Systematic Review: Tolerable Amount of Gluten for People With Coeliac Disease

A. K. Akobeng; A. G. Thomas


Aliment Pharmacol Ther. 2008;27(11):1044-1052. 

In This Article


Whilst it is accepted that the treatment of CD is a ‘gluten-free’ diet, there is a great deal of controversy surrounding what a ‘gluten-free’ diet should be. This confusion arises because of two main reasons: 1) it is extremely difficult to achieve a diet which is completely devoid of gluten and 2) the exact amount of gluten that people with CD can tolerate without experiencing adverse effects is not clearly established. In this study, we systematically examined the available evidence on the threshold amount of ingested gluten that would be tolerable for people with CD and also investigated the evidence base for a tolerable threshold concentration of gluten in foods.

The available evidence shows that the consumption of about 200 mg gluten per day is clearly associated with the development of intestinal mucosal abnormalities after only 4 weeks in patients with CD.[12] In one study, the ingestion of 10 or 50 mg gluten per day was associated with worsening of the villous height/crypt depth ratio in most patients after 3 months.[14] In two other studies, patients who consumed an average of 34-36 mg of gluten per day did not develop histological abnormalities after an average of at least 8 years[21,23] but in another study, Chartrand et al. found that some patients developed symptoms on much smaller amounts within 8 months, but unfortunately, in this study, histological changes were not assessed in either the patients who remained well or those who exhibited symptoms.[15] Thus, although it appears that some patients may tolerate an average of about 34-36 mg gluten per day, it is likely that some other patients may develop histological changes or manifest symptoms with much smaller amounts.

The length of exposure to gluten varied considerably between the included studies. For instance, in the study by Kaukinen et al., patients had been on their diet for a mean of 8 years,[21] whereas in the study by Ciclitira et al., patients were assessed after a one week gluten challenge.[16] It is likely that the length of exposure would have an effect on outcomes.

The evidence regarding the threshold limit of gluten concentration in food is also unclear. Peraaho et al. found that patients consuming either natural ‘gluten-free’ diet or wheat starch-based ‘gluten-free’ diet containing up to 40-60 mg per 100 g of food developed no symptoms or mucosal abnormalities.[13] Selby et al., however, found persistent mucosal abnormalities in patients who were consuming either Codex ‘gluten-free’ products or ‘non-detectable gluten’ ‘gluten-free’ products (containing less than a tenth of the gluten content of the Codex products).[22] It is not clear how the duration of being on Codex ‘gluten-free’ products contributed to these contradictory findings. In the study by Peraaho et al.,[13] assessment was made after one year whereas in the study by Selby et al,[22] patients appeared to have been on these products for the duration of their disease (0.6-29.2 years).

There is considerable debate within the food industry regarding the optimum concentration of gluten in ‘gluten-free products’. This review has highlighted the limited nature of the evidence base in this area. We can deduce from this study that although some people with CD may tolerate products with the current Codex concentration of gluten, others may develop symptoms and/or histological abnormalities when they consume products with even lower concentrations of gluten. It is likely that what is most important is the total amount of gluten ingested rather than just the concentration of gluten in the food products as the amount of gluten ingested will depend on both the concentration and the volume of food products consumed.

It is clear from this study that the current Codex standard of 200 ppm is not sufficiently protective for all people with CD and so there may be a case for lowering the current concentration of gluten permitted in ‘gluten-free’ food products. However, we found no evidence to suggest a single definitive threshold concentration of gluten in food products that would be tolerated by all people with CD. Collin and colleagues argued that if the daily ‘gluten-free’ flour intake of patients with CD is assumed to be that found in their study (300 g or less), a threshold gluten concentration in flour of 100 ppm (100 mg/kg of flour), will mean that patients will not be consuming more than 30 mg gluten per day.[6] However, as Catassi and colleagues have recently shown, some patients who consume an even lower dose of gluten (10 mg daily) will develop histological changes.[14] It can therefore be argued that if the concentration is set at, say, 20 ppm, patients will be consuming around 6 mg per day of gluten which may be less likely to induce mucosal changes.

It is obvious from the results of this study that the amount of tolerable gluten varies among people with CD. The reason for this remains unclear. Future studies should investigate potential reasons (e.g. genetic variability) that may explain the variable response to gluten. Future studies should also assess the exact amount of gluten that can be tolerated by people with CD and over what period of time and the exact concentration of gluten in wheat-starch ‘gluten-free’ products and all other foods that can be tolerated. Tolerance should be assessed by small bowel histology before and after the intervention and reproducibility of assessments by histopathologists should also be assessed. Assessment of tolerance should also include symptoms and quality of life. Factors influencing latency (e.g. age at diagnosis, initial time on a gluten-free diet and time elapsed from diagnosis) should be standardized and clearly defined. We recommend that future studies in this area should be well designed RCTs and should have adequate statistical power to detect any differences between groups. The necessary sample size of future studies may be influenced by the particular outcome being assessed (i.e. histology, symptoms, quality of life) as well as the magnitude of the intervention (i.e. amount of gluten and length of exposure).

Our review included studies from Europe, North America and Australia. We searched multiple databases and reference lists and also contacted key individuals and organizations so it is unlikely that we missed relevant studies. We minimized subjectivity by carrying out study selection, data extraction, and quality assessment in duplicate. However, the validity of the results of a systematic review depends on the validity of the included studies. Considering the number of people affected by CD world-wide, it is surprising that so few good quality studies have been conducted to ascertain tolerable amounts of gluten. Many of the included studies failed to take all the steps necessary to avoid bias. Our conclusions were, therefore, limited by the quality of included studies and the information provided. Despite the inclusion of 13 studies, significant variations in study design, amount of gluten ingested, the length of exposure to gluten, and the way the effect of gluten was assessed prevented the use of meta-analysis to summarize results.

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