What Happens When the Gluten-Free Diet Honeymoon is Over?

gluten free mealThe only current treatment for celiac disease is a life-long gluten-free diet (GFD). Starting a strict diet usually results in prompt relief of clinical symptoms, while recovery of small-bowel mucosal damage may take  years. Although mucosal healing is the ultimate goal of the dietary treatment from the patient’s perspective alleviation of self-perceived clinical symptoms is usually the most rewarding outcome.

In a study by Pilvi Laurikka, Teea Salmi, Pekka Collin, Heini Huhtala, Markku Mäki, Katri Kaukinen and Kalle Kurppa, while there was a good response to the gluten-free diet in  long-term follow-up, not all patients reach the level of healthy individuals.

A good clinical response in the early stages of dietary treatment further motivates to maintain a strict diet, which consequently facilitates mucosal recovery. boredom gluten free dietThere is some evidence that after the initial enthusiasm has faded, many patients experience ongoing symptoms while maintaining an apparently strict gluten-free diet. Such persistence of symptoms despite burdensome dietary restriction is frustrating and may even predispose to poor dietary adherence and thus further worsen the situation.

Until now, the prevalence nor the severity of the persistent symptoms in celiac disease patients on a gluten-free diet has been well characterized, let alone their impact on patients’ daily life. It was felt that data on these aspects would be necessary in order to optimize the follow-up of patients and, in the future, to develop interventions on top of the gluten-free diet.

The aim of the present nationwide study was to define the prevalence and severity of gastrointestinal symptoms in a large cohort of long-term dietary treated adult celiac disease patients and to compare these with those seen in untreated and short-term treated patients and in healthy controls. Further, symptom severity was compared with other common gastrointestinal diseases based on a literature search.

The Study

Altogether, 856 patients were classified into untreated, short-term GFD  and long-term GFD groups. The median age of all 856 celiac disease patients was 54 years (range 15–85 years) and 75% were females.

There were no significant differences between the celiac disease groups in either gender, median age at time of study, clinical presentation at diagnosis or celiac disease in the family.

Gastrointestinal Symptom Rating ScaleParticipants in each group filled a self-administered, structured Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The questionnaire measures five sub-dimensions of gastrointestinal symptoms: Indigestion, diarrhea, abdominal pain, reflux and constipation. It comprises altogether 15 separate items.

Besides between study groups, the GSRS scores in untreated and long-term treated celiac disease patients were compared with those seen in subjects with common gastrointestinal disorders, namely peptic ulcer, gastro-esophageal reflux disease, inflammatory bowel disease and irritable bowel syndrome.


  • Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa.
  • Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls.
  • There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls
  • Patients treated 1–2 years had more diarrhea;  those treated >10 years had more reflux than controls.
  • Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases.

The main finding in the present study was that both short-term and long-term dietary treated celiac disease patients have more symptoms than non-celiac controls. However, although the majority of gastrointestinal symptoms are alleviated well on a strict gluten-free diet, not all patients reach the level of the general population even in long-term follow-up.

The majority of the celiac disease patients showed rapid relief of symptoms during the first year on a gluten-free diet. The only exception here was diarrhea, which, although alleviated on a long-term diet, remained fairly common in short-term-treated patients.

In contrast to the well-documented short-term outcome, the long-term response to a gluten-free diet has thus far been poorly investigated. Judging from our results, in most patients with good adherence and recovered villi the good initial response to the diet remains after several years, demonstrating that it is not only based on a short-term “honeymoon” effect.

unresolving long term symptomsWe observed long-term treated celiac disease women to experience more symptoms than men. One plausible explanation for the gender difference might be the higher prevalence of concomitant functional gastrointestinal disorders in women, which have also been shown to be exacerbated by psychological distress such as that involved in following a burdensome dietary treatment.

Women may also find the inevitable social restrictions caused by the gluten-free diet harder to cope with. Other possible reasons could be differences in fiber intake and the symptom-modifying effect of gonadal hormones. In any case, physicians should acknowledge the higher risk of persistent symptoms in women and provide adequate support if needed.

The most common reason for the persistence of symptoms in celiac disease has been ongoing gluten consumption. If gluten intake is excluded, other explanations for persistent symptoms must be sought in patients with proven strict adherence. These include for example small-intestinal bacterial overgrowth or some other concomitant disorder such as IBD and microscopic colitis, and refractory celiac disease.

An interesting new research topic related to this issue is dysbiosis of the intestinal microbiota. We have recently shown that celiac patients suffering from persistent symptoms on a gluten-free diet had an altered balance and reduced richness of duodenal microbiota. The intestinal microbiota affects the complex gut-brain axis along with the enteric nervous system, immune system and external environment, and alterations in this axis may predispose to chronic pain in functional gastrointestinal disorders and perhaps also in celiac disease. A deeper understanding of these mechanisms would be important in order to make the development of new pharmacological interventions possible.

Notwithstanding this long-lasting positive effect, we found even long-term dietary treated patients to have more symptoms than healthy controls. Such ongoing symptoms may in the long run discourage patients from adhering to what is a socially restrictive and expensive treatment mode if they consider it ineffective.

In such cases, it is particularly important for physicians to urge patients to persist with a strict gluten-free diet in order to prevent disease-associated complications. In addition to the increased GSRS total score, particularly reflux symptoms showed a tendency to persist for several years. Gastro-esophageal reflux is common in general populations and in earlier studies it has appeared to be approximately as common in celiac patients.


In conclusion, we showed that the good initial clinical response to a gluten-free diet is sustained also in the long run. However, it is important for physicians to realize that one year might not be long enough for all symptoms to abate, and that some patients may continue to have mild or moderate gastrointestinal symptoms despite long-term and strict dietary treatment. A fuller understanding of the factors behind persistent symptoms in celiac disease would provide new treatment possibilities in the future.

physician understanding
(This article belongs to the Special Issue From Ptolemaus to Copernicus: The Evolving System of Gluten-Related Disorders)
Received: 17 May 2016 / Revised: 7 July 2016 / Accepted: 11 July 2016 / Published: 14 July 2016
Nutrients 2016, 8(7), 429; doi: 10.3390/nu8070429 as per https://www.mdpi.com/2072-6643/8/7/429/htm