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1.
Virgin Olive Oil Phenolic Compounds Modulate the HDL Lipidome in Hypercholesterolaemic Subjects: A Lipidomic Analysis of the VOHF Study.
Fernández-Castillejo, S, Pedret, A, Catalán, Ú, Valls, RM, Farràs, M, Rubió, L, Castañer, O, Macià, A, Fitó, M, Motilva, MJ, et al
Molecular nutrition & food research. 2021;(9):e2001192
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Abstract
SCOPE The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. METHODS AND RESULTS A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. CONCLUSION VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.
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A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9.
Zeitlinger, M, Bauer, M, Reindl-Schwaighofer, R, Stoekenbroek, RM, Lambert, G, Berger-Sieczkowski, E, Lagler, H, Oesterreicher, Z, Wulkersdorfer, B, Lührs, P, et al
European journal of clinical pharmacology. 2021;(10):1473-1484
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Abstract
PURPOSE AT04A and AT06A are two AFFITOPE® peptide vaccine candidates being developed for the treatment of hypercholesterolemia by inducing proprotein convertase subtilisin/kexin type 9 (PCSK9)-specific antibodies. This study aimed to investigate safety, tolerability, antibody development, and reduction of low-density lipoprotein cholesterol (LDLc) following four subcutaneous immunizations. METHODS This phase I, single-blind, randomized, placebo-controlled study was conducted in a total of 72 healthy subjects with a mean fasting LDLc level at baseline of 117.1 mg/dL (range 77-196 mg/dL). Each cohort enrolled 24 subjects to receive three priming immunizations at weeks 0, 4, and 8 and to receive a single booster immunization at week 60 of either AT04A, AT06A, or placebo. In addition to safety (primary objective), the antigenic peptide- and PCSK9-specific antibody response and the impact on LDLc were evaluated over a period of 90 weeks. RESULTS The most common systemic treatment-related adverse events (AEs) reported were fatigue, headache, and myalgia in 75% of subjects in the AT06A group and 58% and 46% of subjects in the placebo and AT04A groups, respectively. Injection site reactions (ISR) representing 63% of all treatment-emergent adverse events (TEAEs), were transient and mostly of mild or moderate intensity and rarely severe (3%). Both active treatments triggered a robust, long-lasting antibody response towards the antigenic peptides used for immunization that optimally cross-reacted with the target epitope on PCSK9. In the AT04A group, a reduction in serum LDLc was observed with a mean peak reduction of 11.2% and 13.3% from baseline compared to placebo at week 20 and 70 respectively, and over the whole study period, the mean LDLc reduction for the AT04A group vs. placebo was -7.2% (95% CI [-10.4 to -3.9], P < 0.0001). In this group, PCSK9 target epitope titers above 50 were associated with clinically relevant LDLc reductions with an individual maximal decrease of 39%. CONCLUSIONS Although both AT04A and AT06 were safe and immunogenic, only AT04A demonstrated significant LDLc-lowering activity, justifying further development. TRIAL REGISTRATION EudraCT: 2015-001719-11. ClinicalTrials.gov Identifier: NCT02508896.
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Artichoke and Bergamot Phytosome Alliance: A Randomized Double Blind Clinical Trial in Mild Hypercholesterolemia.
Riva, A, Petrangolini, G, Allegrini, P, Perna, S, Giacosa, A, Peroni, G, Faliva, MA, Naso, M, Rondanelli, M
Nutrients. 2021;(1)
Abstract
Botanicals are natural alternatives to pharmacological therapies that aim at reducing hypercholesterolemia. In this context, despite bergamot being effective in modulating lipid profile, some subjects failed to achieve a satisfactory response to supplementation. The aim of this study was to evaluate whether the association of 600 mg of bergamot phytosome® (from Citrus Bergamia Risso) and 100 mg of artichoke leaf standardized dry extract (from Cynara cardunculus L.) can be an alternative in patients with mild hypercholesterolemia who are poor responders to bergamot in a 2-month randomized placebo-controlled trial. Sixty overweight adults were randomized into two groups: 30 were supplemented and 30 received a placebo. The metabolic parameters and DXA body composition were evaluated at the start, after 30 and 60 days. Between the two groups, total and LDL cholesterol in the supplemented group (compared to placebo) showed significant decreases overtime. A significant reduction of waist circumference and visceral adipose tissue (VAT) was recorded in the supplemented group (compared to placebo), even in subjects who did not follow a low-calorie diet. In conclusion, the synergism between Citrus Bergamia polyphenols and Cynara cardunculus extracts may be an effective option and may potentially broaden the therapeutic role of botanicals in dyslipidemic patients.
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Effect of a dietary intervention with functional foods on LDL-C concentrations and lipoprotein subclasses in overweight subjects with hypercholesterolemia: Results of a controlled trial.
Vázquez-Manjarrez, N, Guevara-Cruz, M, Flores-López, A, Pichardo-Ontiveros, E, Tovar, AR, Torres, N
Clinical nutrition (Edinburgh, Scotland). 2021;(5):2527-2534
Abstract
BACKGROUND & AIMS Cardiovascular diseases (CVDs) are the leading cause of global death. Hypercholesterolemia is among the main risk factors for developing cardiovascular events, and is highly prevalent in the Mexican population. The primary objective of the present work was to assess the effect of a dietary portfolio (DP) with functional foods containing dehydrated nopal, soy protein, chia seeds, inulin, and oats in LDL-C and TC concentrations of subjects with mild hypercholesterolemia. Also, we explored the changes in the profile of the lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy (NMR). METHODS Sixty-two subjects (47 women, 15 men) with mild hypercholesterolemia (LDL-C, ≥130 ≤ 190 mg/dL, TC > 200 mg/dL) completed the randomized, parallel, controlled study. The dietary intervention was given in two stages. First, a dietary standardization stage with a low saturated fat diet (LSFD) which matched the habitual energy intake of the volunteers for 2-weeks, followed by 2.5 months of dietary intervention with a LSFD plus placebo (PL) or DP. RESULTS Subjects who consumed the LSFD + DP interventions had a significantly higher reduction of LDL-C (-18.05%, P = 0.003) and TC (-17.08%, P = 0.02) compared to volunteers who consumed an LSFD for the same period. Furthermore, the lipoprotein subclass profiling showed that the small low-density-lipoproteins, and the small high-density-lipoproteins significantly decreased (P = 0.04, P < 0.001, respectively), conveying a less atherogenic state. At the end of the study, 78% of the subjects who consumed LSFD + DP reduced their LDL-C below 160 mg/dL, and of these, 47% reduced it below 130 mg/dL. CONCLUSIONS Based on the results obtained from this study, the inclusion of functional foods as part of the lifestyle modifications is recommended to treat mild hypercholesterolemia and reduce cardiovascular risk. Registered under ClinicalTrials.gov Identifier no. NCT04148976.
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Bergamot phytosome improved visceral fat and plasma lipid profiles in overweight and obese class I subject with mild hypercholesterolemia: A randomized placebo controlled trial.
Rondanelli, M, Peroni, G, Riva, A, Petrangolini, G, Allegrini, P, Fazia, T, Bernardinelli, L, Naso, M, Faliva, MA, Tartara, A, et al
Phytotherapy research : PTR. 2021;(4):2045-2056
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Abstract
Bergamot has been traditionally used for the relief of diseases related to oxidative stress. Our aim was to investigate the effect of bergamot phytosome on visceral adipose tissue (VAT) and on metabolic profile, in overweight and obese subjects with mild hypercholesterolemia. A total of 64 participants were randomized into two groups for 12 weeks: a supplemented group (33 individuals, BMI 27 ± 3 kg/m2 receiving 500 mg of bergamot phytosome, two daily tablets) and placebo group (31 subjects, BMI 28 ± 3 kg/m2 , two daily tablets). As to the within differences, the parameters of VAT, total and LDL-cholesterol were significantly decreased in the bergamot phytosome group, but not in the placebo group. As to between-group differences, a statistically significant interaction between time and group, that is, the change in score over time differs between the two groups was observed 30 days after supplementation for VAT (p-value = .005), total cholesterol (p-value <.0002), and LDL (p = .004) in respect to placebo. The other parameters (glucose, insulin, Homeostasis Model Assessment, high-density lipoprotein cholesterol, triglycerides, fat free mass, fat mass) were not significant. In conclusion, this clinical study gives evidence that bergamot phytosome provides beneficial effects, such as decrease of VAT and modulation of metabolic alterations, after just 30 days of supplementation, resulting a very promising protection of cardiovascular health.
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Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.
Lee, HY, Han, KH, Chung, WB, Her, SH, Park, TH, Rha, SW, Choi, SY, Jung, KT, Park, JS, Kim, PJ, et al
Clinical therapeutics. 2020;(10):2036-2048
Abstract
PURPOSE Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). METHODS In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. FINDINGS Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). IMPLICATIONS The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.
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Supplementation with Cynanchum wilfordii radix extract for 8 weeks lowers serum total cholesterol: A controlled, randomized, double-blind clinical trial.
Shin, SM, Cho, YM, Kwon, JE, Lee, SR, Kang, SC
Phytotherapy research : PTR. 2020;(9):2313-2322
Abstract
This trial aimed to determine the effect of a standardized Cynanchum wilfordii Radix extract (CWE) on the lipid profiles of individuals with elevated total cholesterol (T-Chol) using a double-blind randomized placebo-controlled design. Ninety-six Korean individuals with elevated T-Chol level (200-240 mg/dL) were recruited and randomly allocated to groups that received VasH300 (300 mg CWE/day, n = 32), VasH600 (600 mg CWE/day, n = 32), or a placebo (n = 32) groups. Primary outcomes included T-Chol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, and safety (adverse events, biochemical parameters, and hematological parameters). Data were compared using a one-way analysis of variance followed by Duncan's post-hoc tests (among groups) and paired t tests (within groups). Values for T-Chol and LDL-cholesterol were significantly reduced in the VasH300 and groups (VasH300: 4.0 and 6.4%, respectively; VasH600; 3.8 and 5.8% respectively; both p < .05) compared with the placebo group and were not dose-dependent. VasH300 significantly improved the lipid profiles of individuals with elevated T-Chol without any serious side effects. Daily supplementation with VasH might be an alternative strategy with which to modify cholesterol-related parameters, especially in individuals with elevated T-Chol levels.
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Making Informed CHOICES: The Launch of a "Big Data" Pragmatic Trial to Improve Cholesterol Management and Prevent Heart Disease in Ontario.
Ferreira-Legere, LE, Chu, A, Rashid, M, Sivaswamy, A, O'Neill, T, Marquez, C, Baddeliyanage, R, Straus, S, Udell, JA
Healthcare quarterly (Toronto, Ont.). 2020;(4):6-9
Abstract
Cholesterol-lowering statin medications are a safe and effective therapy to lower cholesterol and reduce the risk of cardiovascular events. Yet physician prescribing patterns and patient adherence remain suboptimal in Canada and the United States, often due to pervasive misconceptions. The Community Heart Outcomes Improvement and Cholesterol Education Study (CHOICES) is a pragmatic, registry-based, cluster randomized controlled trial that aims to improve cholesterol management through appropriate statin use in adults and to ultimately reduce cardiovascular events in high-risk communities across Ontario. The trial uses an innovative, multicomponent intervention and implementation approach that includes audit and feedback reports for family physicians and educational materials and tools for patients.
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Efficacy and tolerability of a nutraceutical combination of red yeast rice, guggulipid, and chromium picolinate evaluated in a randomized, placebo-controlled, double-blind study.
Iskandar, I, Harahap, Y, Wijayanti, TR, Sandra, M, Prasaja, B, Cahyaningsih, P
Complementary therapies in medicine. 2020;:102282
Abstract
Hypercholesterolemia is the major risk factor in the development of coronary heart disease. Coronary heart disease is a leading cause of morbidity and mortality in many countries worldwide. An increasing attention is now paid to nutraceuticals development for prevention and cure of dyslipidemia, especially for patients who do not wish to use chemical statins. The cholesterol lowering effect and the tolerability of NutraforChol®, a nutraceutical product containing red yeast rice extract, guggulipid extract and chromium picolinate, was evaluated on subjects who had total cholesterol level 200-239 mg/dL and LDL cholesterol level 100-159 mg/dL. In this study, a randomized, placebo-controlled, double-blind study which consisted of 4 weeks run-in period and 8 weeks treatment period was performed. Based on the study results, NutraforChol® effectively decreased total cholesterol (-15.9 %) and LDL level (-19.9 %) after two weeks consumption. The total cholesterol and LDL reduction were maintained during 8 weeks study period. At study termination (week 8), there was a significant difference between total cholesterol level of NutraforChol® treated group (173.5 ± 21.7 mg/dL) and placebo-treated group (204.5 ± 22.8 mg/dL) (p < 0.05). In addition, there was a significant difference between LDL level at week 8 in NutraforChol® group (115.5 ± 22.2 mg/dL) and placebo-treated group (145.1 ± 23.7 mg/dL) (p < 0.05). The tolerability of NutraforChol® was also evaluated. There were no significant changes (p > 0.05) on renal and liver function parameters between baseline and study termination. Thus, NutraforChol® may be considered as a complementary or alternative safe nutraceuticals for the treatment of mild dyslipidemic subjects.
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Moderate consumption of a soluble green/roasted coffee rich in caffeoylquinic acids reduces cardiovascular risk markers: results from a randomized, cross-over, controlled trial in healthy and hypercholesterolemic subjects.
Martínez-López, S, Sarriá, B, Mateos, R, Bravo-Clemente, L
European journal of nutrition. 2019;(2):865-878
Abstract
PURPOSE Coffee is rich in bioactive compounds with health beneficial properties, with green coffee presenting higher phenol content than roasted. We evaluated the effects of regularly consuming realistic amounts of a green/roasted coffee blend on cardiovascular health-related biomarkers. METHODS A randomized, cross-over, controlled study was carried out in 25 normocholesterolemic [total cholesterol (TC) < 200 mg/dL] and 27 hypercholesterolemic (TC 200-240 mg/dL) subjects. During 8 weeks, volunteers consumed 6 g/day of soluble green/roasted (35:65) coffee or a control beverage (water or an isotonic drink). Blood pressure, heart rate and body weight were monitored at the end of each intervention, and serum lipids [TC, HDL-C, LDL-C, VLDL-C, triglycerides and phospholipids], cytokines and chemokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCP-1, MIP-1β, TNF-α, INF-γ), adhesion molecules (ICAM-1, VCAM-1), and C-reactive protein were measured. Plasma antioxidant capacity (FRAP, ORAC and ABTS methods), and lipid (malondialdehyde, MDA) and protein (carbonyl groups, CG) oxidation were also determined. RESULTS Attending to the general lineal model of variance for repeated measures, after the green/roasted coffee intervention significant reductions in TC, LDL-C, VLDL-C and triglycerides levels (p = 0.006, 0.001, 0.003 and 0.017, respectively), and a significant group effect were observed (0.001, < 0.001, 0.019 and 0.027, respectively). Only within the hypercholesterolemic group, attending to the Bonferroni test, the aforementioned lipid parameters were significantly lower after regular green/roasted coffee intake compared to baseline values. Moreover, after the coffee stage, plasma antioxidant capacity improved, according to the increase in ORAC and FRAP values (p < 0.001 and p < 0.001, respectively) and decrease of MDA (p = 0.015) and CG (p < 0.001) levels, without differences between groups. Systolic (p = 0.001) and diastolic (p < 0.001) blood pressure, heart rate (p = 0.035), and body weight (p = 0.017) were reduced in both normo- and hypercholesterolemic groups. CONCLUSION Regular consumption of moderate amounts of a soluble green/roasted (35:65) coffee blend may contribute to improve cardiovascular health in moderately hypercholesterolemic people, as reducing serum lipids, blood pressure and body weight effects, as well as increasing plasma antioxidant capacity, have been observed. Moreover, positive influences on blood pressure, body weight, and plasma antioxidant capacity were obtained in the healthy group. Therefore, incorporation of green coffee beans into the coffee brew can be recommended as part of a dietary strategy to protect from cardiovascular disease.