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The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism.
Li, X, Xin, Y, Mo, Y, Marozik, P, He, T, Guo, H
Molecules (Basel, Switzerland). 2022;(2)
Abstract
Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5-2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.
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Assessment of Plant Sterols in the Diet of Adult Polish Population with the Use of a Newly Developed Database.
Witkowska, AM, Waśkiewicz, A, Zujko, ME, Mirończuk-Chodakowska, I, Cicha-Mikołajczyk, A, Drygas, W
Nutrients. 2021;(8)
Abstract
Plant sterols are compounds with multiple biological functions, mainly cholesterol-reducing. There are no comprehensive databases on plant sterols, which makes it difficult to estimate their intake in the Polish population. This work attempted to use international food databases, additionally supplemented by scientific data from the literature, to create a database of plant sterols, which would cover various kinds of foods and dishes consumed in Poland. The aim was to assess the size and sources of dietary plant sterols in the adult population of Poland. The literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify possible sources of published food composition data for plant sterols. The study group consisted of 5690 participants of the WOBASZ II survey. We identified 361 dietary sources of plant sterols based on the consumption of foods and dishes reported by participants. Cereals and fats provided 61% of the total plant sterols, and together with vegetables and fruits, this totaled 80%. The median intake of plant sterols in the Polish population was 255.96 mg/day, and for men and women 291.76 and 230.61 mg/day, respectively. Canola oil provided the most plant sterols at 16.92%, followed by white bread at 16.65% and soft margarine at 8.33%. The study found that plant sterol intake in Poland is comparable to other populations, and women's diets are more dense in plant sterols. Due to the lack of literature sources on plant sterol content in some foods, future studies should expand and complete the databases on plant sterol content in foods.
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Deciphering the Role of Polyphenols in Sports Performance: From Nutritional Genomics to the Gut Microbiota toward Phytonutritional Epigenomics.
Sorrenti, V, Fortinguerra, S, Caudullo, G, Buriani, A
Nutrients. 2020;(5)
Abstract
The individual response to nutrients and non-nutrient molecules can be largely affected by three important biological layers. The gut microbiome can alter the bioavailability of nutrients and other substances, the genome can influence molecule kinetics and dynamics, while the epigenome can modulate or amplify the properties of the genome. Today the use of omic techniques and bioinformatics, allow the construction of individual multilayer networks and thus the identification of personalized strategies that have recently been considered in all medical fields, including sports medicine. The composition of each athlete's microbiome influences sports performance both directly by acting on energy metabolism and indirectly through the modulation of nutrient or non-nutrient molecule availability that ultimately affects the individual epigenome and the genome. Among non-nutrient molecules polyphenols can potentiate physical performances through different epigenetic mechanisms. Polyphenols interact with the gut microbiota, undergoing extensive metabolism to produce bioactive molecules, which act on transcription factors involved in mitochondrial biogenesis, antioxidant systems, glucose and lipid homeostasis, and DNA repair. This review focuses on polyphenols effects in sports performance considering the individual microbiota, epigenomic asset, and the genomic characteristics of athletes to understand how their supplementation could potentially help to modulate muscle inflammation and improve recovery.
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Factors influencing the cardiometabolic response to (poly)phenols and phytosterols: a review of the COST Action POSITIVe activities.
Gibney, ER, Milenkovic, D, Combet, E, Ruskovska, T, Greyling, A, González-Sarrías, A, de Roos, B, Tomás-Barberán, F, Morand, C, Rodriguez-Mateos, A
European journal of nutrition. 2019;(Suppl 2):37-47
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Abstract
PURPOSE Evidence exists regarding the beneficial effects of diets rich in plant-based foods regarding the prevention of cardiometabolic diseases. These plant-based foods are an exclusive and abundant source of a variety of biologically active phytochemicals, including polyphenols, carotenoids, glucosinolates and phytosterols, with known health-promoting effects through a wide range of biological activities, such as improvements in endothelial function, platelet function, blood pressure, blood lipid profile and insulin sensitivity. We know that an individual's physical/genetic makeup may influence their response to a dietary intervention, and thereby may influence the benefit/risk associated with consumption of a particular dietary constituent. This inter-individual variation in responsiveness has also been described for dietary plant bioactives but has not been explored in depth. To address this issue, the European scientific experts involved in the COST Action POSITIVe systematically analyzed data from published studies to assess the inter-individual variation in selected clinical biomarkers associated with cardiometabolic risk, in response to the consumption of plant-based bioactives (poly)phenols and phytosterols. The present review summarizes the main findings resulting from the meta-analyses already completed. RESULTS Meta-analyses of randomized controlled trials conducted within POSITIVe suggest that age, sex, ethnicity, pathophysiological status and medication may be responsible for the heterogeneity in the biological responsiveness to (poly)phenol and phytosterol consumption and could lead to inconclusive results in some clinical trials aiming to demonstrate the health effects of specific dietary bioactive compounds. However, the contribution of these factors is not yet demonstrated consistently across all polyphenolic groups and cardiometabolic outcomes, partly due to the heterogeneity in trial designs, low granularity of data reporting, variety of food vectors and target populations, suggesting the need to implement more stringent reporting practices in the future studies. Studies investigating the effects of genetic background or gut microbiome on variability were limited and should be considered in future studies. CONCLUSION Understanding why some bioactive plant compounds work effectively in some individuals but not, or less, in others is crucial for a full consideration of these compounds in future strategies of personalized nutrition for a better prevention of cardiometabolic disease. However, there is also still a need for the development of a substantial evidence-base to develop health strategies, food products or lifestyle solutions that embrace this variability.
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Cardiovascular Disease Prevention: The Earlier the Better? A Review of Plant Sterol Metabolism and Implications of Childhood Supplementation.
Scolaro, B, Andrade, LFS, Castro, IA
International journal of molecular sciences. 2019;(1)
Abstract
Atherosclerosis is the underlying cause of major cardiovascular events. The development of atherosclerotic plaques begins early in life, indicating that dietary interventions in childhood might be more effective at preventing cardiovascular disease (CVD) than treating established CVD in adulthood. Although plant sterols are considered safe and consistently effective in lowering plasma cholesterol, the health effects of early-life supplementation are unclear. Studies suggest there is an age-dependent effect on plant sterol metabolism: at a younger age, plant sterol absorption might be increased, while esterification and elimination might be decreased. Worryingly, the introduction of low-cholesterol diets in childhood may unintentionally favor a higher intake of plant sterols. Although CVD prevention should start as early as possible, more studies are needed to better elucidate the long-term effects of plant sterol accumulation and its implication on child development.
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Microalgal carotenoids and phytosterols regulate biochemical mechanisms involved in human health and disease prevention.
Le Goff, M, Le Ferrec, E, Mayer, C, Mimouni, V, Lagadic-Gossmann, D, Schoefs, B, Ulmann, L
Biochimie. 2019;:106-118
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Abstract
Microalgae are photosynthetic microorganisms that produce numerous bioactive molecules that can be used as food supplement to prevent chronic disease installation. Indeed, they produce phycobiliproteins, polysaccharides, lipids, carotenoids and sterolic compounds. The use of microalgae in human nutrition provide a mixture of these molecules with synergistic effect. The aim of this review is to present the specific roles played by the xanthophylls, and specifically astaxanthin and fucoxanthin, two high added value carotenoids, and by microalgal phytosterols such as β-sitosterol, campesterol and stigmasterol on several cell mechanisms involved in the prevention of cardiometabolic diseases and cancers. This review explains how these microalgal molecules modulate cell signaling pathways involved in carbohydrate and lipid metabolisms, inflammation, apoptosis, invasion and metastasis. Xanthophylls and phytosterols are involved in the reduction of inflammatory markers in relation with the regulation of the c-Jun N-terminal kinases and nuclear factor-kappa B signaling pathways, and suppression of production of pro-inflammatory mediators. Xanthophylls act on glucose and lipid metabolisms via both the upregulation of peroxisome proliferator-activated receptors (PPARs) and glucose transporters and its effects on the expression of enzymes involved in fatty acid synthesis and cholesterol metabolism. Their anti-cancer effects are related to the induction of intrinsic apoptosis due to down-regulation of key regulatory kinases. The anti-angiogenesis, anti-proliferative and anti-invasive effects are correlated with decreased production of endothelial growth factors and of matrix metalloproteinases. Phytosterols have a major role on cholesterol absorption via modification of the activities of Niemann-Pick C1 like 1 and ATP-binding cassette transporters and on cholesterol esterification. Their action are also related with the modulation of PPARs and sterol regulatory element-binding protein-1 activities.
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Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases.
Cabral, CE, Klein, MRST
Arquivos brasileiros de cardiologia. 2017;(5):475-482
Abstract
Phytosterols are bioactive compounds found in foods of plant origin, which can be divided into plant sterols and plant stanols. Clinical studies consistently indicate that the intake of phytosterols (2 g/day) is associated with a significant reduction (8-10%) in levels of low-density lipoprotein cholesterol (LDL-cholesterol). Thus, several guidelines recommend the intake of 2 g/day of plant sterols and/or stanols in order to reduce LDL-cholesterol levels. As the typical western diet contains only about 300 mg/day of phytosterols, foods enriched with phytosterols are usually used to achieve the recommended intake. Although phytosterols decrease LDL-cholesterol levels, there is no evidence that they reduce the risk of cardiovascular diseases; on the contrary, some studies suggest an increased risk of atherosclerosis with increasing serum levels of phytosterols. This review aims to address the evidence available in the literature on the relationship between phytosterols and risk of cardiovascular disease.
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Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials.
Baumgartner, S, Ras, RT, Trautwein, EA, Mensink, RP, Plat, J
European journal of nutrition. 2017;(3):909-923
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Abstract
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 (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-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 β-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 β-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 β-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.
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Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols.
Fumeron, F, Bard, JM, Lecerf, JM
Nutrition reviews. 2017;(2):134-145
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Abstract
Low-density lipoprotein cholesterol (LDL-C) plays a causal role in atherosclerosis. One way to reduce LDL-C levels is to inhibit cholesterol absorption. Plant sterols and stanols compete with cholesterol for absorption in the intestine and induce an average decrease in LDL-C by 5% to 15% in a dose-dependent manner, but not in all individuals. This review focuses on the interindividual variability in response to dietary supplementation with plant sterols and stanols. Dietary plant sterols and stanols have no significant effects on LDL-C in substantial numbers of individuals. Higher responses, in absolute value and percentage of LDL-C, are observed in individuals with higher cholesterol absorption and a lower rate of cholesterol synthesis. Some data provide evidence of the influence of genetics on the response to plant sterols and stanols. Further studies in large populations are required to extend these conclusions about genetic influences.
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Plant sterols and cardiovascular disease: a systematic review and meta-analysis.
Genser, B, Silbernagel, G, De Backer, G, Bruckert, E, Carmena, R, Chapman, MJ, Deanfield, J, Descamps, OS, Rietzschel, ER, Dias, KC, et al
European heart journal. 2012;(4):444-51
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Abstract
The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four case-control, five nested case-control, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD.