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1.
Noncholesterol Sterols as Surrogate Markers in Patients with Severe Alcoholic Hepatitis.
Sahlman, P, Nissinen, M, Simonen, P, Färkkilä, M
Lipids. 2018;(3):323-334
Abstract
Severe alcoholic hepatitis (AH) is a life-threatening condition lacking good serologic markers to tailor treatment and predict recovery. We examined the cholesterol metabolism in severe AH to explore prognostic markers and evaluate the profile of cholesterol precursors, cholestanol and phytosterols, in this context. We assessed serum cholesterol, cholesterol precursors, cholestanol, phytosterols, and biochemical markers in 24 patients with severe AH treated with prednisolone and randomized to ciprofloxacin in the ratio 1:1. Response to prednisolone was assessed with the Lille model. Evaluations were made between responders and nonresponders to corticosteroid treatment and during follow-up for 180 days. The findings were compared with those from patients with primary sclerosing cholangitis (PSC) (n = 156) and healthy individuals (n = 124). Responders to prednisolone had ~56-60% higher (p-value 0.032-0.044) serum ratios to cholesterol of phytosterols, while the lathosterol/campesterol ratio was ~76% (p = 0.031) lower compared to nonresponders. Stigmasterol/cholesterol predicted response to corticosteroid therapy. Surrogate markers of cholesterol synthesis (lathosterol and desmosterol) inversely reflected those of absorption (cholestanol and phytosterols) in PSC and controls (r-range -0.247 to -0.559, p < 0.01 for all), contrary to AH patients, among whom this reciprocal regulation was partially recovered on day 90 (lathosterol: r-range -0.733 to -0.952, p < 0.05 for all). AH patients had ~26% lower lathosterol/cholesterol, but 1.13-3.87-fold higher cholestanol/cholesterol and sitosterol/cholesterol compared to control groups (p < 0.05 for all). Median ferritin concentration at baseline was ~37% lower (p = 0.011) among the responders. Cholesterol precursors and phytosterols have a disease-specific profile in AH. Phytosterols and ferritin may serve as surrogate markers for short-term response.
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2.
Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial.
Ferguson, JJA, Stojanovski, E, MacDonald-Wicks, L, Garg, ML
Metabolism: clinical and experimental. 2018;:22-35
Abstract
BACKGROUND Dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatory effects in preclinical studies, however, consistent findings in humans are lacking. OBJECTIVE Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatory effects to optimise cardio-protection. The objective of this trial was to investigate the effects of dietary intervention with PS with or without curcumin on blood lipids (primary outcome) in hypercholesterolaemic individuals. METHODS A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d-200 mg/d respectively) for four weeks. Primary outcomes included fasting total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fasting blood glucose concentrations. RESULTS Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC, LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC and LDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC and LDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) and LDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and TG concentrations remained unchanged across all groups. No adverse side effects were reported. CONCLUSIONS The addition of curcumin to phytosterol therapy provides a complementary cholesterol-lowering effect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhanced lipid-lowering and compliance in hypercholesterolaemic individuals. ANZCTR identifier: 1261500095650.
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3.
Effects on oral fat load of a nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols: A randomized, placebo controlled trial.
Derosa, G, Catena, G, Raddino, R, Gaudio, G, Maggi, A, D'Angelo, A, Maffioli, P
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;:75-82
Abstract
BACKGROUND In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking. PURPOSE We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day. METHODS We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load. RESULTS Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination. CONCLUSIONS The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.
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A positive impact on the serum lipid profile and cytokines after the consumption of a plant sterol-enriched beverage with a milk fat globule membrane: a clinical study.
Alvarez-Sala, A, Blanco-Morales, V, Cilla, A, Silvestre, RÁ, Hernández-Álvarez, E, Granado-Lorencio, F, Barberá, R, Garcia-Llatas, G
Food & function. 2018;(10):5209-5219
Abstract
The hypocholesterolemic effect and the modification of serum biomarkers of a dietary plant sterol (PS) intake, cholesterol precursors and cytokines after the consumption of milk-based fruit beverages with a milk fat globule membrane were evaluated by a randomized, double-blind, crossover, multiple dose bioavailability study. Postmenopausal women (n = 38) consumed daily 250 mL of a beverage with or without 2 g of PS added during 6 weeks in each of the study periods. With the intake of the PS-added beverage, significant decreases (mg dL-1) in serum total cholesterol (pre-treatment: 220.0 ± 27.8 vs. post-treatment: 212.9 ± 25.8; p < 0.05) and LDL-cholesterol (129.4 ± 28.5 vs. 121.7 ± 24.4; p < 0.05) were detected. The cholesterol precursor lathosterol (11.2%), markers of the dietary PS intake (campesterol 43.1% and β-sitosterol 32.5%), and anti-inflammatory IL-10 cytokine (22.5%) increased significantly, with a concomitant significant reduction in pro-inflammatory IL-1β (6.7%). No variations in HDL-cholesterol, other sterols (desmosterol and stigmasterol) or cytokines (IL-6, IL-8, IL-12p70 and TNF-α) were detected. These results indicated that this kind of PS-enriched milk-based fruit beverage is suitable during the period of clinical intervention, and its consumption may be an adequate way to improve PS functionality since a significant reduction in cholesterol levels has been observed. Therefore, the intake of this beverage could contribute to reduce the risk of cardiovascular disease also obtaining a beneficial effect on the serum inflammatory status in postmenopausal women.
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The maternal-fetal gradient of free and esterified phytosterols at the time of delivery in humans.
Correani, A, Visentin, S, Cosmi, E, Ponchia, E, D'Aronco, S, Simonato, M, Vedovelli, L, Cogo, P, Carnielli, VP
Clinical nutrition (Edinburgh, Scotland). 2018;(6 Pt A):2107-2112
Abstract
BACKGROUND High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited. OBJECTIVE To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans. DESIGN PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7α-hydroxycholesterol, 7α-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference. RESULTS Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p < 0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p < 0.01), and between total FA and Camp of MB (p < 0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p < 0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p < 0.05). Chol synthesis, as indicated by 7-DHChol to 7α-OHChol, Latho to 7α-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA. CONCLUSION Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated.
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Plasma Phytosterol Half-Life and Levels Are Increased in Very Low Birth Weight Preterm Infants with Parenteral Nutrition-Associated Cholestasis.
Correani, A, Pignotti, A, Marinelli, L, Biagetti, C, D'Ascenzo, R, Vedovelli, L, Verlato, G, Cogo, P, Rocchi, MBL, Carnielli, VP
Lipids. 2018;(7):717-725
Abstract
Parenteral nutrition-associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable-oil-based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half-life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty-seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half-lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 ±6.2 vs 11.8 ±3.0 days, p = 0.001; Stigma: 13.8 ±5.8 vs 9.4 ±3.4 days, p = 0.023; Sito: 15.3 ±5.0 vs 9.8 ±3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC.
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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.