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Links to Research Abstracts for Further Study

These research abstracts and quotes from college level books enable you to examine our approach to therapy, and for the erudite, give a starting point to explore newer research.


IBS Research

Gastroenterology. 2007 Mar;132(3):913-20.  

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: It's not all in your head!

Gut 1996 Jul; 39(1) 130-5

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms. In this study, they took patients who exhibited gastrointestinal symptoms in response to foods and did blinded challenge of thes patients along with skin prick testin and RAST testing, classic measures of IgE sensitivities and for the control and atopic group there was no evidence that IgE or classic allergies were involved, suggesting other immune mechanisms were at play.

*But, The immune reaction is not your classic IgE or Allergic Reaction

Am J Gastroenterol. 2005 Jul;100(7):1558-9

IgG-mediated food intolerance in irritable bowel syndrome: a real phenomenon or an epiphenomenom?

 Shows mediocre results emerging from disease management that relies on the old method of IgG testing to detect sensitivities but hints that foods do play a role)  Right idea, wrong, testing.

Dis Manag Advis.2004 Jan;10(1):6-10, 1. Links

Alternative approach to IBS and migraine is winning over providers.  (a description of the LEAP Program's successes in pinpointing triggers for IBS, migraine and even the more delayed and enigmatic fibromyalgia)


Fibromyalgia Research

Dig Dis Sci. 2006 Mar;51(3):454-60.

Prevalence of irritable bowel syndrome and depression in fibromyalgia. Department of Gastroenterology, Naval Medical Center San Diego, San Diego, California, USA.

This study found that for fibromyalgia patients, the incidence of IBS was 81% and the incidence of rheumatoid symptoms was using the Rome II criteria.  The prevalence of IBS in controls was only 15%, showing a tendency for both conditions to be present together.

Am J Gastroenterol 2000 Jan;95(1):157-65

Risk factors for irritable bowel syndrome: role of analgesics and food sensitivities. Locke GR 3rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ 


Migraine Research

Recenti Prog Med 1989 Feb;80(2):53-5

Migraine was present in 41 out of 300 patients (13.6%). 38 of these 41 subjects have been treated with elimination diet; 25 (65.7%) obtained a significant improvement of migraine and 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 have been subsequently submitted to pharmacological treatment.

*2/3 migraine patients responded to an elimination diet, 96% had "food intolerance" not food allergy non-IgE in other words, but still an immune reaction

Acta Neurol (Napoli) 1991 Oct;13(5):448-56 Martelletti P. Centro Cefalee, Universita La Sapienza, Roma, Italia.

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

We found 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” network.

* Note food-induced T cells Expressing IL-2 Receptor in Migraine.  So, it's not merely a vague intolerance but an immune activation involving proliferation of T-Cells)

Evidence For an Immune-Mediated Mechanism in Food-Induced Migraine from a Study on Activated T-cells, IgG4 subclass, anti-IgG Antibodies and Circulating Immune Complexes.   Martelletti P, Sutherland J, Anastasi E, Di Mario U, Giacovazzo M.

Various immunological studies have revealed controversial outcomes on pathogenic mechanisms of food-induced migraine. In order to better define the immune status of this disease we studied 21 patients (cow milk provoked migraines) for circulating immune complexes (CIC). Six out of them were also studied for lymphocyte subpopulations, IgG4 and anti-IgG antibodies, before  oral challenge (TO), 4 hours after oral challenge (T4), and 72 hours after oral challenge (T72) with 250 ml of cow milk. The ClqSp assay was used to determine CIC. Lymphocyte subpopulations were defined by the following monoclonal antibodies (Mab): OKT3, OKT4, OKT8, 4F2, H366, TAC, 5E9, L.243 and DA6.231. IgG4 subclass was assessed by using a mouse specific Mab. Anti-IgG antibodies were determined by using HPLC. 

No significant variation was observed in the study of the expression of DR antigens (L.243 and DA6.231) at the three times. IgG4 and anti-IgG antibodies values showed no variation in their time-course.

However, the results showed an increased incidence (3x) of CIC (28.6%) when compared to the control group (10%). Total T-cells (OKT3+) showed a marked increase at T4 (p less than 0.01) and a subsequent decrease at T72 (p less than 0.02). Interestingly, T-activated cells (4F2+ and TAC+) showed a parallel trend at T4 (respectively p less than 0.02 and less than 0.01) and a subsequent decrease at T72 only for the Tac+ cells (p less than 0.05). Also K and NK cells (H366+) showed an early increase at T4 (p less than 0.05). 

All of which suggest an aberrant cell-mediated immune response to the food antigen challenge. 

*In this study, there is the search to find whether the cause of the "food intolerance" is IgG activation, but researchers consclude it's most likely a T-cell mediated, delayed-type hypersensitivity reaction or Type 4 reaction is concluded to be the cause.


Reflux Research

DALLAS - Nov. 19, 2009 2010 Digestive Disease Week, held in New Orleans, USA Donald O. Castell, MD, Director, Esophageal Disorders Program, Medical University of South Carolina, Charleston

State of the Art Lecture on improving treatment outcomes in GERD patients. He provided insight about why current therapies do not always achieve durable symptom relief. In particular, he suggested that the long-term focus on acid control has been a successful strategy for healing of lesions caused by GERD but it may not be always be sufficient for control of symptoms and that, after the initial great response of 90% initial remission, only 36% maintain remission on proton pump inhibitor therapy.

UT Southwestern Medical

DALLAS - Nov. 19, 2009 - Contrary to current thinking, a condition called gastroesophageal reflux disease (GERD) might not develop as a direct result of acidic digestive juices burning the esophagus, UT Southwestern Medical Center researchers have found in an animal study.
UT Southwestern researchers report that rather, gastroesophageal reflux spurs the esophageal cells to release chemicals called cytokines, which attract inflammatory cells to the esophagus. It is those inflammatory cells, drawn to the esophagus by cytokines, that cause the esophageal damage that is characteristic of GERD. The condition is manifested by symptoms such as heartburn and chest pain. 


Epilepsy and Autism

Oligoantigenic diet treatment of children with epilepsy and migraine.J Pediatr. 1989 Jan;114(1):51-8.

Egger J, Carter CM, Soothill JF, Wilson J.  Department of Neurology, Hospital for Sick Children, London.
We studied the role of oligoantigenic diets in 63 children with epilepsy; 45 children had epilepsy with migraine,hyperkinetic behavior, or both, and 18 had epilepsy alone.  Of the 45 children who had epilepsy with recurrent headaches, abdominal symptoms, or hyperkinetic behavior, 25 ceased to have seizures and 11 had fewer seizures during diet therapy.

Minerva Pediatr. 1999 May;51(5):153-7 Partial cryptogenetic epilepsy and food allergy/intolerance. A causal or a chance relationship? Reflections on three clinical cases. Pelliccia A, Lucarelli S, Frediani T, D'Ambrini G, Cerminara C, Barbato M, Vagnucci B, Cardi E.

Oligoantigenic diet treatment of children with epilepsy and migraine.

J Pediatr. 1989 Jan;114(1):51-8.

Egger J, Carter CM, Soothill JF, Wilson J.
Department of Neurology, Hospital for Sick Children, London.

We studied the role of oligoantigenic diets in 63 children with epilepsy; 45 children had epilepsy with migraine,hyperkinetic behavior, or both, and 18 had epilepsy alone.  Of the 45 children who had epilepsy with recurrent headaches, abdominal symptoms, or hyperkinetic behavior, 25 ceased to have seizures and 11 had fewer seizures during diet therapy.

Minerva Pediatr. 1999 May;51(5):153-7

Partial cryptogenetic epilepsy and food allergy/intolerance. A causal or a chance relationship? Reflections on three clinical cases.

Pelliccia A, Lucarelli S, Frediani T, D'Ambrini G, Cerminara C, Barbato M, Vagnucci B, Cardi E.

Neurological and Psychiatric Sciences Department, University of Rome, La Sapienza.

The possibility that certain foods or allergens may induce convulsions has already been reported in the literature. None of these studies has, however, shown a close correlation between food allergy and epilepsy, most reports being anecdotal and open to various aetiological hypotheses. The present report concerns 3 children with cryptogenetic partial epilepsy, diagnosed by means of electroencephalography, with behavioural disorders (hyperactivity, sleep disorders and writing difficulties). In these patients, instead of using anticonvulsive agents, treatment was based upon a cows milk-free diet, working on the hypothesis that there could be a casual relationship between intolerance to this food item and the epileptic symptoms. An improvement was observed in the children's behaviour and moreover, the electroencephalographic anomalies disappeared. Upon double blind oral provocation tests, these patients did not present an immediate reaction, but only after a few days. starting the controlled diet again led, in all cases, to disappearance of the electroencephalogram. In conclusion, it would appear feasible to hypothesize the role of food intolerance in the onset of convulsive crises, even if limited to certain types of epilepsy such as the cryptogenetic partial form.

J Pediatr. 2005 May;146(5):582-4. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in childrenwith autism spectrum disorders (ASD)

A high prevalence of elevated TNF-alpha/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH(NON-ALLERGIC FOOD HYPERSENSITIVITY) in GI symptoms observed in children with ASD.

(Translation: They found evidence of gut symptoms and immune activation in autistic children, a "hypersensitivity" but not the classic allergy)

Cincinnati Children's Hospital Medical Center --- May 2004-- A new Cincinnati Children's Hospital Medical Center study provides further evidence of a link between autism and immunologic disorders, including allergy. The study, although preliminary, indicates that children with autism may have an increased prevalence of allergic disorders, particularly of the gastrointestinal system.  Centre for Paediatric Gastroenterology, Royal Free and University College, Medical School, London Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear.To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry.

Clin Immunol. 2003 Nov;23(6):504-17. Autism Foundation and a select group of doctors and scientists in Portlandin Autumn, 2001.

More than 50% of autistic children appear to have GI symptoms, foodallergies, and maldigestion/malabsorption issues.  We need large,evidence-based studies need to be done in order to fully understand thegut-brain association in autism.