By Amy Ratner, Director of Scientific Affairs
The gluten-free diet is the only treatment for celiac disease, but it is far from a complete and effective intervention. It presents challenges to diagnosis, disease management, quality of life and overall understanding of this serious autoimmune condition.
People report regret at having been diagnosed, especially if they were asymptomatic. Among those diagnosed because of increased risk due to family history or by having related autoimmune conditions, only 42 percent said they were glad to find out they had celiac disease, a 2016 study found. This compared to 64 percent of those diagnosed because they had symptoms, according to the study. Interestingly, nearly 70 percent of seemingly asymptomatic patients diagnosed through screening said they realized they actually did have symptoms before diagnosis. After going on the diet, screen-diagnosed patients had a similar quality of life compared to those diagnosed because of symptoms, but still more frequently regretted being diagnosed.
People diagnosed with celiac disease often report family members refusing to be tested because they do not want to go on the gluten-free diet. In a 6-week qualitative research study for Beyond Celiac conducted in 2014 by Edelman, a global communications firm, family members and those with celiac disease explored this topic. The study found that at-risk family members were reluctant to be tested largely because they had no symptoms and were concerned about changing their diet. One family member noted, “I am afraid to get tested. The costs [of gluten-free food] and knowing that I’d have to give up what I love to eat are enough to scare me.”
It is hard to accurately determine the number who avoid the diagnosis because of the diet. People who do not want to be tested are unlikely to visit their doctor to talk about the issue. Physicians do sometimes see adolescents who have been brought in by parents despite objections to being tested.
“People who are avoiding or opting not to get tested are a hard-to-find group,” explained one expert at a celiac disease center.
First, the gluten-free diet has become a popular fad, and this has a negative effect on celiac disease because the true extent of the condition can’t be determined if people are not tested and diagnosed.
A 2016 study by celiac disease researchers at the Mayo Clinic found that the number of people without celiac disease following the gluten-free diet tripled from 2009 to 2014, increasing from .5 to 1.7 percent. Researchers tested the blood of 22,277 participants in the 2009–2014 National Health and Nutrition Examination Surveys (NHANES). While many of the study participants on a gluten-free diet did not have celiac disease, the study authors noted that it is also possible that persons who become symptomatic from undiagnosed celiac disease may try a gluten-free diet on their own without testing. Another investigation of the NHANES data by researchers at Rutgers University concluded that the prevalence of celiac disease in the United States has remained stable, but the increasing numbers of people following the gluten-free diet may be contributing to what looks like plateau in celiac disease. “The two trends may be related,” study authors wrote.
Those who go on a gluten-free diet without testing are potentially celiac disease patients who will never get counted. Nor will first-degree family members who carry an increased risk of celiac disease and often have no symptoms but might be tested if the family connection is discovered. A review of medical records of patients with celiac disease and their first-degree relatives by researchers at the Mayo Clinic found that 44 percent of screened relatives had celiac disease. Of those, about 28 percent had no symptoms, 68 percent had symptoms not typically associated with celiac disease and only 6 percent had classic symptoms.
Second, even those who start the gluten-free diet because they have symptoms may never get diagnosed. Since the gluten-free diet is the only treatment for celiac disease, and patients have to manage it on their own, many people decide there is no reason to visit a doctor. Others may have seen their doctor but were refused the celiac disease test, so they, too, go on a gluten-free diet themselves.
Further complicating the picture is the fact that once someone goes on a gluten-free diet, the tests for celiac disease are not accurate unless the person eats gluten again for an extended period. Those who start the diet because they had symptoms, and thus are more likely to have celiac disease, are often reluctant to resume eating gluten and possibly get sick again.
“For patients who have obtained symptom relief with the gluten-free diet, returning to a gluten-containing diet may be undesirable. This can leave such patients without a clear diagnosis,” a 2017 study explains.
The gluten-free diet presents healthcare challenges even for those who are properly diagnosed. These patients often drop out of the healthcare system for celiac disease treatment because once a doctor advises the gluten-free diet, he or she has nothing else to offer. Those who continue to have symptoms see little value in having a doctor tell them to further scrutinize their diets when they are already being as strict as possible. And those who don’t have symptoms often assume they are doing fine and don’t need to see a physician, potentially missing related conditions and vitamin and nutrient deficiencies that can result from being gluten-free. Sometimes those who are asymptomatic have intestinal damage that goes undetected. Studies of both adults and children have found that those without symptoms can still have gut damage.
More than one out of four celiac disease patients diagnosed at least five years ago have not had follow-up healthcare for the condition in the past five years, a 2017 study by Beyond Celiac and other researchers found. 27 percent of nearly 1,500 adults with celiac disease surveyed for the study did not see a healthcare provider, and most said the reason was that they “were doing fine on their own.” Others said they did not visit a doctor or dietitian because “they did not need to; their provider was not knowledgeable or previous visits were not helpful.”
Twelve percent of more than 1500 people with celiac disease surveyed by Beyond Celiac reported that they intentionally eat gluten at least some of the time. The survey also found that 57 percent are sometimes embarrassed about eating in front of other people at least some of the time, which might contribute to intentional cheating. Cheating is such a difficult topic in celiac disease that many of those who do it don’t like to admit it, even to their doctor. But researchers are grappling with the question of gluten in the gluten-free diet, both unintentional and intended. A 2011 study of about 200 people with celiac disease by researchers in the United Kingdom found that 31 percent reported they partially adhere to the diet and 4 percent reported that they do not follow it at all. Overall, 80 percent reported difficulty adhering to the diet.
Studies show that even when patients are trying to be strict about the gluten-free diet, gluten still sneaks in. Research that measures gluten in urine and stool from celiac disease patients often detects it. Investigators from in Argentina, Canada and El Salvador in 2020 study found that participants were exposed to gluten a median of three times over four weeks. A study by researchers from Boston Children’s Hospital in 2017 similarly found that two thirds of patients who were strictly following a gluten-free diet still showed signs of having consumed gluten. About 50 percent of celiac disease patients had consumed some gluten, detected by gluten protein in their urine, another 2017 study found.
With a diet that both cuts out many foods people love and still lets in some amount of harmful gluten, it’s easy for those with celiac disease to be frustrated and anxious. And it’s no wonder that cheating happens.
A panel of celiac disease patients who spoke at the Beyond Celiac 2019 Summit affirmed the seriousness of the psychosocial burden of the gluten-free diet. Panelists described the overall difficulty of living with celiac disease because, unlike other conditions, the burden is not adequately recognized by the outside world.
The burden of the gluten-free diet is substantial, and often includes a significant negative impact on quality of life by limiting social activities and educational and employment opportunities, the panelists told a broad group of celiac disease stakeholders brought together by Beyond Celiac. Eating out always carries a risk of gluten exposure. The constant focus on finding safe food on the gluten-free diet reduces time and energy for other aspects of life. Traveling for fun or work carries the extra stress of needing to find safe food. Additionally, the whole family, not just the person who has celiac disease, is affected. All of these facts of daily living impact quality of life, the patient representatives said.
Research backs up the psychological struggles detailed by the summit panelists. Celiac disease patients are often told that even one crumb of gluten can cause symptoms, leading to anxiety about eating in general. But hypervigilance about the gluten-free diet can lead to reduced quality of life for adults and teenagers, Columbia University researchers found in a 2018 study. Extreme vigilance to the gluten-free diet may increase symptoms, such as anxiety and fatigue and, therefore, lower quality of life,” researchers from the Department of Health and Behavior Studies and the Columbia University Celiac Disease Center wrote. “In other words, there may be a cost to hypervigilance for some individuals with celiac disease.”
Researchers in 2018 reviewed 300 studies examining fatigue in adults with celiac disease. While fatigue may be a natural and transient part of life, in a chronic condition such as celiac disease, these symptoms are unrelieved by adequate sleep or rest. Once diagnosed, the fatigue suffered by celiac disease patients often improves with the gluten-free diet, though not always, according to the study authors.
Meanwhile, a Beyond Celiac survey of those with celiac disease found that more than 90 percent of about 1500 participants reported that they feel fatigued after exposure to gluten. About 70 percent reported irritability and 66 percent anxiety. Irritability is more commonly seen in children. About 52 percent of participants reported sadness as a symptom of gluten exposure, and about 49 percent reported lack of interest in eating or in food. Many of these psychological symptoms also overlap with symptoms of depression, which can also be a symptom of celiac disease.
Children with celiac disease also suffer psychological impact of the condition. About one-third of children with celiac disease have mental health disorders, primarily anxiety disorder and attention-deficit/hyperactivity disorder (ADHD), according to 2020 study thought to be the first to investigate mental health in children from North America.
These issues contribute to increased psychosocial distress in both parents and children, the study by researchers from Children’s National Hospital found.
Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While anxiety, depression and fatigue may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity, according to a study that reviewed scientific papers on the topic published from 1990 to 2014. Psychological symptoms may affect the quality of life and the dietary adherence, the study concluded.
The psychosocial aspects of living with celiac disease and the gluten-free diet come into high relief when you consider a 2014 study by researchers at Beth Israel Deaconess Medical Center which found that those with celiac disease report a “remarkably” high treatment burden. Celiac disease participants reported greater treatment burden comparable to participants with congestive heart failure and end stage renal disease, according to the study. “This underscores the difficulty of following the gluten-free diet and puts the high treatment burden of celiac disease into context,” the authors wrote. “Greater difficulty with treatment implies a need for non-dietary interventions.”
As researchers have taken a closer look at celiac disease, they’ve uncovered evidence that the gluten-free diet is not the complete treatment it was once thought to be. Studies have shown that people with celiac disease on the gluten-free diet continue to have symptoms, elevated antibodies to gluten detected in blood tests, and damage to the nutrient-absorbing lining of the intestine.
Studies have shown that even after two years on the gluten-free diet, 30 to 60 percent of adults with celiac disease have persistent gut damage. Data also suggests that this is true in more than 33 percent of adults regardless of having symptoms or positive blood tests.
Non-responsive celiac disease, which is defined as persistent symptoms, signs or abnormalities typical of the condition despite 6 to 12 months of strict adherence to a gluten-free diet, affects up to 30 percent of patients, according to a 2020 study.
Researchers at the University of Chicago Celiac Center found in a 2017 study that even after more than two years on the gluten-free diet about 60 percent of children and adults have ongoing non-gastrointestinal symptoms. Short stature, fatigue and headache were most common in children, while iron deficiency anemia, fatigue, headaches and psychiatric symptoms were most common in adults.
A 2016 study of children with celiac disease found one in five may not heal despite following the gluten-free diet for at least a year. The children, who were seen between 2008 and 2015, also had a follow-up biopsy at least 12 months after starting a gluten-free diet. The study found that 19 percent had persistent intestinal damage when the second biopsy was done.
A newly published study by researchers in Rome found that about one-third of people with celiac disease on the gluten-free diet had persistent symptoms or signs of malabsorption at the point when a follow-up biopsy was done. People with celiac disease who seem to be doing well on a gluten-free diet may have ongoing, low-level intestinal inflammation, according to another new study that looked at complete protein profiles in biopsy samples. Study authors said their findings raise the question of whether the standard gluten-free diet is sufficient to stop the immune reaction that occurs in celiac disease.
When researchers study how effective even a strict gluten-free diet is, they often find that the gluten-free diet in fact contains gluten. Celiac disease patients frequently get gluten in their gluten-free diets, according to a 2020 study that used urine and stool samples to measure real-world gluten exposure in celiac disease patients who had been on the gluten-free diet for more than two years and considered themselves to be following it strictly. 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.
Two thirds of patients who were strictly following a gluten-free diet still showed signs of having consumed gluten, according to a 2020 study that measured gluten in food, urine and stool samples contributed by people with celiac disease. The study is an innovative approach to determining how much gluten celiac disease patients who don’t knowingly eat gluten actually consume and how much they excrete through urine and stool samples.
One of the study authors succinctly summed up the problems with the gluten-free diet in celiac disease, saying it is more accurate to call it a low-gluten diet rather than a gluten-free diet. The gluten-free diet, she said, is more aspirational than achievable and explains why symptoms often persist and the intestine does not always heal.
Since the gluten-free diet is currently the only treatment for celiac disease, it leaves patients in a position where the only treatment they have does not reliably and thoroughly work. While most patients would improve with absolutely zero exposure to gluten, it is impossible to completely avoid gluten and many patients continue to suffer harmful effects even on a gluten-free diet. New treatments are being explored in clinical trials, and they are badly needed.