A population-based probabilistic approach to risk estimation.
A recent study published in the American Journal of Clinical Nutrition used a probabilistic modeling approach to determine if the trace amounts of gluten found in gluten-free products could cause mucosal damage. This study was conducted using data and gluten-free products from Italy, Spain, Germany and Norway.
Previous research has demonstrated that a daily tolerable intake limit of <10-50mg/day is unlikely to cause significant histological damage, since minimal gluten cross-contamination is difficult to avoid. For this reason, product labeling regulations in these countries (by the World Health Organization and Food and Agriculture Organization) require a gluten content below 20mg/kg for a product to be considered “gluten-free” and a gluten content below 100mg/kg to claim “very low gluten.” The reason for not requiring products to have absolutely no gluten is reflective of the inability to test below the detection limit of 3mg/kg (and a limit of quantification of 5mg/kg), and also that requiring too strict of limits would likely limit the availability of gluten-free products.
Using a sandwich R5 ELISA (the validated and recommended test for gluten content of foods), researchers found that 94% of gluten-free products tested in these countries had a gluten content that was below the limit of quantification (5mg/kg). Products tested included wheat substituted gluten-free bread, pasta, pastries, biscuits, pizza and breakfast cereals from Italy, Germany, Spain and Norway. All products tested had below 27.8mg/kg of gluten. (Again, the product labeling regulations in these countries requires a gluten content below 20mg/kg for a product to be considered “gluten-free.”)
The probable risk assessment model combined data on gluten-free food consumption, level of gluten in these foods, and a gluten threshold of 10mg/kg to randomly generate 10,000 iterations 25 times and used this data to determine how many people in each country might be at risk for mucosal damage from consuming these products.
When considering each of the four countries independently, they found that for every 10,000 celiac disease patients, 50 in Italy, 20 in Spain and a negligible number in Norway and Germany could have mucosal damage from consuming only products from their own country. Next they considered the likely model where products are accessible in all countries rather than just the country of origin. In this model, 59 people would be at risk of mucosal damage in Italy, 7 in Spain, 9 in Norway and none in Germany. The reason for these differences is the variation in food consumption trends in these countries. For example, Italy has the highest numbers of persons at risk due to the large consumption of gluten-free pasta products. Overall, when combining the food trends of all of these countries and the products available, the risk of mucosal damage for a celiac disease patient is 0.18%.
It is important to note that the prevalence of persistent small intestinal damage in diagnosed celiac disease patients is around 50-80%. Since the risk of damage from gluten-free products is well below 1%, this indicates that damage is not likely caused from the consumption of gluten-free products alone. Persistent damage may be a result from other gluten-free food transgressions (intentional as well as accidental, for example when dining at restaurants), or the inability of a badly damaged small intestine to ever fully heal.
To learn more about this study, the National Foundation for Celiac Awareness (NFCA) interviewed one of the researchers, Prof. Carlo Catassi, Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy, Co-Director, Center for Celiac Research, University of Maryland School of Medicine, Baltimore, USA.
Q. This study used a probabilistic modeling approach to determine if trace amounts of gluten can cause mucosal damage in people with celiac disease. Can you explain what this approach is and why it was used for this study?
A. We knew from previous studies that the threshold for toxicity in celiac disease patients is 10-50 mg of daily gluten. At the population level, however, we had no idea on how many patients are at-risk of intestinal damage due to gluten contamination. This is influenced by (1) the variability of the individual threshold; (2) the amount of wheat substitutes eaten on daily basis and; (3) the real contamination of wheat substitutes. By using the statistical approach of probabilistic modeling, we were able to quantify the percentage of at-risk patients, and found that this was indeed very low (< than 0.5%). It should, however, be noted that this study did not measure other possible sources of gluten contamination, e.g. products eaten at the cafeteria or in pizzerias.
Q. What implications does this study data have for people living with celiac disease in the United States? Similarly, how do you anticipate this data to impact celiac disease researchers worldwide?
A. Our data on the individual intake and contamination of wheat substitutes were collected in different European countries. However, we have no reason to believe that the situation is different in the U.S., since the current limitations for gluten contamination in gluten-free products (wheat substitutes) and the consumption data are quite similar on both sides of the ocean. In my humble opinion, researchers should now focus on investigating the possible gluten contamination of products sold in foodservices, catering, pizzerias and so forth. We also need new analytical tools to exactly measure all the different gluten components (i.e. gliadins and glutenins) in food.
Q. Previous research has stated that the tolerable threshold of gluten ingestion in people with celiac disease is 10-50 mg/kg per day. With this prior research in mind, what do the findings from your recent study mean for people who rely heavily on manufactured gluten-free food in their diet? More specifically, is it possible for people to exceed this 10-50 mg/kg limit by eating too many manufactured gluten-free products in one day?
A. We can definitely state that the gluten-free foods that are currently on the market are almost always safe for patients. Even subjects eating large amount of wheat substitutes (up to 500 g per day) are not exposed to the risk of significant damage of the small intestinal mucosa.