Background:

Over the past few decades, fructose is increasingly being used as a sweetener/ additive in a variety of foods. Incomplete absorption of fructose has been implicated as a cause of gastrointestinal symptoms. In tertiary care centers, the prevalence of fructose malabsorption in subjects with unexplained GI symptoms is thought to be between 11-50%, when assessed with breath tests following administration of 25 grams of fructose in a 10% solution. Restriction of dietary fructose has been shown to improve symptoms in these patients to an extent. Currently, there are no therapeutic agents that improve intestinal fructose absorption and thereby decrease symptoms. Studies in the pediatric population have shown that fructose absorption in the small intestine is increased in the presence of glucose or amino acids, especially alanine.

Objective:

The investigators' objective is to assess whether co-administration of an oral solution of L-alanine facilitates fructose absorption and decreases gastrointestinal (GI) symptoms associated with fructose malabsorption in subjects undergoing standard fructose breath test when compared to placebo.

Methods and analysis:

The investigators propose a randomized, double-blind study in 40 subjects with known fructose intolerance. After an overnight fast, each subject will receive an oral solution of 12.5 grams of alanine in 125cc of water or placebo. Next, the subject will receive an oral solution of 25 grams of fructose in a 10% solution. Serum, urine and breath samples will be collected at baseline and at 30-minute intervals for 4 hours. GI symptoms will also be assessed and recorded at 30 minute intervals using a standard questionnaire. Repeated measures ANOVA will be used to compare the data obtained during the study protocol with the baseline (pre-study) data.

Expected outcomes:

Co-administration of alanine with fructose may improve fructose absorption and decrease symptoms in subjects with fructose intolerance.

Hypothesis: Ingestion of alanine along with fructose, will facilitate intestinal absorption of fructose in subjects with fructose malabsorption.

Aim: To investigate the effects of co-administration of equi-molar doses of alanine on a) the absorption of fructose and b) the occurrence of GI symptoms in subjects with fructose malabsorption.

Inclusion Criteria:

1. Age between 18-70 years
2. Diagnosis of fructose malabsorption (positive breath test after ingestion of 25 grams of fructose defined as either (a) ≥ 20 ppm rise of breath H2/CH4/both over baseline values or a successive rise of ≥ 5 ppm over baseline and in 3 consecutive breath samples)

Exclusion Criteria:

1. Cognitive impairment or any other inability to provide informed consent
2. Prisoners
3. GI surgery except appendectomy, cholecystectomy, caesarean section, hysterectomy
4. Antibiotics in the previous 3 months
5. Bacterial overgrowth or lactose intolerance
6. Major co-morbid illnesses, including chronic pancreatitis, celiac disease, inflammatory bowel disease, diabetes, scleroderma, pseudo-obstruction syndromes etc.
7. Known food allergies
8. Medication use: opioids, Tegaserod, laxatives, enemas
9. Diabetes