Effects of cationic hydroxyethyl cellulose on dyslipidemia in hamsters.

Cationic hydroxyethyl cellulose (cHEC) was supplemented in a high-fat diet to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease using Golden Syrian hamster as an animal model. Supplementation of 3-5% cHEC in a high-fat diet for 4 weeks led to significant weight gain reduction in hamsters. In addition, significant decreases in adipose and liver weights, concentrations of plasma total, VLDL, and LDL cholesterol, and hepatic lipids were shown. No significant improvements in glucose and insulin levels were observed with cHEC; however, a significant increase in plasma adiponectin and a decrease in leptin were observed. As compared with controls, 8% cHEC-fed hamsters had greater levels of mRNA for CYP7A1 (cytochrome P450 7A1; 2-fold of control; P < 0.05), CYP51 (lanosterol 14α-demethylase; 6-fold of control; P < 0.05), and LDLR (LDL receptor; 1.5-fold of control) in the liver. These findings suggest the possibility of the use of cHEC for cholesterol reduction and beneficial effects on the cardiovascular risk factors.

Supplementation of hydroxypropyl methylcellulose into yeast leavened all-whole grain barley bread potentiates cholesterol-lowering effect.

We investigated in Syrian Golden hamsters the biological impact and its underlying mechanism of single whole grain breads supplemented with 2-3% hydroxypropyl methylcellulose (HPMC), a semisynthetic viscous soluble dietary fiber (SDF) as a substitute for gluten. Hamsters were fed high-fat diets supplemented with 48-65% (w/w) differently ground, freeze-dried single grain breads including whole grain wheat, barley, barley supplemented with HPMC, debranned oat, and oat supplemented with HPMC which were compared to a diet containing microcrystalline cellulose (control). All single grain breads significantly lowered plasma LDL-cholesterol concentrations compared to the control. Enrichment with HPMC further lowered plasma and hepatic cholesterol concentrations. Despite the reduced molecular weight of naturally occurring soluble (1--->3),(1--->4)-ß-d-glucan (ß-glucan) caused by the bread-making process, whole grain barley breads downregulated hepatic expression of CYP7A1 and HMG-CoAR genes that are responsible for bile acid and cholesterol synthesis, suggesting a possible role of bioactive compounds such as short-chain fatty acids and phenolic compounds from barley bread. Barley bread enriched with HPMC downregulated expression of ABCG5 gene. Taken together, it appears that distinctive modulation of synthesis and excretion of hepatic cholesterol and bile acid contributes to the cholesterol-lowering properties of whole grain barley breads and breads enriched with HPMC. These data suggests that alternative whole grain breads supplemented with HPMC may provide consumers with a staple food that can assist in cholesterol management.

Dose-response characteristics of high-viscosity hydroxypropylmethylcellulose in subjects at risk for the development of type 2 diabetes mellitus.

BACKGROUND: Hydroxypropylmethylcellulose (HPMC) is a modified cellulose fiber that creates a viscous solution in the gastrointestinal tract. The present study examined the dose-response characteristics of high-viscosity (HV)-HPMC consumption on postprandial glucose and insulin levels in men and women at increased risk for type 2 diabetes mellitus. METHODS: Subjects were a subset of participants in two trials with elevated peak postprandial glucose [>or=7.8 mmol/L (>or=140 mg/dL)] and body mass index (BMI) >or=27 kg/m(2). Subjects (n = 39) consumed breakfast meals containing 75 g of carbohydrate, each of which contained 1, 2, 4, or 8 g of HV-HPMC or a cellulose control in a randomized, double-blind manner. Each subject completed tests with control and two HV-HPMC doses. RESULTS: Peak glucose concentration was lower than control (all P < 0.01) following 2 g (10%), 4 g (18%), and 8 g (20%) of HV-HPMC. Peak insulin was also reduced (P < 0.01) following 2 g (32%), 4 g (35%), and 8 g (46%) of HV-HPMC doses versus control. Incremental areas for glucose from 0 to 120 min were reduced by 8-40% versus control but only reached significance for the 4-g and 8-g conditions, whereas incremental areas under the insulin curves were reduced by 14-53% (P < 0.01 for 2, 4, and 8 g of HV-HPMC). CONCLUSIONS: Among subjects at risk for type 2 diabetes mellitus, 1.0-8.0 g of HV-HPMC blunted postprandial glucose and insulin responses in a dose-dependent manner. Additional research is warranted to assess whether chronic consumption might retard the development or progression of glucose intolerance.

Lipid-altering effects of different formulations of hydroxypropylmethylcellulose.

BACKGROUND: Hydroxypropylmethylcellulose (HPMC), a viscous, soluble dietary fiber, has been shown to be efficacious for lowering total and low-density lipoprotein cholesterol (LDL-C) concentrations. The relative effects of various dosages and viscosities of HPMC have not been fully evaluated. OBJECTIVE: To examine the lipid-altering effects of several formulations of HPMC. METHODS: In this randomized, double-blind pilot study, 165 men and women with primary hypercholesterolemia consumed a control product (snack bar or drink mix) or an HPMC-containing test bar or drink for 4 weeks. HPMC-containing products delivered 3, 5, or 10g of HPMC of low, moderate, moderately high, or high viscosity (9 HPMC groups, each with ∼15 subjects). RESULTS: Data from drink and bar groups were combined because there was no evidence of a vehicle effect. The resulting analysis included data from the control and 6 HPMC dose and viscosity combinations. All HPMC groups showed LDL-C reductions ranging from 6.1 to 13.3% (P < .05 vs. baseline for 6 of the 7 groups), compared with a nonsignificant reduction (1.9%) in the control group. Changes in total and non-high-density lipoprotein cholesterol paralleled those for LDL-C. Concentrations of high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and high-sensitivity C-reactive protein were not significantly altered. CONCLUSION: This pilot study provides preliminary evidence to support the efficacy of various formulations of HPMC for reducing cholesterol carried by atherogenic particles in men and women with primary hypercholesterolemia. Additional research will be required to more clearly define the roles of viscosity and dosage on the lipid-altering effects of HPMC.

Hydroxypropylmethylcellulose and methylcellulose consumption reduce postprandial insulinemia in overweight and obese men and women.

Hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) are modified cellulose dietary fibers that generate viscous solutions in the gastrointestinal (GI) tract. This study assessed the effects of high viscosity (HV) HPMC, ultra-HV (UHV) HPMC, and medium viscosity MC on postprandial glucose and insulin responses in overweight and obese men and women (n = 50). After overnight fasts, subjects consumed 5 breakfast meals containing 75 g carbohydrate, each of which contained 1 of the following: 1 g HV-HPMC, 2 g HV-HPMC, 2 g UHV-HPMC, 4 g medium-viscosity MC or control (2 g cellulose). Test sequence was randomized and double-blind, except the MC test, which was last and single-blind (46 subjects completed all 5 tests). Glucose and insulin responses were determined pre-meal and for 120 min postprandially. Median (interquartile limits) peak glucose concentration was lower (P = 0.001) after the meal containing 2.0 g UHV-HPMC (7.1, 6.3-8.2 mmol/L) compared with the control meal (7.7, 6.6-8.7 mmol/L). The control did not differ from the other conditions for peak glucose or for any of the HPMC/MC conditions for glucose incremental areas under the curves (IAUC). Peak insulin was reduced (P < 0.05) for all HPMC/MC conditions compared with control. Insulin IAUC was lower than control (P < 0.001) after meals containing 2 g HV-HPMC, 2 g UHV-HPMC, and 4 g MC. GI symptoms did not differ among treatments. These findings indicate that HV-HPMC (1 and 2 g), UHV-HPMC (2 g), and MC (4 g) consumption reduced postprandial insulin excursions consistent with delayed glucose absorption.

Simultaneous characterization of bile acid, sterols, and determination of acylglycerides in feces from soluble cellulose-fed hamsters using HPLC with evaporative light-scattering detection and APCI-MS.

The rapid rise in obesity-related diseases has increased interest in oral and dietary agents that disrupt fat metabolism, resulting in the excretion of dietary lipids in the feces. In this study, a rapid and convenient liquid chromatography method to comprehensively analyze fecal lipids in a single injection was developed. An evaporative light-scattering detector (ELSD) for routine analysis or atmosphere pressure chemical ionization tandem mass spectrometry [(+)APCI-MS/MS] for structural confirmation and peak purity was used. The method was applied to characterize lipid components of feces from hamsters fed high-fat diets with either 5% microcrystalline cellulose or 5% hydroxypropyl methylcellulose (HPMC) fibers, to test the effect of HPMC on lipid metabolism. HPMC is a nonfermentable, soluble cellulose fiber. The fecal lipid components identified using this method includes two secondary bile acids, deoxycholic acid, lithocholic acid, and neutral sterols including cholesterol, coprostanol, stigmastanol, and sitosterol. The profile of fecal lipid components was compared between two groups. It was found that the bile acid excretion was increased 2-fold in HPMC-fed hamsters. More interestingly, diacylglycerides and triacylglycerides were detected in feces from hamsters on HPMC-included high-fat diets. We believe that this is the first report of excretion of acylglycerides following neutral soluble fiber feeding.

Determination of methylcellulose and hydroxypropyl methylcellulose food gums in food and food products: collaborative study.

A collaborative study was performed to determine the reproducibility of a method for the determination of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) in food. These widely used food gums possess unusual solubility characteristics and cannot accurately be determined by existing dietary fiber methods. The new method uses the enzyme-digestion procedure of AOAC Official Method 991.43. Digestate solutions must be refrigerated to fully hydrate MC or HPMC. The chilled solutions are filtered and analyzed by size-exclusion liquid chromatography. Collaborating laboratories received 28 samples containing MC or HPMC in the range of 0-100%. The sample set included blind duplicates of 5 food matrixes (bread, milk, fish, potato, and powdered juice drink). Cochran and Grubbs tests were used to eliminate outliers. For food samples containing MC, values for within-laboratory precision, repeatability relative standard deviation (RSDr), ranged from 4.2 to 16%, and values for among-laboratories precision, reproducibility relative standard deviation (RSDR), ranged from 11 to 20%. For HPMC samples, RSDr values ranged from 6.4 to 27%, and RSDR values ranged from 17 to 39%. Recoveries of MC and HPMC from the food matrixes ranged from 78 to 101%. These results show acceptable precision and reproducibility for the determination of MC and HPMC, for which no Official AOAC Methods exist. It is recommended that this method be adopted as AOAC Official First Action.

High-viscosity hydroxypropylmethylcellulose blunts postprandial glucose and insulin responses.

OBJECTIVE: High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women. RESEARCH DESIGN AND METHODS: Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by > or = 72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion. RESULTS: Peak glucose was significantly lower (P < 0.001) after both HV-HPMC-containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P < 0.01). CONCLUSIONS: These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease.

Dissociation of ionized benzophenones investigated by the kinetic method: effective temperature, steric effects and gas-phase CO+* affinities of phenyl radicals.

Ionized benzophenones ([PhC(O)PhY](+*); Y = 4 - NO(2), 4 - CF(3), 4-F, 4-Br, 4-Me, 3,4-diMe, 4-OH, 4-OMe, 2-Cl, 2-Me, 2-OH, 2,6-diMe) undergo competitive dissociation upon collision-induced dissociation (CID) at 20 eV collision energy to generate benzoyl cations ([PhCO](+) and [YPhCO](+)) and phenyl radicals (Ph(*) and YPh(*)). For the para-substituted benzophenones, the natural logarithm of the abundance ratio of the benzoyl cations [ln([PhCO(+)]/[YPhCO(+)])] is found to correlate linearly with the calculated CO(+*) affinities of the phenyl radicals Ph(*) and YPh(*). A deviation from linearity is observed for the ortho-substituted isomers. This is probably due to a significant intramolecular steric interaction between the carbonyl group and the ortho substituent which prevents the formation of a stable planar system. An observed shift in the intercept relative to the origin is interpreted as the result of a systematic error in the calculated CO(+*) affinities and this effect is minimized by calculations at a higher level. The dissociation of ionized para-substituted benzophenones is associated with a relatively high effective temperature of 1816 +/- 41 K, calculated from the slope of the kinetic method plot, a value that is consistent with a covalent bond in the activated ion. In addition, Delta(DeltaS(CO(+) )), the dissociation entropy of the benzoyl cations to form CO(+*) and the aryl radical, is found to be about 4 J mol(-1) K(-1) by employing the extended version of the kinetic method.

Deuterium isotope effects on hydrophobic interactions: the importance of dispersion interactions in the hydrophobic phase.

Hydrogen/deuterium isotope effects on hydrophobic binding were examined by means of reversed-phase chromatographic separation of protiated and deuterated isotopologue pairs for a set of 10 nonpolar and low-polarity compounds with 10 stationary phases having alkyl and aryl groups bonded to the silica surface. It was found that protiated compounds bind to nonpolar moieties attached to silica more strongly than deuterated ones, demonstrating that the CH/CD bonds of the solutes are weakened or have less restricted motions when bound in the stationary phase compared with the aqueous solvent (mobile phase). The interactions responsible for binding have been further characterized by studies of the effects of changes in mobile phase composition, temperature dependence of binding, and QSRR (quantitative structure-chromatographic retention relationship) analysis, demonstrating the importance of enthalpic effects in binding and differentiation between the isotopologues. To explain our results showing the active role of the hydrophobic (stationary) phase we propose a plausible model that includes specific contributions from aromatic edge-to-face attractive interactions and attractive interactions of aliphatic groups with the pi clouds of aromatic groups present as the solute or in the stationary phase.

Membrane introduction mass spectrometry for monitoring complexation equilibria of beta-cyclodextrin with substituted benzenes.

Membrane introduction mass spectrometry (MIMS) was used to monitor complexation reactions between beta-cyclodextrin (CD) and a series of benzene derivatives in aqueous solution. The equilibrium constants for benzene, chlorobenzene, bromobenzene, iodobenzene, toluene, cyanobenzene and nitrobenzene were determined. The suitability of MIMS for monitoring complexation reactions of organic compounds with host molecules was demonstrated. Structure-activity relationship analysis shows that the inclusion phenomena are driven by a variety of chemical forces, of which hydrophobicity is predominant for non-polar compounds, but not the only factor for more polar ones.