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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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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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Effects of Daily Consumption of an Aqueous Dispersion of Free-Phytosterols Nanoparticles on Individuals with Metabolic Syndrome: A Randomised, Double-Blind, Placebo-Controlled Clinical Trial.
Palmeiro-Silva, YK, Aravena, RI, Ossio, L, Parro Fluxa, J
Nutrients. 2020;(8)
Abstract
Metabolic syndrome (MS) affects up to 40% of the population and is associated with heart failure, stroke and diabetes. Phytosterols (PS) could help to manage one or more MS criteria. The purpose of this study was to evaluate the therapeutic effect of daily supplementation of an aqueous dispersion of 2 g of free-phytosterols nanoparticles in individuals with MS over six months of intervention, compared with placebo. This double-blind study included 202 participants with MS randomly assigned into phytosterol (n = 102) and placebo (n = 100) groups. Participants were assessed at baseline, 4, 12 and 24 weeks. General health questions, anthropometric measurements and blood parameters were analysed. At week 24, the proportion of participants with high triglycerides (≥150 mg/dL) in the phytosterol group was 15.65% lower than in the placebo group (p-value = 0.023). Similarly, half of the participants in the phytosterol group decreased their waist circumference up to 4 cm compared with 0 cm in the placebo group (p-value = 0.0001). We reported no adverse effects (diarrhoea or vitamin D reduction); nonetheless, almost 70% of participants in the phytosterol group self-reported an improvement in bowel habits. Daily intake of free-PS nanoparticles improved some MS criteria; therefore, it might be a promising adjuvant therapy for individuals with MS (NCT02969720).
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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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Phytosterols Supplementation Reduces Endothelin-1 Plasma Concentration in Moderately Hypercholesterolemic Individuals Independently of Their Cholesterol-Lowering Properties.
Oliveira Godoy Ilha, A, Sutti Nunes, V, Silva Afonso, M, Regina Nakandakare, E, da Silva Ferreira, G, de Paula Assis Bombo, R, Rodrigues Giorgi, R, Marcondes Machado, R, Carlos Rocha Quintão, E, Lottenberg, AM
Nutrients. 2020;(5)
Abstract
Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNFα, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (-5,5%, p < 0.001), LDL-c (-6.4%, p < 0.05), triglycerides (-8.3%, p < 0.05), and apo B (-5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.
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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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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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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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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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Phytosterol nutritional supplement improves pregnancy and neonatal complications of gestational diabetes mellitus in a double-blind and placebo-controlled clinical study.
Gao, F, Wang, G, Wang, L, Guo, N
Food & function. 2017;(1):424-428
Abstract
Gestational diabetes mellitus (GDM) is an increasingly serious health problem among pregnant women. Phytosterol-enriched spreads are known to reduce total cholesterol (TC) and low-density lipoprotein (LDL), but little is known about their effects on GDM. We aimed to examine the effect of the daily consumption of phytosterol-enriched spreads on both the maternal and neonatal outcomes of GDM patients. GDM patients during the third trimester of pregnancy were enrolled and assigned randomly to consume a regular spread or phytosterol-enriched spread daily until the end of their pregnancy. Maternal diabetic symptoms such as serum lipid profile, glucose and insulin metabolisms, as well as neonatal complications, were analyzed at the beginning and full-term. The daily consumption of the phytosterol-enriched spread exhibited significant beneficial effects on maternal diabetic symptoms, in terms of improved lipid compositions and glucose metabolism. Moreover, the incidence of neonatal complications was also significantly reduced by the phytosterol-enriched spread, in terms of birth weight, macrosomia, hypoglycemia, respiratory distress and Apgar scores. The daily consumption of a phytosterol-enriched spread is able to improve both the maternal and neonatal outcomes in GDM patients.