Age dependent incorporation of 14C-DHA into rat brain and body tissues after dosing various 14C-DHA-esters.

INTRODUCTION: The omega-3 fatty acid docosahexaenoic acid (DHA) accounts for 10% of fatty acids in human brain and is critical for neuronal function and brain development. Mechanisms of transport, accumulation and conservation of DHA in the brain are unclear. The objective of the study was to quantify the age dependent DHA incorporation into the brain of 2-, 4- or 10-week-old rats after a bolus dose of different DHA-esters. METHODS: Rats were gavaged with (14)C-DHA-TAG, (14)C-DHA-PL or (14)C-DHA-TAG+PL at 2 mg DHA/kg BW. After 24h the distribution of radioactivity in body and brain regions was determined using quantitative whole body autoradiography (QWBA). Radiolabeled compounds were extracted from the brains to determine the identity of the radiolabeled compounds. RESULTS: Accumulation of orally ingested (14)C-DHA in rat brain was less than 1% of the dose and decreased with age. Ester specific differences were seen only in 10-week-old rats, where oral (14)C-DHA-PL delivered a 2-fold higher accretion of radioactivity in the brain. CONCLUSIONS: Less than 1% of a dietary achievable DHA dose reached the rat brain within 24h. Optimal efficacy of DHA-PL may occur in older age groups.

Baseline plasma plant sterol concentrations do not predict changes in serum lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a plant sterol-enriched food.

BACKGROUND/OBJECTIVES: Plant sterol (PS) consumption lowers serum cholesterol levels, while modestly increasing plasma PS concentrations. Plasma PS concentrations may reflect sterol absorption, thus individuals with high plasma plant sterol (HPS) concentrations may show greater changes in circulating cholesterol and PS than individuals with low plasma plant sterol (LPS) concentrations. The objective of this study was to examine whether HPS and LPS concentrations are related to subsequent changes in plasma PS, serum lipid and C-reactive protein (CRP) concentrations, following dietary PS intake in otherwise healthy hypercholesterolemic men. SUBJECTS/METHODS: This single-blinded, randomized, diet-controlled study consisted of two 4-week phases, separated by a 4-week washout, where a diet with a placebo or the 2.0 g per day PS-enriched spread was consumed during the phases. RESULTS: At baseline, men with HPS possessed higher (P<0.01) mean serum cholesterol concentration, while those with LPS had higher (P<0.05) body mass index. Following PS intake, plasma sum of campesterol plus sitosterol concentrations were elevated from 34.6+/-4.2 to 46.2+/-3.3 micromol l(-1) (mean+/-SE) and 16.5+/-0.9 to 20.8+/-1.2 micromol l(-1) after PS intake in men with HPS and LPS, respectively. Changes in plasma PS concentrations, however, were not different between individuals with either HPS or LPS baseline concentrations. Total cholesterol and low-density lipoprotein cholesterol levels were decreased (P<0.0001) by 6.3 and 7.8%, respectively, with PS consumption for all individuals. Changes in lipid parameters were not different between individuals with HPS or LPS baseline concentrations. No changes in CRP were apparent subsequent to PS intervention. CONCLUSIONS: Baseline plasma PS concentrations are not associated or predictive of changes in serum cholesterol or plasma PS concentrations after PS intervention. Thus, individuals with HPS show similar increases in PS concentrations as individuals with LPS following PS supplementation. Plasma PS remained in the range of previously reported concentrations.

Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols.

OBJECTIVE: To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread. METHODS: Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated cholesterol concentrations. Subjects received either control for 6 weeks or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks. RESULTS: LDL-c was lowered significantly by consumption of 1.6 g/day of PS (-10.4%, range -7.3 to -11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations further to -14.7%. TO, containing 78% sitosterol, produced an increase in serum sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal, serum sterols declined by 50% within 2 weeks. CONCLUSION: Different PS sources were equally effective in lowering serum LDL-c concentrations. The decrease in absolute concentrations of LDL-c was dependent on the baseline concentrations.

Preferential efflux of phytosterols over cholesterol from macrophages.

Phytosterols are structurally similar to cholesterol. Increased dietary intake of phytosterols effectively lowers LDL-cholesterol. Since phytosterols are incorporated in a growing number of foods and some of the ingested phytosterols reach the circulation, accumulation of phytosterols in foam-cell-prone cells such as macrophages might occur. Therefore we examined the influx and efflux of phytosterols by human THP-1 macrophages. The influx rates of methyl-beta-cyclodextrin delivered phytosterols did not significantly differ from that of cholesterol (approximately 3.8 pmol/min per mg cellular protein), neither did the total influx of oxidised LDL delivered phytosterols differ from that of cholesterol. The efflux of beta-sitosterol and sitostanol from preloaded THP-1 cells to HDL was more efficient than the efflux of campesterol and cholesterol (rate constants of 0.41 +/- 0.04/h, 0.62 +/- 0.08/h, 0.23 +/- 0.05/h and 0.29 +/- 0.03/h, respectively). The efflux of beta-sitosterol was not associated with a dominant transfer to ApoA-I, nor did ABCA1 induction-promoted cholesterol efflux to the level observed for beta-sitosterol. Our data show that THP-1 macrophages take up phytosterols, but have efficient mechanisms to remove phytosterols from their cellular compartments. Consequently, it is less likely that macrophages preferentially accumulate phytosterols over cholesterol and hence promote foam-cell formation in vivo.

Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects.

OBJECTIVE: To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g/day) single-dose yoghurt drink. DESIGN: Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period. SETTING: Subjects recruited from the general community. SUBJECTS: A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women) (age 57+/-2 years) completed the study. INTERVENTIONS: The study product was a 100-g single-dose yoghurt drink with or without added PS in the form of PS esters. The subjects were randomly assigned to one of five 4-week treatments: (i) drink A (0.1% dairy fat, 2.2% total fat) with a meal, (ii) drink A without a meal, (iii) drink B (1.5% dairy fat, 3.3% total fat) with a meal, (iv) drink B without a meal and (v) placebo drink with a meal. RESULTS: LDL-cholesterol (LDL-C) was significantly lowered when the single-dose drink was taken with a meal independent of its fat content (drink A: -9.5% (P<0.001, 95% CI: -13.8 to -5.2); drink B: -9.3% (P<0.001, 95% CI: -13.7 to -4.9)) as compared to placebo. When consumed without a meal, LDL-C was also significantly decreased (drink A: -5.1% (P<0.05, 95% CI: -9.4 to -0.8); drink B: -6.9% (P<0.01, 95% CI: -11.3 to -2.5) as compared to placebo, however the effect was significantly smaller as compared to the intake with a meal. CONCLUSION: These results indicate that a PS-ester-enriched single-dose yoghurt drink effectively reduces LDL-C irrespective of the fat content of the product. A substantially larger decrease in serum cholesterol concentration was achieved when the single-dose drink was consumed with a meal emphasizing the importance of the intake occasion for optimal cholesterol-lowering efficacy. SPONSORSHIP: Unilever Research and Development, Vlaardingen, The Netherlands.