-
1.
The effect of vitamin D supplementation on flow-mediated dilatation, oxidized LDL and intracellular adhesion molecule 1 on type 2 diabetic patients with hypertension: A randomized, placebo-controlled, double-blind trial.
Qasemi, R, Ghavamzadeh, S, Faghfouri, AH, Valizadeh, N, Mohammadi, A, Sayyadi, H
Diabetes & metabolic syndrome. 2021;(4):102200
Abstract
AIMS: Current study aimed to evaluate the effect of vitamin D supplementation on flow-mediated dilatation (FMD), oxidized LDL (oxLDL) and intracellular adhesion molecule 1 (ICAM1) in type 2 diabetic patients with hypertension. METHODS In a double-blinded, placebo-controlled trial, 44 patients were randomly divided into vitamin D group (2000 IU/d, n = 23) and placebo group (control, n = 21) for 12 weeks. Vascular function with FMD, Serum 25-OH vitamin D, oxLDL and ICAM1 were assessed at the baseline and after the intervention. This clinical trial was registered at Iranian Registry of Clinical Trials (IRCT20191223045861N1). RESULTS In intervention group serum level of vitamin D increased from 32.42 ± 10.56 to 40.45 ± 12.94 (p < 0.001). In the vitamin D group, oxLDL and ICAM1 significantly decreased and FMD increased significantly in both groups (p < 0.001). The level of oxLDL (p = 0.017) and ICAM1 (p < 0.001) were significantly lower in the vitamin D group than the placebo group and FMD (p < 0.001) was significantly higher in the vitamin D group. CONCLUSIONS Vitamin D supplementation of 2000 IU/d for 12 weeks can improve endothelial function and decrease ICAM1 and oxLDL in type 2 diabetic patients with hypertension.
-
2.
Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome.
Guevara-Cruz, M, Flores-López, AG, Aguilar-López, M, Sánchez-Tapia, M, Medina-Vera, I, Díaz, D, Tovar, AR, Torres, N
Journal of the American Heart Association. 2019;(17):e012401
Abstract
Background Metabolic syndrome (MetS) is a serious health problem over the world; thus, the aim of the present work was to develop a lifestyle intervention to decrease the dysbiosis of gut microbiota and reduce the biochemical abnormalities of MetS. Methods and Results The prevalence of MetS was evaluated in 1065 subjects of Mexico City, Mexico, and the gut microbiota in a subsample. Subjects with MetS were selected for a pragmatic study based on a lifestyle intervention with a low-saturated-fat diet, reduced-energy intake, with functional foods and physical activity, and a second group was selected for a randomized control-placebo study to assess the gut microbiota after the dietary intervention. Prevalence of MetS was 53%, and the higher the body mass index, the higher the gut microbiota dysbiosis. The higher the Homeostatic Model Assessment for Insulin Resistance, the lower the high-density lipoprotein cholesterol concentration. The pragmatic study revealed that after 15 days on a low-saturated-fat diet, there was a 24% reduction in serum triglycerides; and after a 75-day lifestyle intervention, MetS was reduced by 44.8%, with a reduction in low-density lipoprotein cholesterol, small low-density lipoprotein particles, glucose intolerance, lipopolysaccharide, and branched-chain amino acid. The randomized control-placebo study showed that after the lifestyle intervention, there was a decrease in the dysbiosis of the gut microbiota associated with a reduction in the Prevotella/ Bacteroides ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Conclusions A lifestyle intervention significantly decreased MetS components, small low-density lipoprotein particle concentration, gut microbiota dysbiosis, and metabolic endotoxemia, reducing the risk of atherosclerosis. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03611140.
-
3.
A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: a randomised, double-blind, placebo-controlled trial.
Hermans, N, Van der Auwera, A, Breynaert, A, Verlaet, A, De Bruyne, T, Van Gaal, L, Pieters, L, Verhoeven, V
Trials. 2017;(1):302
Abstract
BACKGROUND Metabolic syndrome (MetS) refers to clustered cardiovascular risk factors (abdominal obesity, pre-diabetes, high blood pressure, dyslipidaemia). Therapies targeting oxidative stress may delay progression to atherosclerosis and diabetes. We investigated the anti-oxidative effect of a supplement combining red yeast rice and olive extract in patients with MetS. METHODS A double-blind, placebo-controlled, randomised trial was conducted with 50 patients with MetS as defined by National Cholesterol Education Program Adult Treatment Panel III criteria. Forty-nine subjects randomly assigned to red yeast rice-olive extract (RYR-olive extract; 10.82 mg of monacolins and 9.32 mg of hydroxytyrosol per Cholesfytolplus capsule) or placebo completed the 8-week trial. Whereas effects on cardiovascular risk parameters of MetS have been reported recently, the observed significant 20% increase in oxidised low-density lipoprotein (OxLDL) prompted us to investigate other oxidative stress-related parameters: malondialdehyde (MDA), lipoprotein-associated phospholipase A2 (Lp-PLA2) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Statistical calculations included univariate quantitative analysis, multivariate linear regression and correlation analysis. RESULTS The updated results indicate that an RYR-olive extract supplement significantly reduced Lp-PLA2 by 7% (p < 0.001), but it failed to show a significant decrease in plasma MDA and 8-OHdG (p > 0.05). Reductions in OxLDL (20%) and Lp-PLA2 (7%) were associated with each other (r = 0.740, p < 0.001). CONCLUSIONS RYR-olive extract significantly reduced Lp-PLA2 in correlation with the marked reduction in plasma OxLDL, which may lead to a reduced risk for cardiovascular disease in patients with MetS. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02065180 . Registered on 13 February 2014.
-
4.
PCSK9 inhibitors: the next frontier in low-density lipoprotein lowering.
Jialal, I, Patel, SB
Metabolic syndrome and related disorders. 2015;(3):99-101
Abstract
The discovery and elucidation of the role of the low-density lipoprotein receptor (LDL-R) in familial hypercholesterolemia (FH) ushered in the statin group of drugs. These drugs, in addition to lowering low-density lipoprotein cholesterol (LDL-C), result in a significant reduction in cardiovascular events (CVE) and mortality. Recently, a gain-of-function mutation in another protein, proprotein convertase subtilisin/kexin type 9 (PCSK9), was reported to result in a FH phenotype by promoting degradation of the LDL-R. More importantly, loss-of-function mutations in the same gene resulted in low LDL-C and a reduction in CVE, making this an enticing target for drug development. Numerous strategies have been developed to target PCSK9, the most successful being monoclonal antibodies (mAbs) that bind PCSK9. These mAbs have been shown to reduce LDL-C around 50% as either monotherapy with diet or in combination with statin therapy. In this short perspective, we discuss the biochemistry and biology of PCSK9 in relation to lipid metabolism and the promising studies in humans demonstrating a substantial reduction in LDL-C with relative good short-term safety of PCSK9 mAbs.
-
5.
Postpartum weight retention is associated with elevated ratio of oxidized LDL lipids to HDL-cholesterol.
Puhkala, J, Luoto, R, Ahotupa, M, Raitanen, J, Vasankari, T
Lipids. 2013;(12):1227-35
Abstract
Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and counselling during pregnancy). During early pregnancy (8-12 weeks) and 1 year postpartum, 141 women participated in measurements for determining of plasma lipids: total cholesterol (T-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triacylglycerols (TAG) and ox-LDL. Subjects were stratified into tertiles (weight loss, unaltered weight and weight gain groups) based on their weight change from baseline to follow-up. Ox-LDL was determined by baseline level of conjugated dienes in LDL lipids. Among the group of weight gainers, concentration of TAG reduced less (-0.14 vs. -0.33, p = 0.002), HDL-C reduced more (-0.31 vs. -0.16, p = 0.003) and ox-LDL/HDL-C ratio increased (3.0 vs. -0.2, p = 0.003) when compared to group of weight loss. Both T-C and LDL-C elevated more (0.14 vs. -0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox-LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs. -0.68, p = 0.026) in unaltered weight group compared to weight loss group. The women who gained weight developed higher TAG and ox-LDL/HDL-C ratio as compared to those who lost weight. Postpartum weight retention of 3.4 kg or more is associated with atherogenic lipid profile.
-
6.
Consumption of polyphenol-rich juar tea increases endothelium-bound extracellular superoxide dismutase levels in men with metabolic syndrome: link with LDL oxidizability.
Uto-Kondo, H, Ayaori, M, Kishimoto, Y, Adachi, T, Takiguchi, S, Yakushiji, E, Sasaki, M, Komatsu, T, Kondo, K, Ikewaki, K
International journal of food sciences and nutrition. 2013;(4):407-14
Abstract
Endothelium-bound extracellular superoxide dismutase (eEC-SOD), a major antioxidative enzyme in the vasculature, is involved in anti-atherogenesis by inhibiting low-density lipoprotein (LDL) oxidation. The objective was to investigate whether the polyphenol-rich juar tea had beneficial effects on LDL oxidation and eEC-SOD levels in patients with metabolic syndrome (MetS). A total of 20 men with MetS participated in a randomized cross-over trial, comparing consumption of five cups/day of juar tea with that of a polyphenol-poor tea, barley tea, for 4 weeks. Although there was no change in LDL oxidizability after consumption of either tea, juar tea significantly increased eEC-SOD levels by 16% (p < 0.05), whereas barley tea significantly decreased levels by 15% (p < 0.05). It is noteworthy that the changes in eEC-SOD were positively associated with those in LDL oxidizability after tea consumption (r(2) = 0.11, p < 0.05). Tea polyphenols may provide anti-atherosclerotic effects by inhibiting LDL oxidation through EC-SOD bound to the endothelium.
-
7.
Lipid and low-density-lipoprotein apheresis. Effects on plasma inflammatory profile and on cytokine pattern in patients with severe dyslipidemia.
Stefanutti, C, Morozzi, C, Petta, A
Cytokine. 2011;(3):842-9
Abstract
Available evidence on the effects of therapeutic plasmapheresis (TP) techniques and in particular lipid- and LDL-apheresis (LDL-a) on plasmatic inflammatory mediators including cytokines were reviewed. Studies on this issue are not numerous. However, the review of existing evidence clearly suggests an active role of apheresis on the profile of inflammatory molecules and on cytokine pattern in plasma. These non-lipid-lowering effects can be defined to some extent pleiotropic or pleiotropic-equivalent. Although further studies are desirable, the data reported in this review confirm that lipid- and LDL-a not only show acute lipid-lowering and cholesterol-lowering effects, but also efficacy in reducing several proinflammatory peptides, including cytokines. This effect was not related apparently to lipids and lipoproteins reduction. Thus, TP (lipid- and LDL-a), commonly utilized in the treatment of severe genetically determined lipid disorders, unresponsive to hypolipidemic drugs, offers new possibilities of interpretation of its role in the mechanisms leading to the blockade of atherosclerotic lesion development and progression. The ability of TP on short-term to induce such a profound change in the plasmatic metabolic and inflammatory profiles must be kept in mind in the treatment of acute coronary syndromes, before and after interventions of coronary revascularization, and in the acute phase of cerebrovascular ischemia, at least in patients with severe dyslipidemia. Further studies are needed, in particular aimed at assessing if circulating cytokines may be downregulated by TP not only by direct removal, but through indirect effects on both gene translation and transcription perhaps via the cytokine receptor function.
-
8.
Long-term effect of betaine on risk factors associated with the metabolic syndrome in healthy subjects.
Schwab, U, Alfthan, G, Aro, A, Uusitupa, M
European journal of clinical nutrition. 2011;(1):70-6
Abstract
BACKGROUND/OBJECTIVES To examine the effects of betaine on serum lipid profile, plasma homocysteine concentration and hemostatic factors in healthy subjects. SUBJECTS/METHODS Altogether, 63 volunteers (27 ± 8 years, body mass index 22.6 ± 2.4 kg/m(2)) participated in a placebo-controlled, randomized, parallel double-blinded study. The intervention lasted for 6 months during which the subjects consumed mineral water 500 ml/day with (betaine group, n = 32) or without (control group, n = 31) a 4-g betaine supplementation. RESULTS There was a significant interaction of time and group (general linear model) in serum total and low-density lipoprotein (LDL)-cholesterol concentrations and total-to-high-density lipoprotein (HDL)-cholesterol ratio without a significant difference between or within the groups. Concentrations of serum HDL-cholesterol, triglycerides or oxidized LDL did not change during the study. Plasma homocysteine concentration did not change in either of the groups. Plasma plasminogen activator inhibitor 1 concentration increased in the betaine group (P = 0.028) and decreased in the control group (P = 0.006). There was a significant interaction of time and group (general linear model) in plasma fibrinogen and blood hemoglobin concentration without a significant difference between or within the groups. There were no changes in parameters regarding the function of the liver or kidney. CONCLUSIONS Betaine had no effect on serum lipid profile in long term in young healthy subjects. The lowering effect on plasma homocysteine concentration was weak.
-
9.
Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial.
Solà, R, Bruckert, E, Valls, RM, Narejos, S, Luque, X, Castro-Cabezas, M, Doménech, G, Torres, F, Heras, M, Farrés, X, et al
Atherosclerosis. 2010;(2):630-7
Abstract
UNLABELLED The objective was to evaluate whether the soluble fibre Plantago ovata (Po)-husk improves cardiovascular disease (CVD) risk biomarkers including low-density lipoprotein cholesterol (LDL-C). METHODS In a multi-centred, double-blind, placebo-controlled, parallel, randomised trial conducted in primary care-clinics in Spain, France and Holland, mild-moderate hypercholesterolaemic patients (age range: 43-67 years) received 14 g/d of Po-husk (n=126) or placebo (microcrystalline-cellulose 14 g/d; n=128) in a low saturated fat diet for 8 weeks. Subsequently, if LDL-C remained > or = 3.35 mmol/L [130 mg/dL], participants proceeded with the fibre plus simvastatin (20mg/d) for further 8 weeks. Lipid profile, blood pressure (BP), insulin, oxidised LDL and some gene polymorphisms involved in CVD risk were measured. RESULTS Relative to placebo, Po-husk reduced plasma LDL-C by -6% (P<0.0002), total cholesterol (TC) by -6%, triglycerides (TG) by -21.6%, apolipoprotein (Apo) B-100 by -6.7%, oxidised LDL by a mean of -6.82 U/L (95%CI: 3.15-10.48), insulin by -4.68 pmol/L (95%CI: 0.68-8.67) and systolic BP by -4.0mm Hg (95%CI; 1.2-6.7) (P<0.05). The TG-lowering effect in the Po-husk group was magnified by variants in plasminogen-activator-inhibitor (PAI-1; rs1799768) and fatty acid-binding protein (FABP-2; rs1799883) genes. At 16 weeks, the intra-group action of simvastatin (20mg/d) added to Po-husk or placebo was a similar LDL-C reduction. CONCLUSIONS Po-husk, apart from lowering LDL-C, also reduced TG, TG related to certain gene variants, TC, Apo B-100, oxLDL, insulin-resistance and systolic BP in mild-moderate hypercholesterolaemic individuals. Thus, the target patients to receive Po-husk would be those who present a cluster of various CVD risk factors, such as metabolic syndrome.
-
10.
Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk.
Rosenson, RS, Davidson, MH, Pourfarzib, R
Atherosclerosis. 2010;(1):1-7
Abstract
Prospective studies of coronary heart disease patients with disorders of insulin resistance, metabolic syndrome (MetSyn) and type 2 diabetes (T2DM), have shown that these patients usually display high levels of low-density lipoprotein particles (LDL-P) and low levels of high-density lipoprotein particles (HDL-P). In multiple prospective studies, high levels of LDL-P are more predictive of CHD risk than low-density lipoprotein cholesterol (LDL-C). The conventional goal of lipid lowering treatment is to lower LDL-C levels; however LDL-C is unrelated to the severity of insulin resistance. Among high cardiometabolic risk patients with LDL-C <100 mg/dL, about two-thirds of patients have a high LDL-P (>1000 nmol/L) despite this "optimal" level of LDL-C. For high cardiometabolic risk patients, LDL-P should be considered a primary goal of therapy due to its stronger association with cardiovascular risk. Further, we propose that certain lipid-altering therapies may be particularly useful in reducing cardiovascular events in statin-treated patients, not simply due to their improvement in LDL-C goal attainment, but due to their effects on lowering the number of low-density lipoprotein particles (LDL-P).