methylcellulose and Hypercholesterolemia

The mechanism for the lowering of plasma cholesterol by water-soluble nonstarch polysaccharides (NSP) could involve alteration of intestinal viscosity leading to attenuated fat and steroid digestion and absorption. Alternatively, there may be direct inhibition of hepatic cholesterol synthesis by short-chain fatty acids produced by large bowel bacterial fermentation. A synthetic NSP, hydroxypropylmethylcellulose (HPMC), has been shown to lower plasma low-density lipoprotein (LDL) cholesterol in humans. This polysaccharide is not fermented by the large bowel microflora and has been shown to lower the plasma and liver cholesterol in hamsters, with no change noted in hepatic sterol synthesis. In further studies with hamsters, a linear relationship has been identified between plasma cholesterol and the logarithm of hydroxymethylcellulose viscosity. Only a relatively small increment in viscosity was necessary to achieve a maximal effect, suggesting that intestinal digestion may be quite sensitive to increased NSP intake.

Topics: Animals; Cholesterol; Cholesterol, LDL; Female; Gastrointestinal Contents; Humans; Hypercholesterolemia; Lactose; Male; Methylcellulose; Oxazines; Solubility; Viscosity

Consumption of hydroxypropylmethylcellulose (HPMC), a viscous dietary fiber, lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, HPMC had not previously been studied in individuals receiving lipid drug therapy.. This randomized, double-blind crossover trial examined the lipid effects of HPMC in subjects with hypercholesterolemia on statin therapy. Men (n=5) and women (n=8) with LDL-C> or =2.59 mmol/l after at least 4 weeks of stable-dose statin therapy, and a mean age of 58.6 years, were enrolled. Subjects received twice daily doses of either 2.5 g HPMC or control, delivered in a lemonade beverage for 4 weeks, then crossed over to receive the opposite treatment for an additional 4 weeks.. Mean baseline concentrations of TC, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, HDL-C, triglyceride (TG), TC/HDL-C ratio and apolipoprotein (Apo) B were 4.95, 3.63, 3.03, 1.33, 1.30 and 3.89 mmol/l and 1.00 g/l, respectively. HPMC consumption resulted in significantly larger reductions (P<0.01 vs control for all) in TC (-10.9 vs -3.5%), non-HDL-C (-12.8 vs -2.9%), LDL-C (-15.7 vs -5.1%), TC/HDL-C ratio (-5.3 vs +1.3%) and Apo B (-8.7 vs -3.9%). There were no differences between treatments for changes in HDL-C (-5.2 vs -4.3%) or TG (+3.9 vs +8.9%).. These results support the view that HPMC is an effective adjunct to statin therapy for further lowering atherogenic lipids and lipoproteins in men and women with primary hypercholesterolemia.

Topics: Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged

To determine the cholesterol-lowering efficacy of hydroxypropylmethylcellulose (HPMC) in mildly hypercholesterolemic humans.. Trial one: entry mean (range) total serum cholesterol values of eight female and four male subjects were 6.48 (5.57-7.51) mmol l(-1) (250 (215-290) mg dl(-1)) and 6.60 (5.57-7.64) mmol l(-1) (255 (215-295) mg dl(-1)), respectively. Trial two: corresponding values for 20 women and 20 men were 5.96 (5.43-6.48) mmol l(-1) 230 (210-250) mg dl(-1)) and 6.05 (5.46-6.63) mmol l(-1) 233 (211-256) mg dl(-1)), respectively.. Trial one: HPMC decreased (P< or =0.05) total and LDL-cholesterol 9.3 and 15.3% (medium), 16.9 and 23.5% (high) and 13.8 and 19.4% (ultra-high), respectively, over placebo. Trial two: total and LDL-cholesterol decreased (P< or =0.05) throughout the 8 weeks, with mean (weeks 4-8) reductions of 7 and 8% at 5 g day(-1), and 12 and 15% at 15 g day(-1), respectively, over placebo. Adverse effects were minimal. Trial one: medium, high and ultra-high viscosity HPMC at 15 g day(-1) for 1 week each;1-week wash-out between treatments. Trial two: ultra-high viscosity HPMC at 5 or 15 g day(-1) for 8 weeks.. HPMC soluble fiber, especially high-viscosity grades, significantly lowers cholesterol at well-tolerated doses, showing promise as a treatment of hypercholesterolemia.

Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Colon; Cross-Over Studies; Dietary Fiber; Female; Humans; Hypercholesterolemia; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged; Regression Analysis; Triglycerides

Hydroxypropylmethylcellulose (HPMC) is a food gum that shares certain characteristics, such as high viscosity, with soluble fibers. In this trial, the safety and cholesterol-lowering efficacy of HPMC consumed with and between meals was evaluated in free-living male volunteers with mild-to-moderate hypercholesterolemia. After a 14-d baseline period, men (n = 51) with LDL cholesterol between 3.36 and 4.91 mmol/L and triglycerides <3.95 mmol/L were randomly assigned to consume 5.0 g/d HPMC in 240 mL of orange drink, taken either with or between meals, for a 2-wk treatment period. In the Between Meals group, total cholesterol was reduced by 8.0% vs. baseline in wk 1 of treatment (P < 0.05) and 5.1% in wk 2 (P < 0.01). LDL cholesterol concentrations fell by 12.0 and 7.7% (P < 0.01). In the With Meals group, reductions were 9.5 and 8.3% for total cholesterol, and 12.5 and 12.8% for LDL cholesterol (wk 1 and 2, respectively, P < 0.01). In both groups, HDL cholesterol decreased by approximately 5% during wk 1 of treatment (P < 0.01), but the wk 2 concentrations were not significantly different from baseline. There were no significant differences between groups in lipid responses, although there was a trend for a smaller LDL cholesterol-lowering effect during wk 2 of treatment in the Between Meals group (P < 0.06). Gastrointestinal-related adverse experiences (mostly mild) were twice as common among participants who ingested HPMC with meals (P < 0.05). These results suggest that HPMC has a lipid-lowering effect, which may be more consistent when taken with meals.

Topics: Adult; Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Digestive System; Fasting; Feeding Behavior; Humans; Hypercholesterolemia; Hypromellose Derivatives; Lipids; Male; Methylcellulose; Molecular Weight; Viscosity

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.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lactose; Male; Methylcellulose; Middle Aged; Oxazines; Viscosity

We assessed the efficacy of a high-molecular-weight hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent, the dose-response profile of its action, and the ability of adult subjects to tolerate its ingestion at effective doses.. These studies were conducted at the Clinical Research Center of The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed in 10 normal and 12 mildly hyperlipidemic subjects in double-blind, randomized crossover trials of 1 and 2 weeks' duration, respectively. The dose-response profile was studied in 12 mildly hypercholesterolemic subjects in a nonrandomized control trial with doses given in escalating order. Tolerance was assessed by a questionnaire of adverse effects and bowel movement habits in all subjects.. We found that 10 g of K8515 ingested in a prehydrated form three times a day with meals lowered total cholesterol levels by an average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1 week. In two studies in subjects with mildly elevated cholesterol levels (with entry levels ranging from 5.35 mmol/L [207 mg/dL] to 6.70 mmol/L [260 mg/dL]), average reductions of 1.00 mmol/L (39 mg/dL) (18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same period. The effect was primarily due to a reduction in low-density lipoprotein cholesterol levels. Low-density lipoprotein levels in normal subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a week of 10 g of K8515 three times a day with meals, and in the two studies in subjects with mild hyperlipidemia, the reductions in low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL) (23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency for high-density lipoprotein cholesterol levels to decrease, this was significant only in normal subjects. Decreases in cholesterol levels were not accompanied by any rise in triglyceride levels. Dose-response studies in those with mildly elevated cholesterol levels indicated that it is possible to achieve a 15% decrease in low-density lipoprotein cholesterol levels within 1 week at a dose of 6.7 g three times a day, with minimal adverse effects.. These results suggest a role for high-molecular-weight hydroxypropylmethylcellulose in the clinical treatment of mild hypercholesterolemia.

Topics: Adult; Anticholesteremic Agents; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Defecation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Tolerance; Feces; Female; Humans; Hypercholesterolemia; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged; Molecular Weight; Placebos; Triglycerides

Hypercholesterolemia is a significant risk factor for coronary heart disease, and the hypocholesterolemic effects of psyllium are well established. This placebo-controlled, parallel study compared psyllium with methylcellulose, calcium polycarbophil, and placebo as dietary adjuncts in treating mild to moderate hypercholesterolemia. Of 163 men and women recruited with serum cholesterol levels above 5.17 mmol/L (200 mg/dL), 105 completed 8 weeks of an American Heart Association step I diet and then augmented the diet with one of the fiber supplements for 8 additional weeks. Incremental differences from placebo for low-density lipoprotein cholesterol were -8.8% for psyllium, -3.2% for methylcellulose (not significant), and +8.7% for calcium polycarbophil; and for total cholesterol the differences were -4.3% for psyllium (not significant), -1.4% for methylcellulose (not significant), and +5.9% for calcium polycarbophil. Compliance was 94% to 96%, and only mild gastrointestinal side effects were observed. In managing mild to moderate hypercholesterolemia, methylcellulose and calcium polycarbophil provide little or no additional benefit, while psyllium significantly enhances the American Heart Association diet effects.

Topics: Acrylic Resins; Adult; Aged; Cathartics; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Male; Methylcellulose; Middle Aged; Patient Compliance; Psyllium; Random Allocation

Topics: Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; Hypromellose Derivatives; Methylcellulose

The influence of a cholesterol-free, semisynthetic diet on the cholesterol content and on the incorporation of radioacetate into cholesterol in liver, aorta and intestinal mucosa of the rabbit was tested over periods of 3 and 6 months. The incorporation of radioacetate in the liver reached a maximum after 3 months. In contrast to this, the rate of acetate incorporation in the aorta and mucosa continued to rise throughout the entire test period. The cholesterol level in serum ran parallel to the hepatic cholesterol synthesis reaching a maximum after 3 months. While the cholesterol content of the liver remained unchanged, it rose in the aorta and mucosa. These results favour the assumption that hypercholesterolemia was not due to a defect in removal of cholesterol from the plasma compartment, but to an increased biosynthesis.

Topics: Animal Feed; Animals; Aorta, Thoracic; Caseins; Cholesterol; Cocos; Diet, Atherogenic; Duodenum; Glycine max; Hypercholesterolemia; Intestinal Mucosa; Liver; Male; Methylcellulose; Oils; Rabbits; Starch; Zea mays

Topics: Animals; Aorta; Female; Histology; Hypercholesterolemia; Hyperlipidemias; Injections, Intravenous; Male; Methylcellulose; Rabbits; Renal Artery

Topics: Anemia; Anemia, Hemolytic; Animals; Hypercholesterolemia; Injections, Intraperitoneal; Kidney Diseases; Methylcellulose; Rats; Splenomegaly