Hyperlipidemias: Demonty I

Hovenkamp E, Demonty I, Plat J, Lütjohann D, Mensink RP, Trautwein EA. · Unilever Food and Health Research Institute, 3130 AC Vlaardingen, The Netherlands. · Prog Lipid Res. · Pubmed #18022398 No free full text.

Abstract: The cholesterol-lowering effect of phytosterols has been extensively studied, and consumption of phytosterols is among the recommendations to lower LDL-cholesterol concentrations. Due to their structural similarity with cholesterol, phytosterols may undergo oxidative processes comparable to those involved in cholesterol oxidation. Consumption of phytosterols could therefore lead to increased systemic concentrations of oxidized phytosterols (oxyphytosterols) via increased dietary intake or in vivo formation from non-oxidized phytosterols. While the biological effects of oxidized cholesterol (oxycholesterol) have been well studied, the amount of biological research on oxyphytosterols is scarce. Most reports on oxyphytosterols cover their quantitative analysis. Whether oxyphytosterols may play similar biological roles as compared to oxycholesterol has not been fully elucidated. The usual perception about oxyphytosterols is that these components present a concern in terms of food quality and health. This perception originates from the parallel that is made with oxycholesterol. Yet, in line with results for oxycholesterol, recent data suggest that oxyphytosterols--depending on the type of oxidation product--may also have beneficial biological properties. Therefore, the objective of this review is to summarise the current understanding of the biological effects, next to identifying future research needs that will help to clarify the possible impact of oxyphytosterols on human health.

Demonty I, Lamarche B, Jones PJ. · School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9. · Nutr Rev. · Pubmed #12903829 No free full text.

Abstract: Epidemiologic data suggest an inverse relationship between the consumption of soy isoflavones and cardiovascular disease risk. The aims of this review are to determine if isoflavones play a role in the hypocholesterolemic effect of soy and whether the studies realized with that scope were adequately designed. In humans, most studies have been performed in postmenopausal women. The results are inconsistent, however; some studies show a decrease in total cholesterol and low-density lipoprotein concentrations, and an increase in high-density lipoprotein levels, and other investigations fail to show any beneficial effect of soy isoflavones on lipid profiles. In most studies, beneficial effects could not be attributed with certainty to soy isoflavones. If these components have any health-protecting effect in humans, it is small in comparison with the effect of soy protein itself. There are currently not enough data to recommend the consumption of isoflavone supplements to lower plasma cholesterol levels.

Santosa S, Demonty I, Lichtenstein AH, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC, Canada. · Int J Obes (Lond). · Pubmed #17264848 No free full text.

Abstract: OBJECTIVE: To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. DESIGN: Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and <30% fat. RESULTS: Participants lost an average of 11.7+/-2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86+/-9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31+/-19.4%, P=0.32 and -0.01+/-6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (beta=-5.04, r=0.38; P=0.03, and beta=-147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (beta=6.82, r=0.36; P=0.04 and beta=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption. CONCLUSIONS: Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

Varady KA, Lamarche B, Santosa S, Demonty I, Charest A, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec, Canada, H9X 3V9. · Metabolism. · Pubmed #16979399 No free full text.

Abstract: Weight loss resulting from diet interventions has been shown to favorably affect low-density lipoprotein (LDL) particle size and distribution, and, hence, decrease cardiovascular disease risk. However, the effect of a dietary weight loss strategy when combined with exercise, on LDL electrophoretic characteristics, has yet to be tested. This study examined the effect of a weight loss intervention that combined a low-fat diet with moderate endurance training, on LDL particle size and distribution in obese women. Thirty obese, hypercholesterolemic women participated in a controlled longitudinal weight loss trial, which consisted of (1) a 2-week pre-stabilization phase, (2) a 20-week weight loss phase, and (3) a 2-week post-stabilization phase. Weight reduction resulted from a low-fat diet (<30% fat, 50%-60% carbohydrate, 20% protein) combined with an endurance training program (>40 minutes moderate training, 3 times per week). Mean weight loss was 14.8% (P < .01) of initial body weight. Total, LDL cholesterol, and triacylglycerol concentrations decreased (P < .01) by 8.9%, 7.5%, and 27.1%, respectively, whereas high-density lipoprotein cholesterol concentrations increased (P < .01) by 9.9%. No significant differences were noted for LDL peak or integrated particle size. The relative proportion of small, medium, and large particles was not significantly different posttreatment. Estimated cholesterol concentrations in large- and medium-sized LDL particles decreased (P < .05) by 15.3% and 5.9%, respectively, as a result of weight loss. No effect was noted for estimated cholesterol concentrations in small size LDL particles. In conclusion, these findings suggest that weight loss, resulting from a low-fat diet/exercise program, has only a minimal effect on LDL particle size and distribution.

Jones PJ, Demonty I, Chan YM, Herzog Y, Pelled D. · School of Dietetics and Human Nutrition, McGill University, Sainte-Anne-de-Bellevue, Canada. · Lipids Health Dis. · Pubmed #17961204 links to  free full text

Abstract: BACKGROUND: Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers. METHODS: Twenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids). RESULTS: There were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma beta-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher beta-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-alpha, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups. CONCLUSION: Our findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.

Santosa S, Demonty I, Lichtenstein AH, Cianflone K, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Montreal, Canada. · J Am Coll Nutr. · Pubmed #17634170 links to  free full text

Abstract: OBJECTIVE: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss. METHODS: Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels. RESULTS: Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss. CONCLUSION: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

Li NY, Li K, Qi Z, Demonty I, Gordon M, Francis L, Molhuizen HO, Neal BC. · The George Institute for International Health, University of Sydney, PO Box M201, Camperdown, Sydney, NSW2050, Australia. · Br J Nutr. · Pubmed #17617940 No free full text.

Abstract: The cholesterol-lowering effects of plant sterols in a format suitable for use in China have not previously been investigated. We conducted the study to quantify in adult Chinese the effects on blood lipid concentrations of a plant sterol-enriched milk tea powder. The study was a double-blind, randomised trial in which 309 participants were randomised to receive daily 2.3 or 1.5 g plant sterol supplementation or placebo for 5 weeks. The milk tea was consumed with the two fattiest meals of the day with half the assigned daily dose taken on each occasion. Fasting venous blood samples were collected before commencement and upon completion of randomised treatment. The mean age of study participants was 44 years, 62% were female and 62% had a history of hypercholesterolaemia. Baseline mean total cholesterol was 5.5 mmol/l and LDL-cholesterol was 3.2 mmol/l. Compared with placebo, the 2.3 g/d plant sterol dose reduced total cholesterol by 0.25 (95% CI 0.07, 0.43) mmol/l (P = 0.01) and the 1.5 g/d dose by 0.23 (95% CI 0.06, 0.41) mmol/l (P = 0.01). For LDL-cholesterol the corresponding reductions were 0.17 (95% CI 0.00, 0.35) mmol/l (P = 0.06) and 0.15 (95% CI -0.02, 0.32) mmol/l (P = 0.08). For neither outcome was there evidence of differences between the effects of the two doses (both P values >0.4). In conclusion, the consumption of plant sterol-enriched milk tea decreased cholesterol concentrations although to a lesser extent than was anticipated. The reason for reduced efficacy is unclear but may be attributable to the novel food format used or the Chinese population studied.

Chan YM, Demonty I, Pelled D, Jones PJ. · The School of Dietetics and Human Nutrition, McGill University, Macdonald Campus, 21,111 Lakeshore Road, Sainte-Anne-de-Bellevue, Quebec, Canada H9X 3V9. · Br J Nutr. · Pubmed #17559697 No free full text.

Abstract: Plant sterols (PS) and MUFA are well-documented cholesterol lowering agents. We aimed to determine the effect of PS esterified to olive oil fatty acids (PS-OO) on blood lipid profile and lipid peroxidation in hypercholesterolaemic subjects. Twenty-one moderately overweight, hypercholesterolaemic subjects consumed three consecutive treatment diets, each lasting 28 d and separated by 4-week washout periods, using a randomized crossover design. Diets contained 30 % energy as fat, 70 % of which was provided by olive oil (OO), and differed only in the treatment oils: OO, PS esterified to sunflower oil fatty acids (PS-SO), and PS-OO. Both PS-SO and PS-OO treatments provided 1.7 g PS /d. PS-OO and PS-SO consumption resulted in a decrease (P = 0.0483) in LDL-cholesterol (LDL-C) concentrations compared with the OO diet. Although total cholesterol and apo B-100 levels were not significantly affected, PS-SO and, to some extent, PS-OO reduced the total:HDL-cholesterol (HDL-C) ratio (P = 0.0142) and the apo B-100:apo A-I ratio (P = 0.0168) compared with the OO diet. There were no differences across diets in lipoprotein(a) (Lp(a)) and lipid peroxidation levels. However, following consumption of OO and PS-SO, Lp(a) concentrations increased (P = 0.0050 and 0.0421, respectively), while PS-OO treatment did not affect Lp(a) levels. Furthermore, there was a decrease (P = 0.0097) in lipid peroxidation levels with PS-OO treatment during the supplementation phase. Our results suggest that supplementing an OO-rich diet with PS-OO favourably alters the plasma lipid profile and may decrease the susceptibility of LDL-C to lipid peroxidation in hypercholesterolaemic subjects.

Jia X, Ebine N, Demonty I, Wang Y, Beech R, Muise V, Fortin MG, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Macdonald Campus, 21, 111 Lakeshore, Ste-Anne-de-Bellevue, QC, Canada, H9X 3V9, Canada. · Br J Nutr. · Pubmed #17459188 No free full text.

Abstract: The hypolipidaemic effects of plant sterols are well established. However, mechanisms by which plant sterols lower plasma cholesterol levels, particularly at the molecular level, have not been clearly elucidated. The objective of the present study was to determine whether different plant sterol analogues reduce plasma cholesterol levels by up regulating the sterol transporters ABCG5 and ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were divided into eight groups. Groups 1 and 2 were fed a maize starch-casein-sucrose-based diet that did not contain cholesterol (control; Con) or the Con diet with the addition of 0.25 % cholesterol (Ch-Con). Groups 3-8 were fed the Ch-Con diet supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and stanol mixture (50:50), 1.76 % plant sterol-fish oil esters, or 0.71 or 1.43 % stanol-ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up regulated the ABCG5 mRNA expression and tended (P = 0.083) to increase ABCG8 mRNA expression in the liver, but did not affect both genes' expression in the small intestine compared with the Con diet. Hamsters fed 0.7 % stanol esters showed lower plasma cholesterol levels (P < 0.001) and also lower liver ABCG5 mRNA expression (P < 0.05) compared with the Ch-Con diet. Plant stanols, stanol esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in the liver and intestine although they reduced plasma cholesterol levels. These results suggest that plant sterols and their derivatives reduce plasma cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8 transporters.

Demonty I, Chan YM, Pelled D, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Sainte-Anne-de-Bellevue, Canada. · Am J Clin Nutr. · Pubmed #17158440 links to  free full text

Abstract: BACKGROUND: Fish-oil fatty acid esters of plant sterols (FO-PS) were shown to have hypotriglyceridemic and hypocholesterolemic properties in animal models. OBJECTIVE: The objective of the study was to evaluate the hypolipidemic effects of FO-PS supplementation in healthy hypercholesterolemic persons fed an olive oil (OO)-based diet. DESIGN: Twenty-one moderately overweight, hyperlipidemic subjects participated in a semi-randomized, single-blind, 4-period crossover study including 4 experimental isoenergetic diets of 4 wk each and 4-wk intervening washout periods. Diets contained 30% of energy as fat, of which 70% was from extra-virgin OO, and differed only in the supplement oil: OO, fish oil, FO-PS, or sunflower oil esters of plant sterols (SU-PS). Both fish oil and FO-PS provided 5.4 g total eicosapentaenoic and docosahexaenoic acids/d. FO-PS, SU-PS, and OO provided the equivalent of 1.7, 1.7, and 0.02 g free plant sterols/d, respectively. RESULTS: Fish oil and FO-PS resulted in fasting and postprandial plasma triacylglycerol concentrations that were markedly lower than those observed with OO and SU-PS (P = 0.0001), but to a different extent. LDL cholesterol was significantly lower after supplementation with FO-PS and SU-PS than at the end of the control OO diet (P = 0.0031 and 0.0407, respectively). HDL cholesterol was not affected. FO-PS and SU-PS resulted in a lower ratio of total to HDL cholesterol and lower apolipoprotein (apo) B concentrations than did OO and fish oil. The ratio of apoB to apoA was significantly lower after SU-PS consumption than after consumption of OO (P = 0.0126) and fish oil (P = 0.0292). FO-PS and SU-PS resulted in similar ratios of apoB to apoA. HDL2 and the ratio of HDL2 to HDL3 were significantly higher at the end of the FO-PS treatment than at the end of the OO (P = 0.0006), fish oil (P = 0.0036), and SU-PS (P = 0.0016) treatments. CONCLUSION: Supplementation of an OO-based diet with FO-PS may reduce cardiovascular disease risk more than does supplementation with fish oil or SU-PS.