Mechanisms of LDL-cholesterol lowering action of psyllium hydrophillic mucilloid in the hamster

Abstract

Psyllium hydrophillic mucilloid (psyllium) is a soluble fiber that significantly lowers plasma low-density lipoprotein (LDL)-cholesterol levels in humans and experimental animals. These studies were designed to determine whether this action is the result of a reduction in LDL-cholesterol production, an increase in receptor-mediated LDL clearance by the tissues, or a combination of these mechanisms. Adult male Golden Syrian hamsters were fed ad libitum for 30 days a cereal-based diet containing added cholesterol (0.1%) and hydrogenated coconut oil (10%), as well as either microcrystalline cellulose (Avicel) (7.5%) or psyllium (7.5%). In contrast to their Avicel-fed controls, the hamsters given psyllium had markedly lower plasma total (122.1 +/- 4.1 vs. 399.4 +/- 39.4 mg/dl) and LDL-cholesterol (46.0 +/- 2.2 vs. 143.5 +/- 12.0 mg/dl) levels. Psyllium feeding also prevented both the dramatic increase in hepatic total cholesterol levels (2.6 +/- 0.1 vs. 16.6 +/- 1.1 mg/g), and the suppression of hepatic cholesterol synthesis (165.1 +/- 27.1 vs. 26.1 +/- 1.2 nmol/h per g) that occurred in the animals given Avicel. Compared to their controls, the psyllium-fed animals also manifested a 44% lower rate of LDL-cholesterol production (167.6 +/- 8.1 vs. 300.2 +/- 16.0 micrograms/h per 100 g bw), and a 2.2-fold higher rate of hepatic LDL clearance (50.1 +/- 2.3 vs. 22.6 +/- 2.1 microliters/h per g). When expressed as a percentage of corresponding values obtained for hamsters fed the basal diet without any additions, the relative rate of LDL-cholesterol production was 175 +/- 10% and 99 +/- 4% for the Avicel- and psyllium-fed groups, respectively. It was similarly determined that the level of whole animal relative LDL receptor activity was marginally higher in the hamsters given psyllium (55.9 +/- 1.4%) than in those fed Avicel (47.5 +/- 3.3%). Thus, it was concluded that while the LDL-cholesterol lowering action of psyllium in the hamster is mediated through two mechanisms, the major effect is exerted at the level of LDL-cholesterol production.