Oat grain is characterized by its good taste and dietetic properties, as well as an ability to stimulate metabolic changes in the bodies of humans and animals. Furthermore, oat grain is a rich source of proteins with favourable amino acid contents and high nutritional value, and as other beneficial ingredients including dietary fibre, antioxidants, vitamins, phenolic compounds, minerals, and essential unsaturated fatty acids[14-16]. When compared with other cereal grains, oat grain contains larger amounts of total protein and crude fat, and a small amount of crude fibre. The major nutritional components of oats are shown in Table 1.

Several studies have described oats as a functional food with the ability to lower blood cholesterol and sugar levels, reduce hypertension, help control childhood asthma, reduce body weight, and also provide immunomodulatory, antioxidant, and antiatherogenic effects[14,17-19] (Table 2). Oats also contain significant amounts of vitamins, minerals, fibre, and phytochemicals that regulate intestinal transit times and increase the production of butyrate and/or other faecal short chain fatty acids produced by gut microflora. As a result, the long-term dietary intake of oats or oat bran might benefit patients suffering from inflammatory bowel disease, ulcerative colitis, colorectal adenoma or cancer. However, further studies are required to accurately assess the benefits provided by increased oat consumption when treating bowel disorders[20].

Additionally, due to the well-established effect of oats on the risk for coronary heart disease, in 1997 the United States Food and Drug Administration (FDA) approved the heart-health benefit claim shown on the label of many foods containing soluble fibre derived from oats. Moreover, in 2010, a European Food Safety Authority (EFSA) panel concluded that current scientific evidence supports the following two-part statement: “Oat β-glucan has been shown to lower/reduce blood cholesterol. Blood cholesterol lowering may reduce the risk of coronary heart disease”.

As the prolamin components of oat seeds, the avenins are known to exist as both monomers and disulfide-linked aggregates[21]. Similar to other cereal prolamins, the avenin polypeptides in oats tend to be rich in proline and glutamine, and the protein regions enriched in these two amino acids are associated with elicitation of CD. However, when compared to prolamins in other cereal grains, oat prolamins show the following differences in their molecular size, percentage, and amino acid content: (1) prolamins account for 10%-20% of the total protein in oats, compared to 40%-50% of the total protein in wheat[22,23]; (2) among the accepted prolamins, those found in maize, sorghum, and rice generally have the lowest contents of proline and glutamine (25%-30%), while prolamines in the Triticeae tribe (wheat, barley, and rye) can have proline plus glutamine contents that exceed 70% of their total amino acids. In contrast, proline and glutamine generally comprise 35%-50% of amino acids found in the prolamins of oats[24]; (3) in contrast to the single longer repetitive domain found in Triticeae prolamins, oat avenins contain two shorter domains with high contents of proline and glutamine[24]; and (4) the disulfide pattern in oat prolamins is different from those reported in wheat γ-gliadins[25] and low molecular weight (LMW)-glutenins[26]. In particular, the tandem cysteines at positions 145-146 in oat prolamins form a disulfide bond. This is in contrast to wheat proteins, where the two tandem cysteines are bonded to more distant cysteines within the prolamin[24].

Despite these reported differences, the avenins have not been well studied. As a result, the complete avenin genes described in current genetic databases represent only a few genotypes, and the variability displayed by avenin genes in oats is not well represented[21].

The inclusion of oats in gluten-free foods is controversial, as previous studies have shown contradictory results regarding their toxicity. Janatuinen et al[27] conducted the first controlled study on the toxic effects of oats in CD patients, and since that time several other similar investigations have been conducted. Some researchers have claimed that celiac patients can consume oats and show no signs of intestinal inflammation[12,28-31]. In a study conducted by Størsrud et al[32,33], a small number of adult celiac subjects consumed pure oats (93 g/d) for 2 years with no reported adverse effects. The same researchers also conducted a study in which a group of celiac children ingested a median of 43 g (up to 81 g/d) of oats daily for 2 years[34] with no adverse effects. Moreover, a randomized double-blind study conducted with newly diagnosed CD children showed that consumption of an oat-containing GFD for 1 year did not interfere with their clinical, serological or small bowel mucosal recovery. However, despite those results, 26% of the children in the oat-containing GFD group withdrew from that study for unknown reasons[34,35].

While the previously mentioned studies appear to support the safety of oat consumption by celiac patients, the results of other studies suggest that regular consumption of certain types of oats may be impossible for such patients, due to their toxic effects. Those studies revealed that oats can trigger an immune reaction in celiac patients[28,36-38] that results in activation of mucosal T-cells, subsequent gut inflammation, and eventual villous atrophy[37]. In those patients, the immune response against avenins may have been triggered by a mechanism similar to that which triggers a response to gluten contained in wheat, rye, or barley. Lundin et al[36] studied 19 celiac patients who consumed 50 grams of oats/day for 12 wk, and found that one patient was oat sensitive. CD patients have circulating anti-avenin antibodies[39,40], and a recent study revealed that dietary oats can alter the mRNA immune status of intestinal mucosa cells; suggesting T-cell activation and the presence of leaky tight-junctions[41]. Such findings indicate the need to distinguish between groups of celiac patients based on their sensitivity to different cereal grains, and also to identify the source of immunogenicity in avenin peptides.

The phrase “pure oats” is used to describe oats that after being analysed using current test methods, appear to be uncontaminated with gluten from other closely related cereal grains, such as wheat, barley, and rye. However, the differences in the oat products used and the testing and reporting of the purity of oats further limited a comprehensive safety assessment. When studying literature reports, the study design or protocol did not always clearly describe the specifications used for defining “pure and uncontaminated” oats. While the most recent reports usually indicate whether the oats used in a particular study were tested for purity, many studies fail to indicate the lower limit of detection for their testing techniques or the cut-off values used when reporting that oat samples were free of gluten from other cereal grains.

According to the Codex Standard for food for special dietary use by persons intolerant to gluten, CODEX STAN118-1979 (revised 2008, http://www.foedevarestyrelsen.dk/SiteCollectionDocuments/25_PDF_word_filer%20til%20download/07kontor/Maerkning/Codex%20standard%20for%20gluten.pdf), oats can be tolerated by most but not all people who are intolerant to gluten. Therefore, whether oats that are not contaminated with wheat, rye or barley and are contained in foods covered by this standard can be considered safe for consumption by celiac patients may eventually be determined at the national level. Moreover, according to Commission Regulation (EC) No 41/2009 (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:016:0003:0005:EN:PDF), which addresses the composition and labelling of foodstuffs suitable for people intolerant to gluten, the risk that oats may become contaminated with wheat, rye or barley during grain harvesting, transport, storage or processing remains a major concern. Therefore, the risk that oat-containing products might be contaminated with exogenous gluten should be taken into consideration when creating their labels.

Some studies have utilized the R5 ELISA method to determine the level of contamination in wheat, barley, or rye in oat products[42-44]. Koerner et al[43] used this method to confirm that the commercial oat supply in Canada is heavily contaminated with gluten from other grains. For example, about 88% of the tested oat samples (n = 133) showed a gluten level > 20 mg/kg. However, the problem with using this method is that the R5 antibody can react with certain types of pure oat seed[45]; hence, a test result suggesting “suspected contamination” from exogenous toxic cereal grains may not be real, due the R5 antibody reacting with certain amino acid sequences in the native oat proteins.

Differences in the type of oat grain, oat purity, study design, as well as the specifications for gluten-free products in different countries, are some reasons why the current studies have not clearly established whether or not oats can be safely consumed by all celiac patients. These apparent contradictions might be explained by the fact that the oat varieties used in the diverse studies were different in regards to their prolamin genes, protein amino acid sequences, and the immunoreactivities of their toxic prolamins[46,47].

Our research group conducted a study using nine different varieties of oats obtained from various Australian and Spanish commercial sources, and demonstrated that oat immunogenicity varies depending on the cultivar used[45]. The oat grains were carefully inspected, controlled to maintain purity, and shown to be free of contamination. An analysis of DNA amplification products confirmed that the oat samples were not contaminated with wheat, barley, rye, or any mixture of these grains. The toxicity of each oat variety was evaluated using a moAb G12 immunoassay. The antibody used in the assay was obtained from the α-2 gliadin 33-mer peptide, which is one of the most toxic peptides for CD patients. The nine varieties of oats were classified into three groups (high reactivity, intermediate activity, and no reactivity) based on their moAb G12 reactivity. We found that reactivity with the anti-33-mer moAb shown by the different oat varieties was correlated with T-cell proliferation and interferon gamma production by blood T-cells isolated from CD patients. These results suggest that a moAb G12-based immunotechnique may be a pragmatic method for evaluating the potential immunotoxicity of commercial cereals and grains[45,48].

Subsequent studies confirmed a direct correlation between the immunogenicity of the different varieties of oats and the presence of specific peptides with higher/lower potential immunotoxicity. This finding may explain why certain varieties of oats produce toxic effects when consumed by celiac patients, while others produce no adverse effects[21,49]. Moreover, oat peptides obtained from toxic cultivars have showed to differentially stimulate bona fide circulating dendritic cells obtained from celiac patients.

While inclusion of oats in a GFD might be beneficial due to their nutritional and health benefits, the source of the oats used and the cultivar selected are important factors to be considered. These factors must also be taken into account when developing food safety regulations, labelling oat-containing products as gluten-free, and designing clinical trials to study the effect of oats in celiac patients.