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The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.
Urakaze, M, Kobashi, C, Satou, Y, Shigeta, K, Toshima, M, Takagi, M, Takahashi, J, Nishida, H
Nutrients. 2021;(12)
Abstract
UNLABELLED Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.
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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.
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Baseline Insulin Resistance Is a Determinant of the Small, Dense Low-Density Lipoprotein Response to Diets Differing in Saturated Fat, Protein, and Carbohydrate Contents.
Wu, X, Roussell, MA, Hill, AM, Kris-Etherton, PM, Walzem, RL
Nutrients. 2021;(12)
Abstract
Individual responses to diet vary but causes other than genetics are poorly understood. This study sought to determine whether baseline values of homeostasis model assessment (HOMA-IR) was related to changes in small, dense low-density lipoprotein (sdLDL, i.e., LDL4, d = 1.044-1.063 g/mL) amounts quantified by isopycnic density profiling, in mildly hypercholesterolemic subjects (n = 27) consuming one of three low saturated fatty acid (SFA) diets: Dietary Approaches to Stop Hypertension (DASH), Beef in an Optimal Lean Diet (BOLD) and BOLD plus extra protein (BOLD+) when compared to a higher-SFA healthy American diet (HAD). The diets were consumed in random order for 5 wk, with 1 wk between diets. BOLD+ reduced fractional abundance (%) LDL4 (p < 0.05) relative to HAD, DASH and BOLD, and reductions in % LDL4 correlated with reductions in triglycerides (p = 0.044), total cholesterol (p = 0.014), LDL cholesterol (p = 0.004) and apolipoprotein B (p < 0.001). Responses to the four diets were similar (~12% decrease in % LDL4, p = 0.890) in the lower (<2.73 median) HOMA-IR subgroup but differed across diet conditions in the higher HOMA-IR subgroup (p = 0.013), in which % LDL4 was reduced with BOLD+ (-11%), was unchanged in BOLD and increased with the HAD (8%) and DASH (6%) diets (p < 0.05 for BOLD+ vs. HAD). Individual responses to diet interventions are influenced by presence and degree of insulin resistance as measured by HOMA-IR.
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Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins.
Ruuth, M, Lahelma, M, Luukkonen, PK, Lorey, MB, Qadri, S, Sädevirta, S, Hyötyläinen, T, Kovanen, PT, Hodson, L, Yki-Järvinen, H, et al
Arteriosclerosis, thrombosis, and vascular biology. 2021;(11):2823-2836
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Abstract
OBJECTIVE We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. APPROACH AND RESULTS The participants (36 subjects; age, 48+/-10 years; body mass index, 30.9+/-6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. CONCLUSIONS The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans.
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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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Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study.
Tani, S, Yagi, T, Matsuo, R, Kawauchi, K, Atsumi, W, Matsumoto, N, Okumura, Y
Journal of cardiology. 2020;(5):487-498
Abstract
BACKGROUND We hypothesized that the addition of eicosapentaenoic acid (EPA) to ongoing statin therapy could change the particle heterogeneity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles, even in stable coronary artery disease (CAD) patients. METHODS We assigned CAD patients already receiving statin therapy to one of two groups: an EPA group (1800 mg/day; n = 30) and a control group (n = 30). A gel permeation high-performance liquid chromatography method was used to measure the particle concentration and number of lipoprotein subclasses. RESULTS In the EPA group, significant decreases of both the concentration and number of medium LDL (p = 0.0002 and 0.0001), small LDL (p = 0.0004 and 0.0005) and very small LDL (p = 0.0005 and 0.002) particles were observed. Conversely, the concentration and number of large HDL particles increased significantly (p = 0.024 and 0.048). The concentration of very large HDL particles also increased significantly (p = 0.028). Furthermore, significant correlations between the variables that showed significant changes in the LDL and HDL particle subclasses, and the EPA/arachidonic acid (AA) ratio were found. No other significant associations of lipoprotein particle heterogeneity with the serum EPA/AA ratio were noted in either the control group or the EPA group. Interestingly, univariate and multivariate regression analyses revealed that increased serum lecithin-cholesterol acyltransferase activity, a key enzyme of HDL cholesterol efflux, was a predictor for increased above-mentioned HDL particles subclasses. CONCLUSIONS Administration of EPA might alter both LDL and HDL particle heterogeneity, causing decreased concentration and number of smaller LDL particles and increased concentration and number of larger HDL particles. Furthermore, addition of EPA to ongoing statin therapy appears to be capable of increasing the EPA/AA ratio, which might have an anti-atherosclerotic effect on lipoprotein particle heterogeneity, even in stable CAD patients with well-controlled serum lipid levels. CLINICAL TRIAL REGISTRATION UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.
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Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis.
Siddiqui, MS, Van Natta, ML, Connelly, MA, Vuppalanchi, R, Neuschwander-Tetri, BA, Tonascia, J, Guy, C, Loomba, R, Dasarathy, S, Wattacheril, J, et al
Journal of hepatology. 2020;(1):25-33
Abstract
BACKGROUND & AIMS Obeticholic acid (OCA), a farnesoid X receptor agonist, increases total and low-density lipoprotein cholesterol (LDL-C) in patients with non-alcoholic steatohepatitis. In the present study, we aimed to evaluate the impact of OCA therapy on lipoprotein sub-particles. METHOD This study included 196 patients (99 OCA group and 97 placebo group) who were enrolled in the FLINT trial and had samples available for lipid analysis and liver biopsies at enrollment and end-of-treatment (EOT) at 72 weeks. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particles were evaluated at baseline, 12 and 72 weeks after randomization, and 24 weeks following EOT. RESULTS Baseline lipoprotein profiles were similar among OCA and placebo groups. OCA did not affect total VLDL particle concentrations, but OCA vs. placebo treatment was associated with decreased large VLDL particle concentration at 12 weeks (baseline-adjusted mean: 6.8 vs. 8.9 nmol/L; p = 0.002), mirrored by an increase in less atherogenic, small VLDL particle concentration (33.9 vs. 28.0 nmol/L; p = 0.02). After 12 weeks, total LDL particle concentration was higher in the OCA group than the placebo group (1,667 vs. 1,329 nmol/L; p <0.0001), characterized by corresponding increases in both less atherogenic, large-buoyant LDL (475 vs. 308 nmol/L; p ≤0.001) and more atherogenic small-dense LDL particles (1,015 vs. 872 nmol/L; p = 0.002). The changes in LDL particle concentrations were similar between treatment groups (OCA and placebo) 24 weeks following EOT due to improvement in the OCA cohort. Compared to placebo, a reduction in total HDL particle concentration, particularly large and medium HDL particles, was noted in the OCA-treated patients, but this resolved after drug discontinuation. CONCLUSION OCA therapy is associated with increases in small VLDL particles, large and small LDL particles, and a reduction in HDL particles at 12 weeks. These lipoprotein concentrations reverted to baseline values 24 weeks after drug discontinuation. LAY SUMMARY Non-alcoholic steatohepatitis is a chronic liver disease that is associated with an increased risk of developing cirrhosis and cardiovascular disease. Recently, obeticholic acid (OCA), a farnesoid X receptor agonist, improved liver disease but led to an increase in cholesterol. However, the impact of OCA on cholesterol is not well understood. In the present study, we show that OCA therapy is associated with a detrimental increase in lipoprotein levels, which improves after drug discontinuation. ClinicalTrials.gov numbers: NCT01265498.
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Comparison of probiotic yogurt and ordinary yogurt consumption on serum Pentraxin3, NT-proBNP, oxLDL, and ApoB100 in patients with chronic heart failure: a randomized, triple-blind, controlled trial.
Pourrajab, B, Naderi, N, Janani, L, Mofid, V, Hajahmadi, M, Dehnad, A, Shidfar, F
Food & function. 2020;(11):10000-10010
Abstract
BACKGROUND AND AIMS Nowadays, the potential beneficial effects of probiotic yogurt as a functional food has raised much interest. Thus, the aim of this study was to compare the probiotic yogurt and ordinary yogurt consumption on some indices in patients with chronic heart failure (CHF). METHODS AND RESULTS In this randomized, triple-blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic yogurt or ordinary yogurt for 10 weeks. The serum levels of pentraxin3 (PTX3), N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low density lipoprotein (oxLDL), and apolipoprotein B100 (ApoB100) were measured at the baseline and at the end of week 10. P-Value <0.05 was defined as statistically significant. Final analyses were performed on 78 patients. The levels of PTX3 and oxLDL in both the groups decreased significantly after 10 weeks, and these reductions were greater in the probiotic group, where the difference between the groups was statistically significant for oxLDL (P-value: 0.051, adjusted P-value: 0.010) but not significant for PTX3 (P-value: 0.956, adjusted P-value: 0.236). The changes in the serum NT-proBNP levels were not statistically significant between the groups (P-value: 0.948, adjusted P-value: 0.306). ApoB100 significantly decreased in the control group compared to the probiotic group and the difference between the groups was significant at first but was not significant after adjusting for the confounders (P-value: 0.004, adjusted P-value: 0.280). CONCLUSION The serum oxLDL significantly reduced due to probiotic yogurt consumption after 10 weeks compared to ordinary yogurt; thus, it may be useful for improving the oxidative status of CHF patients. The clinical trial registry number is IRCT20091114002709N48 (https://www.irct.ir/IRCT20091114002709N48, registered 12 March 2018).
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Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: a nutrigenomic approach for cardiovascular prevention.
Perrone, MA, Gualtieri, P, Gratteri, S, Ali, W, Sergi, D, Muscoli, S, Cammarano, A, Bernardini, S, Di Renzo, L, Romeo, F
Journal of cardiovascular medicine (Hagerstown, Md.). 2019;(7):419-426
Abstract
BACKGROUND AND AIM Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO). METHODS The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P < 0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (P < 0.05). CONCLUSION The current study shows that intake of 25 g of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.Trial registration ClinicalTrials.gov NCT01890070.
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Immune Complexes and the Risk of CVD in Type 1 Diabetes.
Lopes-Virella, MF, Bebu, I, Hunt, KJ, Virella, G, Baker, NL, Braffett, B, Gao, X, Lachin, JM, ,
Diabetes. 2019;(9):1853-1860
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We investigated whether the composition of modified forms of LDL in circulating immune complexes (LDL-ICs) was associated with cardiovascular disease (CVD) outcomes, including any CVD, major adverse cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), and coronary artery disease, in type 1 diabetes (T1D). Our results demonstrate that the baseline levels of oxidized LDL (oxLDL), MDA-modified LDL (MDA-LDL), and advanced glycosylation-modified LDL (AGE-LDL) in circulating ICs were associated with the four CVD outcomes in unadjusted models, and adjustment by age and mean HbA1c only resulted in minimal reduction of these associations. After adjustments were made for other cardiovascular risk factors, particularly LDL cholesterol, oxLDL-IC and MDA-LDL-IC remained independently associated with the risk of CVD, and oxLDL-IC was independently associated with the risk of MACCE and MI. In the majority of cases, the baseline levels of modified LDL-IC (measured many years before the occurrence of any CVD event) were associated with the risk of CVD over a 25-year period even after adjustment for other risk factors (including LDL cholesterol). Therefore, modified LDL biomarkers may help identify patients with T1D at high risk for MACCE and CVD events very early in the evolution of the disease, before other signals of disease are apparent.