Tutkimukset

Dietary advice based on food specific IgG Results

Geoffrey Hardman, Gillian Hart, University of York, Heslington, York, UK
Nutrition and food science Vol 37 No 1 2007 pp 16-23

Purpose – To provide evidence that elimination diet based on food-specific IgG test results is an effective, reliable and valid aid to the management of chronic medical conditions.

Design/methodology/approach – A postal survey, commissioned by Allergy UK, was carried out with 5,286 subjects reporting a wide range of chronic medical conditions, who had taken a foodspecific IgG enzyme-linked immunosorbant assay blood test. Questionnaires, issued three months after the results, were analysed to investigate the effect of eliminating the foods identified by the test.To check for response bias, a separate group of patients who had not responded were interviewed by telephone. The analysis and reporting of the data was carried out at the University of York.

Findings – Of patients who rigorously followed the diet 75.8 per cent had a noticeable improvement in their condition. Of patients who benefited from following the recommendations 68.2 per cent felt the benefit within three weeks. Those who reported more than one condition were more likely to report noticeable improvement. 81.5 per cent of those that dieted rigorously and reported three or more co-morbidities showed noticeable improvement in their condition. For those who dieted rigorously and reported high benefit, 92.3 per cent noticed a return of symptoms on reintroduction of the offending foods. Originality/value – These data provide evidence for the use of elimination diet based on foodspecific IgG blood test results as an aid to management of the symptoms of a range of chronic medical conditions.

Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial

W Atkinson, T A Sheldon, N Shaath, PJ Whorwell Gut 2004:53 1459-1464 doi: 10.1136 Gut 2004;53:1459–1464. doi: 10.1136/gut.2003.037697
BACKGROUND: Patients with irritable bowel syndrome (IBS) often feel they have some form of dietary intolerance and frequently try exclusion diets. Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies. AIMS: To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food. PATIENTS: A total of 150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies. METHODS: Primary outcome measures were change in IBS symptom severity and global rating scores. Non-colonic symptomatology, quality of life, and anxiety/depression were secondary outcomes. Intention to treat analysis was undertaken using a generalised linear model. RESULTS: After 12 weeks, the true diet resulted in a 10% greater reduction in symptom score than the sham diet (mean difference 39 (95% confidence intervals (CI) 5-72); p = 0.024) with this value increasing to 26% in fully compliant patients (difference 98 (95% CI 52-144); p<0.001). Global rating also significantly improved in the true diet group as a whole (p = 0.048, NNT = 9) and even more in compliant patients (p = 0.006, NNT = 2.5). All other outcomes showed trends favouring the true diet. Relaxing the diet led to a 24% greater deterioration in symptoms in those on the true diet (difference 52 (95% CI 18-88); p = 0.003). CONCLUSION: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.

Food allergy in irritable bowel syndrome: new facts and old fallacies.

E Isolauri, S.Rautava, M.Kalliomaki Gut 2004; 53 1391-1393 10.1136 Gut 2004;53:1391–1393. doi: 10.1136/gut.2004.044990
The notion of food allergy in irritable bowel syndrome (IBS) is not new. However, recent evidence suggests significant reduction in IBS symptom severity in patients on elimination diets, provided that dietary elimination is based on foods against which the individual had raised IgG antibodies. These findings should encourage studies dissecting the mechanisms responsible for IgG production against dietary antigens and their putative role in IBS.

A prospective audit of Food Intolerance among Migraine patients in primary care clinical practise.

Trevor Rees1, David Watson2, Susan Lipscombe3, Helen Speight4, Peter Cousins4, Geoffrey Hardman5 and Andrew J. Dowson6 Headache care Vol.2 No 2 2005 105-110
Summary. This prospective audit was set up to investigate whether migraine sufferers have evidence of IgG based food intolerances and whether their condition can be improved by the withdrawal from the diet of specific foods identified by intolerance testing. Conclusion. This pilot study audit demonstrated that migraine attacks may be related to food intolerances mediated via IgG and that changing the diet to eradicate specific foods may be potentially effective treatment for migraine.

Celiac Disease.

Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D.The New England Journal of Medicine 2007; 357:1731-43
Celiac disease is a unique autoimmune disorder, unique because the environmental precipitant is known. The disorder was previously called celiac sprue, based on the Dutch word sprue, which was used to describe a disease similar to tropical sprue that is characterized by diarrhea, emaciation, aphthous stomatitis, and malabsorption.1,2 Celiac disease is precipitated, in genetically predisposed persons, by the ingestion of gluten, the major storage protein of wheat and similar grains.3 Originally considered a rare malabsorption syndrome of childhood, celiac disease is now recognized as a common condition that may be diagnosed at any age and that affects many organ system.

Alterations of food antigen-specific serum immunoglobulins G and E in patients with irritable bowel syndrome and functional dyspepsia.

X. L. Zuo_, Y. Q. Li_, W. J. Li_, Y. T. Guo_, X. F. Lu_, J. M. Li_ and P. V. DesmondwClinical and Experimental Allergy, 37, 823-830
BACKGROUND: Post-prandial worsening of symptoms as well as adverse reactions to one or more foods are common in the patients with functional gastrointestinal diseases, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD). However, the role played by true food allergy in the pathogenesis of these diseases is still controversial and there are no well-established tests to identify food allergy in this condition. OBJECTIVE: To investigate serum food antigen-specific IgG, IgE antibody and total IgE antibody titres in controls and patients with IBS and FD, and to correlate symptoms with the food antigen-specific IgG titres in IBS and FD patients. METHODS: Thirty-seven IBS patients, 28 FD patients and 20 healthy controls participated in this study. Serum IgG and IgE antibody titres to 14 common foods including beef, chicken, codfish, corn, crab, eggs, mushroom, milk, pork, rice, shrimp, soybean, tomatoes and wheat were analysed by ELISA. Serum total IgE titres were also measured. Last, symptomatology was assessed in the study. RESULTS: IBS patients had significantly higher titres of IgG antibody to crab (P=0.000), egg (P=0.000), shrimp (P=0.000), soybean (P=0.017) and wheat (P=0.004) than controls. FD patients had significantly higher titres of IgG antibody to egg (P=0.000) and soybean (P=0.017) than controls. The percentage of individuals with detectable positive food antigen-specific IgE antibodies of the three groups did not show any significant differences (P=0.971). There were no significant differences between IBS patients, FD patients and controls in the serum total IgE antibody titres (P=0.978). Lastly, no significant correlation was seen between symptom severity and serum food antigen-specific IgG antibody titres both in IBS and FD patients. CONCLUSION: Serum IgG antibody titres to some common foods increased in IBS and FD patients compared to controls. But there is no significant correlation between symptom severity and elevated serum food antigen-specific IgG antibodies in these patients.

IgG Antibodies against Food Antigens are Correlated with Inflammation and Intima Media Thickness in Obese Juveniles#

M. Wilders-Truschnig, H.Mangge, C.Lieners, H.J.Gruber, C Mayer, W Marz Exp Clin Endocrinol Diabetes 2008; 116:241-245
OBJECTIVE: Systemic low grade inflammation may contribute to the development of obesity, insulin resistance, diabetes mellitus and atherosclerotic vascular disease. Food intolerance reflected by immunoglobulin G (IgG) antibodies may predispose to low grade inflammation and atherogenesis. We examined the relationship between IgG antibodies specific for food components, low grade inflammation and early atherosclerotic lesions in obese and normal weight juveniles. RESEARCH METHODS AND PROCEDURES: We determined IgG antibodies directed against food antigens, C-reactive protein (CRP) and the thickness of the intima media layer (IMT) of the carotid arteries in 30 obese children and in 30 normal weight children. RESULTS: Obese juveniles showed a highly significant increase in IMT (p=0.0001), elevated CRP values (p=0.0001) and anti-food IgG antibody concentrations (p=0.0001) compared to normal weight juveniles. Anti-food IgG showed tight correlations with CRP (p=0.001/r=0.546) and IMT (p=0.0001/r=0.513) and sustained highly significant in a multiple regression model. DISCUSSION: We show here, that obese children have significantly higher IgG antibody values directed against food antigens than normal weight children. Anti- food IgG antibodies are tightly associated with low grade systemic inflammation and with the IMT of the common carotid arteries. These findings raise the possibility, that anti-food IgG is pathogenetically involved in the development of obesity and atherosclerosis.

A Vegan diet free of gluten improves the signs and symptoms of Rheumatoid Arthritis.

I Hafstöm, B.Ringertz, A. Spångberg, L. Von Zweigbergk, S. Brannemark, I. Nylander, J.Rönnelid, L.Laasonen,L.Klareskog. British Society of Rheumatology, 2001 pp 1175-1179
British Society of Rheumatology, 2001 pp 1175-1179
OBJECTIVE: Whether food intake can modify the course of rheumatoid arthritis (RA) is an issue of continued scientific and public interest. However, data from controlled clinical trials are sparse. We thus decided to study the clinical effects of a vegan diet free of gluten in RA and to quantify the levels of antibodies to key food antigens not present in the vegan diet. METHODS: Sixty-six patients with active RA were randomized to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 yr. All patients were instructed and followed-up in the same manner. They were analysed at baseline and after 3, 6 and 12 months, according to the response criteria of the American College of Rheumatology (ACR). Furthermore, levels of antibodies against gliadin and beta-lactoglobulin were assessed and radiographs of the hands and feet were performed. RESULTS: Twenty-two patients in the vegan group and 25 patients in the non-vegan diet group completed 9 months or more on the diet regimens. Of these diet completers, 40.5% (nine patients) in the vegan group fulfilled the ACR20 improvement criteria compared with 4% (one patient) in the non-vegan group. Corresponding figures for the intention to treat populations were 34.3 and 3.8%, respectively. The immunoglobulin G (IgG) antibody levels against gliadin and beta-lactoglobulin decreased in the responder subgroup in the vegan diet-treated patients, but not in the other analysed groups. No retardation of radiological destruction was apparent in any of the groups. CONCLUSION: The data provide evidence that dietary modification may be of clinical benefit for certain RA patients, and that this benefit may be related to a reduction in immunoreactivity to food antigens eliminated by the change in diet.

The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis

M Hvatum, L Kanerud, R Hällgren, P Brandtzaeg Gut 2006:55 1240-1247 originally published online 16 feb 2006
BACKGROUND AND AIMS: Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response. METHODS: IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow's milk (alpha-lactalbumin, beta-lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat. RESULTS: In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against beta-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein. Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate. CONCLUSIONS: The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.

Toward an understanding of Allergy and In-Vitro Testing

By Mary James N.D Great Smokies Diagnostic Laboratory
Food represents the largest antigenic challenge facing the immune system. Assuming complete digestion, an intact intestine, a sturdy constitution, and minimal antigenic exposure such that the immune system is not over whelmed, all goes well. Weaknesses in one or more of these areas, however, can result in immune attacks upon foods as if they were foreign invaders. A long list of conditions have been associated with food reactions including fatigue, migraine, irritable bowel disease, gallbladder disease, arthritis, asthma, rhinitis, ADHD, enuresis, epilepsy ,eczema, psoriasis, apthous ulcers and recurrent sinusitis, otitis media and other infections.

Reported food intolerance and respiratory symptoms in young adults

R.K.Woods, M.Abramson, J.M.Raven, M Bailey, JM Weiner, E.H.Walters Eur Respir J 1998 11:151-155
The aim of the study was to assess the ability of the European Community Respiratory Health Survey (ECRHS) questionnaire to provide data on the prevalence, type and reported symptoms associated with food intolerance from a group of young adults in Melbourne. Six hundred and sixty nine randomly selected subjects completed the questionnaire with 553 attending the laboratory for skin-prick tests, anthropometry, and ventilatory function tests. A further 207 symptomatic participants completed the questionnaire, with 204 of them attending the laboratory. Seventeen per cent of all respondents reported food intolerance or food allergy. A wide variety of food items was cited as being responsible for food-related illnesses. Those with current asthma did not report food-related illness more frequently than those without asthma. Respondents who reported respiratory symptoms following food ingestion were more likely to be atopic, to have used inhaled respiratory medications in the previous 12 months, reported less exposure to regular passive smoking over the past 12 months and weighed more. These associations between respiratory symptoms and food intolerance require further prospective investigation and verification. The importance of using appropriate dietary methodology in future studies for determining diet-disease relationships was highlighted by this study.

A critical review of IgG Immunoglobulins and Food Allergy- Implications in systemic health

Raymond M. Suen, MT (ASCP), Shalima Gordon, ND 13500 Linden Ave. N. Seattle, WA 98133 Ph: (206) 365-1256, (877) 318-8728, Fax: (206) 363-8790
Food allergy is defined as an adverse clinical reaction due to an immune-mediated hypersensitivity response resulting from the ingestion of a food. A wide variety of foods have been shown to produce allergic reactions including cow's milk; chicken eggs; legumes; fish and shellfish; and cereals. (1) Depending on the speed of onset of symptoms, less than 45 minutes to 2 hours to days, immediate and delayed food allergies have been described throughout the literature encompassing a variety of gastrointestinal, respiratory, and cutaneous pathologies. (2) The inflammatory response is the common theme to all allergic pictures and is characterized by the release of chemical mediators, vasodilation, increased vascular permeability, edema, and tissue damage.

The clinical relevance of IgG food allergy testing through ELISA (Enzyme-Linked Immunosorbent Assay).

From: Townsend Letter for Doctors and Patients, Date: 1/1/2004, Author: Suen, Raymond M.; Gordon, Shalima
Allergic reactions to foods may be classified as either IgE-mediated or nonIgE-mediated--the role of the former in food allergy being well-established. However, interestingly enough, the majority of food allergies are associated with specific nonIgE-mediated immune sensitivities. As such, appropriate tests must be utilized to identify possible causes, including food-antigen specific IgG antibodies. There are many testing methods available for the detection of food allergies including the skin prick test and RAST, or radioallergosorbent test. Unfortunately, both of these methods only look for allergen-specific IgE antibodies from the patient's serum. This poses considerable limitations in the clinical assessment of the chronically unwell patient.

IgG mediated food allergy as trigger of fibromyalgia complaints and the influence of an elimination diet.

Faculty of Ludwig Maximilian University of Munich, Mario Krause from Rotenburg a. d. Fulda 2005
The results show that nutritionally-specific IgG antibodies are involved in the emergence and/or the severity of a fibromyalgia. Alone the percentage of patients with increased IgG is about 20% higher than during a study conducted on a parallel basis with another collective. This is emphasized through the high percentage of patients who indicated an amelioration of their complaints through an elimination diet. For instance, the number of very painful pressure points was reduced from 72.1% to 33.8% after an 8-week dietary change. Other symptoms also improved to a similar extent under elimination of foodstuff with increased IgG levels. A large number of test persons even benefited with a not very consistent change. A significant weight loss was shown as a positive side effect. An elimination diet which rests on the avoidance of IgG-positive foodstuffs significantly reduces the complaints of fibromyalgia patients. A dietary change which avoids foodstuffs with increased IgG levels is successful in the treatment of fibromyalgia. It ameliorated all investigated complaints within 8 weeks by usually more than 50%. In particular, painful events – e.g. migraines, spasmodic abdominal pains, painful defecation, and hyperesthesias of the skin – are subjectively much improved. In the first two weeks it was especially difficult for the test persons to change their previous eating habits, particularly since “favorite dishes” were frequently affected. In the aggregate, two thirds of the patience assessed their consistency as good to very good. The retention of the new eating habits was much easier for the test persons with continuation of the study. A continual accompaniment of the patients and a good presentation of findings are important for the therapeutic success. Of the most overweight (41.2%) or obese (29.4%) patients, 86.8% lost an average of 4.7% of their body weight in the observed 8 weeks. An elimination diet which takes into consideration IgG-specific food allergies is successful in weight reduction. The study participants assessed the success of dietary change as good to very good and were mainly satisfied with the result.

Gastrointestinal Candida colonisation promotes sensitisation against food antigens by affecting the mucosal barrier in mice.

N Yamaguchi, R Sugita, A Miki, N Takemura, J Kawabata, J Watanabe, K Sonoyama
Gut2006;55:954-960. Doi: 10.1136/gut.2005.084954
Backgrounds and aims: Controversy still exists as to whether gastrointestinal colonisation by Candida
albicans contributes to aggravation of atopic dermatitis. We hypothesised that Candida colonisation
promotes food allergy, which is known to contribute to a pathogenic response in atopic dermatitis. We tested this using a recently established murine Candida colonisation model.
Methods: Candida colonisation in the gastrointestinal tract was established by intragastric inoculation with C albicans in mice fed a synthetic diet. To investigate sensitisation against food antigen, mice were
intragastrically administered with ovalbumin every other day for nine weeks, and antiovalbumin antibody
titres were measured weekly. To examine gastrointestinal permeation of food antigen, plasma
concentrations of ovalbumin were measured following intragastric administration of ovalbumin.
Results: Ovalbumin specific IgG and IgE titres were higher in BALB/c mice with Candida colonisation than in normal mice. Gastrointestinal permeation of ovalbumin was enhanced by colonisation in BALB/c mice.
Histological examination showed that colonisation promoted infiltration and degranulation of mast cells.
Candida colonisation did not enhance ovalbumin permeation in mast cell deficient W/Wv mice but did in
congenic littermate control +/+ mice. Reconstitution of mast cells in W/Wv mice by transplantation of bone
marrow derived mast cells restored the ability to increase ovalbumin permeation in response to Candida
colonisation.
Conclusions: These results suggest that gastrointestinal Candida colonisation promotes sensitisation
against food antigens, at least partly due to mast cell mediated hyperpermeability in the gastrointestinal
mucosa of mice.

Ovalbumin-specific immunoglobulin G and subclass responses through the first 5 years of life in relation to duration of egg sensitization and the development of asthma.

G.H.S Vance*, C.A. Thornton*, T.N.Brynat, J.A.Warner * and J.O.Warner*Child Health,Infection, Infammation & Repair Division and Information & Computing Division, University of Southhampton, UK
BACKGROUND: Egg sensitization, particularly persistent sensitization, is a risk factor for later asthma. However, little is known about accompanying IgG and subclass responses and how they might relate to asthmatic outcome. OBJECTIVE: To characterize hen's egg ovalbumin (OVA) IgG and subclass responses through the first 5 years of life in relation to duration of egg sensitization and later asthma. SUBJECTS and METHODS: The subjects (n=46) formed part of a larger cohort, born to atopic parents, who had been evaluated prospectively for the development of asthma. Egg sensitization was classified as transient (positive egg skin prick test at 1 year only) or persistent (positive skin test for at least 2 years). Plasma OVA IgG, IgG1 and IgG4 concentrations at birth (cord), 6 months, 1 and 5 years of age were measured by ELISA. RESULTS: The kinetics of OVA IgG and IgG1 responses, but not IgG4, differed between egg sensitized and non-egg sensitized (NES) children. Only persistently sensitized children had a rise in OVA IgG1 concentration through the first year of life, and at 1 year of age they had significantly higher OVA IgG and IgG1 than either transiently sensitized or NES children. High OVA IgG1 was associated with later asthma: at 1 year of age, OVA IgG1 greater than 14,500 U predicted asthma with a sensitivity 64% and specificity 74%. CONCLUSION: OVA IgG and subclass responses relate to the duration of egg sensitization. Measurement of OVA IgG1 concentration in infancy might offer a useful adjunct to identify those at an increased risk of asthma.

Food allergy mediated by IgG antibodies associated with migraine in adults

Carlos M. Arroyave Hernández,* Mauro Echevarría Pinto,** Hebert Luis Hernández Montiel*** Revista Alergia México 2007;54(5):162-8
Background: Migraine occurs with a high prevalence of 18 per cent. Management requires a tailored regimen of pharmacological and other measures based on individual clinical history. In some patients, allergen-specific IgG has been suspected to be involved in their mechanism, however, serological methods to investigate such possibility, are seldomly used.Objective: The aim of this study was to investigate allergen-specific IgG in serum of patients with migraine refractory to traditional treatment.Material and methods: Serum antibodies to specific 108 food allergens were measured by enzyme immunoassay from 56 patients with migraine and a control group without migraine.Results: In addition to statistical significant differences in the number of positives for IgG food allergens between patients with migraine and a controlled group, elimination diets successfully control the migraine without the need of medications.
Conclusion: According to the results obtained, serum IgG antibodies to common food should be investigated in patients with migraine.Key words: Food allergy, migraine, IgG antibodies. Correspondencia: Dr. Carlos M. Arroyave Hernández. Calle Hacienda Buenavista núm. 322-12, colonia Jardines de la Hacienda, CP 76180, Querétaro, Querétaro, México.Recibido: agosto, 2007. Aceptado: agosto, 2007.La versión completa de este artículo también está disponible en internet: www.revistasmedicasmexicanas.com.mx

Neurodermitis

Neue Möglichkeiten der differenzierten Ursachensuche für eine nachhaltige Therapie
Dr. rer. nat. Sabine Paul Comed 05/2007
Die Haut ist feuerrot, schuppt, juckt unerträglich, ist von Ausschlag und Ekzemen geschädigt.Nicht nur für Kinder, sondern auch für Erwachsene sind die regelmäßig auftretenden Schübe einer Neurodermitis zum „aus der Haut fahren“. Viele Patienten sind zusätzlich von Allergien und Asthma betroffen und leiden unter Ablehnung, Ausgrenzung und einem geringen Selbstwertgefühl auf Grund ihres Hautzustandes. Die Ursachen der Neurodermitis sind bis heute nicht vollständig geklärt. Daher ist die individuelle Ursachenforschung die größte Herausforderung neben dem Kampf gegen Juckreiz und Kratzzwang. Neuartige Ansätze bieten eine vereinfachte und zugleich differenzierte Ursachensuche bezüglich Nahrungsmittel-Allergien. In Kombination mit einer genauen Analyse des Zustandes des Gastrointestinaltrakts, des Vitamin- und Mineralstoffhaushalts sowie der Stärkung des Immunsystems entstehen daraus neue Optionen für eine ganzheitliche und damit nachhaltige Therapie

Nutrition in the Treatment of Attention-Deficit Hyperactivity Disorder:
A Neglected but Important Aspect

Roseanne Schnoll, Dmitry Burshteyn, und Juan Cea-Aravena In: The Lancet, March 9, 1985
Attention-deficit hyperactivity disorder (ADHD) is multidetermined and complex, requiring a multifaceted treatment approach. Nutritional management is one aspect that has been relatively neglected to date. Nutritional factors such as food additives, refined sugars, food sensitivities/allergies,and fatty acid deficiencies have all been linked to ADHD. There is increasing evidence that many children with behavioral problems are sensitive to one or more food components that can negatively impact their behavior. Individual response is an important factor for determining the proper approach in treating children with ADHD. In general, diet modification plays a major role in the management of ADHD and should be considered as part of the treatment protocol.

AD(H)S: Von Genen – und mehr Metabolischen und immunologischen Ursachen von AD(H)S auf der Spur mit neuer Labordiagnostik

Dr. rer. nat. Sabine Paul Co Med 02/2007
Ein typischer Fall: Die Mutter eines ADHS-Kindes ist verzweifelt: „Mein Sohn hatte Wutausbrüche
bis zur Ekstase. Aus der Schule kamen die Anrufe, dass wir sofort etwas unternehmen müssen. Nur mit Psychopharmaka konnte mein Kind am Schulunterricht teilnehmen, sie verhinderten, dass mein Sohn zum Außenseiter wurde. Durch die Medikamente wurde mein Kind richtig gut in der Schule und hatte endlich Erfolgserlebnisse. Zuhause aber hörte er auf zu lachen und hatte Todessehnsucht. Gibst du deinem Kind Psychopharmaka, bist du eine schlechte Mutter, gibst du deinem Kind keine, bist du auch eine schlechte Mutter.“

Metabolic Syndrome-A Comprehensive Perspective Based on Interactions Between Obesity,Diabetes, and Inflammation

1Paresh Dandona, MD, PhD; Ahmad Aljada, PhD; Ajay Chaudhuri, MD; Priya Mohanty, MD; Rajesh Garg, MD Contemporary Reviews in Cardiovascular Medicine DOI: 10.1161/01.CIR.0000158483.13093.9D The original description of the metabolic syndrome by Reaven1 consisted of obesity, insulin resistance, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia and dyslipidemia characterized by elevated triglyceride, and low HDL concentrations. All of the features described above are risk factors for atherosclerosis, and thus, metabolic syndrome constituted a significant risk for coronary heart disease2–5 (Table). The features of obesity/overweight and insulin resistance also provided a significant risk for developing type 2 diabetes.5,6 The risks for coronary heart disease and diabetes with metabolic syndrome are greater than those for simple obesity alone, and therefore, an understanding of the pathogenesis and through it, a rational approach to its therapy are of prime importance.

Is Obesity an Inflammatory disease?

Presented at the 64th Annual Meeting of the Society of University Surgeons, Houston, Texas, February 12-15, 2003.
Eduardo J.B. Ramos, MD, Yuan Xu, MD, Irina Romanova, PhD, Frank Middleton, PhD, Chung Chen, PhD, Robert Quinn, DVM, Akio Inui, MD, PhD, Undurti Das, MD, Michael M. Meguid, MD, PhD
Background. Most obese individuals have elevated concentrations of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), markers of inflammation closely associated with diabetes, hypertension, and stroke. Hypothesis. Obesity is a low-grade inflammatory disease, and Roux-en-Y gastric bypass (RYGB) reduces biochemical markers of inflammation and modifies gene expression in hypothalamic food intake/energy-related nuclei and subcutaneous abdominal fat (SAF). Methods. Obesity was induced in 24 3-week-old Sprague Dawley pups fed a high-energy diet (HED). Three groups (n = 8/group) were studied: RYGB, sham-operated pair-fed, and sham-operated ad libitum HED. Controls were nonobese rats fed chow (n = 6). Rats were killed 10 days after operation, and blood was collected to measure corticosterone and SAF and mesenteric fat to measure IL-6, TNF-α, and corticosterone. Total mRNA from arcuate nucleus and SAF purified for gene expression profiling. Data were analyzed with analysis of variance, Mann-Whitney test, and t test. Results. Before operation, the body weight of the obese groups was 493 ± 7 g and control = 394 ± 12g. The 10-day postoperative weight was RYGB = 417 ± 21 g, pair-fed = 436 ± 14 g, and ad libitum HED = 484 ± 15 g. Mesenteric and SAF weight decreased in RYGB. Mesenteric/SAF ratio of IL-6, TNF-α, corticosterone, and gene profiling showed decrease of inflammation after RYGB. Conclusion. Gastric bypass reduces biochemical markers of inflammation, suggesting that obesity is an inflammatory condition. (Surgery 2003;134:329-35.)

Increase in intranuclear nuclear factor _B and decrease in inhibitor_B in mononuclear cells after a mixed meal: evidence for a proinflammatory effect1–3

Ahmad Aljada, Priya Mohanty, Husam Ghanim, Toufic Abdo, Devjit Tripathy, Ajay Chaudhuri, and Paresh Dandona Am J Clin Nutr 2004;79:682–90. Printed in USA. © 2004 American Society for Clinical Nutrition
Background: In view of the stimulatory effect of glucose on reactiveoxygen species (ROS) generation, we investigated the possibility that a mixed meal stimulates ROS generation and possibly induces concomitant proinflammatory changes.
Objective: The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level.
Design: Nine normal-weight subjects were given a 900-kcal mixed meal, and 8 normal-weight subjects were given 300 mL water after an overnight fast. Blood samples were collected at 0, 1, 2, and 3 h. ROS generation by mononuclear cells and polymorphonuclear leukocytes and the expression of p47phox subunit were measured. Intranuclear nuclear factor _B (NF-_B) binding and the expression of inhibitor _B_ (I_B_), I_B kinase _ (IKK_), and I_B kinase _ (IKK_) were measured. Plasma concentrations of C-reactive protein (CRP) and soluble intercellular adhesion molecule were also measured.
Results: ROS generation by mononuclear cells and polymorphonuclear leukocytes and p47phox expression increased significantly. The expression of IKK_ and IKK_ and DNA-binding activity of NF-_Bincreased significantly, whereas I_B_ expression decreased. Plasma CRP concentrations increased. The intake of 300 mL water did not induce a change in any of the above indexes. Conclusions: These data show that the intake of a mixed meal results in significant inflammatory changes characterized by a decrease in I_B_ and an increase in NF-_B binding, plasma CRP, and the expression of IKK_ , IKK_ , and p47phox subunit. These proinflammatory changes are probably relevant to the state of chronic hypertension and
obesity and to its association with atherosclerosis. Am J Clin Nutr

Diet restriction in migraine, based on IgG against foods: A clinical double-blind, randomised, cross-over trial

Kadriye Alpay1, Mustafa Ertas¸1, Elif Kocasoy Orhan1, Didem Kanca U ¨ stay2, Camille Lieners3 and Betu¨ l Baykan Cephalalgia 0(00) 1–9 International Headache Society 2010 Reprints and permissions:sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102410361404
cep.sagepub.com
Introduction: It is well-known that specific foods trigger migraine attacks in some patients. We aimed to investigate the effect of diet restriction, based on IgG antibodies against food antigens on the course of migraine attacks in this randomised, double blind, cross-over, headache-diary based trial on 30 patients diagnosed with migraine without aura.
Methods: Following a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA. Then, the patients were randomised to a 6-week diet either excluding or including specific foods with raised IgG antibodies, individually. Following a 2-week diet-free interval after the first diet period, the same patients were given the opposite 6-week diet (provocation diet following elimination diet or vice versa). Patients and their physicians were blinded to IgG test results and the type of diet (provocation or elimination). Primary parameters were number of headache days and migraine attack count. Of 30 patients, 28 were female and 2 were male, aged 19–52 years (mean, 35_10 years).
Results: The average count of reactions with abnormally high titre was 24_11 against 266 foods. Compared to baseline, there was a statistically significant reduction in the number of headache days (from 10.5_4.4 to 7.5_3.7; P<0.001) and number of migraine attacks (from 9.0_4.4 to 6.2_3.8; P<0.001) in the elimination diet period.
Conclusion: This is the first randomised, cross-over study in migraineurs, showing that diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks.

The Role of Hidden Food Allergy/Intolerance in Chronic Disease

by Alan R. Gaby, M.D. Alt Med Rev 1998;3(2):90-100)
A large body of medical literature has indicated that hidden food allergy is a frequent cause of a wide range of physical and mental conditions. Hidden allergies can be “unmasked” by means of an elimination diet, followed by individual food challenges.
Although the concept of hidden food allergy remains controversial, the evidence strongly suggests that identification and avoidance of allergenic foods can relieve a number of common and difficult-to-treat medical problems.
(Alt Med Rev 1998;3(2):90-100)

Clinical Relevance of IgG Antibodies against Food Antigens in Crohn’s Disease: A Double-Blind Cross-Over Diet Intervention Study

S. Bentz a M. Hausmann a H. Piberger d S. Kellermeier a S. Paul c L. Held b W. Falk d F. Obermeier d M. Fried a J. Schölmerich d G. Rogler a Division of Gastroenterology and Hepatology, University Hospital Zurich, and b University of Zurich,Institute of Social and Preventive Medicine, Biostatistics Unit, Zurich , Switzerland; c Evomed MedizinServiceGmbH, Darmstadt , and d Department of Internal Medicine I, University of Regensburg, Regensburg , Germany Digestion http://dx.doi.org/10.11592F000264649
Background: Environmental factors are thought to play an important role in the development of Crohn’s disease (CD).Immune responses against auto-antigens or food antigens may be a reason for the perpetuation of inflammation. Methods: In a pilot study, 79 CD patients and 20 healthy controls were examined for food immunoglobulin G (IgG). Thereafter, the clinical relevance of these food IgG antibodies was assessed in a double-blind cross-over study with 40 patients. Based on the IgG antibodies, a nutritional intervention was planned. The interferon (IFN) _ secretion of T cells was measured. Eosinophil-derived neurotoxin was quantified in stool. Results: The pilot study resulted in a significant difference of IgG antibodies in serum between CD patients and healthy controls. In 84 and 83% of the patients, respectively, IgG antibodies against processed cheese and yeast were detected. The daily stool frequency significantly decreased by 11% during a specific diet compared with a sham diet. Abdominal pain reduced and general well-being improved.IFN _ secretion of T cells increased. No difference for eosinophil-derived neurotoxin in stool was detected.
Conclusion: A nutritional intervention based on circulating IgG antibodies against food antigens showed effects with respect to stool frequency. The mechanisms by which IgG antibodies might contribute to disease activity remain to be elucidated. Copyright © 2010 S. Karger AG, Basel

Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics

Jeanne Drisko, MD, CNS, Bette Bischoff, MD, RD, Matthew Hall, PhD, Richard McCallum, MD
Program in Integrative Medicine (J.D.), School of Medicine (B.B.), Preventive Medicine and Public Health (M.H.),Gastrointerology and Hepatology (R.M.), University of Kansas Medical Center, Kansas City, KS Journal of the American College of Nutrition, Vol. 25, No. 6, 514–522 (2006)
Objective: In Irritable Bowel Syndrome, the gut-associated immune system may be up-regulated resulting in immune complex production, low-grade inflammation, loss of Class I bacteria, and translocation of inflammatory mediators and macromolecules outside of the GI lumen. Since food intolerance may be one of the reasons for this upregulation, our goal was to investigate the role of food intolerance in IBS patients. Methods: In this open label pilot study, we enrolled 20 patients with IBS by Rome II criteria (15 women, ages 24–81) who had failed standard medical therapies in a tertiary care GI clinic. Baseline serum IgE and IgG food and mold panels, and comprehensive stool analysis (CSA) were performed. Breath-hydrogen testing and IBS Quality-of-Life (QOL) questionnaires were obtained. Patients underwent food elimination diets based on the results of food and mold panels followed by controlled food challenge. Probiotics were also introduced. Repeat testing was performed at 6-months. We followed up with this cohort at 1 year after trial completion to assess the reported intervention and for placebo effect.
Results: Baseline abnormalities were identified on serum IgG food and mold panels in 100% of the study subjects with significant improvement after food elimination and rotation diet (p _ 0.05). Significant improvements were seen in stool frequency (p _ 0.05), pain (p _ 0.05), and IBS-QOL scores (p _ 0.0001). Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by CSA. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora. The 1-year follow up demonstrated significant continued adherence to the food rotation diet (4.00 _ 1.45), minimal symptomatic problems with IBS (4.00 _ 1.17), and perception of control over IBS (4.15 _ 1.23). The continued use of probiotics was considered less helpful (3.40 _ 1.60).
Conclusion: These data demonstrate that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical response and impacts on overall well being and quality of life in this challenging entity.

IgG-Mediated Food Intolerance in Irritable Bowel Syndrome: A Real Phenomenon or an Epiphenomenom?

Fergus Shanahan, M.D.1 and Peter J. Whorwell, M.D.2
1Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, and 2Department ofMedicine, Education & Research Centre, Wythenshawe Hospital, Manchester, UK
Am J Gastroenterol 2005;100:1558–1559
Abnormal reactions to food probably contribute to the complex pathophysiology of irritable bowel syndrome, but the mechanisms involved remain unclear. Following the recent identification of subtle mucosal inflammation in at least some patients with the disorder, perhaps now is the time to revisit some of the immunological reactions to dietary antigens that, in the past, have been dismissed as irrelevant.

IgG-mediated allergy: A new mechanism for Migraine attacks?

Julio Pascual and Agustı´n Oterino. Cephalalgia 0(00) 1–3! International Headache Society 2010 Reprints and permissions:sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102410364856
Despite recent advances offered by modern neuroimaging and genetic techniques, the pathophysiology of migraine has not been fully clarified. As pointed out by Selby and Lance 50 years ago, a relevant proportion of patients report that their migraine attacks are usually precipitated by dietary items (1). In a survey analysing the prevalence of dietary migraine in 500 new migraine patients, Peatfield et al. found in 1984 that 19.2% of migraine patients reported sensitivity to cheese, 18.2% to chocolate ad 11.1% to citrus fruit (2). The same year, Monro et al. published a paper in the Lancet with the categorical title ’Migraine Is a Food-Allergic Disease’, describing the treatment of just nine patients with severe refractory migraine with either sodium cromoglycate or placebo after the patients ate foods previously identified as provocants (3).

Autism, An Extreme Challenge to Integrate Medicine. Part II: Medical Management

Parris M. Kidd, PhD Altern Med Rev 2002;7(6):472-499)
Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, andeclectic treatment strategies have drivenprogress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and
other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/ DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) andmagnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies
(pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, indepth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management. (Altern Med Rev 2002;7(6):472-499)

Autism and Schizophrenia: Intestinal Disorders

Robert Cadea; Malcolm Privettea; Melvin Freglya; Neil Rowlanda; Zhongjie Suna; Virginia Zelea; Herbert Wagemakera; Charlotte Edelsteina a Department of Medicine, Physiology, Psychology and Psychiatry, University of Florida, Gainesville, FL, USA Nutritional Neuroscience, Volume 3, Issue 1 February 2000 , pages 57 - 72
We examined Dohan’s hypothesis that schizophrenia is associated with the absorption of uexorphins” contained in gluten and casein. In addition, because of the work of Reichelt et al. (Reichelt, K.L., Saelid, G.,Lindback, J. and Orbeck, H. (1986) Biological Psychiaty21:1279-1290) and Rodriguezetal. (Rodriguez,Trav, A.L., Barreiro Marin, P., Galvez, Borrero, I.M., del Olmo Romero-Nieva, F. and Diaz Alvarez, A. (1994) Journal of Nervous and Mental Disease Aug; 182(8): 478-479), we carried out similar studies on a group of children with autism. In both syndromes we found similar patterns of peptide containing peaks (Ninhydrin positive) after molecular screening with Sephadex G-15.Immunoglobulin assay of IgA and IgG against gliadin and casein in serum was done. High titer IgG antibodies to gliadin were found in 87% of autistic and 86% of schizophrenic patients and high titer IgG antibodies to bovine casein were found in 90% of autistic and in 93% of schizophrenic patients. High titer IgA antibodies to gluten or casein were found in 30% of children with autism while in schizophrenic patients 86% had elevated IgA antibodies to gluten and 67% to casein; some normal children and adults have these antibodies but only in trace amounts.When schizophrenic patients were treated with dialysis or a gluten-casein free diet, or both (Cade, R.,Wagemaker, H., Privette, R.M., Fregly, M., Rogers, J. and Orlando, J. (1990) Psychiatry:A World Prespective1: 494-500) peptiduria and Brief Psychiatric Rating Scores fell while abnormal behavior diminished. A gluten-casein free diet was accompanied by improvement in 81% of autistic children within 3 months in most of the behavior categories. Our data provide support for the proposal that many patients with schizophrenia or autism suffer due to absorption of exorphins formed in the intestine from incomplete digestion of gluten and casein.

Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin-specific immunoglobulin responses are ubiquitous, but peanut-specific immunoglobulin responses are up-regulated in peanut allergy

Tay SS, Clark AT, Deighton J, King Y, Ewan PW. Clin Exp Allergy 2007 Oct;37(10):1512-8.
Department of Medicine, Cambridge University, Cambridge, UK. szunszuntay@hotmail.com
BACKGROUND: The clinical significance of food-specific IgG subclasses in food allergy and tolerance remains unclear. Specific IgG titres are often reported in non-standardized units, which do not allow comparisons between studies or allergens. OBJECTIVE: To quantify, in absolute units, ovalbumin (OVA)- and peanut-specific IgG levels in children with peanut or egg allergy (active or resolved) and in non-allergic controls. Methods Children aged 1-15 years were recruited. Peanut allergy was diagnosed by convincing history and a 95% predictive level of specific IgE; egg allergy or resolution was confirmed by oral challenge. Serum IgG, IgG1 and IgG4 levels (microg/mL) to OVA and peanut extract were quantified by ELISA. RESULTS: OVA- and peanut-specific IgG was detected in all subjects. In non-allergic controls (n=18), OVA-specific IgG levels were significantly higher than peanut-specific IgG (median microg/mL IgG=15.9 vs. 2.2, IgG1=1.3 vs. 0.6, IgG4=7.9 vs. 0.7; P<0.01). There were no differences in OVA-specific IgG, IgG1 and IgG4 between egg-allergic (n=40), egg-resolved (n=22) and control (n=18) subjects. In contrast, peanut-specific IgG (median microg/mL IgG=17.0, IgG1=3.3, IgG4=5.2) were significantly higher in peanut-allergic subjects (n=59) compared with controls and with non-peanut-sensitized but egg-allergic subjects (n=26). Overall, the range of IgG4 was greater than IgG1, and IgG4 was the dominant subclass in >60% of all subjects. CONCLUSION: OVA-specific IgG levels of egg-allergic, egg-resolved or control groups are not distinguishable. Higher peanut-specific IgG levels are associated with clinical allergy, but the range of IgG titres of the allergic and control groups overlapped. Hence, OVA and peanut-specific IgG measurements do not appear to be of diagnostic value. Strong IgG responses to OVA may be a normal physiological response to a protein frequently ingested from infancy, whereas up-regulated IgG responses in peanut allergy may be indicative of a dysregulated immune response to peanut allergens.

Humoral immunity to cow's milk proteins and gliadin within the etiology of recurrent aphthous ulcers?

Besu I, Jankovic L, Magdu IU, Konic-Ristic A, Raskovic S, Juranic Z. Oral Dis 2009 Nov;15(8):560-4. Epub 2009 Jun 29.Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia. irina.besu@ncrc.ac.yu
OBJECTIVES: The goal of this study was to determine the incidence of serum antibodies to gliadin and to cow's milk proteins (CMP) using ELISA test, within patients who have recurrent aphthous ulcers (RAU). SUBJECTS AND METHODS: Fifty patients with recurrent aphthous ulcers and fifty healthy people were included in this research. Levels of serum IgA and IgG antibodies to gliadin and IgA, IgG and IgE to CMP were determined using ELISA. RESULTS: The levels of serum antigliadin IgA and IgG antibodies were not significantly higher in patients with RAU in comparison with the controls (P = 0.937 and P = 0.1854 respectively). The levels of serum anti-CMP IgA, IgG and IgE antibodies were significantly higher in patients with RAU in comparison with the controls (P < 0.005, P < 0.002 and P < 0.001 respectively). In general, the increased humoral (IgA or IgG) immunoreactivity to CMP was found in 32 of 50 patients, while 17 of them showed the increased levels of both IgA and IgG immunoreactivity to CMP. At the same time, 16 out of 50 patients had IgA, IgG and IgE immunoreactivity to CMP. CONCLUSION: These results indicate the strong association between high levels of serum anti-CMP IgA, IgG and IgE antibodies and clinical manifestations of recurrent aphthous ulcers.

Serum IgG responses to food antigens in the italian population evaluated by highly sensitive and specific ELISA test.

Volpi N, Maccari F. J Immunoassay Immunichem 2009;30(1):51-69.Department of Biologia Animale, Biological Chemistry Section, University of Modena and Reggio Emilia, Modena, Italy. volp@unimo.it
Using an optimized and validated ELISA method, we performed a serum test for assaying the binding capacity of serum IgG to proteins extracted from approx. 160 different foods to investigate the reactivity of specific IgG antibodies in the Italian population composed of 6,879 subjects (4,551 females and 2,328 males). 44 antigens showed an IgG response greater than 10% and only 14 aliments had an elevated reactivity greater than 20%, in particular, milk, from cow and goat, and several milk derivatives, along with egg albumen and yeasts. The IgG response to the high reactive food antigens depending on the age of the 6880 subjects was also analyzed. We demonstrated a high IgG response in a very large subject group to milk and milk derivatives, and egg albumin antigens, and we conclude that the validated ELISA test may be applied for the serum/plasma IgG antibody level determination as a useful indicator of adverse reactions to food and food hypersensitivity.

Milk protein IgG and IgA: the association with milk-induced gastrointestinal symptoms in adults.

Anthoni S, Savilahti E, Rautelin H, Kolho KL. World J Gatroenterology 2009 Oct 21;15(39):4915-8. Hospital for Children and Adolescents, University of Helsinki, PO Box 281, FIN-00029 HYKS, Helsinki, Finland.
AIM: To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults. METHODS: Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland. Subjects were randomly selected from a total of 1900 adults undergoing laboratory investigations in primary care. All 400 participants had completed a questionnaire on abdominal symptoms and dairy consumption while waiting for the laboratory visit. The questionnaire covered the nature and frequency of gastrointestinal problems, the provoking food items, family history and allergies. Twelve serum samples were disqualified due to insufficient amount of sera. The levels of specific milk protein IgG and IgA were measured by using the ELISA technique. The association of the milk protein-specific antibody level was studied in relation to the milk-related gastrointestinal symptoms and dairy consumption. RESULTS: Subjects drinking milk (n = 265) had higher levels of milk protein IgG in their sera than non-milk drinkers (n = 123, P < 0.001). Subjects with gastrointestinal problems related to milk drinking (n = 119) consumed less milk but had higher milk protein IgG levels than those with no milk-related gastrointestinal symptoms (n = 198, P = 0.02). Among the symptomatic subjects, those reporting dyspeptic symptoms had lower milk protein IgG levels than non-dyspeptics (P < 0.05). However, dyspepsia was not associated with milk drinking (P = 0.5). The association of high milk protein IgG levels with constipation was close to the level of statistical significance. Diarrhea had no association with milk protein IgG level (P = 0.5). With regard to minor symptoms, flatulence and bloating (P = 0.8), were not associated with milk protein IgG level. Milk protein IgA levels did not show any association with milk drinking or abdominal symptoms. The levels of milk protein IgA and IgG declined as the age of the subjects increased (P < 0.004). CONCLUSION: Milk protein IgG but not milk IgA seems to be associated with self-reported milk-induced gastrointestinal symptoms.

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens.

Vojdani A.Nutra Metab London 2009 May 12;6:22 822 S, Robertson Blvd, Ste, 812, Los Angeles, CA 90035, USA. drari@msn.com.
ABSTRACT: BACKGROUND: Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. METHODS: We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. RESULTS: Compared to raw food antigens, IgE antibodies showed a 3-8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. CONCLUSION: We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity.

Testing for food reactions: the good, the bad, and the ugly.

Mullin GE, Swift KM, Lipski L, Turnbull LK, Rampertab SD. Nutr Clin Pract 2010 Apr;25(2):192-8. Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. gmullin1@jhmi.edu
An increasing number of commercial tests for food allergies are marketed to consumers and healthcare practitioners with tenuous claims. The aim of this article is to provide an evidence-based review of the tests and procedures that currently are used for patients with suspected food allergy. A systematic review of the literature evaluating the validity of tests and procedures used in food reactions was performed using conventional search engines (eg, PubMed, Ovid) as well as consumer sites (eg, Google, Bing). The National Library of Medicine Medical Subject Headings (MeSH) term food hypersensitivity was used along with food allergy testing, food sensitivity testing, food intolerance testing, and adverse food reactions. Of the results obtained, testing for immunoglobulin E (IgE)-mediated food allergy was best represented in PubMed. IgE-based testing continues to be the gold standard for suspected food allergies. Among modalities used by many conventional and alternative practitioners, immunoglobulin G (IgG)-based testing showed promise, with clinically meaningful results. It has been proven useful as a guide for elimination diets, with clinical impact for a variety of diseases. Mediator release testing and antigen leukocyte cellular antibody testing were only represented on consumer sites. Further investigation into the validity and the clinical application of these tests and procedures is required. Disclosing the basis for food reactions continues to present a diagnostic challenge, and testing for food allergies in the context of an appropriate clinical history is paramount to making the correct diagnosis.

Physiological and pathophysiological functions of intestinal mast cells.

Bischoff SC. Semin Immunopathol 2009 Jul;31(2):185-205. Epub 2009 Jun 17. Department of Nutritional Medicine & Immunology, University of Hohenheim, Stuttgart, Germany. bischoff.stephan@uni-hohenheim.de
The normal gastrointestinal (GI) mucosa is equipped with mast cells that account for 2-3% of lamina propria cells under normal conditions. Mast cells are generally associated with allergic disease, and indeed, food allergy that manifests in the GI tract is usually mast cell dependent. On the other hand, mast cells have a number of physiological functions in the GI tract, namely regulatory functions such as control of blood flow and coagulation, smooth muscle contraction and peristalsis, and secretion of acid, electrolytes, and mucus by epithelial cells. One of the most intriguing functions of intestinal mast cells is their role in host defense against microbes like bacteria, viruses, or parasites. Mast cells recognize microbes by antibody-dependent mechanisms and through pattern-recognition receptors. They direct the subsequent immune response by attracting both granulocytes and lymphocytes to the site of challenge via paracrine cytokine release. Moreover, mast cells initiate, by releasing proinflammatory mediators, innate defense mechanisms such as enhanced epithelial secretion, peristalsis, and alarm programs of the enteric nervous This initiation can occur in response to a primary contact to the microbe or other danger signals, but becomes much more effective if the triggering antigen reappears and antibodies of the IgE or IgG type have been generated in the meantime by the specific immune system. Thus, mast cells operate at the interface between innate and adaptive immune responses to enhance the defense against pathogens and, most likely, the commensal flora. In this respect, it is important to note that mast cells are directly involved in controlling the function of the intestinal barrier that turned out to be a crucial site for the development of infectious and immune-mediated diseases. Hence, intestinal mast cells perform regulatory functions to maintain tissue homeostasis, they are involved in host defense mechanisms against pathogens, and they can induce allergy once they are sensitized against foreign antigens. The broad spectrum of functions makes mast cells a fascinating target for future pharmacological or nutritional interventions.

Food allergy mediated by IgG antibodies associated with migraine in adults.

Arroyave Hernández CM, Echavarría Pinto M, Hernández Montiel HL.Centro de Inmunología y Alergias, Querétaro, Querétaro, México. Rev Alerg Mex. 2010 Mar-Apr;57(2):49. Echevarría Pinto, Mauro [corrected to Echavarría Pinto, Mauro].

BACKGROUND: Migraine occurs with a high prevalence of 18 per cent. Management requires a tailored regimen of pharmacological and other measures based on individual clinical history. In some patients, allergen-specific IgG has been suspected to be involved in their mechanism, however, serological methods to investigate such possibility, are seldomly used.
OBJECTIVE: The aim of this study was to investigate allergen-specific IgG in serum of patients with migraine refractory to traditional treatment.
MATERIAL AND METHODS: Serum antibodies to specific 108 food allergens were measured by enzyme immunoassay from 56 patients with migraine and a control group without migraine.
RESULTS: In addition to statistical significant differences in the number of positives for IgG food allergens between patients with migraine and a controlled group, elimination diets successfully control the migraine without the need of medications.
CONCLUSION: According to the results obtained, serum IgG antibodies to common food should be investigated in patients with migraine.