Bruce P. Daggy

Psyllium augments the cholesterol-lowering action of cholestyramine in hamsters by enhancing sterol loss from the liver.

BACKGROUND/AIMS Psyllium hydrophilic mucilloid is a nonabsorbable soluble fiber that lowers plasma cholesterol levels in several species, including humans. However, its mechanism of action has not been fully elucidated. Therefore, using a hamster model, experiments were performed to determine whether psyllium given alone or in combination with a submaximal dose of cholestyramine blocks intestinal cholesterol absorption. METHODS The efficiency of cholesterol absorption and concentrations of plasma and hepatic total cholesterol were measured in male hamsters fed a cholesterol-enriched chow diet (0.1%) that contained either avicel (cellulose) (7.5%), surfomer (3%), cholestyramine (1% or 3%), or psyllium (7.5%) as single agents or a fixed level of cholestyramine (1%) combined with variable levels of psyllium (2%, 4%, 6%, or 8%). RESULTS Psyllium, cholestyramine, and surfomer, when given alone, markedly lowered plasma and hepatic cholesterol concentrations. Surfomer, and cholestyramine at the higher dose (3%), blocked cholesterol absorption by 54% and 75%, respectively, whereas psyllium had no effect. Combining psyllium with a submaximal dose of cholestyramine augmented the cholesterol-lowering action of the resin without effecting any marked change in the level of cholesterol absorption, except at the highest dose used. CONCLUSIONS Psyllium, given either as a single agent or as an adjunct to treatment with cholestyramine, exerts a significant hypocholesterolemic effect by enhancing net negative sterol balance across the liver.

Cholesterol-lowering action of psyllium mucilloid in the hamster: Sites and possible mechanisms of action

These studies were undertaken to examine and compare the metabolic effects of psyllium mucilloid and two other nonabsorbable polymers (cholestyramine and surfomer) on sterol metabolism in the hamster. These three agents all significantly lowered the plasma total cholesterol concentration and the level of cholesterol carried in low-density lipoproteins (LDL). Rates of cholesterol synthesis were markedly increased in the livers of the psyllium-fed animals, but not in other tissues. In contrast, cholestyramine and surfomer feeding increased both hepatic and intestinal sterol synthesis. When cholesterol and saturated triacylglycerols were added to the diet, psyllium feeding essentially completely blocked the increase in the plasma cholesterol concentration and hepatic cholesterol content and the suppression of cholesterol synthesis. The pool of bile acid in the small intestine was increased from the control value (17.9 mumol/animal) by both psyllium (23.0 mumol) and cholestyramine (21.9 mumol) feeding. However, this pool was readily absorbed and secreted into the bile in the psyllium-fed animals (27.9 mumol/4 h), but not in the cholestyramine-treated hamsters (13.0 mumol/4 h). This was consistent with the further observation that there was no binding of bile acid by psyllium under in vitro conditions. Thus, these findings indicate that all three polymers lower plasma cholesterol concentrations by inducing a net negative cholesterol balance across the liver. With psyllium, this effect is presumably articulated through a reduction in cholesterol absorption, as well as an increase in the rate of degradation of cholesterol to bile acids.

Flaxseed Reduces Total and LDL Cholesterol Concentrations in Native American Postmenopausal Women

OBJECTIVE The objective of the study was to investigate the extent to which the daily incorporation of approximately 30 g of flaxseed, a rich source of lignans, omega-3 fatty acids, and fiber, for a period of 3 months into the diet of Native American postmenopausal women positively affects their lipid profiles. METHODS Fifty-five mild to moderately hypercholesterolemic (> or =5.1 to < or =9.8 mmol/L) Native American postmenopausal women were randomly assigned to control (A), flaxseed (B) or flaxseed + additional oat bran fiber (C) groups. Overnight fasting venous blood was collected at baseline and at the end of the treatment period to analyze lipid parameters. RESULTS Dietary flaxseed supplementation lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) by approximately 7% and 10%, respectively. However, the levels of high-density lipoprotein (HDL) and triglyceride remained unaltered. No changes were observed in other clinical and hematological parameters. CONCLUSIONS The results of the present study indicate that Native American postmenopausal women benefit from regular consumption of flaxseed by reducing their risk of cardiovascular disease as seen from lowered LDL-C and total cholesterol levels.

Effect of feeding psyllium and cholestyramine in combination on low density lipoprotein metabolism and fecal bile acid excretion in hamsters with dietary-induced hypercholesterolemia.

We wished to determine the effectiveness of submaximal doses of cholestyramine and psyllium given in combination in reversing dietary-induced hypercholesterolemia in Golden Syrian hamsters, and to investigate the mechanism or mechanisms of action through which these agents together decrease plasma low density lipoprotein cholesterol (LDL-C) levels in this model. For 30 days, male hamsters were fed a cholesterol-rich cereal-based diet containing either a submaximal dose of cholestyramine (1% wt/wt) alone or in combination with psyllium (either 2 or 4%), or a high dose of cholestyramine (3%) alone. Although the greatest cholesterol-reducing action was achieved with 3% resin alone, in the animals fed one third as much cholestyramine combined with psyllium (4%) LDL-C production decreased from 288 +/- 15 to 187 +/- 17 micrograms/h per 100 g body weight, the suppression of LDL-receptor activity was almost fully reversed, plasma LDL-C levels were reduced from 90 +/- 8 to 41 +/- 5 mg/dl, and hepatic cholesterol content decreased from 17.1 +/- 1.9 to 2.4 +/- 0.1 mg/g. In the group that received 1% resin alone, the plasma LDL-C and hepatic cholesterol levels were 60 +/- 3 mg/dl and 7.2 +/- 0.6 mg/g, respectively. As compared with animals that received 1% resin alone, those fed both agents manifested higher rates of fecal bile acid excretion and lower levels of intestinal cholesterol absorption. A significant cholesterol-lowering benefit can be derived from using these nonsystemic agents in combination at lower, more tolerable doses.

Cholesterol lowering with high-viscosity hydroxypropylmethylcellulose

Hydroxypropylmethylcellulose (HPMC) is a food gum having several structural and functional properties in common with hypocholesterolemic soluble fibers. The safety and cholestero-lowering efficacy of HPMC, incorporated into a National Cholesterol Education Program Step I diet, was compared with placebo in patients with mild to moderate hypercholesterolemia. After an 8-week National Cholesterol Education Program Step I dietary lead-in phase, 160 patients with low-density lipoprotein (LDL) cholesterol between 130 and 200 mg/dl and triglycerides <300 mg/dl were randomized to placebo, 2.5, 5.0, or 7.5 g/day of HPMC for a 6-week treatment period. Patients returned to the clinic every 2 weeks for lipid measurements and safety assessments. HPMC significantly lowered total, LDL, and non-high-density lipoprotein (HDL) cholesterol. LDL cholesterol concentrations (average of weeks 4 and 6) decreased by 3.0% (4.9 mg/dl), 5.9% (10.3 mg/dl), 12.1% (20.4 mg/dl), and 11.7% (20.3 mg/dl) from baseline levels in the placebo and 2.5, 5.0, and 7.5 g/day HPMC treatment groups, respectively. Statistically significant (p<0.05) reductions in LDL cholesterol were observed in the 5.0 and 7.5 g/day HPMC groups compared with placebo and 2.5 g/day HPMC treatment groups. Total and non-HDL cholesterol responses paralleled those of LDL cholesterol. There were no significant differences between the treatment groups in HDL cholesterol or triglyceride responses, incidence of adverse experiences, or gastrointestinal-related adverse experiences. These results suggest that HPMC is a well-tolerated and effective adjunct to diet for lowering LDL cholesterol in patients with mild to moderate hypercholesterolemia.

Effects of hypocaloric diet, low-intensity resistance exercise with slow movement, or both on aortic hemodynamics and muscle mass in obese postmenopausal women

Objective This study aims to examine the independent and combined impact of hypocaloric diet and low-intensity resistance exercise training (LIRET) on aortic hemodynamics and appendicular skeletal muscle mass (ASM) in obese postmenopausal women. Methods Forty-one obese postmenopausal women (mean [SD] age, 54 [1] y) were randomly assigned to LIRET (n = 13), diet (n = 14), or diet + LIRET (n = 14). Body weight, waist circumference, aortic systolic blood pressure, aortic pulse pressure, augmentation index, subendocardial viability ratio (SEVR; myocardial perfusion), and heart rate (HR) were measured before and after 12 weeks. ASM was assessed by dual-energy x-ray absorptiometry. Results Body weight (P < 0.001) and waist circumference (P < 0.01) decreased similarly after diet and diet + LIRET compared with no changes after LIRET. ASM did not change after diet + LIRET, and the decrease observed after diet (P < 0.001) was significant compared with LIRET. Aortic systolic blood pressure decreased similarly after LIRET (P < 0.05), diet (P < 0.01), and diet + LIRET (P < 0.01). Aortic pulse pressure (P < 0.05) decreased similarly after diet and diet + LIRET, but not after LIRET. SEVR (P < 0.01) increased similarly in both diet groups, whereas HR (P < 0.01) decreased only after diet. Changes in SEVR (P < 0.05) and HR (P< 0.01) with diet were different compared with LIRET. The augmentation index did not change in any group. Conclusions Our findings suggest that diet-induced weight loss may reduce cardiovascular risk by improving SEVR via HR and aortic pulse pressure reductions in obese postmenopausal women. LIRET prevents ASM loss associated with hypocaloric diet but has no additive effects on aortic hemodynamics.

A Combination of Scutellaria Baicalensis and Acacia Catechu Extracts for Short-Term Symptomatic Relief of Joint Discomfort Associated with Osteoarthritis of the Knee

The extracts of Scutellaria baicalensis and Acacia catechu have been shown in previous studies to alleviate joint discomfort, reduce stiffness, and improve mobility by reducing the production of proinflammatory molecules over long periods of supplementation. The acute effects of intake of these extracts have not yet been investigated. Thus, we carried out a 1 week clinical trial to examine the extent to which UP446-a natural proprietary blend of S. baicalensis and A. catechu (UP446)-decreases knee joint pain, mobility, and biomarkers of inflammation in comparison to naproxen. Seventy-nine men and women (40-90 years old) diagnosed as having mild to moderate osteoarthritis (OA) consumed either 500 mg/day of the UP446 supplement or 440 mg/day of naproxen for 1 week in a double-blind randomized control trial. Pain, knee range of motion (ROM), and overall physical activity were evaluated at the start and at the end of treatment. Fasting blood was collected to determine serum interleukins 1β and 6, tumor necrosis factor-α, C-reactive protein, and hyaluronic acid. The UP446 group experienced a significant decrease in perceived pain (P=.009) time dependently. Stiffness was significantly reduced by both treatments (P=.002 UP446, P=.008 naproxen). Significant increases in mean ROM over time (P=.04) were found in the UP446 group. These findings suggest that UP446 is effective in reducing the physical symptoms associated with knee OA.

Soy isoflavones prevent ovariectomy-induced atherosclerotic lesions in Golden Syrian hamster model of postmenopausal hyperlipidemia.

ObjectiveSoy isoflavones, as dietary supplements, may reduce the formation of atherosclerotic lesions that increase in women after menopause. The objectives of this study were to determine whether (1) ovariectomized (ovx) hamsters will develop atherosclerotic lesions and (2) soy isoflavones can dose-dependently prevent the ovariectomy-induced rise in plasma cholesterol and atherosclerotic lesions in hamsters. DesignSeventy-two 6-month-old female Golden Syrian hamsters were randomly assigned to six groups: sham-operated; ovx control; ovx + 17&bgr;-estradiol (E2; 10 &mgr;g E2 per kilogram of body weight); and ovx + 9.5 (low-dose), 19 (medium-dose), or 38 (high-dose) mg isoflavones per kilogram diet. Treatments were initiated immediately after surgery and continued for 120 days. Blood was drawn via abdominal aorta for assessment of circulating lipids, and tissues were collected, including the aortic arch for assessment of atherosclerotic lesions. ResultsAll three doses of isoflavones prevented the rise in plasma total cholesterol from ovx; and, as the isoflavone dose increases, the cholesterol-lowering effects of isoflavones become more pronounced (7.8%, 11.8%, and 19.6% reductions in total cholesterol for low-dose, medium-dose, and high-dose, respectively). Ovx hamsters developed atherosclerotic lesions without being on an atherogenic diet. Ninety-two percent of hamsters in the ovx control group had atherosclerotic lesions compared with only 8% in sham, 62% in the E2 group, 29% in the low-dose group, 38% in the medium-dose group, and 58% in the high-dose group. The aortic fatty streak area was approximately 20 times higher in ovx hamsters compared with the sham animals. All doses of isoflavones were able to significantly reduce fatty streak area to that of the sham group. ConclusionsSoy isoflavones, independent of the protein source, prevent hypercholesterolemia and the formation of atherosclerotic lesions induced by ovarian hormone deficiency in hamsters. The antiatherogenic mechanisms of isoflavones need further investigation.

Ovariectomized hamster:: A potential model of postmenopausal hypercholesterolemia

A suitable and economical animal model of ovarian hormone deficiency can greatly enhance the understanding of postmenopausal-elevated risk of coronary heart disease. The male Golden Syrian hamster is a well-established small animal model of hypercholesterolemia, but the effect of ovariectomy on lipid profile in the female hamster is unclear. The objective of this study was to determine whether ovariectomized hamsters develop hypercholesterolemia and experience changes in body fat distribution consistent with changes observed in postmenopausal women. Twenty-two 90-day-old female Golden Syrian hamsters were divided into two groups and were either ovariectomized or sham-operated and given free access to a standard cholesterol-free laboratory diet for 65 days. Ovariectomized hamsters had significantly (P < 0.05) elevated serum total cholesterol concentrations (16.6%) as well as abdominal fat mass (56%; P< 0.01) despite equal food intake compared with the sham-operated group. In contrast, the mean intestinal weight and in vivo rate of sterol biosynthesis were significantly (P < 0.002 and P = 0.01, respectively) lower in the ovariectomized compared with the sham-operated group. In vivo rates of hepatic sterol biosynthesis were directionally lower (P = 0.1) in the ovariectomized group. No significant differences were observed in final body weight, serum triglycerides, or liver total cholesterol and lipids between the two groups. In conclusion, ovariectomized hamsters undergo changes in serum cholesterol and fat distribution similar to those experienced by postmenopausal women, and thus may serve as an appropriate model for postmenopausal hypercholesterolemia.

Flaxseed Improves Lipid Profile Without Altering Biomarkers of Bone Metabolism in Postmenopausal Women

The risk of cardiovascular disease and osteoporosis drastically increases at the onset of menopause. Phytoestrogens have been suggested to inhibit bone loss and protect the cardiovascular system, in part by improving lipid profiles. The purpose of the present study was to examine the effects of flaxseed, a rich source of the phytoestrogens called lignans, on lipid metabolism and biomarkers of bone turnover in postmenopausal women. Postmenopausal women who were not on hormone replacement therapy were assigned to one of two treatment groups in a double-blind randomized study. Women were asked to consume 40 g of either ground flaxseed or wheat-based comparative control regimen daily for 3 months. In addition, all subjects received 1,000 mg calcium and 400 IU vitamin D daily. Flaxseed supplementation lowered (P < 0.05) both serum total cholesterol and non-high-density lipoprotein cholesterol by 6%, whereas the comparative control regimen had no such effect. Flaxseed regimen reduced serum levels of both low-density- and high-density-lipoprotein cholesterol by 4.7% and triglyceride by 12.8%, albeit not statistically significant. Serum apolipoprotein A-1 and apolipoprotein B concentrations were significantly (P < 0.005) reduced by 6 and 7.5%, respectively, by the flaxseed regimen. Markers of bone formation and resorption were not affected by either of the treatments. The findings of this study indicate that flaxseed supplementation improves lipid profiles but has no effect on biomarkers of bone metabolism in postmenopausal women.