ffect of Psyllium, Calcium Polycarbophil, and Wheat Bran on Secretory Diarrhea Induced by Phenolphthalein

ANDREAS J. EHERER, CAROL A. SANTA ANA, JACK PORTER, and JOHN S. FORDTRAN

Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas

Background： Fiber and water-holding agents are used for the treatment of constipation. In what may appear to be a paradox, they are sometimes also used for the treatment of diarrhea; it has been proposed that they sequester water from liquid stools and/or increase the ratio of fecal solids to fecal water and thereby improve stool consistency. The purpose of the present study was to test the validity of this hypothesis in normal subjects in whom secretory diarrhea was induced by phenolphthalein. Methods： In random sequence, 9 subjects with phenolphthalein-induced diarrhea were treated with placebo, psyllium, calcium polycarbophil, or wheat bran. Results： Calcium polycarbophil and wheat bran had no effect on fecal consistency or on fecal viscosity. By contrast, psyllium made stools firmer and increased fecal viscosity. In a dose-response study in 6 subjects, doses of 9,18, and 30 g of psyllium per day caused a near linear increase in fecal viscosity. Conclusion： Psyllium, but not calcium polycarbophil or wheat bran, improves fecal consistency and viscosity in subjects with experimentally-induced secretory diarrhea.

Increasing the intake of water-holding agents is an accepted method of treating constipation. Products such as psyllium, calcium polycarbophil, and wheat bran are believed to pass through the intestine undigested, to hold water on their "hydrophilic sites'" and thereby to cause fecal water output to increase and stools to become bulkier and softer.

In what might appear to be a paradox, these products sometimes have been used for the treatment of diarrhea. It is proposed that they sequester water from liquid stools² and/or increase the ratio of fecal solids to fecal free water and that they thereby enhance the consistency of diarrheal stools. It was the purpose of the present study to evaluate the validity of this hypothesis in normal subjects in whom secretory diarrhea was induced by phenolphthalein. This model was chosen over a study of patients with diseases that cause diarrhea because phenolphthalein works by known mechanisms, and the severity of the induced diarrhea is consistent from day to day, which makes it relatively easy to measure the effect of a therapeutic modality.

To assess the effect of various treatments, we measured stool consistency by a visual grading system and stool viscosity by viscometry. The fecal output of water, solids, sodium, and potassium was also measured.

Materials and Methods

Effect of Psyllium, Calcium Polycarbophil, and Wheat Bran

Nine normal subjects (7 men and 2 women) ranging in age from 20 to 36 participated in the experiment. The subjects were medical technologists or seminary students and their wives; they were highly motivated to adhere to a strict protocol, and they were all experienced in the technique of quantitative stool collection. Secretory diarrhea was induced by ingestion of 360 mg of white phenolphthalein (Medilax; Mission Pharmaceutical Company, San Antonio, Texas) three times a day at 8 AM, 2 PM, and 8 PM (total dose 1080 mg/day). This was followed by drinking 250 mL of electrolyte solution (NaCl, 60 mmol/L; KC1, 20 mmol/ L; NaHCO₃, 30 mmol/L) to compensate for expected water and electrolyte losses due to diarrhea. The phenolphthalein was ingested on four consecutive days, and stools were quantitatively collected.

This fbur-day experimental diarrheal protocol was repeated on four different occasions in each subject with at least 10 days separating each episode. The subjects were treated with four regimens in random order: (1) placebo, which consisted of empty gelatin capsules, three times a day; (2) psyllium (Konsyl; Lafayette Pharmaceutical Company, Fort Worth, TX), ingested in doses of 6 g three times a day (total dose 18 g/day); (3) calcium polycarbophil (Mitrolan; A. H. Robins Company, Richmond, VA), ingested in doses of 2 g three times a day (total dose 6 g/day); and (4) unprocessed wheat bran (Hodgson Mill, Teutopolis, IL), ingested in doses of 14 g three times a day (total dose 42 g/day, equivalent to about 18 g fiber). This wheat bran is particulate in nature and is made from the outermost layer of the wheat berry. All four therapies were ingested at 10 AM, 4 pm, and 10 pm (2 hours after each dose of phenolphthalein). The doses of psyllium and calcium polycarbophil are within the recommended range of intake for treatment of constipation;

© 1993 by the American Gastroenterological Association 0016-5085/93/$3.00 the dose of bran corresponded to the fiber content of the psyllium dose. Each dose of therapeutic agent or placebo was ingested with 500 mL of water. The total amount of prescribed fluid intake was 2250 mL per day (1500 mL water and 750 mL of electrolyte solution).

The subjects were allowed to eat their normal diet during the experiments, but they kept a record of all ingested foods on diary cards, and they were asked to maintain a similar diet during each of the four study periods. The time of each bowel movement was also recorded on the diary cards.

The stools were collected quantitatively using preweighed containers and were stored in an ice chest. The first day of each study period was considered to be an adaptation period; the collection from this day was not analyzed. Stools collected on days 2, 3, and 4 were weighed, visually graded for consistency (see next paragraph), and measured for viscosity. At the end of the experiment, the stools collected on days 2, 3, and 4 were pooled for analysis of sodium and potassium output after dry ashing and for percent of water content by lyophilization.

The consistency of each daily stool specimen was graded subjectively by a technician who was unaware of which of the four possible therapies the subjects were ingesting. Stools were classified into one of five levels of consistency:⑴ formed: stool maintains its shape; (2) semifbrmed: some of the stool is formed, but part is soft; (3) soft: unformed, will not pour, jellylike; (4) semiliquid: pours, has consistency of a milk shake, honey, or ketchup; (5) runny: pours more easily than a milk shake, honey, or ketchup. In a separate subjective analysis, the subjects recorded on daily diary cards whether or not they had urgency and/or fear of fecal incontinence.

For measurement of stool viscosity we used a viscometer, range of measurement 40-400,000 centipoise (cp) (Model 4535; Lab-Line Instruments, Inc., Melrose Park, IL). The principle by which this viscometer operates is that a cylin- derical spindle rotates at a constant speed in the specimen and the torque (rotating force) for maintaining rotation is converted to viscosity values. Measurements were made with the smallest spindle (#7) of the standard equipment, with a spindle speed of 10 rpm. Based on preliminary experiments, we established a strict protocol for processing the specimens. When the volunteers brought in their stool collections, the containers were removed from the ice chest and taken to a fume hood for 2 hours where they adapted to room temperature. (Measurements were not done at 37°C because at this temperature stools started to ferment, producing visible gas bubbles within the stools that made viscosity readings inconsistent.) The stools were stirred 10 times using a rubber spatula, always applying the same force and speed. Then an aliquot of 120 mL was placed into a plastic beaker (ID, 5.5 cm), and the spindle was inserted and rotated at 10 rpm. The readings for viscosity were done after 2 minutes; in preliminary experiments steady measurements were achieved at this time. Three separate measurements in different locations within the center of the beaker were made; the spindle was cleaned and dried before each of the three readings. The average of the three readings was taken as the viscosity of a daily stool specimen. For the purpose of comparison of different treatments, the viscosity values of stools from days 2, 3, and 4 were averaged.

Statistical analysis was performed by use of analysis of variance and paired t test. P values <0.05 were considered to be statistically significant.

Comparison of Different Doses of Psyllium

Psyllium was selected for further study because it was the only agent that favorably influenced fecal consistency and viscosity in subjects with diarrhea. In the experiment reported in the previous section, the dose of psyllium was 18 g/day; additional studies were performed with 9 and 30 g/day. Six of the 9 subjects who took part in the previous experiment were studied with the additional doses. Meals and phenolphthalein were ingested exactly as described in the first experiment. For the 9 g/day dose, subjects ingested 3 g of psyllium at 10:00 AM, 4:00 pm, and 10:00 pm； each dose was ingested with 250 mL water. For the 30 g/day dose, subjects ingested 6 g of psyllium at 9:30 AM, 11:00 AM, 3:30 pm, 5:00 pm, and at 10:00 pm； each dose was ingested with 500 mL water. The total amount of water ingested with placebo or psyllium was as follows: placebo, 1500 mL; 9 g/day psyllium, 750 mL; 18 g/day psyllium, 1500 mL; 30 g/day psyllium, 2500 mL. (These water volumes correspond to manufacturers recommendations for psyllium therapy in order to prevent esophageal or intestinal obstruction.) For all doses of psyllium and placebo, the subjects ingested 750 mL/day of the electrolyte solution as in the previous set of studies.