Histamine Intolerance: Symptoms, Diagnosis, and Beyond.

Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have attributed several reasons to this condition, such as genetic factors, alcohol, and dietary deficiencies, among other elements. Symptoms of histamine intolerance have been found to extend beyond the gastrointestinal tract and to the whole body, with these symptoms being sporadic and non-specific. This review will explore various aspects related to histamine intolerance, such as its causes, symptoms, diagnosis, and information related to management.

[Food Intolerance]. / Intolerancia alimentaria.

The term food intolerance has been used non-specifically to define a wide range of disorders related to food intake. Recently, the use of the term "non-immunological adverse reactions to foods" (RANIAs) was recommended as a more correct clinical definition. The pathophysiological mechanisms can be diverse, sometimes unknown, and there are no validated diagnostic tests, making it difficult to obtain accurate data. The clinical manifestations of non-immunological adverse reactions to foods affect more than one organ or system; and gastrointestinal symptoms (pain, abdominal distension, flatulence, and diarrhea) are the most common. Non-immunological adverse reactions to foods are divided into independent and dependent on host factors. Foods may contain chemicals with pharmacological activity and be present naturally, such as vasoactive amines (histamine) and salicylates, or added for preservation, to improve appearance or flavor (monosodium glutamate, tartrazine, sulfites, and benzoates). In some cases, these types of reactions may be like to hypersensitivity reactions. Concomitant alcohol consumption may worsen symptoms by inhibiting histamine breakdown and increasing intestinal permeability. In patients diagnosed with non-immunological adverse reactions to foods, it is important to rule out some psychological problems: aversions or eating disorders.

El término intolerancia alimentaria se ha utilizado de manera inespecífica para definir una amplia gama de trastornos relacionados con la ingesta de alimentos. Recientemente se recomendó el uso de la expresión "reacciones adversas no inmunológicas a alimentos" (RANIAs) como una definición clínica más correcta. Los mecanismos fisiopatológicos pueden ser diversos, a veces desconocidos, y no existen pruebas diagnósticas validadas, por lo que es difícil obtener datos certeros. Las manifestaciones clínicas de las reacciones adversas no inmunológicas a alimentos afectan a más de un órgano o sistema; y los síntomas gastrointestinales (dolor, distensión abdominal, flatulencias y diarrea) son los más frecuentes. Las reacciones adversas no inmunológicas a alimentos se dividen en independientes y dependientes de factores del huésped. Los alimentos pueden contener productos químicos con actividad farmacológica y estar presentes en forma natural, como las aminas vasoactivas (histamina) y los salicilatos, o añadirse para su conservación, mejorar la apariencia o el sabor (glutamato monosódico, tartrazina, sulfitos y benzoatos). En algunos casos, este tipo de reacciones pueden ser similares, desde el punto de vista clínico, a las reacciones de hipersensibilidad. El consumo de alcohol concomitante puede empeorar los síntomas, al inhibir la degradación de la histamina y aumentar la permeabilidad intestinal. En pacientes con diagnóstico de reacciones adversas no inmunológicas por alimentos es importante descartar algunos problemas de índole psicológica: aversiones o trastornos de la conducta alimentaria.

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.

Food Allergy and Intolerance: A Narrative Review on Nutritional Concerns.

Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food-along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.

Histamine Intolerance Originates in the Gut.

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.

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal-Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal-Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.

Histamine Intolerance: The Current State of the Art.

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine.

Development and validation of the paediatric Carbohydrate Perception Questionnaire (pCPQ), an instrument for the assessment of carbohydrate-induced gastrointestinal symptoms in the paediatric population.

BACKGROUND: There is an unmet need for a validated, test-specific symptom questionnaire to evaluate carbohydrate perception during breath tests. Our aim was to develop and validate a questionnaire for the assessment of symptoms after a provocative carbohydrate load. METHODS: After a literature search and initial focus group-style interviews, five relevant complaints were identified. Responses were given on a Likert-type faces scale with a language children use and understand. Reliability, validity and responsiveness to change were established by the implementation of the questionnaire during breath tests in 215 pediatric subjects. Correlation between the questionnaire and a medical interview by a pediatrician who was blinded to the results of the questionnaire (n = 19) was determined. KEY RESULTS: The questionnaire had good face and content validity (Lawshe ratio = 1). Intraclass correlation coefficients for test-retest reliability (n = 116) demonstrated good repeatability (P < .001), and effect sizes were small (Cohen's d < 0.15 for all symptoms). Convergent validity and discriminant validity were supported according to the multitrait-multimethod matrix method. The results obtained by the questionnaire correlated highly with the result of the medical interview (P < .001; Fisher's exact test). Cronbach's alpha was 0.81. Responsiveness was verified for the whole patient group and subgroups with medium to high effect sizes. CONCLUSIONS AND INFERENCES: The paediatric Carbohydrate Perception Questionnaire (pCPQ) is a simple, test-specific questionnaire for a pediatric population. It is a valid instrument with excellent psychometric properties to assess gastrointestinal symptoms after carbohydrate ingestion. The pCPQ can replace non-validated symptom assessment during carbohydrate breath tests and allows a standardized diagnosis of carbohydrate intolerance.

Living with Gluten and Other Food Intolerances: Self-Reported Diagnoses and Management.

People suffering from a food intolerance (FI) tend to initiate restrictive diets such as a gluten-free diet (GFD), to alleviate their symptoms. To learn about how people live with these problems in daily life (independent of their medical diagnoses), 1203 participants answered a previously validated questionnaire and were divided into: G1 (those self-reporting symptoms after gluten consumption) and G2 (those informing no discomfort after gluten consumption). Self-reported clinical characteristics, diagnoses and diets followed were registered. Twenty nine percent referred some FI (8.5% in G1). In G1, self-reported diagnoses were more frequent (p < 0.0001), including a high proportion of eating and mood disorders. Diagnoses were reported to be given by a physician, but GFD was indicated by professional and nonprofessional persons. In G2, despite declaring no symptoms after gluten consumption, 11.1% followed a GFD. The most frequent answer in both groups was that GFD was followed "to care for my health", suggesting that some celiac patients do not acknowledge it as treatment. Conclusion: close to one third of the population report suffering from some FI. Those perceiving themselves as gluten intolerant report more diseases (p < 0.0001). A GFD is followed by ~11% of those declaring no symptoms after gluten ingestion. This diet is perceived as a healthy eating option.

A Population Survey of Dietary Attitudes towards Gluten.

It is unclear how the prevalence of people who believe the gluten-free diet (GFD) to be generally healthy ("Lifestylers") is impacting the overall rates of self-reported gluten sensitivity (GS). We repeated a population survey from 2012 in order to examine how attitudes towards GS have changed over time. Our survey (N = 1004) was administered in Sheffield (UK) in 2015, replicating the 2012 experiment. The questionnaire included a food frequency survey and assessed self-reported GS as well as associated variables (prevalence, current diet, pre-existing conditions, etc.). The overall rates of key variables and chi-squared analysis in comparison to the previous survey were as follows: self-reported GS was 32.8% (previously 12.9%, p < 0.001), pre-existing coeliac disease (CD) was 1.2% (previously 0.8%, p = 0.370), following a GFD was 3.7% (previously 3.7%, p = 0.997). Self-reported GS was positively associated with some pre-existing conditions, including anxiety, depression, chronic fatigue, headaches, and other food allergies/intolerances (including irritable bowel syndrome (IBS); chi-squared analyses, all p < 0.001). Over a 3-year period, the fraction of people who self-reported GS increased by over 250%. Despite this, arguably more meaningful indications of underlying physiological GS remained comparable. This research suggests that the public perception of gluten is causing a marked increase in the number of people who erroneously believe they are sensitive to it.

Improvement in Food Intolerance Resulting from Roux-En-Y Gastric Bypass after Speech Therapy Intervention in Chewing.

INTRODUCTION: Food intolerance is expected during the postoperative period following gastric bypass and may be associated with inadequate chewing. OBJECTIVE: To evaluate chewing before and after speech therapy intervention in subjects undergoing Roux-en-Y gastric bypass who present with food intolerance. MATERIALS AND METHODS: This was a randomized controlled trial, approved by the Brazilian Ethics and Research Committee under n. 438,600. The study population was allocated into two groups: the study group (SG), who received speech therapy intervention, and the control group (CG), who did not receive any intervention, in six visits at 7, 15, 30, 60, and 90 days (v7, v15, v30, v60, and v90) after the initial visit (v0). During v0 and v90, a chewing evaluation was performed according to the MBGR protocol adapted. The significance level adopted was 5%. RESULTS: A total of 30 females (88%) and 4 males (12%) were analyzed. The SG had 18 subjects, and the CG had 16, with mean ages of 50.17 ± 12.28 years and 45.69 ± 9.78 years, respectively. The postoperative time ranged from 4 to19 months. In the SG, a marked improvement in the number of episodes of food intolerance was observed (p < 0.001), an improvement in the intake of cereals and meats (p = 0.004 and p < 0.001, respectively), and an improvement in chewing capacity and swallowing (p = 0.002 and p = 0.011, respectively). CONCLUSION: Speech therapy intervention in chewing led to a marked improvement of food acceptance and food intolerance resulting from Roux-en-Y gastric bypass.

Cow milk protein allergy and other common food allergies and intolerances.

The prevalence of food allergy and food intolerance is increasing and it is an important public health problem affecting children. Food allergy results from an immunological reaction to certain food(s) and affects numerous organs in the body. Food intolerances are non-immunological reactions including metabolic, toxic, pharmacological and undefined mechanisms. Cow milk is the most common cause of food allergy and food intolerance, especially in young children. Food intolerance can present with similar symptoms to those of food allergy. Health-care personnel, patients and their caregivers often confuse food intolerance with food allergy. This review focuses on the clinical manifestations, diagnostic evaluation, treatment and prevention of food allergy and food intolerance.

Diagnosis and treatment of chronic abdominal pain 5 years after Roux-en-Y gastric bypass.

BACKGROUND: Knowledge of optimal diagnostic workup, etiology, and response to treatment of chronic abdominal pain after Roux-en-Y gastric bypass (RYGB) is limited. OBJECTIVE: To define the etiology of chronic abdominal pain presenting at the 5-year follow-up after RYGB and to evaluate response to treatment. SETTING: Oslo University Hospital (tertiary referral center for obesity surgery). METHODS: Of 234 patients operated during a randomly selected 12-month period, 165 (71%) returned for 5-year follow-up, and 160 responded to study questionnaires. Of these, 54 (34%) reported chronic abdominal pain and were invited to participate in a structured diagnostic and treatment algorithm. These patients were contacted for the evaluation of their response to treatment. RESULTS: Fifty-one of 54 patients (94%) reporting chronic abdominal pain at the 5-year follow-up were included in the study. Of the 45 patients with onset of symptoms post-RYGB, 28 (62%) underwent one or more radiologic evaluations, 10 (22%) underwent endoscopy, and 13 (29%) underwent laparoscopy. Diagnosis and treatment were established for 34 patients (76%), whereas 11 (24%) had abdominal pain of unknown cause. The most common etiology was internal herniation (n = 6), dumping (n = 6), food intolerance (n = 6), gallstones (n = 5), and irritable bowel syndrome (n = 4). After a median follow-up of 13.0 months (standard deviation, 11.5), 37 (82%) patients reported remission or improvement of symptoms, 6 had unchanged symptoms, and 2 patients were lost to follow-up. CONCLUSIONS: The etiology of long-term chronic abdominal pain post-RYGB is diverse. A multidisciplinary team can help most patients with dedicated follow-up, but a subset of patients has symptoms of unknown etiology.

[Clinical characteristics and risk factors for feeding intolerance in preterm infants].

OBJECTIVE: To investigate the clinical characteristics and risk factors for feeding intolerance (FI) in preterm infants and to provide evidence for early identification, effective prevention and treatment of FI.
 Methods: A total of 116 preterm infants were recruited in the Department of Neonatology, West China Second Hospital, Sichuan University, from July 2016 to December 2016. Self-designed "the clinical observation table for feeding intolerance of preterm infant" was used to find out the main risk factors of FI in preterm infants.
 Results: 1) There were 62 cases of FI. The incidence of FI in preterm infants was 53.45% (62/116). It was 44.93% (31/69) and 65.96% (31/47) for males and females, respectively, with significant difference between them (P<0.05). The incidence of FI in very low birth weight infants was 48.57% (34/70), and in the extremely low birth weight infant was 88.89% (8/9). FI in preterm infants mainly occurred in the period of being fed within 48-72 h. The symptoms included abdominal distension, gastric retention, vomiting and stomach brown color for clinical manifestations. Among them, abdominal distension was the main clinical manifestation. 2) The logistic multivariate regression analysis showed that birth weight <1 000 g (P<0.05), the use of caffeine citrate (P<0.05) and the formula feeding (P<0.05) were the main risk factors for FI.
 Conclusion: The incidence of FI is very high in preterm infants. Birth weight <1 000 g, the use of caffeine citrate, and formula feeding are main risk factors for FI.

A review of feeding intolerance in critically ill children.

Ensuring optimal nutrition is vital in critically ill children and enteral feeding is the main route of delivery in intensive care. Feeding intolerance is the most commonly cited reason amongst pediatric intensive care unit healthcare professionals for stopping or withholding enteral nutrition, yet the definition for this remains inconsistent, nebulous, and entirely arbitrary. Not only does this pose problems clinically, but research in this field frequently uses feeding intolerance as an endpoint and the heterogeneity in this definition makes the comparison of studies difficult and meta-analysis impossible. We reviewed the use of, and definitions of, the term feed intolerance in pediatric intensive care research papers in the last 20 years. Gastric residual volume remains the most common factor used to define feed intolerance, despite the lack of evidence for this. Healthcare professionals would benefit from further education to improve their awareness of the limitations of the markers to define feeding intolerance, and the international PICU community needs to agree a consistent definition of this phenomenon to improve consistency in both practice and research.Conclusion: This paper will provide a narrative review of the definitions of, evidence for, and markers of feeding intolerance in critically ill children. What is Known?: • Feeding intolerance is a commonly cited reason amongst pediatric intensive care unit healthcare professionals for stopping or withholding enteral nutrition. • There is no agreed definition for feeding intolerance in critically ill children. What is New?: • This paper provides an up to date review of the definitions of, evidence for, and markers of feeding intolerance in critically ill children. • Despite no evidence, gastric residual volume continues to drive clinical bedside decisions about enteral feeding and feeding tolerance.

Differential Diagnoses of Food-Related Gastrointestinal Symptoms in Patients with Anorexia Nervosa and Bulimia Nervosa: A Review of Literature.

OBJECTIVES: The present review investigates the prevalence and medical causes of food-related gastrointestinal symptoms in eating disorder (ED) patients and recommends a diagnostic algorithm based on the current literature. METHODS: A literature search was conducted, which included publications from January 2000 until January 2017 Results: Over 90% of ED patients suffer from food-related symptoms. There is no evidence for a higher prevalence of immunological or structural gastrointestinal disorders in ED patients compared to the healthy population. Most food-related symptoms in ED patients are likely to be functional. CONCLUSIONS: Diagnostic work-up of food-related symptoms in ED patients needs to be based on clinical history. Only if timing and quality of symptoms point towards a disorder independent from the ED is a comprehensive diagnostic work-up necessary.

No effect of adding dairy lipids or long chain polyunsaturated fatty acids on formula tolerance and growth in full term infants: a randomized controlled trial.

BACKGROUND: When breastfeeding is not possible, infants are fed formulas in which lipids are usually of plant origin. However, the use of dairy fat in combination with plant oils enables a lipid profile in formula closer to breast milk in terms of fatty acid composition, triglyceride structure and cholesterol content. The objectives of this study were to investigate the impact on growth and gastrointestinal tolerance of a formula containing a mix of dairy lipids and plant oils in healthy infants. METHODS: This study was a monocentric, double-blind, controlled, randomized trial. Healthy term infants aged less than 3 weeks whose mothers did not breastfeed were randomly allocated to formula containing either: a mix of plant oils and dairy fat (D), only plant oils (P) or plant oils supplemented with long-chain polyunsaturated fatty acids (PDHA). Breastfed infants were included in a reference group (BF). Anthropometric parameters and body composition were measured after 2 and 4 months. Gastrointestinal tolerance was evaluated during 2 day-periods after 1 and 3 months thanks to descriptive parameters reported by parents. Nonrandomized BF infants were not included in the statistical analysis. RESULTS: Eighty eight formula-fed and 29 BF infants were enrolled. Gains of weight, recumbent length, cranial circumference and fat mass were similar between the 3 formula-fed groups at 2 and 4 months and close to those of BF. Z-scores for weight, recumbent length and cranial circumference in all groups were within normal ranges for growth standards. No significant differences were noted among the 3 formula groups in gastrointestinal parameters (stool frequency/consistency/color), occurrence of gastrointestinal symptoms (abdominal pain, flatulence, regurgitation) or infant's behavior. CONCLUSIONS: A formula containing a mix of dairy lipids and plant oils enables a normal growth in healthy newborns. This formula is well tolerated and does not lead to abnormal gastrointestinal symptoms. Consequently, reintroduction of dairy lipids could represent an interesting strategy to improve lipid quality in infant formulas. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01611649 , retrospectively registered on May 25, 2012.