Professional Research

Oral Tolerance and its Relation to Food Hypersensitivities

J Allergy Clin Immunol, Jan 2005: 3-12 - Mirna Chehade, MD and Lloyd Mayer, MD

The Gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens. Once proteins contact the intestinal surface, they are sampled by different cells and depending on their characteristics, result in different responses. Antigens might be taken up by the Microfold cells overlying Peyer’s patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related and other are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerances and cite data related to food hypersensitivity wherever evidence is available.


Immune Activation in Patients with Irritable Bowel Syndrome

Gastroenterology, 2007 Mar;132(3):913-20. Liebregts T, Adam B, Bredack C, Roth A,et al.

Researchers test the hypothesis that irritable bowel syndrome is characterized by a cellular immune response with the production of proinflammtory cytokines and also explore psychiatric symptoms associated with IBS. IBS-D patients who had greater than 3 bowel movements per day with watery stools, pain and cramping showed significantly higher cytokine levels in all categories, with accompanying anxiety.

***Cytokine activation is indicative of an immune response:


Migraine and Food

Prog Med 1989 Feb;80(2):53-5. Pacor ML, Nicolis F, Cortina P, Peroli P, Venturini G, Andri L, Corrocher R, Lunardi C.

Migraine was present in 41 out of 300 patients (13.6%). 38 of these 41 subjects had been treated with elimination diets; 25 (65.7%) obtained a significant improvement of migraine on subsequently performed challenge test. 24 patients were affected by food intolerance and only one by food allergy. The remaining 13 non-responder subjects suffering from migraine had been subsequently submitted to pharmacological treatment.


T Cells Expressing IL-2 receptors in Migraine

Acta Neurol (Napoli) 1991 Oct;13(5):448-56. Mertelletti, P

A group of migraine patients were studied for circulating immune complexes, lymphocyte subpopulations, IgG4 and anti-IgG antibodies, before, after 4 hours and after 72 hours a specific challenge test. 

There was an increased incidence of circulating immune complexes. Total T cells showed a marked increase after challenge test. The most important finding was the presence of T-activated cells. Also K and NK cells showed an early increase after the challenge. 

In commenting on the outcomes of this investigation, it must be stressed that the evidence of an early lymphocyte activation after the challenge test indicates an involvement of interleukin-2 related receptor in food-induced migraine. 

The results have reinforced the idea of immune mechanism involvement in food-induced migraine, but it seems to be a different mechanism from that previously hypothesized, with the involvement of the “complex cytokines."


The Diet Factor in Pediatric and Adolescent Migraine

Millichap JG, Yee MM. Pediatr Neurol 2003 Jan;28(1):9:15

Division of Neurology; Children's Memorial Hospital; and Northwestern University Medical School;, Chicago, Illinois, USA

Diet can play an important role in the precipitation of headaches in children and adolescents with migraine. The diet factor in pediatric migraine is frequently neglected in favor of preventive drug therapy. The list of foods, beverages, and additives that trigger migraine includes cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine withdrawal, and alcoholic drinks, especially red wine and beer. Underage drinking is a significant potential cause of recurrent headache in today's adolescent patients. Tyramine, phenylethylamine, histamine, nitrites, and sulfites are involved in the mechanism of food intolerance headache. Immunoglobulin E-mediated food allergy is an infrequent cause. Dietary triggers affect phases of the migraine process by influencing release of serotonin and norepinephrine, causing vasoconstriction or vasodilatation, or by direct stimulation of trigeminal ganglia, brainstem, and cortical neuronal pathways. Treatment begins with a headache and diet diary and the selective avoidance of foods presumed to trigger attacks. A universal migraine diet with simultaneous elimination of all potential food triggers is generally not advised in practice. A well-balanced diet is encouraged, with avoidance of fasting or skipped meals. Long-term prophylactic drug therapy is appropriate only after exclusion of headache-precipitating trigger factors, including dietary factors.


A Gut Check For Many Ailments

"The gut is important in medical research, not just for problems pertaining to the digestive system but also problems pertaining to the rest of the body," says Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine.

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Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial

Charly Gaul1,2*, Hans-Christoph Diener2, Ulrich Danesch3 and on behalf of the Migravent® Study Group

Background: Non-medical, non-pharmacological and pharmacological treatments are recommended for the prevention of migraine. The purpose of this randomized double-blind placebo controlled, multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium, riboflavin and Q10 as prophylactic treatment for migraine.
Methods: 130 adult migraineurs (age 18 – 65 years) with ≥ three migraine attacks per month were randomized into two treatment groups: dietary supplementation or placebo in a double-blind fashion. The treatment period was 3 months following a 4 week baseline period without prophylactic treatment. Patients were assessed before randomization and at the end of the 3-month-treatment-phase for days with migraine, migraine pain, burden of disease (HIT-6) and subjective evaluation of efficacy.
Results: Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group (p = 0.23 compared to placebo). The intensity of migraine pain was significantly reduced in the supplement group compared to placebo (p = 0.03). The sum score of the HIT-6 questionnaire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group (p = 0.01). The evaluation of efficacy by the patient was better in the supplementation group compared to placebo (p = 0.01).
Conclusions: Treatment with a proprietary supplement containing magnesium, riboflavin and Q10 (Migravent® in Germany, Dolovent® in USA) had an impact on migraine frequency which showed a trend towards statistical significance. Migraine symptoms and burden of disease, however, were statistically significantly reduced compared to placebo in patients with migraine attacks.

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The Patented Mediator Release Test (MRT): A Comprehensive Blood Test for Inflammation Caused by Food and Food-Chemical Sensitivities

Mark J. Pasula, PhD

There are a wide range of chronic inflammatory conditions wherein food and food-chemical sensitivities play either a primary or secondary role in generating inflammation and symptoms (Table 1). Fully addressing food sensitivities can have a major impact on the speed and completeness of clinical outcomes. It can also improve the effectiveness of other therapies, as a chronic source of inflammation has been eliminated.

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