoided within the framework of a low-histamine diet were found. Overall, the comparative review brought out the great heterogenicity in the type of foods that are advised against for histamine intolerant individuals. Excluded foods were, in most cases, different depending on the considered diet. Only fermented foods were unanimously excluded. The exclusion of 32% of foods could be explained by the occurrence of high contents of histamine. The presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas) were also frequently reported in low-histamine diets. Finally, there was a range of excluded foods with an absence or very low levels of biogenic amines. In this case, certain foods have been tagged as histamine-liberators, although the mechanism responsible has not yet been elucidated.

The Impact of Food Histamine Intake on Asthma Activity: A Pilot Study.

Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controversial. The objective of this pilot crossover, randomized, two-period study was to examine the effect of dietary histamine intake on asthma symptoms in twenty-one children with mild intermittent asthma. Children were randomly assigned to either a high- or low-histamine diet, based on the Mediterranean pattern, for 4 weeks. After a 2-week washout period, patients crossed to the alternative diet for 4 additional weeks. Asthma symptoms were assessed at baseline and after the completion of each diet period by a clinician. Daily symptoms and peak flow were recorded throughout the intervention. Adherence to the dietary intervention was assessed via analysis of four random 24-h recalls, for each intervention period. Eighteen children completed the study. Significantly higher mean air flow obstruction was recorded and a trend for prolonged and more severe symptoms was observed during the high-histamine period. Diet may have an active and direct impact on asthma symptoms. Food choice is affected and/or may affect symptoms in children with mild asthma. Diet intervention is promising yet challenging, for asthma control.

Lyophilised legume sprouts as a functional ingredient for diamine oxidase enzyme supplementation in histamine intolerance

Diamine oxidase (DAO) is one of the key enzymes involved in the degradation of dietary histamine. An imbalance of histamine scavenging systems leads to histamine intolerance, a diet-related disorder that may be tackled by following a low-histamine diet. Recently, the supplementation with exogenous DAO enzyme of animal origin has received the green light as a novel food to enhance intestinal degradation of histamine. This work performed a screening for histamine-degrading capacity of Leguminosae species in order to explore its potential suitability as plant-derived active ingredient of enzymatic supplements. In vitro DAO activity was determined both in raw pulses and lyophilised sprouts by an enzymatic assay coupled to UHPLC-FLD and several germination and storage conditions were assessed. The sprouts of edible legumes showed an in vitro histamine-degrading capacity ranging from 36.0 to 408.3 mU g−1, much higher than that found for the non-germinated seeds (0.14–1.95 mU g−1). The germination of legume seeds for 6 days in darkness provided the maximum DAO activity. Only the freezing storage of the lyophilised sprouts kept the enzymatic activity intact for at least 12 months. These results demonstrate that certain edible legumes could be suitable for the formulation of DAO supplements for the treatment of histamine intolerance.

In vitro determination of diamine oxidase activity in food matrices by an enzymatic assay coupled to UHPLC-FL.

Intestinal diamine oxidase (DAO) acts as a protective barrier against exogenous histamine. A deficit of DAO activity can lead to the appearance of histamine intolerance, a clinical condition that may be treated by a low-histamine diet and oral DAO supplementation to enhance intestinal histamine degradation. As sources of DAO, porcine kidneys and certain legume seedlings are suitable components for the formulation of a DAO supplement. The aim of this work was to develop a rapid and reliable methodology for the in vitro determination of DAO activity in food matrices based on an enzymatic assay coupled to UHPLC-FL. The proposed method showed a satisfactory linearity and sensitivity and provided a relative standard deviation lower than 3%, guaranteeing method precision, and a mean recovery greater than 99% both for lyophilized pea sprouts and porcine kidney protein extracts. A high specificity is a key attribute of this method due to the use of histamine as the reaction substrate and the direct quantification of its degradation. Moreover, the lack of interference of catalase and hydrogen peroxide is another advantage in comparison with previously published methods. Lyophilized pea sprouts showed the greatest histamine-degrading activity (0.40 ± 0.01 mU/mg), followed by porcine kidney protein extracts (0.23 ± 0.01 mU/mg) and commercial DAO supplements (0.09 ± 0.06 mU/mg). This technique could be used as a tool to validate the DAO activity of food matrices of potential interest for the treatment of histamine intolerance.

Effect of Diet in Chronic Spontaneous Urticaria: A Systematic Review.

Strategies for diets in chronic spontaneous urticaria (CSU) are controversial. This systematic review assessed the interest in diet for managing CSU. We searched for original reports in MEDLINE, EMBASE, CENTRAL and LILACS. Among the 278 reports screened, 20 were included, involving 1,734 patients. Reports described 3 types of systematic diet: pseudoallergen-free diet (n = 1,555 patients), low-histamine diet (n = 223) and diet without fish products (n = 47), which induced complete remission in 4.8%, 11.7% and 10.6% of patients, respectively, and partial remission in 37.0%, 43.9% and 4.3%. Eight reports described personalized exclusion diets (66 patients) adapted to symptoms/allergological test results and led to complete remission in 74.6% of patients, although the diagnosis of CSU was doubtful. No comparative randomized studies of diets were available. The only randomized studies were based on oral provocation tests with the suspected responsible diet. Population and outcomes were heterogeneous. In conclusion, there is evidence for the benefit of diets in CSU only in individual patients with clinical symptoms. However, the level of evidence is low for the benefit of systematic diets in CSU because systematic double-blind controlled trials of diet are lacking.

Anti-inflammatory and antioxidant feeding and supplementation may serve as adjuvants in women with fibromyalgia

ObjectivesFibromyalgia syndrome is a chronic pain disorder of unknown causation associated with debilitating fatigue, unrefreshing sleep, cognitive and affective symptoms. There are no markers to monitor fibromyalgia progression and no cure. We aimed to analyze the effects of a turmeric-based supplement and a gluten-free, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols and low histamine diet (IGUBAC Diet®), with antioxidant and anti-inflammatory characteristics, in women with fibromyalgia. Methodsa randomized, controlled, clinical trial, with 13 women (51.46 ± 8.04 years) diagnosed with fibromyalgia were assessed using the Chronic Pain Grade Scale, the Pain Catastrophizing Scale, the Fatigue Severity and Impact Scale and the Pittsburgh Sleep Quality Index. Anthropometric parameters, antioxidant and anti-inflammatory analysis and symptoms progression were measured before and after one month of treatment with turmeric supplement and IGUBAC Diet®. ResultsNo significant improvement was observed after one month of treatment as shown by Chronic Pain Grade-, Pain Catastrophizing-, Fatigue Severity- and Fatigue Impact Scales and Pittsburgh Sleep Quality Index, except for pain disturbances in work activities. Significant variations (p < 0.05) were observed in the intensity of symptoms, except for nausea and vomiting. ConclusionAdditional research is necessary to further elucidate the effects of a turmeric-based supplement with IGUBAC Diet® in women with fibromyalgia. A multidisciplinary approach should be the goal of treatment for fibromyalgia.

Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review.

Hypereosinophilic syndrome and mastocytosis are relatively rare proliferative diseases encountered in the general population. However, allergists frequently consider these disorders in the differential of patients presenting with gastrointestinal, pulmonary, cutaneous, and allergic symptoms. Gastrointestinal symptoms are some of the most frequent and/or debilitating aspects of both disease states and in many cases lead to poor quality of life and functional limitation for the patient. They are the third most common clinical manifestation in hypereosinophilic syndrome and have been found to be the most distressful aspect of the disorder in those with systemic mastocytosis. Both eosinophils and mast cells play integral parts in normal gut physiology, but when and how exactly their effector functionality translates into clinically significant disease remains unclear, and the available literature regarding their pathophysiology remains sparse. Eosinophils and mast cells even, in fact, may not necessarily function in isolation from each other but can participate in bidirectional crosstalk. Both are affected by similar mediators and can also influence one another in a paracrine fashion. Their interactions include both production of soluble mediators for specific eosinophil and mast cell receptors (for example, eosinophil recruitment and activation by mast cells releasing histamine and eotaxin) as well as direct physical contact. The mechanistic relationship between clonal forms of hypereosinophilia and systemic mastocytosis has also been explored. The nature of gastrointestinal symptomatology in the setting of both hypereosinophilic syndrome and mast cell disease is frequently manifold, heterogeneous, and the lack of better targeted therapy makes diagnosis and management challenging, especially when faced with a substantial differential. Currently, the management of these gastrointestinal symptoms relies on the treatment of the overall disease process. In hypereosinophilia patients, systemic corticosteroids are mainstay, although steroid-sparing agents such as hydroxyurea, IFN-α, methotrexate, cyclosporine, imatinib, and mepolizumab have been utilized with varying success. In mastocytosis patients, anti-mediator therapy with antihistamines and mast cell stabilization with cromolyn sodium can be considered treatments of choice, followed by other therapies yet to be thoroughly studied, including the role of the low-histamine diet, corticosteroids, and treatment of associated IBS symptoms. Given that both eosinophils and mast cells may have joint pathophysiologic roles, they have the potential to be a combined target for therapeutic intervention in disease states exhibiting eosinophil or mast cell involvement.

Short-Time Strategy for Fibromyalgia Treatment Based on Olive Nutraceutical and Inflammatory Gut-Brain Axis Control Diet (IGUBAC) Diet®

Fibromyalgia syndrome is defined as chronic widespread pain and tenderness. It is associated with fatigue, sleep disorder, functional somatic syndromes, mental and physical disorders, as well as disability and diminished quality of life. We aimed to analyse the effects of an olive tree-based supplement and a gluten-free, FODMAP and low histamine diet (IGUBAC-Diet®), with antioxidant and anti-inflammatory characteristics, in women with fibromyalgia. A randomized, controlled, clinical trial, with 31 women (55.87±11.86 years) diagnosed with fibromyalgia was conducted in 2016. Chronic Pain Grade Scale, Pain Catastrophizing Scale, Fatigue Severity and Impact Scale were used. Anthropometric parameters and symptoms progression were measured before and after two months of treatment with olive tree-based supplement and IGUBAC-Diet®. Other secondary outcome measures include blood biochemical analysis. Patients improved Chronic Pain Grade Scale scores after intervention and all groups experienced a reduction in the perception of pain catastrophizing. Positive changes were found all groups for Fatigue Severity Scale, but not for Fatigue Impact Scale scores. Significant variations (p &lt; 0.05) were observed in symptoms frequency. The olive tree-based food supplement and the gluten-free, FODMAP and low histamine diet had beneficial effects on the intensity of fibromyalgia symptoms. This short-time strategy may be used to improve fibromyalgia patient’s well-being.

A Popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction?

Chronic spontaneous urticaria (CsU) is a frequent dermatological disease that might last for months or years with high impact on quality of life. Known causes are autoreactive phenomena, infections or intolerances, rarely IgE-mediated allergies. One-third of CsU patients benefit from a low-pseudoallergen diet. Additionally, it is often discussed, that reducing histamine ingestion alone might improve clinical symptoms and quality of life in CsU patients despite the uncertain role of the histamine-degrading enzyme diamine oxidase (DAO). Aim of this study was to investigate the impact of low-histamine diet on symptoms and quality of life in patients with CsU. Patients suffering from CsU accompanied by gastrointestinal symptoms were included in the study. They underwent low-histamine diet for at least 3 weeks. During the whole study, urticaria activity score (UAS) was recorded daily in a patient's diary. Quality of life was assessed during screening, baseline and post diet visits by completing questionnaires (DLQI and Cu-Q(2)oL). DAO activity was measured before and after elimination diet. A total of 75% of the patients had a benefit from the low-histamine diet. Thirty-four of 56 patients (61%) reached the primary endpoint of the study, an improvement of UAS 4 of ≥3. Overall, a significant reduction from 9.05 to 4.23 points (P = 0.004) was achieved; the average reduction in a strongly affected subgroup was 8.59 points (P < 0.001). DAO activity remained stable. Low-histamine diet is a therapeutically useful, simple and cost-free tool to decrease symptoms and increase quality of life in CsU patients with gastrointestinal involvement. Further research is needed to understand the role of diamine oxidase.