Plant Sterol Esters Research Articles

Composition of Plant Sterols and Stanols in Supplemented Food Products.

All fruits, vegetables, grains and other plant materials contain small amounts of plant sterols, which are essential for the function of the biological membranes in living cells. The average human consumption of plant sterols has been estimated to be about 150-350 mg/day and trace amounts of stanols (which are defined as saturated sterols such as sitostanol), but this number varies regionally and is higher for vegetarians. When consumed in the diet, plant sterols reduce the levels of serum cholesterol. In 1995 the first functional food product, Benecol spread (enriched in plant stanol fatty acid esters), was developed by Raisio and marketed, first in Finland and then globally. Since then many other functional food products have been developed and are now available globally. In addition to stanol esters, other functional food products contain plant sterol esters and/or free (unesterified) plant sterols and stanols. In essentially all of the current functional foods that are enriched in sterols and stanols, the feedstock from which the sterols and stanols are obtained is either tall oil (a byproduct/coproduct of the pulping of pine wood) or vegetable oil deodorizer distillate (a byproduct/coproduct of the refining of vegetable oils).

LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

Antioxidant activity of phenolic compounds added to a functional emulsion containing omega-3 fatty acids and plant sterol esters

The effect of eleven compounds extracted from red propolis on the oxidative stability of a functional emulsion was evaluated. Emulsions prepared with Echium oil as omega 3 (ω-3 FA) source, containing 1.63g/100mL of α-linolenic acid (ALA), 0.73g/100mL of stearidonic acid (SDA) and 0.65g/100mL of plant sterol esters (PSE) were prepared without or with phenolic compounds (vanillic acid, caffeic acid, trans-cinnamic acid, 2,4-dihydroxycinnamic acid, p-coumaric acid, quercetin, trans-ferulic acid, trans,trans-farnesol, rutin, gallic acid or sinapic acid). tert-Butylhydroquinone and a mixture containing ascorbic acid and FeSO4 were applied as negative and positive controls of the oxidation. Hydroperoxide, thiobarbituric acid reactive substances (TBARS), malondialdehyde and phytosterol oxidation products (POPs) were evaluated as oxidative markers. Based on hydroperoxide and TBARS analysis, sinapic acid and rutin (200ppm) showed the same antioxidant activity than TBHQ, representing a potential alternative as natural antioxidant to be applied in a functional emulsion containing ω-3 FA and PSE.

Postprandial plasma oxyphytosterol concentrations after consumption of plant sterol or stanol enriched mixed meals in healthy subjects

Epidemiological studies have reported inconsistent results on the relationship between increased plant sterol concentrations with cardiovascular risk, which might be related to the formation of oxyphytosterols (plant sterol oxidation products) from plant sterols. However, determinants of oxyphytosterol formation and metabolism are largely unknown. It is known, however, that serum plant sterol concentrations increase after daily consumption of plant sterol enriched products, while concentrations decrease after plant stanol consumption. Still, we have earlier reported that fasting oxyphytosterol concentrations did not increase after consuming a plant sterol- or a plant stanol enriched margarine (3.0g/d of plant sterols or stanols) for 4weeks. Since humans are in a non-fasting state for most part of the day, we have now investigated effects on oxyphytosterol concentrations during the postprandial state. For this, subjects consumed a shake (50g of fat, 12g of protein, 67g of carbohydrates), containing no, or 3.0g of plant sterols or plant stanols. Blood samples were taken up to 8h and after 4h subjects received a second shake (without plant sterols or plant stanols). Serum oxyphytosterol concentrations were determined in BHT-enriched EDTA plasma via GC–MS/MS. 7β-OH-campesterol and 7β-OH-sitosterol concentrations were significantly higher after consumption of a mixed meal enriched with plant sterol esters compared to the control and plant stanol ester meal. These increases were seen only after consumption of the second shake, illustrative for a second meal effect. Non-oxidized campesterol and sitosterol concentrations also increased after plant sterol consumption, in parallel with 7β-OH concentrations and again only after the second meal. Apparently, plant sterols and oxyphytosterols follow the same second meal effect as described for dietary cholesterol. However, the question remains whether the increase in oxyphytosterols in the postprandial phase is due to absorption or endogenous formation.

Effects of margarine enriched with plant sterol esters from rapeseed and tall oils on markers of endothelial function, inflammation and hemostasis

Background and aims. The sterol profile of rapeseed oil differs from that of tall oil with higher contents of campesterol and brassicasterol. We previously found that margarines providing 2 g/day of sterols from rapeseed or tall oil resulted in similar reductions in LDL cholesterol of 8–9%. The aim of the present study was to investigate whether the consumption of these margarines affected markers of endothelial function, inflammation and hemostasis. Methods. Blood samples were collected from 58 hypercholesterolemic volunteers who completed a double-blinded, randomized, crossover trial. Subjects consumed each of the two sterol margarines and a control non-sterol margarine for 4 weeks separated by one-week washout periods. All the margarines had the same fatty acid composition. Concentrations of vascular cell adhesion molecule-l (VCAM-1), E-selectin, circulating tumor necrosis factor α (TNFα) and plasminogen activator inhibitor-1 (total, tPAI-1; active, PAI-1) were quantified. Results. Rapeseed-sterol margarine reduced E-selectin concentrations compared to the control margarine (p = 0.012) while tall-sterol margarine had no effect. The rapeseed-sterol margarine also reduced tPAI-1 (p = 0.008) compared to the tall-sterol margarine. No significant changes were observed in TNFα and VCAM-1. No association was found between LDL reduction and changes in E-selectin and tPAI-1. Conclusion. Rapeseed-sterol margarine demonstrated favorable effects on vascular risk markers.

Fatty acid moieties have little effect on cholesterol‐lowering potency of plant sterol esters

Plant sterol esters are the popular cholesterol‐lowering dietary supplements. In order to understand the role of fatty acid moieties in the cholesterol‐lowering activity of plant sterol esters, the present study was to: (i) compare the cholesterol‐lowering activity of sterol esters of sunflower oil (SSF) with that of sterol esters of canola oil (SCO); and (ii) to systematically investigate the effect of SSF and SCO on the gene expression of sterol transporters, enzymes, receptors and proteins involved in cholesterol metabolism in hamsters fed a high cholesterol diet. GC analysis showed that SSF and SCO had similar sterol profile but they had different fatty acid moieties. Results showed both SSF and SCO could equally reduce plasma cholesterol in a dose‐dependent manner. Both SSF and SCO could inhibit the cholesterol absorption and enhance the excretion of bile acids. In the similar ways, dietary SSF and SCO could up‐regulate hepatic cholesterol‐7α‐hydroxylase (CYP7A1) and down‐regulate intestinal sterol transporter Niemann‐Pick C1‐like 1 (NPC1L1), acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2) and hepatic 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMG‐CoA reductase). It was concluded that the fatty acid moieties had little effect on the cholesterol‐lowering activity of SSF and SCO.Practical applications: Plant sterols are effective in reducing plasma cholesterol. Commercially, plant sterol esters of sunflower oil and plant sterol esters of canola oil are mostly used for this purpose. The present study found that SSF and SCO were equally effective in reducing plasma cholesterol in a dose‐dependent manner regardless the significant difference in their fatty acid compositions.Fatty acid moieties have little effect on cholesterol‐lowering potency of plant sterol esters.

Serum TG-lowering properties of plant sterols and stanols are associated with decreased hepatic VLDL secretion

Plant sterols and stanols are structurally similar to cholesterol and when added to the diet they are able to reduce serum total- and LDL-cholesterol concentrations. They also lower serum triglyceride concentrations in humans, particularly under conditions of hypertriglyceridemia. The aim of this study was to unravel the mechanism by which plant sterols and stanols reduce serum triglyceride concentrations in high-fat diet (HFD) fed mice. Male C57BL/6J mice were fed HFD for 4 weeks. Subsequently, they received HFD, HFD supplemented with 3.1% plant sterol ester (PSE) or HFD supplemented with 3.1% plant stanol ester (PSA) for another three weeks. Both PSE and PSA feeding resulted in decreased plasma triglyceride concentrations compared with HFD, while plasma cholesterol levels were unchanged. Interestingly, hepatic cholesterol levels were decreased in the PSE/PSA groups compared with HFD and no differences were found in hepatic triglyceride levels between groups. To investigate the mechanism underlying the hypotriglyceridemic effects from PSE/PSA feeding, we measured chylomicron and VLDL secretion. PSE and PSA feeding resulted in reduced VLDL secretion, while no differences were found between groups in chylomicron secretion. In conclusion, our data indicate that plasma triglyceride-lowering resulting from PSE and PSA feeding is associated with decreased hepatic VLDL secretion.

Protective role of plant sterol and stanol esters in liver inflammation: insights from mice and humans.

The inflammatory component of non–alcoholic steatohepatitis (NASH) can lead to irreversible liver damage. Therefore there is an urgent need to identify novel interventions to combat hepatic inflammation. In mice, omitting cholesterol from the diet reduced hepatic inflammation. Considering the effects of plant sterol/stanol esters on cholesterol metabolism, we hypothesized that plant sterol/stanol esters reduces hepatic inflammation. Indeed, adding plant sterol/stanol esters to a high-fat-diet reduced hepatic inflammation as indicated by immunohistochemical stainings and gene expression for inflammatory markers. Finally, adding sterol/stanol esters lowered hepatic concentrations of cholesterol precursors lathosterol and desmosterol in mice, which were highly elevated in the HFD group similarly as observed in severely obese patients with NASH. In vitro, in isolated LPS stimulated bone marrow derived macrophages desmosterol activated cholesterol efflux whereas sitostanol reduced inflammation. This highly interesting observation that plant sterol/stanol ester consumption leads to complete inhibition of HFD-induced liver inflammation opens new venues in the treatment and prevention of hepatic inflammation.

Effect of plant sterols compared with ezetimibe on oxidative stress in patients treated with statins

This study aimed to compare the action of a drug (ezetimibe) and a functional food containing plant sterol esters on oxidative stress biomarkers. In this double-blind study, 37 type 2 diabetic patients on statin treatment were randomly assigned to receive ezetimibe 10.0 mg/day or to consume a chocolate containing 2.1 g of plant sterol esters for 6 weeks. It was observed that ezetimibe promoted an increase of superoxide dismutase and glutathione reductase activities, while plant sterols did not change these biomarkers. Among individuals who showed the greatest LDL-C and oxLDL-C reduction, the oxLDL-C reduction observed in individuals under plant sterol treatment (−20.0%) did not differ from the values found in individuals treated with ezetimibe (−21.1%). In addition, 16 patients on plant sterol treatment reached the optimal therapeutic goal for LDL-C (<70 mg/dL). Plant sterols added to a non-sugar chocolate bar represent an alternative to statin co-therapy.

Cholesterol modulates LRP5 expression in the vessel wall

ObjectiveMacrophages are key players in atherosclerotic lesion formation and progression. We have recently demonstrated that lipid-loaded macrophages show activation of the canonical Wnt signaling pathway. MethodsTo test the in vivo role of the canonical Wnt pathway in atherosclerosis we used mice deficient in the Wnt signaling receptor LRP5 (LRP5−/−) fed a hypercholesterolemic diet (HC) to induce atherosclerosis. These dietary groups were further subdivided into two subgroups receiving their respective diets supplemented with 2% plant sterol esters (PSE). All mice remained on their assigned diets until age 18 weeks. ResultsHC WT mice had mildly increased non-HDL cholesterol levels, developed aortic atherosclerotic lesions and showed upregulated expression levels of aortic Lrp5. HC LRP5−/− mice develop larger aortic atherosclerotic lesions than WT mice indicating that LRP5 has a protective function in atherosclerosis progression. The oral administration of PSE, a dietary cholesterol-lowering agent, had an effect in the expression levels of the Wnt signaling receptor and in atherosclerosis progression. We found that PSE reduced serum total cholesterol levels, abolished HC-induced LRP5 overexpression and reduced aortic atherosclerotic plaques. ConclusionThe proatherogenic effects of the excess of plasma lipids are in part mediated by modulation of LRP5 in the aorta. LRP5 and canonical Wnt signaling exert a protective defense mechanism against hyperlipidemia and atherosclerosis lesion progression.

Response to comments on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL‐cholesterol; high blood LDL‐cholesterol is a risk factor in the development of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006,

Response to comments on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL‐cholesterol; high blood LDL‐cholesterol is a risk factor in the development of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006,

The CETP polymorphism rs5882 is associated with triglyceride lowering in response to plant sterol consumption (1038.3)

Plant sterol (PS) consumption may lower triglyceride (TG) concentrations. However, human clinical trial evidence is inconsistent, with only some trials showing TG reductions. This heterogeneity in responsiveness of TG concentrations to PS consumption could have a genetic basis. Our objective was to investigate whether SNPs in genes related to TG metabolism could be associated with changes in TG concentrations following PS consumption. 63 mildly hypercholesterolemic adults, pre‐assessed for cholesterol synthesis using lathosterol to cholesterol ratio (L/C) (High, n=24, L/C = 2.03 ± 0.39 umol/mmol; Low, n=39, L/C =0.99±0.28 umol/mmol) consumed either 2g/d (free sterol) of PS ester or placebo in margarine for 28 d in a dual‐center, single‐blind, randomized, crossover design. Serum TG concentrations were measured at the end of each phase. Candidate SNPs and ApoE variant were accessed by TaqMan assay. PS consumption did not lower TG overall (p=0.0506), but had an interaction with rs5882 in CETP (p=0.0080). Homozygous minor allele (G/G=‐0.47mmol/L, p=0.0002, n=10) carriers of rs5882 had reductions in TG concentrations with PS consumption, while A/A (+0.01mmol/L, p =0.6634, n=25) and A/G (‐0.04mmol/L, p= 0.3399, n=28) carriers did not. rs5882 in CETP associated with TG lowering due to PS consumption, and could serve as a genetic marker to identify individuals who derive TG lowering benefits from PS consumption.Grant Funding Source: CIHR

Scientific Opinion on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL‐cholesterol; high blood LDL‐cholesterol is a risk factor in the development of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006, following a request in accordance with Article 19 of Regulation (EC) No 1924/2006

Following an application from SANOFI-AVENTIS FRANCE, submitted pursuant to Article 19 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL-cholesterol (high blood LDL-cholesterol is a risk factor in the development of (coronary) heart disease), pursuant to Article 14 of Regulation (EC) No 1924/2006. The applicant requested an extension of the conditions of use to powder supplements to be diluted in water at a dose of 2 g per day, which would lower blood LDL-cholesterol concentrations by “5.4-8.1 %” after six weeks of daily consumption. Plant sterol esters are sufficiently characterised. Lowering blood LDL-cholesterol concentrations is a beneficial physiological effect and elevated blood LDL-cholesterol concentration is a risk factor for coronary heart disease. The target population is subjects who need and want to lower their blood cholesterol. In weighing the evidence, the Panel took into account that only one human intervention study showed a reduction in blood LDL-cholesterol concentrations after six weeks of consuming 2 g/day of plant sterol esters in powder, the large uncertainty surrounding the estimates of this effect, and that the results of that study have not been replicated in other studies. The Panel reiterates its previous conclusion that, while plant sterols added to foods such as margarine-type spreads, mayonnaise, salad dressings, and dairy products have been shown consistently to lower blood LDL-cholesterol concentrations in a large number of studies, the effective dose of plant sterols (as powder diluted in water) needed to achieve a given magnitude of effect in a given timeframe cannot be established with the data provided.

Plant Sterol Feeding Induces Tumor Formation and Alters Sterol Metabolism in the Intestine of Apc MinMice

Dietary plant sterols reduce the absorption of cholesterol and therefore increase intraluminal cholesterol concentration. We examined how plant sterol esters from functional foods affect intestinal tumorigenesis in tumor-prone adenomatous polyposis coli (Apc) Minmice. Feeding plant sterols at 0.8% increased the number of intestinal adenomas, and the effect was significant in female mice. The concentration of mucosal free sitosterol increased by eightfold in plant sterol males and by threefold in plant sterol females when compared with respective controls. The concentration of mucosal free cholesterol was significantly lower in plant sterol males than in control males, and the decrease in free cholesterol was accompanied with a significant increase in nuclear sterol regulatory element binding protein-2. No difference was found in the levels of β-catenin, cyclin D1, epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or caveolin-1 in either gender after plant sterol feeding. Among all measured parameters, higher levels of estrogen receptor β and free cholesterol in the mucosa were among the strongest predictors of increased intestinal tumorigenesis. In addition, gene expression data showed significant enrichment of up-regulated genes of cell cycle control and cholesterol biosynthesis in plant sterol females. The results indicate that high intake of plant sterols accelerates intestinal tumorigenesis in female Apc Minmice; however, the mechanism behind the adverse effect remains to be discovered.

Water dispersible plant sterol formulation shows improved effect on lipid profile compared to plant sterol esters

While the cholesterol-lowering efficacy of plant sterols (PS) is known, issues surrounding reduced PS solubility of some dietary formulations remain to be elucidated. This study determined the efficacy of a water dispersible formulation of free plant sterols (WD-PS) versus plant sterol esters (PS-esters). Forty-seven mild-to-moderately hypercholesterolemic individuals in a randomized, crossover study were provided for 4wk with a single-dose daily regimen of PS-enriched yogurt (2g/d of PS from WD-PS or PS-esters) or placebo. Yogurt enriched with WD-PS or PS-esters induced similar decreases in serum total (7.7% and 6.3%, respectively) and LDL cholesterol levels (11.7% and 11.6%, respectively), as percentage relative to the control (p<0.001; all). Ratios of total to HDL cholesterol and non-HDL to HDL cholesterol decreased more (p<0.05) with WD-PS (10.6% and 15.2%, respectively) than with PS-esters (7.0% and 10.8%, respectively) compared with control. Consumption of WD-PS reduced serum triglyceride levels (13.9%, p<0.05) compared to consumption of PS-esters (0.6%). Both WD-PS and PS-esters contributed effectively to LDL cholesterol lowering, however, the formulation of WD-PS yield additional effects on preventing cardiovascular diseases by improving serum TG and the ratio of total to HDL cholesterol.Trial registration (clinicaltrials.gov): NCT01478789.

Results from a post-launch monitoring survey on consumer purchases of foods with added phytosterols in five European countries

Phytosterols (plant sterols and stanols), in the form of phytosterol-esters, are used in food products as active ingredients to lower elevated blood low density lipoprotein-cholesterol concentrations. In Europe, plant sterol-esters gained Novel Foods authorisation in 2000. As a requirement of the authorisation, Unilever developed a post-launch monitoring program to monitor the use of products with added phytosterols. This paper reports findings from the 2011 post-launch monitoring survey on consumer purchase behaviour of foods with added phytosterols. 91,000 households in the Netherlands, Belgium, United Kingdom, France and Germany were included. 11,612 purchased foods with added phytosterols, including spreads, salad dressings, milk- and yoghurt-type products. The results show that 71-82% of households purchasing products with added phytosterols were 1-2 person households. These households were also purchasing the majority of the volume sold in each country (75-85%). The average phytosterol intakes per household were 0.35-0.86 g/day; well below the 1.5-3.0 g/day phytosterols needed to achieve a significant blood cholesterol lowering benefit. Post-launch monitoring is an accepted and useful tool to estimate the consumption behaviour amongst different consumer groups. Data show that average phytosterol intakes per household were well below 1g/day, suggesting that overconsumption is unlikely.

Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol therapy in a dual center, randomized, single‐blind placebo controlled trial.

Plant sterol (PS) therapy for LDL‐C lowering has highly variable efficacy across individuals. It has been suggested that cholesterol synthesis levels may affect PS response. A study was conducted to test lathosterol to cholesterol ratio (L/C), a marker of cholesterol synthesis, as a predictor of response to PS consumption. 63 mildly hypercholesterolemic adults, with high (n=24, L/C = 2.03 ± 0.39) or low (n=39, L/C =0.99±0.28) L/C ratio at baseline, consumed either 0 or 2g/d (free sterol) of PS ester in margarine for 28 days in a dual‐center, single‐blind, randomized, crossover design. Plasma lipids, non‐cholesterol sterols, and 7‐α hydroxy‐cholesterol (7αHC) a marker of bile acid (BA) synthesis, were measured at the end of each phase. PS consumption significantly lowered LDL‐C, with a significant interaction with L/C ratio. LDL‐C was lowered in the low L/C group (−0.29 mmol/L 95% CI [−0.39, −0.19] p=&lt;0.0001), but not the high L/C group (−0.04 mmol/L 95% CI [−0.18, 0.09] p=0.4904). 7αHC after PS consumption correlated with LDL response in high L/C group (r=−0.59, p=0.002), but not in the low or combined L/C groups. The L/C ratio predicts reductions in LDL‐C in response to PS consumption. BA synthesis may be associated with PS response in individuals with high cholesterol synthesis. These findings could help in identifying non‐responders to PS therapy. Registered at clinicaltrials.gov as NCT01131832.Grant Funding Source: CIHR

Oxyphytosterol formation in humans: Identification of high vs. low oxidizers

Animal studies suggest that oxyphytosterols are atherogenic. However, we have previously shown that plasma oxyphytosterol concentrations did not increase after consuming a diet enriched in plant sterol esters (3g/day), while minor reductions were seen after consuming a plant stanol ester-enriched diet. Large variations in oxyphytosterol concentrations between individuals however existed. The aim of this study was to identify factors that may explain inter-individual differences in plasma oxyphytosterol concentrations. For this, 43 subjects consumed for 4 weeks in random order a plant sterol, stanol and control margarine. Plasma oxyphytosterol concentrations were determined in butylated hydroxytoluene (BHT)-enriched EDTA plasma via GC–MS and serum oxidized low-density lipoprotein (oxLDL) concentrations were analyzed via ELISA. Trolox equivalent antioxidant capacity (TEAC) values, α-tocopherol concentrations and iron/copper status were determined to assess plasma oxidative and anti-oxidative capacity. Serum (non-oxidized) sitosterol and campesterol concentrations did not correlate with plasma oxysitosterol and oxycampesterol concentrations during any of the three dietary interventions. Moreover, plasma oxyphytosterol concentrations remained relatively stable over time. Six subjects could be arbitrarily classified as having consistent low or high plasma oxyphytosterol concentrations, which was also reflected in oxLDL concentrations. However, oxidative and anti-oxidative capacity markers, such as iron/copper status, α-tocopherol concentrations and TEAC values, could not explain these differences. In conclusion, subjects seem to have consistent plasma oxyphytosterol concentrations, which resulted in the identification of ‘low and high oxidizers’. Differences, however, could not be attributed to the oxidative and anti-oxidative capacity markers analyzed.

Diet-Induced Alterations of Host Cholesterol Metabolism Are Likely To Affect the Gut Microbiota Composition in Hamsters

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.

Effect of plant sterol esters on cardiovascular risk factors in hypercholesterolemic adults

Daily consumption of plant sterol esters has been shown to decrease total and LDL cholesterol. We examined whether delivery of plant sterol esters in a low‐fat dairy dessert could decrease cardiovascular risk factors. We enrolled 49 hypercholesterolemic adults in a randomized, double‐blind, crossover study with 4‐week control and treatment periods. Participants consumed two 68g portions of the dessert daily, providing 2 g/d free plant sterols, and were counselled to follow the Therapeutic Lifestyle Changes diet. Lipids, apolipoproteins, cellular adhesion molecules (CAM), inflammatory markers, blood pressure, and cardiovascular reactivity to stress were assessed at baseline and after each treatment period. Total and LDL cholesterol decreased more after consumption of the plant sterol dessert compared to placebo (−6.0% vs −2.4% and −8.3% vs −2.7%, respectively, p&lt;0.0001). Apolipoprotein A‐I increased after the plant sterol dessert (p&lt;0.05). No significant changes were observed between treatments for HDL, triglycerides, CAM, and inflammatory markers. Blood pressure and total peripheral resistance during stress were lower following the placebo dessert compared to the plant sterol dessert (p&lt;0.05). These results demonstrate that delivering 2 g/d of free plant sterols through a low‐fat dairy dessert for four weeks is clinically effective in reducing total and LDL cholesterol.Funding: Unilever