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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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[Research advance of functional plant pharmaceutical cycloartenol about pharmacological and physiological activity].
Zhang, ZL, Luo, ZL, Shi, HW, Zhang, LX, Ma, XJ
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2017;(3):433-437
Abstract
Cycloartenol, a phytosterol compound, also one of the key precusor substances for biosynthesis of numerous sterol compounds, has a variety of pharmacological activities such as anti-inflammatory, anti-tumor, antioxidant, antibiosis and anti-alzheimer's disease. Furthermore, cycloartenol also plays an important role in the process of plant growth and development. This article reviewed the research progress on cycloartenol pharmacological activity in domestic and foreign articles, and summarized the effect of cycloartenol and "cycloartenol pathway" on the plant growth and development, laying foundation for the its further study, development and utilization.
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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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The effects of cinnamon supplementation on blood lipid concentrations: A systematic review and meta-analysis.
Maierean, SM, Serban, MC, Sahebkar, A, Ursoniu, S, Serban, A, Penson, P, Banach, M, ,
Journal of clinical lipidology. 2017;(6):1393-1406
Abstract
BACKGROUND Cinnamon is a rich botanical source of polyphenols, whose positive effects on blood lipid concentrations have been hypothesized, but have not been conclusively studied. OBJECTIVE The objective of the study was to systematically review and evaluate the effect of administration of cinnamon on blood lipid concentrations. METHODS We assessed 13 randomized controlled trials with 750 participants investigating the effect of cinnamon supplementation on blood lipid concentrations. A meta-analysis was performed using random effect models, with weighted mean differences (WMDs; with 95% confidence interval [CI]) for endpoints calculated using a random effects model. RESULTS No statistically significant effect of cinnamon was observed on blood low-density lipoprotein cholesterol (LDL-C; WMD: -0.16 mmol/L [-6.19 mg/dL], 95% CI: -0.35, 0.03 [-13.53, 1.16], P = .10) and high-density lipoprotein cholesterol (HDL-C; WMD: 0.05 mmol/L [1.92 mg/dL], 95% CI: -0.03, 0.12 [-0.03, 4.64], P = .21) concentrations. However, a statistically significant reduction in blood triglycerides (WMD: -0.27 mmol/L [-23.91 mg/dL], 95% CI: -0.39, -0.14 [-34.54, -12.40], P < .01) and total cholesterol concentrations (WMD: -0.36 mmol/L [-13.92 mg/dL], 95% CI: -0.63, -0.09 [-24.36, -3.48], P < .01) was observed. HDL-C was significantly elevated after the omission of 1 study (WMD: 0.04 mmol/L [1.54 mg/dL], 95% CI: 0.03, 0.06 [1.16, 2.32], P < .01) during our sensitivity analysis. A meta-regression analysis was conducted, and no significant association was found between changes in lipid parameters and cinnamon dose. In contrast, changes in blood levels of total cholesterol (slope: 0.09; 95% CI: 0.02, 0.16; P < .01), LDL-C (slope: 0.05; 95% CI: 0.001, 0.10; P = .05) and triglycerides (slope: 0.06; 95% CI: 0.04, 0.09; P < .01) were significantly and positively associated with the duration of supplementation. No statistically significant association was found between blood HDL-C changes and duration of supplementation. CONCLUSION Cinnamon supplementation significantly reduced blood triglycerides and total cholesterol concentrations without any significant effect on LDL-C and HDL-C.
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The Use of Plant Sterols and Stanols as Lipid-Lowering Agents in Cardiovascular Disease.
Rysz, J, Franczyk, B, Olszewski, R, Banach, M, Gluba-Brzozka, A
Current pharmaceutical design. 2017;(17):2488-2495
Abstract
BACKGROUND The prevalence of premature atherosclerosis and cardiovascular disease (CVD) is constantly increasing worldwide. It has been proved that LDL-cholesterol (LDL-C) plays causal role in the development of coronary atherosclerosis. The fact that atherosclerosis is a chronic and progressive disease which onsets during the first three decades of life bores questions what to do to maintain LDL-C at low levels throughout life and thus to delay and/or prevent the progress this disease. Currently, most of public health expenses are spared on treatment, but not on prophylaxis. METHODS This is a review article summarizing novel reports concerning the efficacy of sterols/stanols as lipidlowering agents, assessing their influence on cardiovascular risk and safety. RESULTS It has been suggested that sterols and stanols are effective in the lowering of low-density cholesterol levels and diminishing cardiovascular risk. However, the results of other studies suggest that phytosterols may not exert positive effects during atherogenesis. Firstly, patients with phytosterolaemia (genetic disease in which high plant sterol plasma concentrations are observed) develop malignant premature atherosclerosis. Moreover, several epidemiological studies demonstrated the association between upper normal plasma concentrations of plant sterols and increased risk of cardiovascular events. Finally, the supplementation with plant stanols and plant sterols may be not beneficial due to their incorporation in various tissues and potentially resulting in adverse effects. CONCLUSION Despite the worldwide promotion of sterols as health improving supplements, it seems that in some people responding with relatively high phytosterol serum levels after its consumption such additives may turn out to be as good as it has been believed.
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Application of ITC in foods: A powerful tool for understanding the gastrointestinal fate of lipophilic compounds.
Arroyo-Maya, IJ, McClements, DJ
Biochimica et biophysica acta. 2016;(5):1026-1035
Abstract
BACKGROUND Isothermal titration calorimetry (ITC) is a biophysical technique widely used to study molecular interactions in biological and non-biological systems. It can provide important information about molecular interactions (such as binding constant, number of binding sites, free energy, enthalpy, and entropy) simply by measuring the heat absorbed or released during an interaction between two liquid solutions. SCOPE OF THE REVIEW In this review, we present an overview of ITC applications in food science, with particular focus on understanding the fate of lipids within the human gastrointestinal tract. In this area, ITC can be used to study micellization of bile salts, inclusion complex formation, the interaction of surface-active molecules with proteins, carbohydrates and lipids, and the interactions of lipid droplets. MAJOR CONCLUSIONS ITC is an extremely powerful tool for measuring molecular interactions in food systems, and can provide valuable information about many types of interactions involving food components such as proteins, carbohydrates, lipids, surfactants, and minerals. For systems at equilibrium, ITC can provide fundamental thermodynamic parameters that can be used to establish the physiochemical origin of molecular interactions. GENERAL SIGNIFICANCE It is expected that ITC will continue to be utilized as a means of providing fundamental information about complex materials such as those found in foods. This knowledge may be used to create functional foods designed to behave in the gastrointestinal tract in a manner that will improve human health and well-being.