By Amy Ratner, Medical and Science News Analyst

In one of the first studies to calculate the amount of gluten consumed, researchers found that many people with celiac disease on a gluten-free diet are regularly exposed to enough of the harmful protein to cause symptoms and intestinal damage.

Researchers looked at results from previous studies measuring the amount of gluten in stool and urine and data from clinical trials investigating a drug to treat celiac disease in the study published recently in the American Journal of Clinical Nutrition.

They estimated that the average inadvertent gluten exposure per day for adult celiac disease patients on a gluten-free diet was 244 milligrams (mg) based on stool tests, 363 mg based on urine tests and greater than 228 mg based on results of a clinical trial for latiglutenase, the drug being studied to treat celiac disease.

The celiac disease research study was conducted by scientists from ImmunogenX, the company developing latiglutenase, and BioMedal/Glutenostics, the company that makes the urine and stool tests being used in research and available for consumer use.

How many patients consume unsafe levels of gluten

Up to 10 mg of gluten per day is generally considered a safe level of gluten consumption, according to the University of Chicago Celiac Disease Center. The exact level below which gluten is harmless is not known, but a recent review suggests less than 10 mg per day is unlikely to cause damage in most patients, according to the American College of Gastroenterology

“Only 25 to 30 percent of patients are regularly exposed to gluten and have moderate to severe symptoms, said Francisco Leon, M.D., a founder of Glutenostics, a partner in Biomedal and a study author. “Most patients are able to avoid gluten most of the time, but even the most careful and educated have contamination episodes.”

“Gluten ingestion as low as 50 mg per day can be harmful to some celiac disease patients,” the authors wrote, noting that elimination of even 99 percent of the five to 15 grams of gluten in the typical Western non-gluten free diet “may still be insufficient” to prevent symptoms and damage to the absorbing lining of the intestine for those who have celiac disease.

The challenges of following the gluten-free diet are widely known, especially to patients who struggle with cross-contact and other sources of inadvertent gluten exposure. But “surprisingly very little is known about the quantity of gluten that is accidently consumed episodically and continually for those on the gluten-free diet,” the authors said. “We are unaware of any studies that attempt to analytically determine the actual quantity of gluten that is consumed while on a gluten-free diet.”

“The study has many limitations in its methods, but the take home message is clear,” said Ciaran Kelly, M.D., one of the study authors and a member of the Beyond Celiac Board of Directors. “This is not a big surprise to those of us working in the field.” He said patients who have non-responsive or refractory celiac disease, the more severe forms, are often put on an extremely strict gluten-free diet because of the link between minimum gluten exposure and symptoms and damage.

How the study was done

Meta-analysis: a statistical technique to analyze the total data from a large, already-existing collection of experiments

The gluten consumption study was based on meta-analysis of clinical trial results that focused primarily on celiac disease patients who had moderate to severe symptoms. Consequently, the conclusions do not apply to patients who have mild or no symptoms, Leon said.

Results of urine tests found about that 30 percent of adults and 32 percent of children regularly consume greater than 300 mg of gluten, while stool tests put the number at 18 percent.

Leon said he believes it is “nearly impossible to be gluten-free all the time.” But he backed the study’s recommendation that results be used by celiac disease patients to re-evaluate their diets under the guidance of a clinician or dietitian. “The consequences of a monthly contamination are much less serious than a daily or weekly contamination,” Leon said. “Education, measurement, vigilance and dietitian and physician consultation should be able to shift many from the gluten-free diet non-responders to responders.”

Need for new treatments

Study results should also “provide a guide for drug development” for celiac disease, an autoimmune condition for which there is currently no effective drug therapy, the authors wrote.

“The need for treatments in addition to the gluten-free diet is already very clear,” Kelly said. “These findings suggest that approaches or devices that bind, inactivate, degrade or detect dietary gluten can be very useful as an adjunct to the current gluten-free diet.”

Learn More: How celiac disease is triggered and might be treated

In the gluten consumption study, researchers linked earlier data that showed a range of gluten exposure – from undetectable to very detectable – to measurement in other research of the amount of immunogenic gluten peptides in stool and urine after a known of amount of gluten was given to participants, according to Jack Syage, Ph.D., the lead study author and ImmunogenX Chief Executive Officer.

The combined data could then be used to analyze much larger studies where gluten was consumed in real-world conditions, such as the latiglutenase study. This approach results in assumptions and approximations of how much gluten is consumed, one of the limitations of the study.

The data from the latiglutenase trial suggests that “individuals on a gluten-free diet cannot avoid accidental gluten intrusions and these small amounts are sufficient to trigger severe symptomatic responses and may contribute to histologic (i.e. biopsy proven) damage,” authors of the gluten consumption study wrote.

DOGGIE BAG study

A study to determine how often and how much gluten contaminates the gluten-free diet of celiac disease patients is underway at the Celiac Disease Program at Boston Children’s Hospital in conjunction with the Manitoba Celiac Disease cohort study and with University of Seville.

In this co-called DOGGIE BAG study, patients have been providing food, urine and stool samples, all of which are being tested for gluten exposure. Both stool and urine tests that detect gluten are frequently positive, early results show. Likewise, food samples often test positive for gluten content, some with levels below the 20 parts per million considered safe for those who have celiac disease and some far above that standard.

“I expect the message from that study will be similar, that is, an absolutely gluten-free diet is extremely difficult to achieve in our dietary environment,” said Kelly. “That said most patients do well and are healthy on their ‘extremely-low-gluten’ diets.”

What patients should do

While researchers pursue precise information about how much gluten patients are being exposed to, Leon said patients who have symptoms should talk to their doctor or dietitian and consider measuring gluten in stool or urine in coordination with healthcare providers to “get to the bottom of it.”

Those who do not have symptoms may be fine, but they should be aware that they may have reduced gluten consumption to the level where symptoms are not being triggered, but intestinal damage is still occurring, according to Leon. These patients “should not lower their guard” and should consult with their doctors if they have unexplained signs, such as anemia or osteoporosis, he said.

You can help advance celiac disease research by sharing your story on

Go Beyond Celiac.