Increased bioavailability of a transdermal application of a nano-sized emulsion preparation.

The aim of this study was to compare the transdermal application of a nano-sized emulsion versus a micron-sized emulsion preparation of delta tocopherol as it relates to particle size and bioavailability. Two separate experiments were performed using seven F1B Syrian Golden hamsters, 1 week apart. Each emulsion preparation consisted of canola oil, polysorbate 80, deionized water and delta tocopherol; the only difference between the two preparations was processing the nano-sized emulsion with the Microfluidizer Processor. Both were formulated into a cream and applied to the shaven dorsal area. The particle size of the micron-sized emulsion preparation was 2788 nm compared to 65 nm for the nano-sized emulsion formulation. Two hours post-application, hamsters that were applied the nano-sized emulsion had a 36-fold significant increase of plasma delta tocopherol, where as hamsters that were applied the micron-sized emulsion only had a 9-fold significant increase, compared to baseline, respectively. At 3h post-application, plasma delta tocopherol had significantly increased 68-fold for hamsters applied the nano-sized emulsion, whereas only an 11-fold significant increase was observed in hamsters applied the micron-sized emulsion, compared to baseline, respectively. Significant differences were also observed between the nano-sized and micron-sized emulsion at 2 and 3h post-application. This study suggests that nano-sized emulsions significantly increase the bioavailability of transdermally applied delta tocopherol.

Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy.

Glucosamine is widely used to relieve symptoms from osteoarthritis. Its safety and effects on glucose metabolism are critically evaluated in this review. The LD50 of oral glucosamine in animals is approximately 8000 mg/kg with no adverse effects at 2700 mg/kg for 12 months. Because altered glucose metabolism can be associated with parenteral administration of large doses of glucosamine in animals and with high concentrations in in vitro studies, we critically evaluated the clinical importance of these effects. Oral administration of large doses of glucosamine in animals has no documented effects on glucose metabolism. In vitro studies demonstrating effects of glucosamine on glucose metabolism have used concentrations that are 100-200 times higher than tissue levels expected with oral glucosamine administration in humans. We reviewed clinical trial data for 3063 human subjects. Fasting plasma glucose values decreased slightly for subjects after oral glucosamine for approximately 66 weeks. There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.

Efficacy of vitamin E, phosphatidyl choline and pyruvate on Abeta neurotoxicity in culture.

Oxidative stress is a pivotal factor in neuronal degeneration including that induced by exposure to amyloid-beta (Abeta). Treatment with antioxidants such as vitamin E can alleviate Abeta neurotoxicity. However, vitamin E was only marginally effective in clinical trials in Alzheimer's disease. Recent studies indicate that treatment with vitamin E (as a-tocopherol), sodium pyruvate and phosphatidyl choline (PC) is more effective than vitamin E alone against neuronal oxidative stress. We demonstrate herein that treatment of cultured murine cortical neurons with these 3 agents is also more effective than vitamin E alone against Abeta neurotoxicity as assayed by generation of reactive oxygen species and increased levels of phospho-isoforms of the microtubule-associated protein tau. These data underscore the potential efficacy of a combinatorial neuroprotective formulation against Abeta neurotoxicity.

Dietary effects on cardiovascular disease risk factors: beyond saturated fatty acids and cholesterol.

Hypercholesterolemia represents a significant risk for cardiovascular disease (CVD). While diet intervention remains the initial choice for the prevention and treatment of CVD, the nature of the dietary modification remains controversial. For example, reducing calories from total fat, without decreasing saturated fat intake results in insignificant changes in low density lipoprotein cholesterol (LDL-C). Similarly, diet interventions that focus solely on lowering dietary cholesterol and saturated fat intake not only decrease LDL-C, but also high density lipoprotein cholesterol (HDL-C) and therefore may not improve the lipoprotein profile. This brief review summarizes dietary interventions that lower LDL-C without affecting HDL-C levels. These interventions include soy protein, soluble fiber, soy lecithin and plant sterols. This review also includes some of the reported dietary interventions, such as polyphenols, isoflavones, folic acid and vitamins B6 and B12, which reduce the risk of CVD without changes in lipoprotein cholesterol.

Trans fatty acids and cardiovascular risk.

Trans fatty acids are found in partially hydrogenated vegetable oil, in meats, and in dairy products. Their effect on blood cholesterol concentrations was examined decades ago, but recently there has been renewed interest in understanding how trans fatty acids affect blood lipids and lipoprotein cholesterol concentrations. Current advice to reduce cardiovascular disease (CVD) risk includes decreasing the consumption of saturated and total fat to help manage blood cholesterol concentrations. Saturated fat contributes significantly to total fat intake and markedly raises blood cholesterol concentrations. Trans fatty acids, which are consumed in much smaller quantities, have been shown to be modestly hypercholesterolemic in studies that have substituted hydrogenated vegetable oils for unhydrogenated oils. In contrast, when partially hydrogenated vegetable oils containing trans fatty acids are substituted for cholesterol-raising saturated fats, blood cholesterol levels are reduced. Partially hydrogenated vegetable oils are used in place of saturated fat in many food products. These foods can help consumers lower their saturated fat intake to achieve dietary recommendations. The following review critically examines the role of hydrogenated fats in the food supply, the metabolism of trans fatty acids, and the scientific literature surrounding the effects of partially hydrogenated vegetable oils and trans fatty acids on blood cholesterol concentrations and cardiovascular disease risk.

Soluble fiber and soybean protein reduce atherosclerotic lesions in guinea pigs. Sex and hormonal status determine lesion extension.

These studies were undertaken to assess guinea pigs as potential models for early atherosclerosis development. For that purpose, male, female, and ovariectomized (to mimic menopause) guinea pigs were fed a control or a TEST diet for 12 wk. Differences between diets were the type of protein (60% casein/40% soybean vs. 100% soybean) and the type of fiber (12.5% cellulose vs. 2.5% cellulose/5% pectin/5% psyllium) for control and TEST diets, respectively. Diet had no effect on plasma cholesterol or triacylglycerol (TAG) concentrations; however, there were significant effects related to sex/hormonal status. Ovariectomized guinea pigs had higher plasma cholesterol and TAG concentrations than males or females (P < 0.01). In contrast to effects on plasma lipids, hepatic cholesterol and TAG were 50% lower in the TEST groups (P < 0.01) compared to controls. Low density lipoproteins (LDL) from guinea pigs fed the TEST diet had a lower number of cholesteryl ester (CE) molecules and a smaller diameter than LDL from controls. Atherosclerotic lesions were modulated by both diet (P < 0.0001) and sex (P < 0.0001). Guinea pigs fed the TEST diet had 25% less lesion extension whereas males had 20% larger occlusion of the arteries compared to both female and ovariectomized guinea pigs. Significant positive correlations were found between LDL CE and atherosclerotic lesions (r = 0.495, P < 0.05) and LDL size and fatty streak area (r = 0.56, P < 0.01). In addition, females fed the TEST diet had the lowest plasma and hepatic cholesterol concentrations, the smallest LDL particles, and the least atherosclerosis involvement compared to the other groups. These data indicate that dietary factors and sex/hormonal status play a role in determining plasma lipids and atherosclerosis in guinea pigs.

Asthma in Head Start children: prevalence, risk factors, and health care utilization.

PURPOSES: 1. To identify the prevalence and severity of asthma in a Massachusetts Head Start program; 2. To identify associated risk factors for children with asthma; 3. To assess factors associated with health care utilization for asthma management. METHOD: Parents of 316 Head Start children were interviewed using a close-ended survey questionnaire. Survey A was used for demographics and general health screening. Survey B documented more specific asthma information. FINDINGS: There was a 35% prevalence rate of asthma in this preschool Head Start population. Most children had mild to moderate degrees of severity. Atopy, environmental triggers, and tobacco smoke exposure were common risk factors. Seventy-four percent of these children with asthma had used the emergency department at least once in their lifetime for asthma management. Forty-one percent had been hospitalized at least one time for asthma. CONCLUSIONS: These findings are consistent with previous studies that support the need for asthma outreach and interventions in at-risk Head Start preschool populations.

Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters.

The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol compared to the stanol diet. The CFO, sterol, and stanol diets excreted significantly more fecal cholesterol compared to the coconut oil and CO diets. In summary, CFO reduces plasma and hepatic cholesterol concentrations and increases fecal cholesterol excretion greater than CO through some other mechanism(s) in addition to increase dietary sterols and stanols-possibly oryzanols.

Corn husk oil lowers plasma LDL cholesterol concentrations by decreasing cholesterol absorption and altering hepatic cholesterol metabolism in guinea pigs.

To test the hypocholesterolemic mechanisms of corn husk oil (CoHO), male Hartley guinea pigs were fed diets containing increasing doses of CoHO, either 0 (control), 5, 10, or 15 g/100 g, and 0.25 g/100 g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. Fat was adjusted to 15 g/100 g in all diets by the addition of regular corn oil. Plasma low density lipoprotein (LDL) cholesterol concentrations were 32, 55, and 57% (P < 0.0005) lower with increasing doses of CoHO. In addition, intake of CoHO resulted in 32 to 43% lower hepatic total and esterified cholesterol and 55 to 60% lower triacylglycerol concentrations compared with the control group (P < 0.01). CoHO intake resulted in plasma and hepatic cholesterol concentrations similar to those in guinea pigs from the LC group. The number of cholesteryl ester and free cholesterol molecules was higher in LDL from the control group than in LDL from the CoHO or the LC groups. Hepatic beta-hydroxy-beta-methylglutaryl-coenzyme A reductase activity was not modified by CoHO intake whereas cholesterol 7alpha-hydroxylase was up-regulated by 45 to 49% (P < 0.01) in the 10 and 15 g/100 g CoHO groups. Hepatic acyl coenzyme A cholesterol acyltransferase activity was down-regulated in a dose-dependent manner by 54, 58, and 63% with increasing doses of CoHO. CoHO intake resulted in increased fecal cholesterol excretion by 40 to 55% compared with the control and LC groups. Total fecal neutral sterol excretion was enhanced 42 to 55% by CoHO compared with the control group and by 59 to 68% compared with the LC group. The data from these studies suggest that CoHO has its hypocholesterolemic effect by decreasing cholesterol absorption and increasing bile acid output. These alterations in the intestinal lumen alter hepatic cholesterol metabolism and may affect the synthesis and catabolism of lipoproteins.

Comparative cholesterol lowering properties of vegetable oils: beyond fatty acids.

OBJECTIVE: Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS. METHODS: To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS). RESULTS: Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (-25%) and low density lipoprotein cholesterol (LDL-C) (-30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO. CONCLUSIONS: These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.

Gender differences in response to a hypercholesterolemic diet in hamsters: effects on plasma lipoprotein cholesterol concentrations and early aortic atherosclerosis.

Gender is a strong predictor of coronary heart disease (CHD) susceptibility and reports indicate that males are more likely to develop CHD compared to age-matched premenopausal females. To test whether similar gender differences exist in hamsters, 16 male and 16 female F1B Golden Syrian hamsters, aged 10 weeks, were fed a hypercholesterolemic nonpurified diet (HCD) containing 10% coconut oil and 0.05% cholesterol for 12 weeks. Plasma lipid and lipoprotein cholesterol concentrations, LDL oxidative susceptibility, LDL tocopherol concentrations, LDL fatty acid composition, LDL particle size, plasma estradiol and testosterone concentrations, and early aortic atherosclerosis were analyzed. Female hamsters had significantly lower plasma total cholesterol and nonhigh-density lipoprotein cholesterol (nonHDL-C) and greater high-density lipoprotein cholesterol (HDL-C) concentrations compared to male hamsters (-15, -33, and 33%; respectively). Female hamsters had significantly greater LDL particle size (4%), LDL 22:6 (21%) fatty acid, and rate of LDL oxidation (34%) compared to male hamsters. Female hamsters had a significantly higher concentration of plasma estradiol (49%) compared to male hamsters. Female hamsters also had significantly less early aortic atherosclerosis compared to male hamsters (-77%). In female hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.76, P<0.0007), LDL particle size (r = -0.66, P<0.005), plasma TC (r = 0.68. P<0.004), and lag phase of LDL oxidation (r = 0.84. P<0.02). In male hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.52, P<0.04), plasma TC (r = 0.55, P<0.03), plasma TG (r = 0.79, P<0.0003), and LDL 22:6 (r = -0.78, P<0.03) with no association with any measures of LDL oxidation susceptibility. This study demonstrates that female hamsters have an improved plasma lipoprotein cholesterol profile, larger LDL particle size, and less early aortic atherosclerosis compared to male hamsters fed the same HCD.

Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein, soluble fiber, or cholesterol content.

There were two objectives to these studies: 1) to compare the lipoprotein cholesterol distribution in two animal models in response to different dietary treatments and 2) to assess whether the hypercholesterolemia induced by high cholesterol intake could be reversed by consumption of vegetable-protein and/or dietary fiber. Guinea pigs, which carry the majority of plasma cholesterol in LDL, and hamsters, with a higher distribution of cholesterol in HDL, were evaluated in three different studies. In Study 1, animals were fed semi-purified diets for 4 wk with proportions of 60:40, 20:80 or 0:100 (w/w) of casein/ soybean protein. Hamsters and guinea pigs that consumed 100% soybean protein had lower plasma total cholesterol (TC) than those fed diets containing casein (P < 0.01). In Study 2, three doses of dietary pectin (2.7, 5.4, or 10.7 g/100g) added in place of cellulose were tested. Intake of 10.7 g/100 g pectin resulted in the lowest plasma TC concentrations for both species (P < 0.01). Although the TC lowering was similar in studies 1 and 2, the lipoprotein cholesterol distribution differed. Whereas the differences in plasma cholesterol were in LDL in guinea pigs, hamsters exhibited differences in both non-HDL and HDL cholesterol. In study 3, animals were fed 100% soybean protein, 10.7 g/100 g pectin, and three doses of dietary cholesterol: 0.04, 0.08, or 0.16 g/100 g, which is equivalent to 300, 600, or 1,200 mg/d in humans. Guinea pigs and hamsters had the highest plasma LDL and hepatic cholesterol concentrations when they consumed 0.16 g/100 g of cholesterol (P < 0.01). However, intake of 0.08 g/100 g of cholesterol resulted in lower plasma LDL cholesterol concentrations than did consuming high animal protein (60:40 casein/ soy) or low soluble fiber (2.7 g/100 g). Relatively high levels of dietary cholesterol combined with vegetable protein and soluble fiber resulted in desirable lipoprotein profiles in animal models that significantly differ in their lipoprotein cholesterol distribution.

Plasma lipid changes after supplementation with beta-glucan fiber from yeast.

BACKGROUND: Dietary fiber has been shown to improve blood lipids. OBJECTIVE: The purpose of this study was to evaluate the effect on serum lipids of a yeast-derived beta-glucan fiber in 15 free-living, obese, hypercholesterolemic men. DESIGN: After a 3-wk period in which subjects ate their usual diet, 15 g fiber/d was added to the diet for 8 wk and then stopped for 4 wk. Plasma lipids were measured weekly during baseline and at week 7 and 8 of fiber consumption, and again at week 12. RESULTS: Compared with baseline, fiber consumption significantly reduced plasma total cholesterol (by 8% at week 7 and 6% at week 8; P < 0.05 using Bonferroni correction); week 12 values did not differ from baseline. No significant differences were noted between baseline LDL cholesterol and values at weeks 7, 8, or 12 when comparing individual groups by using Bonferroni correction, even though the overall one-way analysis of variance with repeated measures was highly significant (P < 0.001). LDL-cholesterol concentrations did decline by 8% at week 8 compared with baseline. There was a significant effect of diet on plasma HDL-cholesterol concentrations (P < 0.005 by one-way ANOVA with repeated measures). However, a group difference was observed only between baseline and week 12 (16% increase; P < 0.05 by Bonferroni correction). Triacylglycerol concentrations did not change. CONCLUSIONS: The yeast-derived beta-glucan fiber significantly lowered total cholesterol concentrations and was well tolerated; HDL-cholesterol concentrations rose, but only 4 wk after the fiber was stopped.

Effect of physician-delivered nutrition counseling training and an office-support program on saturated fat intake, weight, and serum lipid measurements in a hyperlipidemic population: Worcester Area Trial for Counseling in Hyperlipidemia (WATCH).

OBJECTIVE: To evaluate the effectiveness of a training program for physician-delivered nutrition counseling, alone and in combination with an office-support program, on dietary fat intake, weight, and blood low-density lipoprotein cholesterol levels in patients with hyperlipidemia. PARTICIPANTS AND METHODS: Forty-five primary care internists at the Fallon Community Health Plan, a central Massachusetts health maintenance organization, were randomized by site into 3 groups: (1) usual care; (2) physician nutrition counseling training; and (3) physician nutrition counseling training plus an office-support program. Eleven hundred sixty-two of their patients with blood total cholesterol levels in the highest 25th percentile, having previously scheduled physician visits, were recruited. Physicians in groups 2 and 3 attended a 3-hour training program on the use of brief patient-centered interactive counseling and the use of an office-support program that included in-office prompts, algorithms, and simple dietary assessment tools. Primary outcome measures included change at 1-year of follow-up in percentage of energy intake from saturated fat; weight; and blood low-density lipoprotein cholesterol levels. RESULTS: Improvement was seen in all 3 primary outcome measures, but was limited to patients in group 3. Compared with group 1, patients in group 3 had average reductions of 1.1 percentage points in percent of energy from saturated fat (a 10.3% decrease) (P = .01); a reduction in weight of 2.3 kg (P<.001); and a decrease of 0.10 mmol/L (3.8 mg/dL) in low-density lipoprotein cholesterol level (P = .10). Average time for the initial counseling intervention in group 3 was 8.2 minutes, 5.5 minutes more than in the control group. CONCLUSION: Brief supported physician nutrition counseling can produce beneficial changes in diet, weight, and blood lipids.

Studies of cholesterol and bile acid metabolism, and early atherogenesis in hamsters fed GT16-239, a novel bile acid sequestrant (BAS).

The purpose of this study was to compare the efficacy of GT16-239, an alkylated, cross-linked poly(allylamine) bile acid sequestrant with cholestyramine on cholesterol and bile acid metabolism, and early aortic atherosclerosis in hypercholesterolemic male F1B Golden Syrian hamsters. In this controlled study, 42 hamsters were divided into six groups and were fed a chow-based hypercholesterolemic diet supplemented with a 10% oil blend (55% coconut/45% corn), 0.1% cholesterol (w/w) (control) and either 0.9 or 1.2% cholestyramine or 0.2, 0.4 or 0.6% GT16-239 for 13 weeks. Laboratory analyses included evaluating plasma lipoprotein cholesterol and triglyceride concentrations, hepatic HMG-CoA reductase and 7 alpha-hydroxylase activities, fecal excretion of bile acids and neutral sterols, hepatic cholesterol concentrations, and early atherosclerosis (aortic fatty streak area). Relative to the control diet, the 0.6% GT16-239 versus the 1.2% cholestyramine significantly inhibited the elevation of plasma lipoprotein total cholesterol (TC) (-69% vs -40%), high density lipoprotein-cholesterol (HDL-C) (-49% vs -30%), and non-HDL-C (-81 vs -48%) concentrations; increased the activities of both HMG-CoA reductase (1492% vs 62%) and 7 alpha-hydroxylase (175% vs 86%); lowered the concentration of hepatic cholesteryl ester (-94% vs -59%); increased fecal cholesterol concentration (+28% vs -10%); and decreased aortic fatty streak area (-100% vs -86%). Unexpected findings of this comparison were increased fecal concentrations of cholic acid (533%) and chenodeoxycholic acid (400%) and the reduction in lithocholic acid (-50%) in the 0.6% GT16-239 compared to the 1.2% cholestyramine group. In summary, GT16-239 had a greater impact on cholesterol metabolism and early atherosclerosis in hypercholesterolemic hamsters than cholestyramine.

Effects of specific fatty acids (8:0, 14:0, cis-18:1, trans-18:1) on plasma lipoproteins, early atherogenic potential, and LDL oxidative properties in the hamster.

Although comparative studies of the cholesterolemic properties of trans fatty acids relative to cis-unsaturates and saturates have been conducted in humans and animals, there is no recent information relating these lipid responses to susceptibility to atherosclerosis. Therefore, hamsters were fed diets containing equivalent amounts of cholesterol (0.12% wt/wt) and test fats (20% wt/wt) for 8 weeks. Each test fat contained between 50-52% of the-total triacylglycerols as a single fatty acid, i.e., 8:0, 14:0, 18:0, cis-18:1, or trans-18:1 while the balance consisted of 16:0, cis-18:1 and 18:2 that were the same for all groups. Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels were not different for 8:0, cis-18:1, and trans-18:1, whereas 14:0 caused a significant rise in plasma TC, LDL-C, and HDL-C. LDL oxidation measurements showed that the lag phase of conjugated diene formation was longest for the trans-18:1 and cis-18:1 groups while rate of conjugated diene formation was lowest for the trans-18:1 and cis-18:1 groups. The trans-18:1- and cis-18:1-fed animals had significantly higher levels of LDL alpha-tocopherol relative to the 8:0- and 14:0-fed animals. Aortic fatty streak formation was highest for the 14:0- and 8:0-fed animals and lowest for the trans-18:1. In conclusion, the plasma lipid and antioxidant properties of trans-18:1 and cis-18:1 were comparable while the trans-18:1-fed hamsters had the least amount of early atherosclerosis. In addition, 8:0-fed animals unexpectedly had early atherosclerosis formation similar to the 14:0-fed animals.

Soy lecithin reduces plasma lipoprotein cholesterol and early atherogenesis in hypercholesterolemic monkeys and hamsters: beyond linoleate.

The current study was designed to investigate the hypocholesterolemic and anti-atherogenic properties of soy lecithin beyond its fatty acid content. In experiment 1, 18 cynomolgus monkeys were divided into three groups of six and fed diets which approximated either the average American diet (AAD), the American Heart Association (AHA) Step I diet, or a modified AHA (mAHA) Step I diet containing 3.4% soy lecithin for 8 weeks. Plasma samples were collected from food-deprived monkeys and analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very low- and low-density lipoprotein cholesterol (non-HDL-C), and triglyceride (TG) concentrations. Group comparisons revealed that monkeys fed the mAHA Step 1 diet had significantly lower plasma TC (-46%) and non-HDL-C (-55%) levels compared to the AAD diet, whereas monkeys fed the AHA Step 1 diet had lesser reductions in plasma TC (-21%) and non-HDL-C (-18%) levels. The monkeys fed the mAHA Step I diet had significantly lower plasma TC (-32%) and non-HDL-C (-45%) compared to the monkeys fed the AHA step diet. Also, only the mAHA Step I diet significantly reduced pre-treatment plasma TC and non-HDL-C levels by - 39 and -51% respectively with no significant effect on plasma HDL-C or TG levels. In experiment 2, 45 hamsters were divided into three groups of 15 and fed the following three modified non-purified diets for 8 weeks: a hypercholesterolemic diet (HCD) containing 10%, coconut oil and 0.05%, cholesterol, HCD plus 3.4%, soy lecithin (+SL), or the HCD with added levels of linoleate and choline equivalent to the +SL diet but no lecithin (-SL). Plasma lipids were determined as in experiment 1 and aortas were perfusion-fixed and Oil Red O stained for morphometric analyses of fatty streak area. Relative to the HCD group, the +SL-treated hamsters had significantly lower plasma TC (-58%), non-HDL-C (-73%) and aortic fatty streak area (-90%). Relative to the -SL group, hamsters fed the +SL diet had significantly lower plasma TC (-33%), non-HDL-C (-50%) and significantly reduced aortic fatty streak area (-79%). In conclusion, the first experiment suggests that the cholesterol-lowering efficacy of the AHA Step I diet can be enhanced with the addition of soy lecithin without reducing plasma HDL-C levels. whereas the second experiment suggest that the hypocholesterolemic, and in particular, the anti-atherogenic properties of soy lecithin cannot be attributed solely to its linoleate content.

Addition of guar gum and soy protein increases the efficacy of the American Heart Association (AHA) step I cholesterol-lowering diet without reducing high density lipoprotein cholesterol levels in non-human primates.

The aim of this study was to determine whether the addition of soy protein and guar gum to the American Heart Association (AHA) Step I diet would increase its efficacy compared with the typical "Average American Diet" (AAD) in a non-human primate model. Twenty adult female cynomolgus monkeys (Macaca fascicularis) were fed one of three diets for 6 wk. The AAD contained 36% energy from fat; the standard Step I diet contained 30% energy from fat; and the modified AHA Step I diet contained 30% energy from fat with the addition of soy protein isolate (10% of total energy) and guar gum (5.8 g/d). Plasma samples were collected from food-deprived monkeys at 4, 5 and 6 wk of dietary treatment for analyses of plasma total cholesterol (TC), lipoprotein cholesterol and triacylglycerol (TAG) concentrations. Plasma TC, LDL-C, HDL-C and TAG concentrations were not significantly different in wk 4, 5 and 6 within any of the diet periods; thus the three measurements were averaged. After 6 wk of dietary treatment, monkeys fed the standard Step I diet had lower plasma TC (-19%) (P < 0.05) and LDL cholesterol (LDL-C) (-24%) (P < 0.09) than when they were fed the AAD, with no effect on HDL cholesterol (HDL-C), the lipoprotein cholesterol profile or TAG. Beyond the effect of the standard Step I diet, the modified AHA Step I diet further reduced plasma TC and LDL-C (-24% and -40%) (P < 0. 05) and the TC/HDL-C and LDL-C/HDL-C ratios (-37% and -52%) (P < 0. 05) with no significant changes in plasma HDL-C or TAG. The primary conclusions of this study are that the efficacy of the AHA Step I cholesterol-lowering diet can be increased with the addition of soy protein and guar gum and provide a more favorable lipoprotein cholesterol profile. Whether the cholesterol-lowering effect is the result of soy protein or guar gum or a synergistic effect of both remains to be determined.

The hypocholesterolemic and antiatherogenic effects of Cholazol H, a chemically functionalized insoluble fiber with bile acid sequestrant properties in hamsters.

Cholazol H (Alpha-Beta Technology, Worcester, MA), a chemically functionalized, insoluble dietary fiber with bile acid sequestrant properties, was studied in 30 male F1 B Golden Syrian hamsters for its effect on plasma lipid concentrations and early atherogenesis in experiment 1. In experiment 2, 30 male Golden Syrian hamsters were studied for the effects on plasma lipids and fecal excretion of bile acids. In experiment 1, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 5% coconut oil and 0.1% cholesterol for 6 weeks. After 6 weeks, hamsters were continued on the diet with either 0% drug (hypercholesterolemic diet [HCD]), 0.5% cholestyramine (CSTY), or 0.5% Cholazol H for 8 weeks. Fasting plasma lipids were measured at weeks 6, 10, and 14, and early atherosclerosis (fatty streak formation) was measured at week 14. Relative to HCD, CSTY and Cholazol H significantly lowered plasma total cholesterol (TC) (-37%, P < .03, and -30%, P < .04, respectively) and plasma very-low and low-density lipoprotein-cholesterol (nonHDL-C) (-45%, P < .02, and -36%, P < .03, respectively) with no significant effects on plasma HDL-C or triglycerides (TG). Despite similar reductions in nonHDL-C, only Cholazol H significantly prevented early atherosclerosis (-38%, P < .02) relative to HCD. In experiment 2, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 10% coconut oil and 0.05% cholesterol and either 0% drug HCD, 0.5% CSTY, or 0.5% Cholazol H for 4 weeks. Fasting plasma lipids were measured at weeks 2 and 4, and fecal bile acids were measured at week 4. Both Cholazol H and CSTY were equally effective in significantly lowering plasma TC (-16%, P < .003, and -13%, P < .01, respectively) and nonHDL-C (-22%, P < .004, and -18%, P < .02, respectively), with no significant effect on HDL-C and TG relative to HCD. Cholazol H and CSTY produced a significantly greater concentration of fecal total bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.

Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in cynomolgus monkeys in a dose-dependent manner.

To examine the mechanism(s) underlying the cholesterolemic response to dietary cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of total energy as fat. At each dietary fat level, the same group of monkeys was sequentially fed three dietary cholesterol concentrations as egg yolk in the following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ) for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated fatty acids were the same in the two groups; the 6% difference in fat was due to the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with dietary cholesterol in a dose-dependent manner in both fat groups. These elevations were the result of generally increasing LDL apolipoprotein B production rates, concomitant with reduced LDL apolipoprotein B fractional clearance at the high cholesterol intake. Serum HDL cholesterol and HDL apolipoprotein A-I concentrations were not affected in a consistent manner. These results demonstrate that cynomolgus monkeys are hyperresponsive to dietary cholesterol compared with humans, suggesting that this model may be useful in identifying metabolic and genetic predictors for hyperresponsiveness to dietary cholesterol in humans as well as assessing the metabolic heterogeneity of responses to dietary cholesterol.