Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate.

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations--a meta-analysis of randomized controlled studies.

OBJECTIVE: Intake of plant sterol (PS)-enriched foods effectively lowers plasma total- and LDL-cholesterol concentrations while increasing plasma PS concentrations. The magnitude of this increase has not been systematically assessed. This study aimed to investigate the effect of PS-enriched foods on plasma PS concentrations by performing a meta-analysis of randomized controlled studies. METHODS: Published PS intervention studies reporting plasma PS concentrations were searched through June 2012. Studies were selected that fulfilled pre-defined in- and exclusion criteria. Data were extracted, particularly on campesterol, sitosterol, total- and LDL-cholesterol. Random-effects models were used to calculate net effects while weighing each study by the inverse of its variance. Potential sources of heterogeneity were investigated. RESULTS: The meta-analysis included data from 41 studies (55 strata) with in total 2084 subjects. The average dose of PS from enriched foods was 1.6 g/d (range: 0.3-3.2 g/d). Plasma sitosterol and campesterol concentrations were increased by on average 2.24 µmol/L (31%) and 5.00 µmol/L (37%), respectively, compared to control. Total- and LDL-cholesterol were reduced by on average 0.36 mmol/L (5.9%) and 0.33 mmol/L (8.5%), respectively. The increase in sitosterol and campesterol was impacted by the dose of PS, the baseline PS concentration and the PS composition of the test products. In the highest PS dose category (2.0-3.2 g/d), increases in sitosterol and campesterol were on average 3.56 and 7.64 µmol/L, respectively. CONCLUSION: Intake of PS-enriched foods increases plasma sitosterol and campesterol concentrations. However, total PS remain below 1% of total sterols circulating in the blood.

Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial.

BACKGROUND: Extracts from Hoodia gordonii have been shown to decrease food intakes and body weights in animals and were proposed as a food supplement or ingredient for weight management. OBJECTIVE: We assessed the safety and efficacy of a 15-d repeated consumption of H. gordonii purified extract (HgPE) relative to a placebo in humans. DESIGN: Healthy, overweight women, who were stratified by percentage body fat, received either HgPE (n = 25) or a placebo (n = 24) for 15 d. Subjects were resident in a clinic for a 4-d run-in period and a 15-d treatment period in which they received 2 servings/d of 1110 mg HgPE or a placebo formulated in a yogurt drink 1 h before breakfast and dinner. Subjects were otherwise allowed to eat ad libitum from standardized menus. RESULTS: There were no serious adverse events, but HgPE was less well tolerated than was the placebo because of episodes of nausea, emesis, and disturbances of skin sensation. Blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant (P < 0.05) increases in the HgPE group. Mean effects on ad libitum energy intakes and body weights did not differ significantly between the HgPE- and placebo-treatment groups (P > 0.05). CONCLUSIONS: In comparison with a matched placebo, the consumption of HgPE for 15 d appeared to be associated with significant adverse changes in some vital signs and laboratory parameters. HgPE was less well tolerated than was the placebo and did not show any significant effects on energy intakes or body weights relative to the placebo. This trial was registered at clinicaltrials.gov as NCT01306422.

Action of plant sterol intervention on sterol kinetics in hypercholesterolemic men with high versus low basal circulatory plant sterol concentrations.

BACKGROUND: The relationship between plant sterol (PS) absorption and circulatory concentrations with cholesterol absorption and biosynthesis during PS consumption has yet to be clearly elucidated in humans. It is therefore essential to examine campesterol, ß-sitosterol, and cholesterol absorption and cholesterol fractional synthesis rate (FSR) following PS consumption in individuals with high versus low basal circulatory PS concentrations. DESIGN: A randomized, crossover trial was conducted in 82 hypercholesterolemic men consuming spreads with or without 2 g/d of PS for two 4-week periods, each separated by a 4-week washout. Endpoint tracer enrichments after ingestion of (2)H-labeled campesterol or ß-sitosterol and (13)C-labeled cholesterol were determined by isotope ratio mass spectrometry. RESULTS: For both phases of dietary intervention, the endpoint cholesterol absorption index was positively correlated with campesterol (r = 0.5864, p < 0.0001) and ß-sitosterol (r = 0.4676, p < 0.0001) absorption indices; inversely, endpoint cholesterol FSR correlated negatively with the absorption indices of campesterol (r = -0.5004, p < 0.0009), ß-sitosterol (r = -0.4154, p < 0.05), and cholesterol (r = -0.4056, p < 0.0001). PS intervention reduced absorption indices of campesterol, ß-sitosterol, and cholesterol by 36.5% ± 2.7%, 39.3% ± 2.9%, and 34.3% ± 1.9%, respectively, but increased cholesterol FSR by 33.0% ± 3.3% relative to control. Endpoint circulatory PS levels (cholesterol adjusted) were positively associated with endpoint absorption indices of campesterol (r = 0.5586, p < 0.0001, for placebo; r = 0.6530, p < 0.0001, for PS intake) and cholesterol (r = 0.3683, p < 0.001 for placebo; r = 0.3469, p < 0.002, for PS intake) and were negatively associated with cholesterol FSR (r = -0.3551, p < 0.002, for placebo; r = -0.3643, p < 0.001, for PS intake). The cholesterol-lowering effect of PS was most pronounced among individuals falling within the 50th-75th percentiles of basal PS concentrations. CONCLUSION: These data suggest that basal PS concentrations indicate not only sterol absorption efficiency but also the extent of PS-induced cholesterol reduction and thus might be clinically useful to predict the extent of cholesterol response to PS intervention within a given individual.

Effect of milk and brewing method on black tea catechin bioaccessibility.

The aim of this study was to investigate whether milk reduces the bioaccessibility of tea catechins, which would compromise tea beneficial effects ascribed to polyphenols. Adding milk to black tea has been shown to lead to polyphenol-protein complexes. So far, data on the intestinal stability of polyphenol-protein complexes are scarce. English black tea (0.93 ± 0.06 mol/L total catechins) and Indian black tea (1.83 ± 0.08 mol/L catechins) were prepared with skimmed or full-fat milk and subjected to simulated gastric, small intestinal, and brush border digestion. Adding milk (5.6-40%) to tea results in a decrease of total catechin (TCAT) recovery. However, the bioaccessibilities of TCAT of tea with milk versus tea controls were comparable (p > 0.05). The type of milk did not influence TCAT recovery during all digestive stages (p > 0.05). Polyphenol-protein complexes are degraded during digestion. It is very unlikely that consumption of tea with or without milk will result in differences in catechin plasma concentration.

Random serial sampling to evaluate efficacy of iron fortification: a randomized controlled trial of margarine fortification with ferric pyrophosphate or sodium iron edetate.

BACKGROUND: Random serial sampling is widely used in population pharmacokinetic studies and may have advantages compared with conventional fixed time-point evaluation of iron fortification. OBJECTIVE: Our objective was to validate random serial sampling to judge the efficacy of iron fortification of a low-fat margarine. DESIGN: We conducted a 32-wk placebo-controlled, double-blind, iron-intervention trial in 18-40-y-old Swiss women (n = 142) with serum ferritin (SF) concentrations <25 µg/L. Women were randomly assigned to 3 groups to receive 20 g margarine, with 14 mg added iron as either micronized ground ferric pyrophosphate (MGFePP) or sodium iron edetate (NaFeEDTA), or placebo daily. We measured hemoglobin and iron status of subjects at 2 fixed time points (at baseline and the endpoint) plus 3 randomly assigned time points between 4 and 28 wk. With the use of bootstrapping, the number of observations per individual was reduced to 3 and then compared with the 5-time-point data. Mixed-effects models were used to estimate iron repletion over time for random sampling, and analysis of covariance was used for fixed time-point sampling. RESULTS: Body iron stores increased in women who received MGFePP or NaFeEDTA compared with women who received placebo (P < 0.05). The increase in body iron stores with NaFeEDTA fortification was 2-3 times the increase with MGFePP fortification (P < 0.05); the difference was more marked in women with baseline SF concentrations <15 µg/L (P < 0.05). Random serial sampling reduced the required sample size per group to one-tenth of that for 2 fixed time points. Compared with the 5-time-point analysis, the 3-time-point sparse sampling generated comparable estimates of efficacy. CONCLUSIONS: When used to evaluate the efficacy of iron fortificants, random serial sampling can reduce the sample size, invasiveness, and costs while increasing sensitivity. Random serial sampling more clearly describes the pattern of iron repletion and may prove useful in evaluating other micronutrient interventions.

Current in vitro testing of bioactive peptides is not valuable.

Dietary peptides have been suggested to possess biological activity in vivo and could affect cardiovascular disease parameters, based on data derived from in vitro experiments. Isolated peptides are often tested in in vitro cellular assays or on heterologously expressed molecular target proteins. The stimulatory or inhibitory effect on target proteins in vitro has often been used as the justification to test these compounds directly in vivo. Unfortunately, this research approach has an inherent flaw. It neglects the poor absorption, distribution, metabolism, and excretion (ADME) properties of peptides resulting in low peptide bioavailability. Because peptides are prone to extensive hydrolysis in the gastrointestinal tract by stomach, small intestinal, and brush border peptidases, most of them do not reach the absorption stage in the duodenum and jejunum. Therefore, a valid research approach should include the demonstration of stability of the peptide toward luminal and brush border peptidases and evaluate its ADME properties. Surprisingly, only very few animal and human studies determined absolute concentrations and kinetics of bioactive peptides. These studies have shown the presence of selected peptides in plasma samples at pico- and nanomolar concentrations with fast elimination kinetics in the minute range. For the correct interpretation of results, it is advised that researchers refer to the data currently available concerning bioavailability and ADME properties in humans. Two mandatory criteria for future in vitro studies investigating potential biological activities of peptides should be using physiologically relevant concentrations and times.

Modeling of the relationship between dipeptide structure and dipeptide stability, permeability, and ACE inhibitory activity.

Selected di- and tripeptides exhibit angiotensin-I converting enzyme (ACE) inhibitory activity in vitro. However, the efficacy in vivo is most likely limited for most peptides due to low bioavailability. The purpose of this study was to identify descriptors of intestinal stability, permeability, and ACE inhibitory activity of dipeptides. A total of 228 dipeptides were synthesized; intestinal stability was obtained by in vitro digestion, intestinal permeability using Caco-2 cells and ACE inhibitory activity by an in vitro assay. Databases were constructed to study the relationship between structure and activity, permeability, and stability. Quantitative structure-activity relationship (QSAR) modeling was performed based on computed models using partial least squares regression based on 400 molecular descriptors. QSAR modeling of dipeptide stability revealed high correlation coefficients (R > 0.65) for models based on Z and X scales. However, amino acid (AA) clustering showed the best results in describing stability of dipeptides. The N-terminal AA residues Asp, Gly, and Pro as well as the C-terminal residues Pro, Ser, Thr, and Asp stabilize dipeptides toward luminal enzymatic peptide hydrolysis. QSAR modeling did not reveal significant correlation models for intestinal permeability. 2D-fingerprint models were identified describing ACE inhibitory activity of dipeptides. The intestinal stability of 12 peptides was predicted. Peptides were synthesized and stability was confirmed in simulated digestion experiments. Based on the results, specific dipeptides can be designed to meet both stability and activity criteria. However, postabsorptive ACE inhibitory activities of dipeptides in vivo are most likely limited due to the very low intestinal permeability of dipeptides.

Phenotyping tea consumers by nutrikinetic analysis of polyphenolic end-metabolites.

An integration of metabolomics and pharmacokinetics (or nutrikinetics) is introduced as a concept to describe a human study population with different metabolic phenotypes following a nutritional intervention. The approach facilitates an unbiased analysis of the time-response of body fluid metabolites from crossover designed intervention trials without prior knowledge of the underlying metabolic pathways. The method is explained for the case of a human intervention study in which the nutrikinetic analysis of polyphenol-rich black tea consumption was performed in urine over a period of 48 h. First, multilevel PLS-DA analysis was applied to the urinary 1H NMR profiles to select the most differentiating biomarkers between the verum and placebo samples. Then, a one-compartment nutrikinetic model with first-order excretion, a lag time, and a baseline function was fitted to the time courses of these selected biomarkers. The nutrikinetic model used here fully exploits the crossover structure in the data by fitting the data from both the treatment period and the placebo period simultaneously. To demonstrate the procedure, a selected set of urinary biomarkers was used in the model fitting. These metabolites include hippuric acid, 4-hydroxyhippuric acid and 1,3-dihydroxyphenyl-2-O-sulfate and derived from microbial fermentation of polyphenols in the gut. Variations in urinary excretion between- and within the subjects were observed, and used to provide a phenotypic description of the test population.

Calcium absorption from fortified ice cream formulations compared with calcium absorption from milk.

OBJECTIVE: Optimal bone mass in early adulthood is achieved through appropriate diet and lifestyle, thereby protecting against osteoporosis and risk of bone fracture in later life. Calcium and vitamin D are essential to build adequate bones, but calcium intakes of many population groups do not meet dietary reference values. In addition, changes in dietary patterns are exacerbating the problem, thereby emphasizing the important role of calcium-rich food products. We have designed a calcium-fortified ice cream formulation that is lower in fat than regular ice cream and could provide a useful source of additional dietary calcium. Calcium absorption from two different ice cream formulations was determined in young adults and compared with milk. SUBJECTS/SETTING: Sixteen healthy volunteers (25 to 45 years of age), recruited from the general public of The Netherlands, participated in a randomized, reference-controlled, double-blind cross-over study in which two test products and milk were consumed with a light standard breakfast on three separate occasions: a standard portion of ice cream (60 g) fortified with milk minerals and containing a low level (3%) of butter fat, ice cream (60 g) fortified with milk minerals and containing a typical level (9%) of coconut oil, and reduced-fat milk (1.7% milk fat) (200 mL). Calcium absorption was measured by the dual-label stable isotope technique. STATISTICAL ANALYSIS: Effects on calcium absorption were evaluated by analysis of variance. RESULTS: Fractional absorption of calcium from the 3% butterfat ice cream, 9% coconut oil ice cream, and milk was 26%+/-8%, 28%+/-5%, and 31%+/-9%, respectively, and did not differ significantly (P=0.159). CONCLUSIONS: Results indicate that calcium bioavailability in the two calcium-fortified ice cream formulations used in this study is as high as milk, indicating that ice cream may be a good vehicle for delivery of calcium.

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.

Genetic variation in ABC G5/G8 and NPC1L1 impact cholesterol response to plant sterols in hypercholesterolemic men.

ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

Pharmacokinetics of proline-rich tripeptides in the pig.

Tripeptides may possess bioactive properties. For instance, blood pressure lowering is attributed to the proline-rich tripeptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP), and Val-Pro-Pro (VPP). However, little is known about their absorption, distribution, and elimination characteristics. The aim of this study was to characterize the pharmacokinetic behavior of IPP, LPP, and VPP in a conscious pig model. Synthetic IPP, LPP, and VPP were administered intravenously or intragastrically (4.0 mg kg(-1) BW in saline) to 10 piglets (approximately 25 kg body weight) in the postabsorptive state. After intravenous dosing, the elimination half-life for IPP was significantly higher (P<0.001) than for LPP and VPP (2.5+/-0.1, 1.9+/-0.1, and 2.0+/-0.1 min, respectively). After intragastric dosing, however, the elimination half-lives were not significantly different between the peptides (9+/-1, 15+/-4, and 12+/-6 min, respectively). Maximum plasma concentrations were about 10 nmol l(-1) for the three tripeptides. The fraction dose absorbed was 0.077+/-0.010, 0.059+/-0.009, and 0.073+/-0.015%, for IPP, LPP, and VPP, respectively. Proline-rich tripeptides reach the blood circulation intact, with an absolute bioavailability of about 0.1% when administered via a saline solution. Because half-lives of absorption and elimination were maximally about 5 and 15 min, respectively, this suggests that under these conditions a bioactive effect of these tripeptides would be rather acute.

The angiotensin converting enzyme inhibitory tripeptides Ile-Pro-Pro and Val-Pro-Pro show increasing permeabilities with increasing physiological relevance of absorption models.

Transepithelial transport of the ACE inhibitory peptides Ile-Pro-Pro and Val-Pro-Pro was studied in different models of absorption. Apparent permeability (P(app)) values for absorptive transport across Caco-2 monolayers were 1.0+/-0.9 x 10(-8) (Ile-Pro-Pro) and 0.5+/-0.1 x 10(-8)cms(-1) (Val-Pro-Pro). Ex vivo transport across jejunal segments in the Ussing chamber was 5-times (Ile-Pro-Pro) to 10-times (Val-Pro-Pro) higher with no significant differences (p>0.05) observed between both peptides. The peptidase inhibitor bestatin increased permeability for the absorptive direction for Ile-Pro-Pro by twofold. Neither a transepithelial pH gradient nor increased apical tripeptide concentration nor longitudinal localization of the intestinal segment influenced P(app) in the ex vivo experiments. Val-Pro-Pro transport across Peyer's patches, however, was 4-times higher (P(app)=21.0+/-9.3 x10(-8)cms(-1)) as compared to duodenum (P(app)=4.8+/-1.4 x 10(-8)cms(-1)). In the in situ perfusion experiments P(app) values varied greatly among different animals ranging from 0.5 to 24.0 x10(-8)cms(-1) (Ile-Pro-Pro) and from 1.0 to 15.6 x 10(-8)cms(-1) (Val-Pro-Pro). In summary, Caco-2 and ex vivo absorption models differ considerably regarding their peptide permeability. The in situ model seems to be less appropriate because of the observed large variability in peptide permeability. The results of this study demonstrate that the ACE inhibitory peptides Ile-Pro-Pro and Val-Pro-Pro are absorbed partially undegraded.

Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter.

Dietary supplementation with plant sterols, stanols, and their esters reduces intestinal cholesterol absorption, thus lowering plasma LDL cholesterol concentration in humans. It was suggested that these beneficial effects are attributable in part to induction of genes involved in intestinal cholesterol transport, e.g., Abcg5 and Abcg8, via the liver X receptor (LXR), but direct proof is lacking. Male C57BL/6J mice were fed a purified diet (control), diets containing cholesterol (0.12 g/100 g) only, or in combination with either plant sterols or stanols (0.5 g/100 g) for 4 wk. Plant sterols and stanols dramatically increased neutral fecal sterol excretion (2.2 and 1.4-fold, respectively, compared with cholesterol-fed mice; P < 0.05). Cholesterol and cholesterol ester concentrations were higher in livers of mice fed cholesterol compared with controls (+135% and +925%; P < 0.05). Plant sterols and stanols completely prevented cholesterol accumulation as well as induction of LXR target genes in liver. Feeding plant sterols and stanols did not alter intestinal expression of Abcg5, Abcg8, or other LXR target genes nor of Npc1l1. Fractional cholesterol absorption in Abcg5-/- mice was reduced to the same extent by dietary plant sterols (49%) as in wild-type littermates (44%). Plant sterol and stanol-induced reduction of cholesterol absorption in mice is not associated with upregulation of intestinal LXR target genes nor is it influenced by Abcg5-deficiency. Our data indicate that dietary plant sterols and stanols inhibit cholesterol absorption within the intestinal lumen independently of LXR.

Effects of various amounts of dietary plant sterol esters on plasma and hepatic sterol concentration and aortic foam cell formation of cholesterol-fed hamsters.

Dietary intake of plant sterol esters (PSE) lowers plasma LDL-cholesterol (LDL-C), but can modestly increase plasma plant sterol concentrations. The objective of the present study was to investigate the impact of increasing doses of dietary PSE on plasma and liver sterol concentrations as well as on aortic foam cell development as a marker of atherogenesis. One-hundred and twenty F(1)B hybrid Syrian golden hamsters (20 per group) were fed a basal atherogenic diet containing 30% of energy as fat and 0.12% (w/w) cholesterol and supplemented with 0, 0.24, 0.48, 0.96, 1.92 and 2.84% (w/w) PSE. After 12 weeks, plasma total cholesterol (TC) and LDL-C were significantly lower in the groups fed PSE compared with control. Plasma plant sterol concentrations increased with increasing dietary PSE intake up to the dietary level of 1.92% and then reached a plateau. On the other hand, hepatic campesterol and sitosterol concentrations plateaued at 0.24% PSE. Foam cell presence in the aortic arch showed an inverse relationship with dietary PSE intake (P<0.0001). Lipid-filled foam cell areas of hamsters receiving 0.24, 0.48 or 2.84% PSE were approximately 70, 90 and 100% smaller than in control hamsters fed no PSE. In summary, dietary PSE lowered plasma TC and LDL-C. Despite an increase in plasma plant sterol concentrations they did not contribute to aortic foam cell development. In fact dietary PSE significantly inhibited aortic foam cell formation. This study supports the concept that PSE through their cholesterol-lowering action prevent development of atherogenesis in this animal model.

A healthy diet rich in carotenoids is effective in maintaining normal blood carotenoid levels during the daily use of plant sterol-enriched spreads.

Blood cholesterol levels are affected by diet and in particular by the type and amount of fat intake. In recent years, vegetable oil spreads containing plant sterols/stanols (as their fatty acid esters) have been developed. Numerous clinical trials on spreads with added plant sterols/stanols have shown that they have much greater cholesterol-lowering properties than conventional vegetable oil spreads. Plant sterols decrease both dietary and biliary cholesterol absorption in the small intestine, with a consequential increase in excretion of cholesterol. It is also recognized that plant sterol/stanol-enriched, cholesterol-lowering spreads, if consumed regularly, may induce a 10-20% decrease in plasma carotenoids, adjusted for changes in plasma lipids. A 10-20% decrease in plasma carotenoids falls well within the seasonal variation observed in individuals. Our current understanding of the physiological functions of carotenoids does not indicate any health risk associated with the slight decrease in their blood levels due to the intake of plant sterol/stanol. The questions that have been raised, though, are how plant sterols/stanols affect plasma carotenoid levels, and in addition, what quantity of fruits and vegetables (the richest dietary sources of carotenoids) would have to be consumed to improve plasma carotenoid levels? The current mini-review covers the cholesterol-lowering effect of plant sterols, their mechanisms of action and effect on blood carotenoids, and concludes with the potential heath benefits of daily intake of plant sterol-enriched spreads.