Serum diamine oxidase activity as a predictor of gastrointestinal toxicity and malnutrition due to anticancer drugs
Serum diamine oxidase activity as a predictor of gastrointestinal toxicity and malnutrition due to anticancer drugs.
- Department of Gastroenterology and Oncology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
- Department of General Medicine and Community Health Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
BACKGROUND AND AIM:
Objective evaluation of intestinal mucosal damage due to anticancer drugs is generally difficult. Serum diamine oxidase (DAO) activity is reported to reflect the integrity and maturity of the small intestinal mucosa. Therefore, we investigated whether serum DAO activity is an indicator of gastrointestinal toxicity or nutritional status in patients receiving chemotherapy.
We prospectively enrolled 20 patients with unresectable metastatic gastric cancer who received oral S-1 (80 mg/m(2) ) on days 1-14, and intravenous cisplatin (60 mg/m(2) ) and docetaxel (50 mg/m(2) ) on day 8 every 3 weeks. Serum DAO activity was measured by colorimetry. Gastrointestinal toxicity was evaluated by Common Toxicity Criteria for Adverse Events version 4.0. Endoscopic examination and biopsy of duodenal mucosa assessed mucosal damage. Malnutrition was evaluated by measuring serum total protein and albumin levels.
Serum DAO activity decreased step-by-step significantly during anticancer drug treatment and recovered after drug holidays. In all 14 patients who experienced diarrhea, serum DAO activity significantly decreased prior to diarrhea onset. Percent decrease in DAO activity was significantly correlated with severity of diarrhea. Significant correlation was observed between percent decrease in DAO activity and percent decrease in duodenal villus height or surface area from baseline. There were also significant correlations between percent decrease in serum DAO activity at day 14 and percent decrease in serum total protein or albumin levels at day 21 from baseline.
Serum DAO activity sensitively indicates gastrointestinal damage prior to symptom onset and can be a useful predictor of intestinal mucosal damage and nutritional status in patients receiving chemotherapy.
© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
anticancer drugs; diamine oxidase; diarrhea; gastrointestinal toxicity; malnutrition
Serum diamine oxidase activity in patients with histamine intolerance.
Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.
Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients.
We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated.
We found that 10 out of 14 patients had serum DAO activity <10 U/mL, which was the threshold suggested as a cutoff for probable histamine intolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (± SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04 ± 6.90 U/mL compared to 39.50 ± 18.16 U/mL in 34 healthy controls (P = 0.0031).
In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.
Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy.
Evaluation of Diamine Oxidase deficiency in patients with migraine.
Vidal Carou ● A1, Sabater Sales ● B2, Titus Albareda ● C3.
(A1) Nutrition and Bromatology Department of University of Barcelona.
(B2) MD in Pharmacy. Responsible for scientific research at Sabater Analysis (LABCO).
(C3) Honorary Member of the Spanish Society of Neurology, and Scientific Advisor of the Spanish Association of Headache Patients, AEPAC
Migraine is a complex, recurrent and disabling disease, but its etiopathogeny remains unknown, so it is necessary to find new approaches to the biochemical mediators of the disease. Histamine, one of the most important mediators, is mainly metabolized by DAO (Diamine Oxidase enzyme). Therefore, it is believed that a decrease in DAO activity may cause histamine excess, increasing the risk of suffering from clinical pictures such as migraine, among others.
To determine the rate of migraine patients presenting DAO deficiency compared to the observed rate in general population without migraine.
Target population consisted of migraine volunteers. Healthy controls were selected among volunteers of their micro social environment. Given a total sample size of 160 individuals, the studied aimed to determine DAO activity level in the participants by analytical determination using a validated procedure.
IHS diagnostic sheet, patient information sheet, informed consent form, 160 analytical tests to determine DAO, data collection logbook, documents for the registration in the data protection agency.
48.8 % of migraine patients presented values of much reduced DAO activity, and 46% of reduced activity. 95% of migraine patients experienced other symptoms related to histamine intolerance. The average value obtained for DAO activity is lower in the migraine group, with a significant difference (p=0.001).
The results confirm the scope of the research and show that DAO activity is significantly lower in migraine patients compared to controls.
Role of histamine and diamine oxidase enzyme in Multiple Sclerosis.
- Farokhi, M. Etemadifar, A. Rezaei, A. Amani, H. Jahanbani
Multiple Sclerosis and related disorders, November 2014, Volume 3, Issue 6, Page 746
Chronic rhinitis and its association with headache frequency and disability in persons with migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study
Chronic rhinitis and its association with headache frequency and disability in persons with migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study.
- Department of Internal Medicine, University of Cincinnati, OH, USA.
Rhinitis is a comorbidity of migraine, but its relationship to migraine headache frequency and headache-related disability is unknown.
To determine if rhinitis and its subtypes are associated with an increased frequency and associated disability of migraine.
The AMPP Study is a longitudinal study of individuals with “severe” headache from the US population. Respondents meeting ICHD-2 criteria for migraine in 2008 were identified and the presence of rhinitis was determined using the European Community Respiratory Health Survey (ECRHS). Those with rhinitis were subtyped as allergic, non-allergic, mixed and unclassified based on a rhinitis questionnaire. The primary outcome measures were categories of headache-day frequency and headache-related disability as measured by the Migraine Disability Assessment Scale (MIDAS). Logistic regression for ordered categories was used for modeling each outcome separately, adjusted for sociodemographics profile, headache features, headache treatments and comorbidities.
The AMPP Study questionnaire was mailed to 17,892 persons and returned by 60.1% of respondents. Among the migraine sample ( N = 5849), 66.8% had rhinitis with mixed rhinitis as the most common form. The presence of rhinitis of any type was associated with headache frequency after adjusting for sociodemographic variables only (OR 1.33; 95% CI 1.16, 1.53) and in the fully adjusted model (OR 1.25; 95% CI 1.05-1.49). Headache-related disability (MIDAS category) was associated with rhinitis after adjusting for sociodemographic features (OR 1.30; 95% CI 1.17-1.46), but lost significance in the fully adjusted model (OR 1.10; 95% CI 0.96-1.26). Mixed rhinitis was associated with an increased headache frequency category in the model adjusted for sociodemographics (OR 1.45; 95% CI 1.24-1.70) and in that adjusted for all covariates (OR 1.28; 95% CI 1.05-1.57). The odds ratio for MIDAS categories were similarly increased in both models for the mixed rhinitis group.
The frequency and disability of migraine are higher in persons with rhinitis, particularly those with mixed rhinitis. These results, however, should be considered preliminary until confirmed in future studies because of the modest questionnaire response rate in this study.
Rhinitis; allodynia; comorbidities; depression; headache frequency; headache-related disability; migraine
Diamine oxidase activity levels in anorexia nervosa.
Int J Eat Disord. 2014 Mar;47(2):203-5. doi: 10.1002/eat.22202. Epub 2013 Oct 30.
- Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Anorexia nervosa (AN) patients often experience gastrointestinal complications caused by their malnutrition. We hypothesized that intestinal integrity is disturbed in AN. Therefore, the objective of the present study was to investigate serum diamine oxidase (DAO) activity, which is considered to be a clinical indicator of the integrity of the intestinal mucosa, in AN patients.
Thirty-six AN female patients including 21 AN restricting type (AN-R) and 15 AN binge-eating/purging type (AN-BP) were compared with twenty healthy women on serum DAO activity using immunoassay.
DAO levels in AN-R patients were significantly lower than in AN-BP patients and healthy controls.
DAO levels were decreased in AN-R patients. This finding suggests the presence of intestinal structural disturbance as one of the physical complications of malnutrition in AN-R patients.
Copyright © 2013 Wiley Periodicals, Inc.
PMID: 24488839 DOI: 10.1002/eat.22202
A randomized doubled blinded trial of treatment with diamino-oxidase (DAO) in patients with migraine and deficit of enzyme’s activity
A randomized doubled blinded trial of treatment with diamino-oxidase (DAO) in patients with migraine and deficit of enzyme’s activity
J. Izquierdoa, D. Mona, M. Lorenteb, L. Soler Singlaa.
a Hospital General de Catalunya, Sant Cugat del Vallès, Spain;b Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain
Abstract — WCN 2013
Topic: 8 — Headache
October 15, 2013Volume 333, Supplement 1, Pages e505–e506
Histamine has been considerate as a chemical mediator of migraine. The degradation is done in two different pathways. One
of the enzymes that allow this process is the diamino-oxidase (DAO).
The aim of this study is to identify the prevalence of the deficit in the activity of DAO in patients with migraine, and test the supplementation of this enzyme in a randomized controlled doubleblind trial.
Material and methods:
This was a randomized parallel-group controlled study. After a 1-month run-in, patients with migraine attacks/month between 4 and 14 were randomized 1:1 to placebo or DAO three times at day during one month. Primary outcome measures were diminution of hours of pain, and the use of antimigraine drugs.
We studied 137 patients with migraine, and find the deficit of DAO activity (b80 HDU/ml) in 119 (87%).One hundred patients were randomized and included in the intentionto-treat analysis. Between run-in and first month of treatment, the mean number of hours of pain decreases in both groups but with significant difference in the final control in the group treated with DAO compared with placebo (6,3 vs 5,1: p b 0.03). The use of the acute antimigraine drug was significantly reduced in the DAO but not in placebo group (p N 0.022). There were no adverse events in either group.
Deficit in the activity of DAO is very prevalent in population with migraine. The supplementation with the enzyme is effective and safe as a preventive therapy for migraine.
Histamine intolerance as a cause of chronic digestive complaints in pediatric patients.
Rev Esp Enferm Dig. 2013 Apr;105(4):201-6.
histamine intolerance (HI) is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic.
MATERIAL AND METHODS:
observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital.They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO) levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests.
sixteen patients were diagnosed. Males predominated versus females (11/5). Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months) and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months), with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years). Predominant symptoms included diffuse abdominal pain (16/16), intermittent diarrhea (10/16), headache (5/16), intermittent vomiting (4/16), and skin rash (2/16). The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L) in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases.
histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement.
Serum diamine oxidase activity as a diagnostic test for histamine intolerance.
- University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204 Golnik, Slovenia.
Histamine intolerance (HIT) is characterized by an imbalance between histamine intake and the capacity for histamine degradation. The main enzyme for metabolizing ingested histamine is diamine oxidase (DAO). Determining DAO activity in serum may be useful in diagnosing HIT.
Over a period of 3.5 years we recruited 316 subjects with clinically suspected HIT and 55 healthy controls. Serum DAO activity was measured with a quantitative enzyme immunoassay. Twenty patients with highly reduced DAO activity went on a histamine-free diet for 6-12 months. Afterwards, their DAO activity was determined again.
We found that DAO activity was significantly lower in patients than in healthy control subjects (P < 0.0001). Furthermore, 54 patients had highly reduced serum DAO activity (< 40 HDU/ml). Their main symptoms involved the skin, gastrointestinal tract, respiratory system, and eyes. In all the 20 patients with highly reduced DAO activity, the main clinical symptoms typical of histamine intolerance disappeared after they adopted a histamine-free diet. Furthermore, the serum DAO activity values measured increased significantly (P < 0.0001).
Our results suggest that determining DAO activity in serum is a useful tool in diagnosing HIT. Furthermore, our results showed the benefit of a histamine-free diet because after the diet the majority of symptoms disappeared and the serum DAO activity significantly increased.
Effect of the menstrual cycle on serum diamine oxidase levels in healthy women.
Clin Biochem. 2013 Jan;46(1-2):99-102. doi: 10.1016/j.clinbiochem.2012.10.013. Epub 2012 Oct 22.
- Department of Nutrition, Kobe University Hospital, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. email@example.com
Serum diamine oxidase (DAO) level is employed as a useful marker of intestinal mucosal integrity. As reported previously, the range of serum DAO levels in women is wider than that in men. We hypothesized that the menstrual cycle may affect DAO levels.
DESIGN AND METHODS:
Thirty-six women of Japanese descent were recruited. All participants, aged 20-29 years, were healthy. Food surveys utilized in this study were based on questionnaires validated by dietitians. Complete blood counts, biochemical parameters, female hormones, and serum DAO levels during the follicular and luteal phases were measured in each subject.
Biochemical parameters, except for DAO levels, were comparable between the two phases. However, serum DAO levels during the luteal phase were significantly higher than those during the follicular phase.
Serum DAO levels were influenced by the menstrual cycle. Furthermore, our findings suggest that serum DAO levels should be interpreted cautiously in premenopausal women.
Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.