Effect of a gluten-free diet on gastrointestinal symptoms in celiac
Joseph A Murray, Tureka Watson, Beverlee Clearman, and Frank Mitros
presentation rather than the classic presentation of malabsorptive
Background: Atypical presentations of celiac disease appear to be
symptoms (5–10). Patients who have so-called atypical presen-
at least as common as is the classic presentation of steatorrhea,
tations seem to be at least as common as are those with the classic
diarrhea, and weight loss.
syndrome. There are few detailed reports of the effectiveness of
Objective: We examined the effect of a gluten-free diet on gastro-
a gluten-free diet on these atypical symptoms. The aims of the
intestinal symptoms in a cohort of US patients with celiac disease.
present study were to identify the frequency and nature of gas-
Design: A follow-up survey was conducted in 215 patients who were
trointestinal symptoms in a large cohort of patients with diag-
evaluated at the University of Iowa from 1990 through 1997 as
nosed celiac disease and to determine the effect of a gluten-free
having biopsy-confirmed celiac disease. The systematic survey
diet on these symptoms.
asked detailed questions regarding gastrointestinal symptoms before
and after the institution of a gluten-free diet in the patients, all of
whom had been given the same dietary advice.
SUBJECTS AND METHODS
Results: The group consisted of 160 female and 55 male patients.
Although diarrhea was the most frequent symptom in untreated
A systematic survey of subjects with diagnosed celiac
celiac disease, steatorrhea occurred in only one-fifth of patients.
Other complaints were common, and most responded to gluten ex-
The study population consisted of 215 patients in whom celiac
clusion. The benefit of gluten exclusion was equally apparent in men
disease was diagnosed according to internationally accepted cri-
and women. Diarrhea responded in most patients, usually within
teria (11). All the patients had an intestinal biopsy specimen
days, and the mean time to resolution was 4 wk. Many patients had
compatible with celiac disease and a clinical response to a gluten-
by on October 11, 2010
alternating diarrhea and constipation, both of which were responsive
free diet. These patients were seen at a single institution in the
to the gluten-free diet. Most patients had abdominal pain and bloat-
upper-midwestern region of the United States. The disease was
ing, which resolved with the diet.
diagnosed in the 215 patients between 1984 and 1998; the disease
Conclusions: Celiac disease causes a wide range of gastrointestinal
was diagnosed in 195 of the patients after 1990 and in 188 of the
symptoms. Clinicians must have a high level of suspicion to detect
patients after 1995. The age at diagnosis ranged from 1 to 90 y,
the atypical forms of celiac disease. With a gluten-free diet, patients
with a median of 48 y. There was a female-to-male predominance
have substantial and rapid improvement of symptoms, including
of 3 to 1. The mean age at diagnosis was 55 y. Eighty percent of
symptoms other than the typical ones of diarrhea, steatorrhea, and
the patients were adults at the time of diagnosis.
Am J Clin Nutr 2004;79:669 –73.
Identification of subjects
Celiac disease, gluten-free diet, abdominal
For all subjects, the diagnosis of celiac disease was made at a
pain, enteropathy, irritable bowel syndrome
single institution. Histologic evidence based on duodenal or je-
junal biopsy specimens was obtained for all subjects and was
interpreted by a single experienced gastrointestinal pathologist.
Sixty-two percent of the patients had follow-up biopsies for
Celiac disease, otherwise known as gluten-sensitive enterop-
evaluation of recovery of the duodenal mucosa. Those who did
athy, is considered a rare disease in the United States (1). The
not have a follow-up biopsy had a dramatic, clinically obvious
classic syndrome of celiac disease as originally described by Gee
response to a gluten-free diet. All the subjects fulfilled the ac-
(2) consists of steatorrhea, diarrhea, and weight loss in adults and
failure to thrive in children and evidence of overt nutritional
1 From the Division of Gastroenterology and Hepatology, Mayo Clinic,
deficiencies due to small-bowel malabsorption. Subtle presen-
Rochester, MN (JAM), and the Departments of Psychiatry (TW), Clinical
tations of celiac disease were first described 30 y ago (3). A
Nutrition (BC), and Pathology (FM), University of Iowa, Iowa City.
serum survey of anonymous US blood donors found a high fre-
Supported by NIH grant DK 57892-01 (to JAM).
3 Address reprint requests to JA Murray, Division of Gastroenterology
quency of markers for covert celiac disease (4).
and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
The European experience with celiac disease has provided a
perspective that illustrates a broad spectrum of modes of presen-
Received July 22, 2003.
tation of the disorder and the frequency of monosymptomatic
Accepted for publication October 2, 2003.
Am J Clin Nutr 2004;79:669 –73. Printed in USA. © 2004 American Society for Clinical Nutrition
MURRAY ET AL
cepted criteria for establishing the diagnosis of celiac disease
(11). All the subjects received similar dietary instruction on a
Effect of a gluten-free diet on BMI in patients with celiac disease1
gluten-free diet, and this instruction was provided by the same
After 6 mo of a
dietitian, who was experienced in the dietary treatment of celiac
disease. Identical written material was used to aid in the educa-
tion of each patient. Every effort was made to see that the patients
BMI category (%)
adhered to a strict gluten-free diet. All the patients were seen
routinely by the same dietitian for at least one follow-up visit and
were actively encouraged to join local or national support groups
for celiac disease. Just one patient openly acknowledged eating
gluten-containing foods on a regular basis. All the others denied
deliberately consuming gluten more than once a month. Except
for the one noncompliant patient, all the subjects showed sub-
BMI category (%)
stantial improvement on follow-up biopsy, if performed. The
noncompliant patient, however, had persistently positive en-
domysial antibodies and villous atrophy. Two other patients
could not be interviewed because they died before the survey.
A scripted telephone interview was carried out by trained,
215. Underweight, BMI (in kg/m2) 20; normal, BMI
experienced gastrointestinal nurses who were not involved in the
24.9; overweight, BMI
25–29; obese, BMI
care of the patients. The interviews were done between 1997 and
SD (all such values).
6 mo after the diagnosis of celiac disease and the start of
a gluten-free diet. Detailed questions were asked concerning 1)
the presence of gastrointestinal symptoms at the time of diagno-
12.5 kg (range: 1– 63 kg). This weight loss was most pronounced
sis, 2) the patient’s perspective on how the gluten-free diet had
in the patients who were obese at diagnosis. However, 12 patients
affected each of these symptoms, and 3) the duration, frequency,
who had normal or low weight at diagnosis actually lost weight
severity, and features of the patient’s bowel movements at diag-
despite a gluten-free diet. This was largely due to excessive food
6 mo after the start of a gluten-free diet. On the basis
restriction rather than persistent disease.
of a search of the records of the Departments of Pathology,
Gastroenterology, and Dietetics and the hospital diagnostic in-
dex, the 215 patients who participated in the present study con-
The prevalence of various gastrointestinal symptoms before
by on October 11, 2010
stituted all the patients in whom celiac disease was diagnosed
the diagnosis of celiac disease is shown in Table 2. Seventy-five
between 1984 and 1997. The study was approved by the Institu-
percent of the patients said that they had had diarrhea, which was
tional Human Research Board of the University of Iowa.
defined as liquid or unformed stools at least monthly, before the
diagnosis of celiac disease. However, only 47% of the patients
reported daily diarrheal stools before diagnosis (Figure 1). More
McNemar’s chi-square test was used to compare paired cate-
than one-half of the patients with diarrhea had buoyant and mal-
gorical variables. The sign test was used to examine trends in the
odorous stools suggestive of steatorrhea. Not surprisingly, only
frequency of symptoms over time. A P value 0.05 was con-
12% reported bloody diarrhea. Sixty-one percent complained of
sidered significant. An analysis of variance test based on ranks
frequent flatulence, and 64% had urgency. Thirty-one percent
was used to test for any significance of sex on outcomes of the
complained of significant tenesmus, and 38% had experienced
gluten-free diet. Statistical analyses were performed by using
fecal incontinence. Just over one-half of the patients reported
SAS (version 6; SAS Institute Inc, Cary, NC).
Gastrointestinal symptoms before and after a gluten-free diet in patients
with celiac disease1
Weight change and body mass index
The median (
SEM) body mass index (BMI; in kg/m2) of the
6.2) was not significantly different from that of
the men (23.4
5.1). Two-thirds of the patients reported weight
loss in the 6 mo before diagnosis. One-half of these patients had
a BMI 20, and of the 23% who had a BMI
25, 11% were
30) (Table 1). The same proportions of males and
Nausea or vomiting
females gained or lost weight after the institution of a gluten-free
diet (for the males, 31% gained and 41% lost; for the females,
36% gained and 35% lost). Ninety-one patients gained weight
2,3 Significantly different from before diet (McNemar’s chi-square test):
between the time of diagnosis and 6 mo after starting a gluten-
2P 0.001, 3P 0.02.
free diet, and the weight gain ranged from 0.5 to 46 kg (average
4 Significantly different from before diet, P 0.01 (binomial propor-
of 7.5 kg). In the same period, 25 patients lost an average of
GLUTEN-FREE DIET IN CELIAC DISEASE
ence of both diarrhea and constipation before diagnosis of celiac
Seventy-nine percent of all the subjects reported having had
significant recurrent abdominal pain before the diagnosis of ce-
liac disease. Although the pain could be present in any part of the
abdomen, it was most commonly reported in the lower part or
diffusely throughout the abdomen. A substantial minority of
patients cited the right upper quadrant or epigastrium as the
primary site of abdominal pain. Forty-six percent of the patients
indicated that the pain was worse with eating. Sixty percent said
the pain improved after defecation. The pain was described as
FIGURE 1. Change in frequency of diarrhea in patients with celiac
cramping and intermittent or, less commonly, sharp. Most of the
215) before and 6 mo after starting a gluten-free diet (GFD).
patients described it as being severe. Fully 48% of the reported
symptoms were consistent with the Rome II criteria for irritable
bowel syndrome. After 6 mo of consuming a gluten-free diet, just
postprandial diarrhea (Figure 2). The effect of a gluten-free diet
2 patients still met these criteria (P 0.0001 for comparison with
was dramatic in most patients, with resolution of the symptoms
the number who met the criteria before diagnosis of celiac dis-
related to diarrhea. The prevalence and frequency of diarrhea
ease), and 95% of the patients had substantial relief or com-
dropped substantially (P 0.001) after the institution of a gluten-
plete resolution of their pain, usually within days of the intro-
free diet (Figure 1). Sixty-six percent of the subjects who had
duction of a gluten-free diet. Postprandial pain decreased
diarrhea initially had complete resolution of the diarrhea by 6 mo.
significantly after a gluten-free diet (P
In the subjects who reported persistent diarrhea after the gluten-
free diet, most had a dramatic reduction in the frequency of
diarrhea (P 0.001). Fecal incontinence became very uncom-
Other gastrointestinal symptoms
mon after treatment (P
0.004). When asked to estimate when
Nausea was reported by 42% of the patients before the diag-
the diarrhea started to subside after they began using a gluten-free
nosis of celiac disease; vomiting occurred in just over one-fifth of
diet, most of the patients reported significant improvement
these patients. These symptoms usually resolved with a gluten-
within 31 d; only 23% said that 31 d were needed for signif-
free diet (Table 2). Lactose intolerance was self-reported in 39%
icant improvement (Figure 3).
of the patients before diagnosis of celiac disease. Seventy-two
Constipation, which was defined as the infrequent passage of
percent of these patients had a formal laboratory or medically
by on October 11, 2010
firm stool associated with a sense of discomfort, was reported in
confirmed diagnosis of lactose intolerance before the diagnosis
38.6% of the subjects before diagnosis (Table 2). Most of these
of celiac disease. Interestingly, less than one-half of the patients
patients reported resolution of the constipation within 6 mo of
with lactose intolerance before the diagnosis of celiac disease
adapting to a gluten-free diet (P 0.02). The patients reported a
reported that they had successfully incorporated lactose into their
significant reduction in the need for straining (P
diet after starting a gluten-free diet. It is possible that this was an
need for laxatives (P
0.001), and subjective problems with
underestimate because it took a mean of 8 mo (range: 1–36 mo)
0.001). Patients frequently reported the pres-
for a complete resolution of lactose intolerance to occur.
FIGURE 2. Percentage distribution of specific bowel features or symptoms at diagnosis in patients with celiac disease (n
MURRAY ET AL
the amount of small intestine affected by the disease. Interest-
ingly, many of those who were obese at diagnosis lost weight on
the gluten-free diet. Micronutrient deficiencies may have driven
specific food cravings, as occurs in pica, which has been reported
in iron-deficient children with celiac disease (13).
The high frequency of abdominal pain was unexpected. It
almost certainly contributes to the misery of patients with un-
treated celiac disease. The relation of pain to meals suggests a
maldigestive component to the pain. Among children with celiac
disease, abdominal pain was found to be more common in those
who tested positive for Helicobacter pylori than in those who did
not (14). However, because the abdominal pain resolved with the
gluten-free diet, it is possible that a combination of celiac disease
and the effects of H. pylori infection caused the pain. In many
patients with celiac disease, the disease is initially diagnosed as
FIGURE 3. Time required for alleviation of diarrhea after patients with
celiac disease (n
215) started a gluten-free diet.
irritable bowel syndrome. In this cohort of patients, fully 46%
would have met the symptomatic criteria for irritable bowel
syndrome laid down by the Rome II system, namely, frequent
Seventy-three percent reported abdominal bloating, which was
abdominal pain associated with a disordered bowel habit (15).
usually described as generalized abdominal distention that usu-
The variety of symptoms experienced by patients who ulti-
ally occurred after eating. Almost all of these patients reported
mately prove to have celiac disease is a major impediment to
complete relief of bloating with the institution of a gluten-free
diagnosis. Many of these features are nonspecific and are more
diet (P 0.0001) (Table 2). Seven subjects (4 females and 3
often seen as manifestations of other diseases, such as irritable
males) had no specific gastrointestinal symptoms; among these
bowel syndrome. Before the diagnosis was made, the physicians
patients, 2 males had weight loss and the other patients had
of many of these patients assumed that functional causes were to
blame for the symptoms. However, the dramatic response of
these symptoms to restriction of dietary gluten implies that those
Onset of new symptoms after introduction of a
symptoms were not due to a coexistent irritable bowel syndrome.
The frequent misdiagnosis of irritable bowel syndrome in pa-
After starting a gluten-free diet, 6.2% of the patients who had
tients with celiac disease may in part be due to a low degree of
not had diarrhea before the diagnosis of celiac disease experi-
suspicion for celiac disease, but it may also be attributable to the
enced diarrhea. Constipation occurred in 18.6%; in many cases,
erroneous assumption that abdominal pain is a rare symptom in
by on October 11, 2010
it responded to a subsequent increase in fiber intake.
celiac disease. Indeed, a study from the United Kingdom reported
a 5% prevalence of celiac disease among patients referred by
their general practitioner for irritable bowel syndrome (16). Se-
rologic screening tests may be useful for the primary care prac-
This detailed report in a cohort of US patients with diagnosed
titioner in identifying patients with celiac disease (17).
celiac disease illustrates the broad spectrum of gastrointestinal
One of the strengths of the present study was the very high
symptoms and the efficacy of intervention with a gluten-free diet.
response rate ( 98%) of the subjects, probably because 90%
Celiac disease has traditionally been thought of as a diarrheal
of the patients had routine follow-up with the same gastroenter-
illness. However, although most of our patients had some diar-
ologist and dietitian. The benefit of a gluten-free diet was clearly
rhea before diagnosis, less than one-half of them had daily diar-
established in this group of patients and is not surprising. How-
rhea; a substantial portion of them had constipation after con-
ever, not all the patients had complete resolution of their symp-
suming the gluten-containing diet. These results are consistent
toms. Although symptoms may persist or recur after 6 mo, they
with the symptoms reported in a large questionnaire study (12);
are usually much less severe. Quality of life was not directly
however, unlike that study, all the patients in the present study
measured in this study but probably improved substantially with
were from a specific geographic location and received uniform
the dramatic reduction in symptoms. In the small proportion of
dietary intervention. In many cases the diarrhea was not the
patients who continue to have diarrhea or constipation or in
feature that precipitated medical evaluation. Indeed, many pa-
whom such symptoms develop with treatment, these persistent
tients with long-standing, undiagnosed celiac disease regarded
symptoms may be associated with a lower quality of life, espe-
their bowel movements as normal or even as typical of consti-
cially in female patients (18). Fine et al (19) systematically
pation, and only on direct questioning was the symptom elicited.
investigated persons with celiac disease who had persistent di-
However, direct questioning about the nature of the stools and the
arrhea and identified lymphocytic colitis, disaccharidase defi-
frequency of diarrhea may provide useful information in the
ciency, and pancreatic exocrine insufficiency as causative fac-
evaluation of patients who have other features of the disease.
tors, all of which may be amenable to treatment. The new onset
Celiac disease has been regarded as a malabsorptive condition
of constipation after the introduction of a gluten-free diet
that results in weight loss in adults and in failure to thrive in
probably reflects a decrease in fiber intake, and many such
children. Our patients showed substantial differences in BMI at
patients respond to the addition of dietary fiber. In other
the time of diagnosis: one-half of the patients were underweight;
patients, the new onset of constipation may reflect a return of
yet a substantial minority was overweight, and some were even
a predisposition to constipation after resolution of the malab-
obese. These differences may be accounted for by differences in
GLUTEN-FREE DIET IN CELIAC DISEASE
Is it likely that these results can be replicated in other popu-
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ern US population, who generally tend to be very compliant.
5. Bottaro G, Cataldo F, Rotolo N, Spina M, Corazza GR. The clinical
Another feature that may have increased the likelihood of com-
pattern of subclinical/silent celiac disease: an analysis on 1026 consec-
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utive cases. Am J Gastroenterol 1999;94:691– 6.
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in a large cohort of patients.
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measured the benefit only on an intention-to-treat basis.
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JAM undertook the design and execution of the study, wrote the manu-
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script, and was primarily responsible for the research presented here. TW
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participated in the design of the methods, undertook data collection, oversaw
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was involved in the design of the instruments used for questioning; and
14. Luzza F, Mancuso M, Imeneo M, et al. Helicobacter pylori infection in
provided commentary on the draft of the manuscript. FM undertook patho-
children with celiac disease: prevalence and clinicopathologic features.
logic examinations, verified the diagnosis in the cohort, and provided com-
J Pediatr Gastroenterol Nutr 1999;28:143– 6.
mentary on the methods and the draft of the manuscript. None of the authors
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had any conflicts of interest.
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