Cholesterol Interference in the Assessment of Vitamin D Status: A Canadian Health Measures Survey Biobank Project.

BACKGROUND: Matrix effects are a known problem with immunoassays measuring serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVES: To determine if the inverse association between serum 25(OH)D and serum cholesterol concentrations is a function of assay method: Diasorin Liaison 25(OH) Vitamin D Total Assay (Liaison Total Assay), an immunoassay, compared with liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: Canadian Health Measures Survey data and biobank serum (White males aged 20-79 y, n = 392) were evaluated for bias in serum 25(OH)D using Bland-Altman plots. Differences in serum 25(OH)D (Liaison Total Assay - LC-MS/MS) were compared among non-HDL-cholesterol <4.2 (n = 295) compared with ≥4.2 (n = 97) mmol/L and total cholesterol groups <5.2 (n = 256) compared with ≥5.2 (n = 136) mmol/L, and associations tested between 25(OH)D and non-HDL-cholesterol or total cholesterol concentrations, using regression. RESULTS: Serum 25(OH)D measured using Liaison Total Assay ranged from 10.7 to 137.0 nmol/L and 14.4 to 137.9 nmol/L by LC-MS/MS. Liaison Total Assay - LC-MS/MS showed a negative bias of 5.5 (95% limits of agreement -23.8, 12.7) nmol/L. Differences in 25(OH)D were -4.0 ± 9.0 (±SD) nmol/L if non-HDL-cholesterol was <4.2 mmol/L and -10.2 ± 8.7 nmol/L if ≥4.2 mmol/L (P < 0.0001). Differences in 25(OH)D, if total cholesterol was <5.2 mmol/L, were -3.4 ± 8.6 nmol/L and -9.6 ± 9.3 nmol/L if ≥5.2 mmol/L (P < 0.0001). Serum non-HDL-cholesterol (beta -3.17, P = 0.0014) and total cholesterol (beta -2.77, P = 0.0046) were inversely associated with Liaison Total Assay 25(OH)D (adjusted for age, fasting, and body mass index), but not with LC-MS/MS measured 25(OH)D. Interference by these lipoproteins was not eliminated by standardization of the Liaison Total Assay. Similar associations were observed with triglycerides as for the lipoproteins. CONCLUSIONS: Total cholesterol inversely associates with 25(OH)D, which is likely due to elevated non-HDL-cholesterol lipoprotein or triglyceride interference with the Liaison Total Assay. This is important as elevated cholesterol is common, and an underestimation of vitamin D status could be an unnecessary cause for concern.

Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women.

Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3 (ω-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose-response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL-C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [ßln (TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3-16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n-3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at clinicaltrials.gov as NCT01313988.

Proportions of trans fatty acids in erythrocytes of Canadian adults before the prohibition of partially hydrogenated oils in foods: results from the Canadian Health Measures Survey 2012-2015.

BACKGROUND: The partially hydrogenated oil (PHO) prohibition came into effect in Canada in September 2018 to reduce the intakes of total trans fatty acids (t-TFAs) and industrially produced TFAs (i-TFAs). OBJECTIVES: We aimed to estimate the red blood cell (RBC) proportions of t-TFA (primary objective) and total 18:1 TFA (secondary objective) of adults in Canada before the PHO prohibition and to identify the population subgroups at risk of higher TFA intakes. METHODS: We pooled data from 4025 adult participants of the cross-sectional Canadian Health Measures Survey cycles 3 and 4 (2012-2015). We estimated mean proportions, relative to total fatty acids (FAs), of RBC t-TFA and 18:1 TFA and their associations with sociodemographic, health, and lifestyle characteristics using multiple linear regression models. RESULTS: The nonadjusted mean RBC proportions of t-TFA and total 18:1 TFA were 0.59% (95% CI: 0.54, 0.63) and 0.27% (95% CI: 0.25, 0.29), respectively. In the adjusted models, the same participant characteristics were associated with t-TFA and 18:1 TFA but differences were generally smaller for 18:1 TFA than for t-TFA. Race, BMI, and alcohol intake were independently associated with RBC t-TFA and 18:1 TFA. Asian and Black participants had lower RBC t-TFA (-0.05% and -0.10% of total FA, respectively) than White participants. Obesity and high risk alcohol drinking were associated with slightly lower (≤0.06%) t-TFA proportions than lower adiposity and alcohol intake concentrations, respectively. CONCLUSIONS: Pre-PHO prohibition in food in Canada, t-TFA proportions were relatively low compared with a proposed threshold of 1% of total RBC FAs, over which cardiovascular disease risk may be higher. Previous voluntary initiatives to reduce i-TFA in the food supply may explain these relatively low RBC t-TFA concentrations. Some population subgroups had higher baseline RBC TFA than other subgroups, but the physiological implications of these small differences, at relatively low baseline RBC TFA proportions, remain to be determined.

The effect of plant sterols on serum triglyceride concentrations is dependent on baseline concentrations: a pooled analysis of 12 randomised controlled trials.

PURPOSE: Plant sterols (PS) are well known for their low-density lipoprotein cholesterol-lowering effect. Until recently, they were believed to have little or no impact on blood triglycerides (TG). However, studies taken individually were possibly lacking statistical power to detect modest TG decreases. This study was performed to quantify the TG-lowering effect of PS by pooling individual subject data from 12 randomised controlled trials that investigated the effects of PS on blood lipids. METHODS: The main outcome variable was the control-adjusted PS effect on relative (%) and absolute (mmol/L) changes in TG. The relative and absolute changes in high-density lipoprotein cholesterol (HDL-C) were also assessed. Differences in changes of serum lipid concentrations between PS and control treatments were estimated by an ANCOVA using a random effect model which included PS intake (active or control), study and predefined subject characteristics. RESULTS: The twelve randomised controlled trials included in total 935 hypercholesterolaemic subjects not preselected based on their baseline TG concentrations. In most studies, the PS dose ranged between 1.6 and 2.5 g/day. PS intake significantly lowered serum TG by 6.0% (95% CI: -10.7, -1.2) or 0.12 mmol/L (95% CI: -0.20, -0.04). No significant interaction was observed between PS intake and baseline TG concentrations on relative changes, but, on absolute changes, interaction was significant with larger TG decreases observed with higher TG concentrations at baseline. No effects were observed on HDL-C concentrations. CONCLUSIONS: These results show that PS exert a modest TG-lowering effect which is dependent on baseline concentrations.

Proportions of long-chain ω-3 fatty acids in erythrocyte membranes of Canadian adults: Results from the Canadian Health Measures Survey 2012-2015.

BACKGROUND: The Omega-3 Index (OI) is a proposed marker of coronary artery disease (CAD) risk. Another index, the EPA/arachidonic acid (AA) ratio has also been proposed as a possible risk marker for CAD. OBJECTIVE: Our primary objective was to characterize the Canadian population subgroups that have an undesirable OI (<4%, associated with high CAD risk) and to identify the participants' characteristics most strongly associated with the OI. Our secondary objective was to identify the characteristics most strongly associated with the EPA/AA ratio. DESIGN: Data from 4025 adult participants of cycles 3 and 4 (2012-2015) of the cross-sectional Canadian Health Measures Survey were pooled. Adjusted mean proportions of erythrocyte membrane ω-3 (n-3) fatty acids, total ω-6 fatty acids, and ratios were analyzed by sociodemographic, health, and lifestyle characteristics using covariate-adjusted models. RESULTS: The mean OI was 4.5%. Almost 40% of Canadians had an undesirable (<4%) OI. ω-3 supplement use, fish intake, and race were the variables most strongly associated with OI scores. The prevalence of undesirable OI was significantly higher among participants consuming fish less than twice a week (43.8%; 95% CI: 39.0%, 48.6%) than among those consuming more fish (12.7%; 95% CI: 7.8%, 19.9%), among smokers (62.7%; 95% CI: 52.9%, 71.7%) than nonsmokers (33.4%; 95% CI: 29.4%, 37.7%), in whites (42.7%; 95% CI: 38.2%, 47.4%) than in Asians (23.0%; 95% CI: 15.4%, 33.0%), and in adults aged 20-39 y (49.6%; 95% CI: 42.3%, 56.9%) than in those aged 60-79 y (24.4%; 95% CI: 21.0%, 28.1%). ω-3 supplement intake and fish intake were the characteristics most strongly associated with EPA/AA. All P ≤ 0.05. CONCLUSIONS: An important proportion of Canadian adults has an undesirable (<4%) OI, with higher prevalence in some subgroups. Further assessment is required to determine the value and feasibility of an increase in the population's OI to the currently proposed target of ≥8% as a potential public health objective.

The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women.

The citrus flavonoids hesperidin and naringin have been suggested to lower blood total (TC) and LDL-cholesterol (LDL-C) both in animal models and humans. However, the evidence from previous studies in humans is not convincing. This study evaluated the LDL-C-lowering efficacy of pure hesperidin and naringin in moderately hypercholesterolemic individuals. A total of 204 healthy men and women with a serum TC concentration of 5.0-8.0 mmol/L participated in a randomized, placebo-controlled, parallel trial with 3 groups. A 4-wk preintervention period during which participants refrained from consuming hesperidin and naringin sources preceded the intervention. During the 4-wk intervention, the participants applied the same dietary restrictions and consumed 4 capsules/d providing either placebo (cellulose) or a daily dose of 800 mg hesperidin or 500 mg naringin. Blood samples to measure serum lipids were taken on 2 consecutive days at the beginning and end of the intervention phase. One hundred ninety-four participants completed the study. They maintained their prestudy body weights (mean changes lt 0.2 kg in all groups). In all groups, the mean consumption of scheduled capsules was gt 99%. Hesperidin and naringin did not affect TC or LDL-C, with endpoint LDL-C concentrations (adjusted for baseline) of 4.00 +/- 0.04, 3.99 +/- 0.04, and 3.99 +/- 0.04 mmol/L for control, hesperidin, and naringin groups, respectively. These citrus flavonoids also did not affect serum HDL-cholesterol and triglyceride concentrations. In conclusion, pure hesperidin and naringin consumed in capsules at mealtime do not lower serum TC and LDL-C concentrations in moderately hypercholesterolemic men and women.

Biological effects of oxidized phytosterols: a review of the current knowledge.

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.

Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.

Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults.

The present study was designed to evaluate the independent and interactive effects of a once-a-day yoghurt drink providing 2 g plant sterols/d and capsules providing 2 g fish oil n-3 long-chain (LC) PUFA/d on plasma lipids, apolipoproteins and LDL particle size. Following a 2-week run-in period, 200 mildly hypercholesterolaemic Indian adults aged 35-55 years were randomised into one of four groups of a 2 x 2 factorial, double-blind controlled trial. The 4-week treatments consisted of (1) control yoghurt drink and control capsules, (2) control yoghurt drink and fish oil capsules, (3) plant sterol-enriched yoghurt drink and control capsules, or (4) plant sterol-enriched yoghurt drink and fish oil capsules. Blood was drawn before and after the 4-week intervention. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The main effects of plant sterols were a 4.5 % reduction in LDL-cholesterol and a 15 % reduction in TAG without a significant change in HDL-cholesterol. Overall, fish oil n-3 LC-PUFA did not significantly affect cholesterol concentrations but reduced TAG by 15 % and increased HDL-cholesterol by 5.4 %. The combination significantly lowered TAG by 15 % v. control. No significant interaction between plant sterols and n-3 LC-PUFA was observed on plasma cholesterol concentrations. In conclusion, once-a-day intake of 2 g plant sterols/d in a yoghurt drink, 2 g fish oil n-3 LC-PUFA/d in capsules, and their combination had beneficial effects on the lipid profile of mildly hypercholesterolaemic Indian adults. The potent hypotriacylglycerolaemic effect of plant sterols observed in the present study and this population warrants additional investigation.

Dietary calcium affects body composition and lipid metabolism in rats.

Calcium (Ca) intakes may affect cardiovascular disease risk by altering body composition (body weight and fat) and serum lipid profile, but results have been inconsistent and the underlying mechanisms are not well understood. The effects of dietary Ca on body composition and lipid metabolism were examined in rats. Male Sprague-Dawley rats were fed high-fat, high-energy diets containing (g/kg) low (0.75Ca, 0.86 ± 0.05; 2Ca, 2.26 ± 0.02), normal (5Ca, 5.55 ± 0.08) or high (10Ca, 11.03 ± 0.17; 20Ca, 21.79 ± 0.15) Ca for 10 weeks. Rats fed the lowest Ca diet (0.75Ca) had lower (p < 0.05) body weight and fat mass compared to other groups. Rats fed the high Ca diets had lower serum total and LDL cholesterol compared to rats fed normal or low Ca. Liver total cholesterol was lower in rats fed high compared to low Ca. In general, liver mRNA expression of genes involved in cholesterol uptake from the circulation (Ldlr), cholesterol synthesis (Hmgcr and Hmgcs1), fatty acid oxidation (Cpt2) and cholesterol esterification (Acat2) were higher in rats fed higher Ca. Apparent digestibility of total trans, saturated, monounsaturated and polyunsaturated fatty acids was lower in rats fed the high compared to the low Ca diets, with the largest effects seen on trans and saturated fatty acids. Fecal excretion of cholesterol and total bile acids was highest in rats fed the highest Ca diet (20Ca). The results suggest little effect of dietary Ca on body composition unless Ca intakes are very low. Decreased bile acid reabsorption and reduced absorption of neutral sterols and saturated and trans fatty acids may contribute to the better serum lipid profile in rats fed higher Ca.

Moderate weight loss: a self-directed protocol for women.

This innovative, self-directed diet and physical activity program was designed to achieve moderate weight loss in women. Thirty-five overweight or obese hyperlipidemic women completed a 20-week weight loss study. The weight loss intervention consisted of a 20% decrease in energy intake through diet and a 10% increase in energy expenditure through physical activity. The diet consisted of 50-60% carbohydrates, 20% protein, and 20-30% fat. A personal trainer prescribed physical activity regimens. A progress-tracking system and monthly group sessions were used to maintain participant motivation throughout the weight loss period. Participants lost an average of 11.7 +/- 2.5 kg (p<0.001). The pattern of weight loss was linear (p<0.001) throughout the study period. Average weight loss per week was 0.59 +/- 0.55 kg. This 20-week program, combining a structured self-selected diet and independent preplanned physical activity with motivational strategies, resulted in weight loss comparable to that observed in more controlled interventions. The lower cost, ease of use, and outcome success make this approach potentially useful in a clinical setting.

Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects.

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.

Fish-oil esters of plant sterols improve the lipid profile of dyslipidemic subjects more than do fish-oil or sunflower oil esters of plant sterols.

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.

Effect of weight loss resulting from a combined low-fat diet/exercise regimen on low-density lipoprotein particle size and distribution in obese women.

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.

Fish oil fatty acid esters of phytosterols alter plasma lipids but not red blood cell fragility in hamsters.

In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil FA, plant sterols have recently been esterified to fish oil n-3 PUFA. The objective of this study was to determine the effects of plant sterols esterified to n-3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters were fed diets varying in cholesterol and plant sterol content: (i) Non-cholesterol (semipurified diet with no added cholesterol or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols), or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols). The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P = 0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters fed nonesterified plant sterols (P < 0.0001). Despite higher (P < 0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of plant sterols exert no detrimental effect on erythrocyte fragility.

Effects of a water-soluble phytostanol ester on plasma cholesterol levels and red blood cell fragility in hamsters.

The aim of this study was to assess the efficacy of a novel water-soluble phytostanol analog, disodium ascorbyl phytostanyl phosphates (DAPP), on plasma lipid levels and red blood cell fragility in hamsters fed atherogenic diets. For 5 wk, 50 male Golden Syrian hamsters were fed a semipurified diet without added cholesterol (noncholesterol, group 1), or a semipurified diet with 0.25% cholesterol (cholesterol-control, group 2). Groups 3-5 were fed the cholesterol-control diet with an addition of 1% phytostanols (diet 3), 0.71% DAPP (DAPP 0.7%, diet 4), or 1.43% DAPP (DAPP 1.4%, diet 5). Diets 4 and 5 provided 0.5 and 1% phytostanols, respectively. Supplementation of 0.71 and 1.43% DAPP decreased plasma total cholesterol concentrations by 34 (P < 0.001) and 46% (P< 0.001), respectively, in comparison with the cholesterol-control group, whereas free stanols reduced (P = 0.007) plasma cholesterol concentrations by 14%. Similarly, non-HDL-cholesterol concentrations were reduced by 39 (P < 0.001) and 54% (P < 0.001) in hamsters supplemented with DAPP 0.7% and DAPP 1.4%, respectively, relative to the cholesterol-control group. The hypocholesterolemic effect of DAPP 1.4% was threefold stronger than that of free stanols. In hamsters supplemented with DAPP 1.4%, plasma TG concentrations were 45% lower (P= 0.018) than in cholesterol-control-fed hamsters, whereas no such beneficial effect was observed in the free stanol group. Erythrocyte fragility was unaffected by DAPP or free phytostanols. Results of the current study demonstrate that DAPP lowers cholesterol more efficiently than free stanols, without an adverse effect on erythrocyte fragility in hamsters.

The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses.

SCOPE: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles. CONCLUSION: The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone.

Role of isoflavones in the hypocholesterolemic effect of soy.

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.

Interaction between dietary protein and fat in triglyceride metabolism in the rat: effects of soy protein and menhaden oil.

The objective of the present study was to determine the mechanisms by which dietary proteins interact with dietary lipids in the regulation of triglyceridemia in rats. Male Sprague-Dawley rats (n = 56) were subjected to 28-d experimental diets containing different combinations of proteins (20% w/w) and lipid sources (14% w/w): (i) casein-menhaden oil, (ii) casein-beef tallow, (iii) soy protein-menhaden oil, and (iv) soy protein-beef tallow. Significant protein-lipid interactions were observed on triglyceridemia and hepatic cholesterol in fasted rats. The combination of casein and beef tallow was associated with high plasma TG and hepatic cholesterol concentrations, which were reduced by substitution either of soy for casein or of menhaden oil for beef tallow. Therefore, triglyceridemia and liver cholesterol remained low with soy protein feeding, independently of the lipid source, as well as with menhaden oil feeding, regardless of the protein source. The menhaden oil diets reduced plasma cholesterol, hepatic TG, and TG secretion compared with beef tallow diets independently of the dietary protein source. Modifying the source of dietary proteins and lipids had no effect on post-heparin plasma lipoprotein lipase activity. These results demonstrate that soy protein can lower rat triglyceridemia relative to casein when associated with beef tallow consumption, whereas menhaden oil can attenuate hypertriglyceridemia when rats are fed casein. The data further suggest that part of the hypotriglyceridemic effect of soy protein in the rat may be mediated by reduced hepatic lipid synthesis, as is the case for menhaden oil.

Olive oil containing olive oil fatty acid esters of plant sterols and dietary diacylglycerol reduces low-density lipoprotein cholesterol and decreases the tendency for peroxidation in hypercholesterolaemic subjects.

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.