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Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine
This activity is intended for internists, family physicians, pediatricians, gastroenterologists, physician assistants, nurse practitioners, and nurses who treat patients with celiac disease.
The goal of this activity is to educate health professionals about the current best evidence regarding the amount of dietary gluten allowed for patients with celiac disease.
Upon completion of this activity, participants will be able to:
As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine
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Systematic Review: Tolerable Amount of Gluten for People With Coeliac Disease
Akobeng AK, Thomas AG
Aliment Pharmacol Ther. 2008;27:1044-1052. Epub 2008 February 29.
This study was selected from Medscape Best Evidence, which uses the McMaster Online Rating of Evidence System. Of a possible top score of 7, this study was ranked as 6 for newsworthiness and 6 for relevance by clinicians who used this system.
Celiac disease affects nearly 1% of individuals worldwide,[1] but the diagnosis of celiac disease is often delayed for years. The accepted treatment for celiac disease is maintenance of a diet free of gluten. However, gluten is present in many processed foods, and many patients with celiac disease consume an unspecified amount of gluten on a regular basis. The current review examines the threshold for gluten consumption among patients with celiac disease.
Celiac disease is a common condition that can be difficult to diagnose based on symptoms alone. In a study of 4126 asymptomatic individuals, 1 of 133 subjects was found to have celiac disease.[2] The prevalence of celiac disease among patients with gastrointestinal (GI) symptoms was higher (1 in 56 subjects tested). A genetic predisposition for the development of celiac disease exists, with most patients who have celiac disease expressing human leukocyte antigen DQ2 or DQ8 haplotypes. In the study cited above, the prevalence of celiac disease was 1:22 among first-degree relatives of patients with celiac disease and 1:39 among second-degree relatives. In a review of worldwide epidemiologic data on celiac disease, the prevalence of the disease was reported to be between 0.2% and 1%.[3]
A population-based study of 1612 patients with celiac disease is informative regarding the demographics and symptoms of the disease.[4] Celiac disease was almost 3 times as common among women compared with men. Diarrhea was the most common symptom, present in 85% of subjects, and the average duration of symptoms prior to the diagnosis of celiac disease was 11 years. Nearly one third of patients had consulted 2 or more gastroenterologists.
The diagnosis of celiac disease can be delayed because its symptoms are common to many GI disorders. In addition to diarrhea, the majority of patients with celiac disease experience fatigue.[5] Other common symptoms include:
Celiac disease is also associated with numerous medical conditions outside of the GI tract, including osteoporosis, iron-deficiency anemia, neuropathy, asthma, and dermatitis herpetiformis.
The pathophysiology of celiac disease involves an immune reaction in the mucosa of the small intestine. Ingested gluten from wheat, rye, and barley induces an inflammatory reaction in the lamina propria, leading to symptoms. Although there is no single means to diagnose celiac disease, a review article from 2007 proposed a diagnostic algorithm to help clinicians.[5] Gliadin antibodies were previously used to test for celiac disease, however, they are no longer used because of their poor sensitivity and specificity. Rather, serologic testing remains a good initial examination in the evaluation of celiac disease and should focus on immunoglobulin (Ig)A endomysial antibody or IgA tissue transglutaminase (tTG) antibody, which have been demonstrated to have sensitivity and specificity values exceeding 95% for celiac disease.[6] Using both tests is rarely necessary, and the relatively lower price of the tTG antibody test makes it a good choice for initial screening for celiac disease.
A positive tTG antibody test is insufficient to assure the diagnosis of celiac disease, and patients with such results should undergo small bowel biopsy. A negative tTG antibody test does not necessarily rule out celiac disease if a high suspicion for it exists. In such cases, a small bowel biopsy should also be considered. A negative small bowel biopsy should prompt reconsideration of diagnoses other than celiac disease, although a repeat biopsy may be indicated for patients with positive serologic testing. Genetic testing for histocompatibility leukocyte antigen (HLA)-DQ2 and HLA-DQ8 can also be useful in cases when the diagnosis of celiac disease is in doubt.[5] These genetic tests have a high sensitivity, so negative results make celiac disease much less likely.
The treatment of celiac disease is focused on the exclusion of foods containing wheat, rye, and barley. The inclusion of oats in the diet of patients with celiac disease is controversial. Oats had also been considered to be harmful for patients with celiac disease, but more recent data suggest this harm is primarily because of contamination with gluten in oat products.[7] For adults, some recommendations allow for daily oat consumption up to 70 g or 1/2 to 3/4 cup if the oats are free of gluten contamination. Children may consume up to 25 g (1/4 cup) of pure oats per day.[8]
One of the greatest difficulties in controlling celiac disease with diet is the wide use of gluten in processed foods, which can include dried fruit and fruit pie fillings, cold cuts, sandwich spreads, canned meats, many salad dressings and condiments, prepared soups, flavored yogurt, and even flavored instant coffees and herbal teas.[5]
The World Health Organization (WHO) defines naturally gluten-free foods as having 20 parts per million (PPM) or less of gluten, whereas foods that have been artificially rendered gluten-free should have a maximum of 200 PPM of gluten.[9] However, this standard is not accepted everywhere, in part because of the difficulty of precisely determining the amount of gluten present in different foods. Nonetheless, it is clear that most patients with celiac disease can tolerate at least some minimal amount of gluten in their diet. The current review examines this issue.
Researchers reviewed electronic databases using a broad search strategy to include randomized controlled trials, cohort studies, case control studies, and cross-sectional studies. Patients included in these studies had celiac disease confirmed by small intestinal histology.
The initial review found 35 studies, but only 13 were included for data analysis. The most common reason for exclusion of research was that the articles were reviews of the diet in celiac disease. Of the studies included in the full analysis, 7 were cross-sectional in design and 3 were randomized controlled trials. The cross-sectional studies were judged to have a moderate risk for bias. Because results reported in the included studies were disparate in nature, a pooled statistical analysis of these results was not possible.
The review concludes that the total amount of gluten ingested, as opposed to the concentration of gluten in individual food products, is the key factor associated with histologic abnormalities in the small intestine. Collectively, the included studies were more focused on these histologic changes rather than on patient symptoms of celiac disease. Consumption of gluten at levels of 200 mg/ day or more was definitely associated with the development of intestinal abnormalities. Whereas these changes were generally evident within several weeks, one trial compared different levels of gluten consumption and demonstrated a difference in villous height/crypt depth ratio within 1 week.
The results of research evaluating consumption of lower levels of gluten were more uneven. In one study, more than half of subjects consuming only 10 mg of gluten per day experienced worsening of their villous height/crypt ratio. However, another study demonstrated no histologic abnormalities among a cohort of patients who consumed an average of 34 mg of gluten daily.
Consumption of a "gluten-free" diet was no guarantee against mucosal abnormalities associated with celiac disease. Nearly half of subjects in 2 studies of these diets had villous atrophy. However, the exact amount of gluten in these diets was not measured.
The current review is in line with other recent examinations of the limits of gluten consumption in celiac disease. One study recommended a daily gluten consumption limit between 10 mg and 100 mg.[10] Another study involving 83 subjects found that an average daily gluten consumption of 80 mg was not associated with negative long-term changes to the mucosa of the small intestine.[11]
It is difficult to draw precise conclusions from the current review. However, it suggests that the current standard of 200 PPM or less of gluten in foods labeled as gluten-free will not be protective for all patients with celiac disease. Instead, the current review suggests that a new standard set at a maximum of 20 PPM of gluten will equate to an approximate daily gluten consumption of 6 mg. The current body of research suggests that this level of gluten intake would not promote mucosal abnormalities among the majority of patients with celiac disease.
The review also clarifies the need for further research into the threshold of gluten consumption in the setting of celiac disease. In particular, research would benefit from standardization of outcomes as well as trials comparing particular concentrations of dietary gluten. Until such research becomes available, the current review provides a good guideline regarding gluten consumption in celiac disease.
