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.

Grape polyphenols do not affect vascular function in healthy men.

Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors. Grape and wine contain high amounts of polyphenols, but effects of these polyphenols have hardly been investigated in isolation in randomized controlled studies. Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation (FMD). Blood pressure and other vascular function measures, platelet function, and blood lipids were secondary outcomes. Thirty-five healthy males were randomized in a double-blind, placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods. The test products, containing 800 mg of polyphenols, were consumed as capsules. At the end of each intervention period, effects were measured after consumption of a low-fat breakfast (~751 kJ, 25% fat) and a high-fat lunch (~3136 kJ, 78% fat). After the low-fat breakfast, the treatments did not significantly affect FMD. The absolute difference after the wine grape solid treatment was -0.4% (95% CI = -1.8 to 0.9; P = 0.77) and after grape seed solids, 0.2% (95% CI = -1.2 to 1.5; P = 0.94) compared with after the placebo treatment. FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment. In conclusion, consumption of grape polyphenols has no major impact on FMD in healthy men. Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in populations with increased cardiovascular risk.

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.

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.

Effect of a 12-mo micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children: 2 parallel, randomized, placebo-controlled studies in Australia and Indonesia.

BACKGROUND: Little is known about the combined effect of micronutrients and essential fatty acids on cognitive function in school-aged children. OBJECTIVE: We assessed the effect of micronutrients, long-chain n-3 fatty acids, or both on indicators of cognitive performance in well-nourished and marginally nourished school-aged children. DESIGN: Two 2-by-2 factorial randomized controlled double-blind trials were performed home-based in Adelaide, South Australia, and at 6 primary schools in Jakarta, Indonesia. A total of 396 children (aged 6-10 y) in Australia and 384 children in Indonesia were randomly allocated to receive a drink with a micronutrient mix (iron, zinc, folate, and vitamins A, B-6, B-12, and C), with docosahexanoic acid (DHA, 88 mg/d) and eicosapentaenoic acid (EPA, 22 mg/d), or with both or placebo 6 d/wk for 12 mo. Biochemical indicators were determined at baseline and 12 mo. Cognitive performance was measured at baseline, 6 mo, and 12 mo. RESULTS: The micronutrient treatment significantly improved plasma micronutrient concentrations in Australian and Indonesian children. DHA+EPA treatment increased plasma DHA and total plasma n-3 fatty acids in both countries. The micronutrient treatment resulted in significant increases in scores on tests representing verbal learning and memory in Australia (estimated effect size: 0.23; 95% CI: 0.01, 0.46). A similar effect was observed among Indonesian girls (estimated effect size: 0.32; 95% CI: -0.01, 0.64). No effects were found on tests measuring general intelligence or attention. No effects of DHA+EPA on the factors of cognitive tests were observed. CONCLUSION: In well-nourished school-aged children, fortification with multiple micronutrients can result in improvements in verbal learning and memory.

Effect of fortification with multiple micronutrients and n-3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children's Health and Mental Performance Influenced by Optimal Nutrition) Study.

BACKGROUND: Fortification with multiple micronutrients has been shown to improve growth and cognitive performance among children in developing countries, but it is unknown whether higher concentrations are more effective than lower concentrations. OBJECTIVE: We compared the effect of 2 different concentrations of a combination of micronutrients and n-3 (omega-3) fatty acids on indicators of growth and cognitive performance in low-income, marginally nourished schoolchildren in Bangalore, India. DESIGN: In a 2-by-2 factorial, double-blind, randomized controlled trial, 598 children aged 6-10 y were individually allocated to 1 of 4 intervention groups to receive foods fortified with either 100% or 15% of the Recommended Dietary Allowance of micronutrients in combination with either 900 mg alpha-linolenic acid plus 100 mg docosahexaenoic acid or 140 mg alpha-linolenic acid for 12 mo. Anthropometric and biochemical assessments were performed at baseline and 12 mo. Cognitive performance was measured at baseline and at 6 and 12 mo. RESULTS: The high micronutrient treatment significantly improved linear growth at 12 mo (0.19 cm; 0.01, 0.36) and short-term memory at 6 mo (0.11 SD; 0.01, 0.20) and was less beneficial on fluid reasoning at 6 (-0.10 SD; -0.17, -0.03) and 12 (-0.12 SD; -0.20, -0.04) mo than was the low micronutrient treatment, whereas no differences were observed on weight, retrieval ability, cognitive speediness, and overall cognitive performance. No significant differences were found between the n-3 treatments. CONCLUSIONS: The high micronutrient treatment was more beneficial for linear growth than was the low micronutrient treatment. However, with some small differential effects, higher micronutrient concentrations were as effective as lower concentrations on cognitive performance. This trial was registered at clinicaltrials.gov as NCT00467909.