The Role of Specific Components of a Plant-Based Diet in Management of Dyslipidemia and the Impact on Cardiovascular Risk.

Convincing evidence supports the intake of specific food components, food groups, or whole dietary patterns to positively influence dyslipidemia and to lower risk of cardiovascular diseases (CVD). Specific macro- and micro-components of a predominantly plant-based dietary pattern are vegetable fats, dietary fibers, and phytonutrients such as phytosterols. This review summarizes the current knowledge regarding effects of these components on lowering blood lipids, i.e., low-density lipoprotein cholesterol (LDL-C) and on reducing CVD risk. The beneficial role of a plant-based diet on cardiovascular (CV) health has increasingly been recognized. Plant-based dietary patterns include a Mediterranean and Nordic diet pattern, the dietary approaches to stop hypertension (DASH), and Portfolio diet, as well as vegetarian- or vegan-type diet patterns. These diets have all been found to lower CVD-related risk factors like blood LDL-C, and observational study evidence supports their role in lowering CVD risk. These diet patterns are not only beneficial for dyslipidemia management and prevention of CVD but further contribute to reducing the impact of food choices on environmental degradation. Hence, the CV health benefits of a predominantly plant-based diet as a healthy and environmentally sustainable eating pattern are today recommended by many food-based dietary as well as clinical practice guidelines.

Genetic basis for prediction of non-responders to dietary plant sterol intervention (GenePredict-PS): a study protocol for a double-blind, placebo-controlled, randomized two-period crossover study.

BACKGROUND: Functional food ingredients and natural health products have been demonstrated to reduce disease risk and thereby help to lower health care costs across populations at risk for chronic or degenerative diseases. However, typically a wide range of interindividual variability exists in response across individuals to nutritional and natural health product bioactives, such as plant sterols (PS). This study aims to determine and utilize information on the associations between genosets and the degree of responsiveness to dietary PS intervention, with a long-term objective of developing genetic tests to predict responses to PS. METHODS: This clinical trial is designed as a double-blind, placebo controlled, randomized two-period crossover study. Sixty-four eligible participants with the specific a priori-determined single nucleotide polymorphisms (SNPs) associated with a responsiveness to PS will consume PS or a placebo treatment for two 4-week periods. The PS treatment consists of two daily single portions of margarine, each providing 1 g PS during the PS period (2.0 g/day of PS in total). The placebo will be an identical margarine containing no added PS. Low-density lipoprotein cholesterol (LDL-C) responsiveness to the controlled administration of PS will be investigated as the primary outcome, and the associations between interindividual genoset variabilities and response to PS consumption will be determined. DISCUSSION: This research will provide further insight into whether the associations between previously identified SNPs and the response of LDL-C to PS consumption can be used in a predictive manner. It will also provide insight into the complexities of undertaking a nutrigenetic trial with prospective recruitment based on genotype. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02765516. Registered on 6 May 2016.

'Diet and lifestyle' in the management of dyslipidaemia and prevention of CVD - Understanding the level of knowledge and interest of European Atherosclerosis Society members.

To better understand the level of knowledge and interest in 'diet and lifestyle' for cholesterol management and CVD prevention, European Atherosclerosis Society (EAS) members were invited to take part in an online survey. In total, 269 EAS members participated of which 64 (24%) were students/postdocs, 102 (38%) researchers involved with CVD-related research and 103 (38%) doctors and clinicians who directly interact with patients. All (99%) of the participants either agreed or strongly agreed that 'diet and lifestyle' have a role to play in cholesterol management, with 80% indicating that 'diet and lifestyle' is very or extremely important. Of the clinicians, 75% indicated that their patients voluntarily ask for 'diet and lifestyle' advice and over 80% said they continuously provide 'diet and lifestyle advice' to their patients. Of the surveyed clinicians, 91% feel sufficiently educated and confident to provide expert advice and over 90% recommend medication, diet change, frequent exercise and smoking cessation to their patients. In view of more specific dietary advice, clinicians reportedly recommend a 'Mediterranean diet', and advise to avoid high-fat foods, and to increase intake of high-fibre foods. Interestingly, smoking cessation and alcohol avoidance were mentioned less frequently. In view of educational needs, over half of the surveyed EAS members use the internet and 'guidelines' to learn about 'diet and lifestyle' in relation to cholesterol and CVD risk management. Clinicians tend to use 'guidelines' more often, while students/postdocs tend to use the internet significantly more than clinicians and CVD researchers. Regarding unmet needs for educational tools addressing specifically 'diet and lifestyle', clinicians feel that patient-oriented leaflets and pocket guidelines would be most beneficial materials to introduce, while students/postdocs would prefer an app. In summary, the role of 'diet and lifestyle' as a cornerstone of cholesterol management and CVD risk prevention seems well recognised amongst EAS members surveyed.

Impact of isocaloric exchanges of carbohydrate for fat on postprandial glucose, insulin, triglycerides, and free fatty acid responses-a systematic review and meta-analysis.

Varying the macronutrient composition of meals alters acute postprandial responses, but the effect sizes for specific macronutrient exchanges have not been quantified by systematic reviews. Therefore the aim is to quantify the effect size of exchanging fat for carbohydrates in mixed meals on postprandial glucose (PPG), insulin (PPI), triglycerides (PPTG), and free fatty acids (PPFFA) responses by performing a systematic review and meta-analysis of randomized controlled trials. A systematic literature search was undertaken on randomized controlled trials comparing isocaloric high fat with high carbohydrate meals, with comparable protein contents and at least one postprandial glycemic- and one lipid outcome. The outcome data were extracted and expressed as mean postprandial levels over 2 h. Ten studies involving 14 comparisons met the eligibility criteria. Data were available for meta-analysis from 347 participants, consuming mixed meals containing 250-1003 kcal, and total fat contents of 33.3-75.6 percentage of energy (en%) (intervention) versus 0-31.7 en% (control). Each 10en% increase in fat, replacing carbohydrates produced a mean reduction in PPG of 0.32 mmol/l (95% CI -0.64 to -0.00, p = 0.047), a reduction in PPI of 18.2 pmol/l (95% CI -24.86 to -11.54), an increase in PPTG of 0.06 mmol/l (95% CI 0.02 to 0.09, p = 0.004), with no statistically significant effect on PPFFA. Modest exchange of carbohydrates for fats in mixed meals significantly reduces PPG and PPI and increases PPTG responses. The quantitative relationships derived here may be applied to predict responses, and to design and optimize meal macronutrient compositions in dietary intervention studies.

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose‒Response Pilot Study.

Plant sterols (PS) are oxidized to PS oxidation products (POP). This study quantified the change in serum POP compared to cholesterol oxidation products (COP) after the intake of increasing POP doses. This was a double-blind, randomized, placebo-controlled, dose‒response pilot study with healthy individuals in four groups (15 per group). The control group received products with no added PS or POP and treatment groups received daily 20-25 g margarine with added PS (mean 3 g/d) and two cookies (~28 g) for six weeks. Cookies delivered 8.7 (low-dose), 15.2 (medium-dose), or 37.2 (high-dose) mg/d POP. Fasting serum POP and COP were measured at the baseline, days 14, 28, and 42 in all participants and days 7, 21, and 35 in a subset. Sixty individuals completed the study; 52 were included in per protocol analysis. Serum POP increased with increasing POP intake and plateaued at dose >15 mg/d. Stabilized POP concentrations were (mean ± SD) 38.9 ± 6.9, 91.0 ± 27.9, 144.4 ± 37.9 and 203.0 ± 63.7 nmol/L, for control, low-, medium-, and high-dose POP groups, respectively. For all groups, the serum COP ranged from 213 to 262 nmol/L and the average POP/COP ratio was <1. Serum POP concentrations increased non-linearly, reaching stabilized concentrations in <7 days, and remained below COP concentrations after the intake of increasing POP doses.

Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants.

Dietary plant sterols, such as campesterol and sitosterol, reduce plasma cholesterol concentrations, but any relationship to plaque development and CVD remains unclear. Some epidemiologic studies have suggested that elevated plasma plant sterol concentrations are atherogenic, including the Framingham Offspring Study that identified a positive association between plant sterol concentrations and CVD status. We hypothesized that this suggested atherogenicity relates to the oxidation status of plant sterols (i.e., concentrations of plasma oxyphytosterols). Therefore, in the Framingham Offspring Study cohort, we measured plasma oxyphytosterol concentrations in 144 patients with documented CVD and/or more than 50% carotid stenosis and 383 matched controls. We analyzed plasma oxyphytosterol concentrations by GC/MS/MS and performed conditional logistic regression analysis to determine associations between plasma plant sterol or oxyphytosterol concentrations and CVD status. We found that higher total cholesterol (TC)-standardized campesterol concentrations [odds ratio (OR): 2.36; 95% CI: 1.60, 3.50] and higher sitosterol concentrations (OR: 1.47; 95% CI: 1.09, 1.97) were significantly associated with increased CVD risk, as in the earlier study. However, the sum of absolute oxyphytosterol concentrations (OR: 0.99; 95% CI: 0.81, 1.21) and the sum of TC-standardized oxyphytosterol concentrations (OR: 0.98; 95% CI: 0.80, 1.19) were not associated with an increased CVD risk. Results were comparable for individual absolute and TC-standardized oxycampesterol and oxysitosterol concentrations. Plasma nonoxidized TC-standardized sitosterol and campesterol concentrations showed weak or no correlations with oxyphytosterol concentrations, while all individual plasma concentrations of oxyphytosterol correlated with each other. In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study.

A low-fat spread with added plant sterols and fish omega-3 fatty acids lowers serum triglyceride and LDL-cholesterol concentrations in individuals with modest hypercholesterolaemia and hypertriglyceridaemia.

PURPOSE: The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread. METHODS: This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3.4 mmol/L) concentrations consumed either the placebo or intervention spread for 4 weeks. The intervention spread contained 2.0 g/day PS and 1.0 g/day eicosapentaenoic acid (EPA) + docosahexanoic acid (DHA) from fish oil. Fasting serum lipids and apolipoproteins (Apo) (exploratory) were measured at the end of the run-in and intervention phases. RESULTS: Four-week consumption of the intervention spread resulted in significantly lower TG (- 10.6%, 95% CI - 16.0 to - 4.9%; P < 0.001) and LDL-C concentrations (- 5.2%; 95% CI - 7.8 to - 2.4%) as compared to placebo. Total cholesterol (- 3.9%; 95% CI - 6.1 to - 1.5%), non-HDL-C (- 5.4%; 95% CI - 8.1 to - 2.7%), remnant-cholesterol (- 8.1%; 95% CI - 3.4 to - 12.5%), ApoAII (- 2.9%; 95% CI - 5.5 to - 0.2%), ApoCIII (- 7.7%; 95% CI - 12.1 to - 3.1%) and ApoB (- 3.2%; 95% CI - 5.9 to - 0.4%) concentrations were also significantly lower, as compared to placebo. No significant treatment effects were found for HDL-cholesterol, ApoAI, ApoCII, Apo E or ApoB/ApoAI. CONCLUSIONS: Four-week consumption of the intervention spread led to significant and clinically relevant decreases in serum TG, LDL-C and other blood lipid concentrations. The study was registered at clinicaltrials.gov (NCT02728583).

LDL-Cholesterol Lowering of Plant Sterols and Stanols-Which Factors Influence Their Efficacy?

The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is summarized in several meta-analyses showing a dose-response relationship with intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes evidence for the impact of various factors potentially influencing the LDL-C-lowering efficacy of PSS. PSS are efficacious in all food formats and in food supplements. Some factors related to food format, e.g., solid vs. liquid foods, seem to impact efficacy, while there is no difference between free PSS and esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially in the morning with light breakfast, leads to a sub-optimal LDL-C lowering. However, intake frequency seems influenced by intake occasion, i.e., with or without a meal, and time of day. Meal intake is a critical factor for an optimal LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to influence the LDL-C lowering effect of PSS with greater reductions reported for men than women; but overall evidence is inconclusive and larger studies show no gender by treatment interaction. In conclusion, PSS are efficacious in all foods and food supplements; for optimal efficacy they should be consumed with a (main) meal and twice daily.

Progress and perspectives in plant sterol and plant stanol research.

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study.

BACKGROUND: Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS: In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS: Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS: In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.

Oxidation of sitosterol and campesterol in foods upon cooking with liquid margarines without and with added plant sterol esters.

Plant sterol (PS) oxidation products (POP) derived from sitosterol and campesterol were measured in 15 foods cooked with liquid margarine without (control) and with added 7.5% PS. POP were analyzed using a GC-MS method. PS liquid vs. control margarine resulted in a higher median POP content per food portion (1.35mg, range 0.08-13.20mg versus 0.23mg, 0.06-0.90mg), a lower PS oxidation rate (0.63 vs. 1.29%) and lower oxidation susceptibility of sitosterol vs. campesterol. POP formation was highest in shallow-fried potatoes with PS liquid margarine (64.44mg per portion food plus residual fat). Mean relative abundances of epoxy-, 7-keto-, 7-hydroxy- and triol-PS derived from sitosterol and campesterol were 40.0, 34.4, 21.5 and 4.0% with control vs. 44.1, 23.8, 29.6 and 2.4% with PS liquid margarine. In conclusion, PS liquid margarine increased POP content in foods with a POP profile characterized by a higher ratio of epoxy- to 7-keto-derivatives.

Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations.

Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

Consumer purchase behaviour of foods with added phytosterols in six European countries: Data from a post-launch monitoring survey.

A variety of foods with added phytosterols (plant sterols and stanols, PS) known to lower elevated blood cholesterol is available on the European market. This paper reports findings from a 2015 post-launch monitoring survey on consumer purchase behaviour of foods with added PS in UK, Germany, France, Netherlands, Belgium and Greece. Data from 80,825 households were included. Households were divided into categories depending on number of purchases, household size, age of primary shopper and presence of children <5 years. Penetration rates of households purchasing foods with added PS ranged between 3 and 34%. Of households purchasing PS, 34-61% purchased infrequently (≤2 times/year), 29-36% occasionally (

Thermal stability of plant sterols and formation of their oxidation products in vegetable oils and margarines upon controlled heating.

Fat-based products like vegetable oils and margarines are commonly used for cooking, which may enhance oxidation of plant sterols (PS) present therein, leading to the formation of PS oxidation products (POP). The present study aims to assess the kinetics of POP formation in six different fat-based products. Vegetable oils and margarines without and with added PS (7.5-7.6% w/w) in esterified form were heated in a Petri-dish at temperatures of 150, 180 and 210°C for 8, 12 and 16min. PS and POP were analysed using GC-FID and GC-MS-SIM, respectively. Increasing PS content, temperature and heating time led to higher POP formation in all tested fat-based products. PS (either naturally occurring or added) in margarines were less susceptible to oxidation as compared to PS in vegetable oils. The susceptibility of sitosterol to oxidation was about 20% lower than that of campesterol under all the applied experimental conditions. During heating, the relative abundance of 7-keto-PS (expressed as% of total POP) decreased in all the fat-based products regardless of their PS contents, which was accompanied by an increase in the relative abundance of 7-OH-PS and 5,6-epoxy-PS, while PS-triols were fairly unchanged. In conclusion, heating time, temperature, initial PS content and the matrix of the fat-based products (vegetable oil vs. margarine) showed distinct effects on POP formation and composition of individual POP formed.

Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials.

PURPOSE: Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. METHODS: Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (ß-carotene, α-carotene, lycopene, lutein, zeaxanthin and ß-cryptoxanthin) using a random effects model. Heterogeneity was assessed using predefined subject and treatment characteristics. RESULTS: Average plant sterol or stanol intake was 2.5 g/d. Relative non-standardized and TC-standardized concentrations of ß-carotene decreased by, respectively, -16.3 % (95 % CI -18.3; -14.3) and -10.1 % (-12.3; -8.0), α-carotene by -14.4 % (-17.5; 11.3) and -7.8 % (-11.3; -4.3), and lycopene by -12.3 % (-14.6; -10.1) and -6.3 % (-8.6; -4.0). Lutein concentrations decreased by -7.4 % (-10.1; -4.8), while TC-standardized concentrations were not changed. For zeaxanthin, these values were -12.9 % (-18.9; -6.8) and -7.7 % (-13.8; -1.7) and for ß-cryptoxanthin -10.6 % (-14.3; -6.9) and -4.8 % (-8.7; -0.9). Non-standardized α-tocopherol concentrations decreased by -7.1 % (-8.0; -6.2) and γ-tocopherol by -6.9 % (-9.8; -3.9), while TC-standardized tocopherol concentrations were not changed. Non-standardized retinol and vitamin D concentrations were not affected. Results were not affected by baseline concentrations, dose, duration and type of plant sterols/stanols, except for significant effects of duration (≤4 vs. >4 weeks) on TC-standardized lutein concentrations (1.0 vs. -5.6 %) and type of plant sterol/stanol on TC-standardized ß-carotene concentrations (-8.9 vs. -14.2 %). CONCLUSIONS: Plant sterol and stanol intake lowers TC-standardized hydrocarbon carotenoid concentrations, differently affects TC-standardized oxygenated carotenoid concentrations, but does not affect TC-standardized tocopherol concentrations or absolute retinol and vitamin D concentrations. Observed concentrations remained within normal ranges.

Phytosterol oxidation products (POP) in foods with added phytosterols and estimation of their daily intake: A literature review.

1To evaluate the content of phytosterol oxidation products (POP) of foods with added phytosterols, in total 14 studies measuring POP contents of foods with added phytosterols were systematically reviewed. In non-heated or stored foods, POP contents were low, ranging from (medians) 0.03-3.6 mg/100 g with corresponding oxidation rates of phytosterols (ORP) of 0.03-0.06%. In fat-based foods with 8% of added free plant sterols (FPS), plant sterol esters (PSE) or plant stanol esters (PAE) pan-fried at 160-200°C for 5-10 min, median POP contents were 72.0, 38.1, and 4.9 mg/100 g, respectively, with a median ORP of 0.90, 0.48, and 0.06%. Hence resistance to thermal oxidation was in the order of PAE > PSE > FPS. POP formation was highest in enriched butter followed by margarine and rapeseed oil. In margarines with 7.5-10.5% added PSE oven-heated at 140-200°C for 5-30 min, median POP content was 0.3 mg/100 g. Further heating under same temperature conditions but for 60-120 min markedly increased POP formation to 384.3 mg/100 g. Estimated daily upper POP intake was 47.7 mg/d (equivalent to 0.69 mg/kg BW/d) for foods with added PSE and 78.3 mg/d (equivalent to 1.12 mg/kg BW/d) for foods with added FPS as calculated by multiplying the advised upper daily phytosterol intake of 3 g/d with the 90% quantile values of ORP. In conclusion, heating temperature and time, chemical form of phytosterols added and the food matrix are determinants of POP formation in foods with added phytosterols, leading to an increase in POP contents. Practical applications: Phytosterol oxidation products (POP) are formed in foods containing phytosterols especially when exposed to heat treatment. This review summarising POP contents in foods with added phytosterols in their free and esterified forms reveals that heating temperature and time, the chemical form of phytosterols added and the food matrix itself are determinants of POP formation with heating temperature and time having the biggest impact. The estimated upper daily intakes of POP is 78.3 mg/d for fat-based products with added free plant sterols and 47.7 mg/d for fat-based products with added plant sterol esters. Phytosterols in foods are susceptible to oxidation to form phytosterol oxidation products (POP). This review summarizes literature data regarding POP contents of foods with added phytosterols that were exposed to storage and heat treatments.

Effects of phytosterols on markers of inflammation: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Regular intake of phytosterols (PS) is proven to dose-dependently lower LDL-cholesterol (LDL-C). Whether PS consumption can also impact low-grade inflammation is unclear. Considering the low feasibility of outcomes studies involving PS consumption, investigation of surrogate markers of atherosclerosis represents a valuable approach. This study assessed the anti-inflammatory effect of PS consumption, according to inflammatory biomarkers, mainly C-reactive protein (CRP). METHODS AND RESULTS: A systematic search of Medline, Cab Abstracts, and Food Science & Technology Abstracts was conducted through January 2015. Our study selection included randomized controlled trials (RCT), involving intake of PS-enriched foods as active treatment, and measurement of plasma inflammatory biomarkers. Random-effects meta-analyses were performed using average baseline and end-of-intervention concentrations and control-adjusted absolute changes in CRP and blood lipids. There were 20 eligible RCTs including a total of 1308 subjects. The absolute change of plasma CRP levels with PS consumption was -0.10 mg/L (95%CI -0.26; 0.05), a non-significant change, and heterogeneity had borderline significance (I(2) = 29.1; p-value = 0.073). The absolute reduction of LDL-C was -14.3 mg/dL (95%CI -17.3; -11.3). Meta-regression analyses showed that both the dose and duration of PS intake significantly influenced the absolute changes in plasma CRP (ß = -0.35, p = 0.0255 and ß = -0.03, p = 0.0209, respectively). CONCLUSIONS: In this meta-analysis, regular intake of PS-enriched foods did not significantly change CRP, whilst LDL-C concentrations were significantly reduced. Further studies with higher PS doses may provide more definite conclusions on a potential anti-inflammatory effect of PS intake.

Formation of Plant Sterol Oxidation Products in Foods during Baking and Cooking Using Margarine without and with Added Plant Sterol Esters.

Plant sterols (PS) in foods are subject to thermal oxidation to form PS oxidation products (POP). This study measured POP contents of 19 foods prepared by typical household baking and cooking methods using margarines without (control) and with 7.5% added PS (as 12.5% PS-esters, PS-margarine). Median POP contents per portion size of cooked foods were 0.57 mg (range 0.05-1.11 mg) with control margarine versus 1.42 mg (range 0.08-20.5 mg) with PS-margarine. The oxidation rate of PS (ORP) was 0.50% (median) with the PS-margarine and 3.66% with the control margarine. Using the PS-margarine, microwave-cooked codfish had the lowest POP content, with 0.08 mg per portion, while shallow-fried potatoes had the highest POP content, 20.5 mg per portion. Median POP contents in cookies, muffins, banana bread, and sponge cake baked with the control or PS-margarine were 0.12 mg (range 0.11-0.21 mg) and 0.24 mg (range 0.19-0.60 mg) per portion, with a corresponding ORP of 1.38% and 0.06%, respectively. POP contents in all the cooked and baked foods did not exceed 20.5 mg per typical portion size. A wide variation in the distribution of individual POP among different foods existed, with 7-keto-PS and 5,6-epoxy-PS being the major oxidation products.

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.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study.

BACKGROUND: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. OBJECTIVES: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. DESIGN: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. RESULTS: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: -0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: -0.40, -0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 µmol/L and 13.9 µmol/L (expressed as geometric means), respectively. CONCLUSIONS: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.