Celiac Disease and Gluten-Free Oats: A Canadian Position Based on a Literature Review.

This paper provides an overview of the latest scientific data related to the safety of uncontaminated oats (<20 ppm of gluten) in the diet of individuals with celiac disease (CD). It updates the previous Health Canada position posted on the Health Canada website in 2007 and a related paper published in 2009. It considers a number of recent studies published between January 2008 and January 2015. While recognizing that a few people with celiac disease seem to be clinically intolerant to oats, this review concludes that oats uncontaminated by gluten-containing cereals (wheat, rye, and barley) can be safely ingested by most patients with celiac disease and that there is no conclusive evidence that the consumption of uncontaminated or specially produced oats containing no greater than 20 ppm gluten by patients with celiac disease should be limited to a specific daily amount. However, individuals with CD should observe a stabilization phase before introducing uncontaminated oats to the gluten-free diet (GFD). Oats uncontaminated with gluten should only be introduced after all symptoms of celiac disease have resolved and the individual has been on a GFD for a minimum of 6 months. Long-term regular medical follow-up of these patients is recommended but this is no different recommendation to celiac individuals on a GFD without oats.

Introduction of oats in the diet of individuals with celiac disease: a systematic review.

Celiac disease is an immune-mediated disease, triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. The only treatment for celiac disease is a strict gluten-free diet for life. This paper presents a systematic review of the scientific literature on the safety of pure oats for individuals with celiac disease, which historically has been subject to debate. Limitations identified within the scientific database include: limited data on long-term consumption, limited numbers of participants in challenge studies, and limited reporting about the reasons for withdrawals from study protocols. Furthermore, some evidence suggests that a small number of individuals with celiac disease may be intolerant to pure oats and some evidence from in vitro studies suggests that an immunological response to oat avenins can occur in the absence of clinical manifestations of celiac disease as well as suggesting that oat cultivars vary in toxicity. Based on the majority of the evidence provided in the scientific database, and despite the limitations, Health Canada and the Canadian Celiac Association (CCA) concluded that the majority of people with celiac disease can tolerate moderate amounts of pure oats. The incorporation of oats into a gluten-free diet provides high fiber and vitamin B content, increased palatability, and beneficial effects on cardiovascular health. However, it is recommended that individuals with celiac disease should have both initial and long-term assessments by a health professional when introducing pure oats into a gluten-free diet.

Domoic acid toxicologic pathology: a review.

Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health.

Regional susceptibility to domoic acid in primary astrocyte cells cultured from the brain stem and hippocampus.

Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk), and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-alpha, IL-Beta, IL-6, the small inducible cytokine, interferon protein 10P-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all down-regulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity.

The monkey (Macaca fascicularis) heart neural structures and conducting system: an immunochemical study of selected neural biomarkers and glutamate receptors.

The neural markers, protein gene product 9.5 (PGP 9.5), neurofilaments (NF) and glutamate receptors (GluRs) were visualized by immunohistochemistry in the monkey heart. PGP 9.5 showed the greatest affinity for intramural ganglia cells and nerve fibres. Structural components of the conducting system were also stained, particularly the bundle of His, AV node and Purkinje fibres. Anti-NF 200 and NF 160 showed strong, preferential affinity to nerve fibres and ganglia throughout the heart. Further studies concentrated on the presence and the distribution of glutamate receptors: NMDAR 1, GluR 1, GluR 2/3, GluR 5/6/7, mGluR 2/3, and mGluR 5. Positive immunoreactivity of GluRs was evident in nerve terminals within the atrium, myocardium, intramural ganglia and elements of the conducting system. The intensity of the stain varied for each antibody according to the anatomical distribution within neural structures and conducting system. The specificity of immunolabelling was confirmed by absorption studies with each corresponding peptide. There is preferential affinity to and differential distribution of staining with PGP 9.5, NFs and several subtypes of GluRs in the various components of the cardiac conducting system in adult monkeys. The expression of specific neural markers and glutamate receptors common to nerve fibers and ganglia cells is consistent to our previous report in rodents. These expressions suggests that such structures in the heart share common characteristics with a variety of neural tissues and hence are potential targets for neurotoxins. Furthermore, the strong affinity and specific distribution of several subtypes of GluRs in the monkey heart fosters our view that these receptors may be able to influence the physiology and pathophysiology of cardiac rhythm and excitation. Hence as in the brain, the GluRs may be involved in the mediation of excitatory effects in the heart.