ORIGINAL ARTICLE Fructose Intolerance in IBS and Utility of Fructose-Restricted Diet Young K. Choi, MD,* Nancy Kraft, RD, LD,w Bridget Zimmerman, PhD,z Michelle Jackson,w and Satish S. C. Rao, MD, PhD, FRCPw ructose is naturally present in fruits and vegetables, Introduction: Whether dietary fructose intolerance causes Fbut today it is avidly consumed in beverages and symptoms of irritable bowel syndrome (IBS) is unclear. We canned products as high fructose corn syrup.1 In the examined the prevalence of fructose intolerance in IBS and long- United States, the consumption of fructose has increased term outcome of fructose-restricted diet. several fold during the last 2 decades. A United States Methods: Two hundred and nine patients with suspected IBS Department of Agriculture study estimated that the annual consumption of fructose has risen from less than were retrospectively evaluated for organic illnesses. Patients 2 with IBS (Rome II) and positive fructose breath test received a ton in 1966 to 8.8 million tons in 2003. Unlike other instructions regarding fructose-restricted diet. One year later, sugars such as sucrose or lactose which are digested by their symptoms, compliance with, and effects of dietary sucrase or lactase enzymes produced by the intestinal brush border, the gut does not appear to have a specific modification on lifestyle were assessed using a structured 3,4 interview. enzyme for digesting or transporting fructose. Recent studies have shown that GLUT-5 and GLUT-2 which Results: Eighty patients (m/f = 26/54) fulfilled Rome II criteria. actively transport glucose across the mucosa may also Of 80 patients, 31 (38%) had positive breath test. Of 31 patients, play a role in facilitating absorption of fructose.4 26 (84%) participated in follow-up (mean = 13 mo) evaluation. Consequently, if fructose is ingested in large quantities, Of 26 patients, 14 (53%) were compliant with diet; mean the capacity of the gut to absorb fructose can be easily compliance = 71%. In this group, pain, belching, bloating, overwhelmed leading to fructose malabsorption and fullness, indigestion, and diarrhea improved (P<0.02). Of 26 symptoms.5–9 patients, 12 (46%) were noncompliant, and their symptoms were Dietary fructose intolerance is associated with many unchanged, except belching. The mean impact on lifestyle, common symptoms such as abdominal bloating, pain, compliant versus noncompliant groups was 2.93 versus 2.57 flatulence, and diarrhea.5,8 These symptoms are also (P>0.05). similar to those described by patients with lactose10 or 6,7,11 12 Conclusions: About one-third of patients with suspected IBS had sorbitol intolerance or bacterial overgrowth. Pre- 8 5 fructose intolerance. When compliant, symptoms improved on viously, we and others have reported a higher pre- fructose-restricted diet despite moderate impact on lifestyle; valence of fructose intolerance in patients with noncompliance was associated with persistent symptoms. unexplained gastrointestinal symptoms and dyspepsia. Fructose intolerance is another jigsaw piece of the IBS puzzle In contrast, a controlled study showed that the frequency that may respond to dietary modification. of gastrointestinal symptoms and the occurrence of fructose malabsorption were similar between Key Words: IBS, fructose intolerance, diet, breath test controls and patients with functional bowel disorder.13 (J Clin Gastroenterol 2008;42:233–238) Furthermore, the prevalence of fructose intolerance in patients with irritable bowel syndrome (IBS) is not clearly known. IBS affects 10% to 15% of the population in the 14 Received for publication August 23, 2006; accepted October 20, 2006. United States. The prevalence of fructose intolerance From the *Immanuel St Joseph’s, Mayo Health System, Mankato, MN; in patients with suspected IBS has not been systematically wDepartment of Internal Medicine; and zClinical Research Center, examined. Furthermore, whether IBS patients with University of Iowa Carver College of Medicine, Iowa City, IA. fructose intolerance benefit from a fructose-restricted diet The authors declare no conflict of interest. Supported in part by NIH RO1 grant DK 57100-05 and grant RR00059 is not known. from the General Clinical Research Centers program, National The aims of our study were to examine: (1) the Center for Research Resources. prevalence of fructose intolerance in patients with Reprints: Satish S.C. Rao, MD, PhD, FRCP, Department of Internal suspected IBS and to assess their symptom profiles and Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive/4612 JCP, Iowa City, IA 52242-1009 (e-mail: satish-rao@ (2) the effects of fructose-restricted diet on symptom uiowa.edu). patterns and lifestyle in patients with IBS and fructose Copyright r 2008 by Lippincott Williams & Wilkins intolerance. J Clin Gastroenterol Volume 42, Number 3, March 2008 233 Choi et al J Clin Gastroenterol Volume 42, Number 3, March 2008 METHODS From these data, a mean score was calculated for each Patients referred to our tertiary care center with symptom. suspected IBS or with persistent, unexplained, nonspecific Patients with a positive fructose breath test received gastrointestinal complaints between January 2001 and both written and verbal dietary instructions by a dietician January 2002 were evaluated with appropriate diagnostic regarding a fructose exclusion or restricted diet. The tests to identify organic illnesses including fructose breath written instructions comprised of a fructose-restriction test. Subsequently, case records were reviewed to identify diet manual that was developed by our dietician. This those patients who fulfilled the Rome II criteria for IBS patient-directed, self-guide informs the patient about the and/or functional abdominal bloating,15 together with an fructose content of common foods and how to avoid food absence of alarm symptoms. In particular, we excluded items such as fruit juice, cola products, carbonated patients with abnormal findings on a barium study, beverages, corn products, chocolates, and foods contain- computed tomography/ultrasound scan of abdomen, ing high fructose corn syrup. One year later, fructose upper or lower gastrointestinal endoscopy, hematologic intolerant patients were invited to participate in a follow- or biochemical studies or stool tests. Patients were also up telephone survey. Through a structured interview excluded if they had any coexisting active or inactive conducted by one of the investigators (Y.C.), we enquired gastrointestinal problems such as previous abdominal about their current symptoms, their compliance with the surgery (except appendectomy or hysterectomy), lactose fructose-restricted diet, and the effects of dietary restric- intolerance (negative lactose breath test), bacterial over- tion on their lifestyle. The patient’s symptoms at 1 year growth (negative glucose breath test), peptic ulcer disease, were compared with those obtained at baseline. The gastroparesis, dumping syndrome, pancreatic disorders, compliance with a fructose-restricted diet was designated biliary disease, liver disease, any malignancy, celiac as compliant, if the patient reported that they had disease, inflammatory bowel disease, gastrointestinal modified their diet substantially to reduce consumption reflux disease, eosinophilic gastritis, or lymphocytic of fructose products by Z50% of the amount consumed colitis. before testing and as noncompliant if it was <50%. The The following protocol was used to test dietary effect of dietary restriction on lifestyle was scored on a fructose intolerance. Patients were asked to refrain from modified Likert-like scale as follows: 0 (none), 1 (mini- taking high fat, lactose, or fructose containing foods for 1 mal), 2 (mild), 3 (moderate), 4 (significant), and 5 day before the test. Patients were also asked to fast from (extreme). midnight and refrain from smoking. After arrival in the The extra amount of time spent per week to comply motility laboratory, the patient was instructed to blow with the diet was assessed during the follow-up interview into a modified Haldane-Priestley bag (QuinTron, Mil- using the following scale: 1 = no extra time spent per waulkee, WI), and an end-expiratory breath sample was week; 2 = spending 1 extra hour; 3 = spending 3 extra collected. A 50 cm3 sample of air was taken from the bag hours; 4 = spending 4 extra hours; and 5 = spending and injected into a gas chromatography analyzer (Quin- more than 5 extra hours. tron Microlyzer Self Correcting Model SC, QuinTron, To assess the test-retest reliability of the bowel Milwaukee, WI), and baseline values for hydrogen (H2) symptom questionnaire, we administered the symptom and methane (CH4) were measured. These values were questionnaire twice, at 1-week interval to 25 additional corrected for CO2. Next, the patients were asked to drink participants that included 8 healthy volunteers and 17 a solution containing 25 g of fructose dissolved in 250 mL patients who were undergoing breath tests for either of water (10% solution). This dose was chosen on dose research or clinical purposes. During this period of response studies of fructose absorption in healthy hu- assessment, these participants were advised to continue mans.16 Thereafter, breath samples were collected at 30- with their usual diet and were unaware of the results of minute intervals for 5 hours, and analyzed for H2 and the breath test. CH4. During the test, any symptoms experienced by the The study was approved by the University of Iowa patient were recorded. An incremental