Cholesterol reduction using psyllium husks—do gastrointestinal adverse effects limit compliance? Results of a specific observational study

Phytomedicine: International Journal of Phytotherapy & Phytopharmacology, March, 2008 by B. Uehleke, M. Ortiz, R. Stange

Introduction

Despite the known cholesterol reducing effect of psyllium seed husks (PSH) that has been shown in a number of studies (Garvin et al., 1965; Levin et al., 1990; Chan and Schroeder, 1995; Anderson et al., 2000), their use for therapy of mild or moderate hypercholesterolemia in Germany is quite rare. One reason may be that until now there were only a few registered herbal drug products with this indication since PSH is mainly used as a laxative. Although patients often express a preference for herbal products over synthetically manufactured drug products, patients may be somewhat reticent to use the PSH products due to unwanted intestinal effects. It is known that ingesting PSH can cause meteorism from bacterial fermentation in the colon which is associated with gastrointestinal complaints of bloating, flatulence and even painful cramps. Although these unwanted effects are usually considered minor compared with rare but severe adverse reactions associated with commonly prescribed statins used to lower cholesterol, it is possible that the side effects associated with ingesting PSH limit patient compliance. Therefore we designed a study to characterize the incidence and tolerability of PSH treatment in an outpatient population with mild to moderate hypercholesterolemia and a medical indication for laxative treatment.

As an herbal product, PSH (Plantaginis ovatae testa, Ispaghula husks) is differentiated from the unprocessed psyllium (Plantaginis ovatae semen). PSH are processed through fractional grinding of the outer layer of the seed ESCOP (2003). Since the water-binding mucoid substances are located exclusively in the epidermis of the husks (Jamal et al., 1987), PSH have a much higher water-binding capacity swelling up to 40-100 times of their volume compared to unprocessed psyllium. The mucoid polysaccharide fraction of Indian PSH contains highly branched arabinoxylan with a xylose backbone and arabinose- and xylose-containing side chains (Sandhu et al., 1981; Marlett and Fischer, 2003). In contrast to arabinoxylans in cereal grains that are extensively fermented. PSH possesses a structural feature that hinders its fermentation by typical colonic microflora. The increased concentration of gel forming mucoids in PSH compared to unprocessed psyllium correlates with recommended daily dosages of 4-20 g for PSH and 12-40g for unprocessed psyllium. Clinical observations also suggest the bloating effect is higher for PSH.

The mechanism of action for PSH efficacy in lowering cholesterol is thought to involve altered cholesterol metabolism with increased hepatic cholesterol catabolism and increased fecal bile acid excretion (Vahouny et al., 1980; Everson et al., 1992: Romero et al., 2002).

Most studies report a very high compliance with psyllium or with PSH that ranges from 90% to 95% (Levin et al., 1990; Anderson et al., 1991; Chan and Schroeder, 1995). However, other investigators indicate that unpleasant side-effects, including abdominal distention, flatulence, and discomfort may limit adherence to dosing regimens with PSH (Flannery and Raulerson, 2000). Studies may differ in evaluating gastrointestinal adverse drug reactions (ADRs). Flatulence and bloating may be considered as only minor expected complaints or subjects might be reluctant to report unless tactfully queried which may result in possible under-reporting. Additionally study populations selected to investigate the effects of PSH on cholesterol often exclude patients with gastrointestinal disorders. Selected patient populations are likely to impact PSH tolerability outcomes. In a double blinded crossover study, healthy volunteers showed no increase in gas passage with psyllium, but reported a significant increase in bloating sensation (Levitt et al., 1996). Dietary fiber can trigger pain or bloating in some patients among the 10-15% of population with irritable bowel syndrome (Talley, 1999) and large amounts of fiber reaching the colon has been suggested as a potential mechanism of irritable bowel symptoms in patients with overeating disorder (Dapoigny et al., 2003). Interestingly, psyllium was more effective in lowering cholesterol in a population of veterans less than 60 years old compared to older patients undergoing evaluation at a Veterans Administration Medical Center lipid clinic. The study correlated efficacy and compliance for several lipid lowering agents (Schectman et al., 1993).

Flatulence is the gastrointestinal symptom most often associated with PSH that is likely to impact compliance; however, the effect has not been further characterized in terms of dose response for incidence or severity. Reports with healthy volunteers or patients with mild hypercholesterolemia often minimize gastrointestinal effects compared to effects on lipid profiles and emphasize high compliance. We questioned whether high compliance reported in study populations that excluded gastrointestinal disorders would be expected in patients with mild to moderately elevated cholesterol and gastrointestinal disorders requiring laxative therapy. A prospective study in out-patients with mild to moderate hypercholesterolemia and constipation was designed to assess PSH tolerance and compliance. Evaluation instruments included validated questionnaires and patient diaries that were employed to capture in detail all gastrointestinal symptoms over a 3-week treatment period. Additionally, the motivation for PSH continuation and the manner in which PSH was administered relative to meals and amount of liquid were specifically queried.