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1.
Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis.
Scholz, M, Horn, K, Pott, J, Gross, A, Kleber, ME, Delgado, GE, Mishra, PP, Kirsten, H, Gieger, C, Müller-Nurasyid, M, et al
Nature communications. 2022;(1):143
Abstract
Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.
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Phytosterol metabolism in plant positive-strand RNA virus replication.
Altabella, T, Ramirez-Estrada, K, Ferrer, A
Plant cell reports. 2022;(2):281-291
Abstract
The genome of most plant viruses consists of a single positive-strand of RNA (+ ssRNA). Successful replication of these viruses is fully dependent on the endomembrane system of the infected cells, which experiences a massive proliferation and a profound reshaping that enables assembly of the macromolecular complexes where virus genome replication occurs. Assembly of these viral replicase complexes (VRCs) requires a highly orchestrated interplay of multiple virus and co-opted host cell factors to create an optimal microenvironment for efficient assembly and functioning of the virus genome replication machinery. It is now widely accepted that VRC formation involves the recruitment of high levels of sterols, but the specific role of these essential components of cell membranes and the precise molecular mechanisms underlying sterol enrichment at VRCs are still poorly known. In this review, we intend to summarize the most relevant knowledge on the role of sterols in ( +)ssRNA virus replication and discuss the potential of manipulating the plant sterol pathway to help plants fight these infectious agents.
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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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Safety and tolerability of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids in adult women: a randomized phase I, placebo-controlled, multi-arm, double-blinded clinical trial.
Villar-López, M, Soto-Becerra, P, Curse Choque, R, Al-Kassab-Córdova, A, Bernuy-Barrera, F, Palomino, H, Rojas, PA, Vera, C, Lugo-Martínez, G, Mezones-Holguín, E
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(10):906-913
Abstract
OBJECTIVE To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women. METHODS This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes. RESULTS All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant. CONCLUSION The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.
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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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Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial.
Song, L, Zhao, XG, Ouyang, PL, Guan, Q, Yang, L, Peng, F, Du, H, Yin, F, Yan, W, Yu, WJ, et al
The British journal of nutrition. 2020;(10):1148-1158
Abstract
The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.
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Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids: The BLOOD FLOW Randomized Intervention Study.
Ruuth, M, Äikäs, L, Tigistu-Sahle, F, Käkelä, R, Lindholm, H, Simonen, P, Kovanen, PT, Gylling, H, Öörni, K
Arteriosclerosis, thrombosis, and vascular biology. 2020;(9):2310-2321
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Abstract
OBJECTIVE Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m2. Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. CONCLUSIONS Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964.
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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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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.
Shamloo, M, Granger, MJ, Trautwein, EA, House, JD, MacKay, D
Trials. 2020;(1):452
Abstract
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.
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Diet and Cardiovascular Disease Risk Among Individuals with Familial Hypercholesterolemia: Systematic Review and Meta-Analysis.
Barkas, F, Nomikos, T, Liberopoulos, E, Panagiotakos, D
Nutrients. 2020;(8)
Abstract
BACKGROUND Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. OBJECTIVES To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. SEARCH METHODS Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. SELECTION CRITERIA Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. DATA COLLECTION AND ANALYSIS Two authors independently assessed the eligibility of the included trials and their bias risk and extracted the data which was independently verified by other colleagues. RESULTS A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the assessed risk parameters. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients' lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference (MD): -0.27 mmol/L, 95% confidence interval (CI): -0.47 to -0.07, p < 0.01) when compared with placebo. A non-significant trend towards a reduction in subjects' total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p = 0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p = 0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/L, 95% CI: -1.13 to -0.11, p = 0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/L, 95% CI: -1.08 to -0.09, p = 0.02). The same was by plant sterols (MD: -0.46 mmol/L, 95% CI: -0.76 to -0.17, p < 0.01 for cholesterol and MD: -0.45 mmol/L, 95% CI: -0.74 to -0.16, p < 0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. CONCLUSIONS Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the efficacy of cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in patients with familial hypercholesterolemia.