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1.
Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome.
Velarde, GP, Choudhary, N, Bravo-Jaimes, K, Smotherman, C, Sherazi, S, Kraemer, DF
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(2):634-640
Abstract
BACKGROUND AND AIM Specific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes. METHODS AND RESULTS This randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference. CONCLUSIONS In conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.
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2.
Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome.
Fuentes, GC, Castañer, O, Warnberg, J, Subirana, I, Buil-Cosiales, P, Salas-Salvadó, J, Corella, D, Serra-Majem, L, Romaguera, D, Estruch, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3092-3098
Abstract
BACKGROUND There is limited prospective evidence on the association between physical activity (PA) and inflammation in older adults. Our aim was to assess the associations between changes in PA and changes in the inflammatory profile in older individuals who are overweight or obese. METHODS This prospective study included 489 men and women, aged 55-75 years, from the PREDIMED-Plus trial. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), monocyte chemo-attractant protein-1 (MCP-1), C-peptide, high-sensitivity C-reactive protein (hs-CRP), leptin, and regulated on activation, normal T-cell expressed and secreted chemokine (RANTES) were obtained from fasting blood samples and a composite inflammatory score based on these biomarkers was calculated. Physical activity was measured by a validated questionnaire. All measures were taken at baseline and one-year follow-up. RESULTS Multiple linear regression models showed an association between an increase in total PA and a decrease in the inflammatory score (p = 0.012), which was particularly driven by a decrease in C-peptide (p = 0.037). Similarly, the inflammatory score decreased with increasing moderate PA (p = 0.001), and moderate-to-vigorous PA (p = 0.006). CONCLUSIONS Increases in total PA, moderate and moderate-to-vigorous PA were associated with a decrease in the inflammatory profile of obese or overweight older individuals. This finding is relevant for PA recommendations and public health strategies. CLINICAL TRIAL REGISTRY Clinical trial identifier: International Standard Randomized Controlled Trial 89898870.
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3.
Impact of resveratrol supplementation on inflammatory, antioxidant, and periodontal markers in type 2 diabetic patients with chronic periodontitis.
Javid, AZ, Hormoznejad, R, Yousefimanesh, HA, Haghighi-Zadeh, MH, Zakerkish, M
Diabetes & metabolic syndrome. 2019;(4):2769-2774
Abstract
BACKGROUND Diabetes mellitus and periodontal disease are two common and chronic diseases with bidirectional relationship influence public health and quality of life. The aims of this study was to study the impact of resveratrol supplementation in adjunct with non-surgical periodontal therapy on inflammatory, antioxidant, and periodontal markers in patients with type 2 diabetes with periodontal disease. MATERIALS AND METHODS In this randomized clinical trial, 43 patients with diabetes and chronic periodontitis were randomly allocated into two intervention and control groups receiving either resveratrol supplements or placebo for 4 weeks. Serum levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), total antioxidant capacity (TAC) and clinical attachment loss (CAL) as the main index of periodontal marker were measured pre-intervention and post-intervention. RESULTS In the intervention group, the mean serum level of IL6 was reduced significantly (P = 0.039) post-intervention (2.19 ± 1.09 and 1.58 ± 1.06). No significant differences were seen in the mean levels of IL6, TNFα, TAC and CAL between two groups post-intervention. CONCLUSIONS It is suggested that daily consumption of resveratrol supplement may not change TNFα, TAC and CAL, but it would be beneficial in reducing serum levels of IL6. Therefore, further studies are suggested to investigate the effects of resveratrol supplementation along with NST on periodontal status.
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4.
The Effects of Synbiotic Supplementation on Body Mass Index, Metabolic and Inflammatory Biomarkers, and Appetite in Patients with Metabolic Syndrome: A Triple-Blind Randomized Controlled Trial.
Rabiei, S, Hedayati, M, Rashidkhani, B, Saadat, N, Shakerhossini, R
Journal of dietary supplements. 2019;(3):294-306
Abstract
It has been shown recently that metabolic syndrome is associated with gut dysbiosis. The gut microbiota may be the main target for prevention or treatment of metabolic syndrome. We investigated the effects of synbiotic supplementation on metabolic syndrome. In this triple-blinded clinical trial, 46 Iranian patients with metabolic syndrome, from both sexes, aged 25-70 years, who fulfilled inclusion criteria were randomly categorized to receive either the synbiotic or a placebo capsule, twice a day for three months, plus a weight-loss diet using stratified random sampling based on body mass index (BMI). Each synbiotic capsule consisted of seven strains probiotic bacteria (2× 108) plus fructooligosaccharide as a prebiotic. Anthropometric measurements and biochemical tests were assessed at baseline and at the end of week 12 for fasting blood sugar (FBS), insulin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). The mean changes of weight, BMI, FBS, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and GLP-1 between the two groups was statistically significant (p < .001). Furthermore, peptide YY (PYY) increased significantly in the synbiotic group (p ≤ .05). The trend of weight loss in the synbiotic group was significant until the end of the study (p < .001) while it stopped at week 6 in the placebo group. Synbiotic treatment may improve the status of BMI, FBS, insulin resistance, HOMA-IR, GLP-1, and PYY in patients with metabolic syndrome.
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5.
Effect of metformin combined with lifestyle modification versus lifestyle modification alone on proinflammatory-oxidative status in drug-naïve pre-diabetic and diabetic patients: A randomized controlled study.
Bulatova, N, Kasabri, V, Qotineh, A, Al-Athami, T, Yousef, AM, AbuRuz, S, Momani, M, Zayed, A
Diabetes & metabolic syndrome. 2018;(3):257-267
Abstract
BACKGROUND Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. RESULTS Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P<0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods. CONCLUSION In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P<0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P<0.05) with total cholesterol.
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6.
Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
Smits, LP, Kootte, RS, Levin, E, Prodan, A, Fuentes, S, Zoetendal, EG, Wang, Z, Levison, BS, Cleophas, MCP, Kemper, EM, et al
Journal of the American Heart Association. 2018;(7)
Abstract
BACKGROUND Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR 4338.
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7.
Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects Upon High-Sensitivity C-Reactive Protein and Lipid Parameters in Patients With Metabolic Syndrome.
Bays, HE, Ballantyne, CM, Braeckman, RA, Stirtan, WG, Doyle, RT, Philip, S, Soni, PN, Juliano, RA
Metabolic syndrome and related disorders. 2015;(6):239-47
Abstract
BACKGROUND The aim of this analysis was to examine the effects of icosapent ethyl (eicosapentaenoic acid ethyl ester, IPE) on high-sensitivity C-reactive protein (hsCRP) and lipid parameters in patients with metabolic syndrome, with and without stable statin therapy. METHODS This post hoc exploratory analysis evaluated patients with metabolic syndrome treated with IPE 4 grams/day, IPE 2 grams/day, or placebo in phase 3, randomized, placebo-controlled studies entitled: MARINE [triglyceride (TG) levels ≥500 and ≤2000 mg/dL] and ANCHOR [TG levels ≥200 and <500 mg/dL, despite low-density lipoprotein cholesterol (LDL-C) control with stable statin therapy]. RESULTS Compared with placebo in patients with metabolic syndrome in MARINE (n=204) and ANCHOR (n=645), at the approved dose of 4 grams/day, IPE significantly lowered hsCRP levels 40.0% (P=0.0007) in MARINE and 23.0% (P=0.0003) in ANCHOR. Compared with placebo in MARINE, which included patients with and without statin therapy, IPE 4 grams/day significantly reduced hsCRP levels 78.0% in statin-treated patients (P=0.0035, n=16). Compared with placebo in MARINE, IPE 4 grams/day significantly reduced TG levels (35.0%; P<0.0001), non-high-density lipoprotein cholesterol (non-HDL-C; 19.9%; P<0.0001), and apolipoprotein B levels (ApoB) (9.1%; P=0.0015) without raising LDL-C levels. Compared with placebo in ANCHOR, IPE 4 grams/day significantly reduced TG (21.7%; P<0.0001), non-HDL-C (13.5%; P<0.0001), ApoB (8.8%; P<0.0001), LDL-C (5.2%; P=0.0236), and HDL-C levels (4.0%; P=0.0053). CONCLUSIONS Compared with placebo, IPE 4 grams/day significantly lowered hsCRP levels and improved lipids without raising LDL-C levels in patients with metabolic syndrome and high (≥200 and <500 mg/dL) or very high (≥500 and ≤2000 mg/dL) TG levels, with or without stable statin therapy.
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8.
Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors.
Broekhuizen, LN, van Wijk, DF, Vink, H, Stalmach, A, Crozier, A, Hutten, BA, Kastelein, JJ, Hugenholtz, PG, Koenig, W, Stroes, ES
The British journal of nutrition. 2011;(9):1416-22
Abstract
Inflammation is a hallmark of the metabolic syndrome, which also contributes to a pro-atherogenic state. NF-κB activation, a critical step in regulating inflammatory reactions, can be inhibited by polyphenol (PF) extracts, at least in vitro. In the present study, we set out to study whether a PF-rich extract could attenuate the chronic inflammatory state and/or an acute immune response in vivo in subjects with clustered metabolic risk factors. A commercially available, PF-rich extract (500 mg daily) or placebo was administered for 4 weeks to thirty-four subjects with two or more metabolic risk factors using a randomised, double-blind, cross-over design. During the final study visit, an acute inflammatory challenge (lipopolysaccharide (LPS) 1 ng/kg body weight) was administered to a random subgroup of subjects (PF-rich extract (n 12) and placebo (n 12)). The PF-rich extract modestly reduced the inflammatory chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor (MIF) (MCP-1 - 6.5 % (PF, median 116 (interquartile range 97-136) pg/ml v. placebo, median 124 (interquartile range 105-153) pg/ml; P < 0.05); MIF - 10.8 % (PF, median 2512 (interquartile range 1898-3972) pg/ml v. placebo, median 2814.5 (interquartile range 2296-3852) pg/ml; P < 0.05); however, other measured markers of inflammation and cardiometabolic disease, such as C-reactive protein, IL-6, HDL-cholesterol, adiponectin and oxidised LDL, remained unaffected. Following the LPS challenge, we found a statistically significant 48 % reduction of MCP-1 production in the PF-rich extract group (n 12) v. placebo (n 12) over 6 h (PF 766 (sd 155) v. placebo 1466 (sd 989) ng/ml; P < 0.05, area under the curve). In conclusion, short-term oral administration of the PF-rich extract caused a modest anti-inflammatory effect in subjects with clustered metabolic risk factors. Further dose-ranging studies are needed to evaluate whether and to what extent PF-rich extracts can be used to reduce the pro-inflammatory state in subjects with metabolic diseases at increased cardiovascular risk.
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9.
Effects of a therapeutic lifestyle modification program on inflammatory chemokines and insulin resistance in subjects with metabolic syndrome.
Oh, EG, Chu, SH, Bang, SY, Lee, MK, Kim, SH, Hyun, SS, Jeon, JY, Im, JA, Lee, JE
Biological research for nursing. 2011;(2):182-8
Abstract
BACKGROUND Although therapeutic lifestyle modification (TLM) effectively improves the values of diagnostic biomarkers of metabolic syndrome, less is known about its effects on inflammatory chemokines and insulin resistance (IR) in patients with this syndrome. Objectives. To examine the effects of a short-term TLM program on inflammatory chemokines (monocyte chemoattractant protein-1 [MCP-1], retinol binding protein-4 [RBP-4]) and IR in subjects with metabolic syndrome. METHOD Twenty-nine women (aged 66.5 ± 9.5 years) with metabolic syndrome were randomly assigned to the TLM intervention group (n = 16) or control group (n = 13). The TLM intervention group was provided with 4 weeks of health screening, education, exercise, diet, and counseling. Participants in the control group were instructed to maintain their usual lifestyle behavior. Outcome variables measured included MCP-1, RBP-4, fasting glucose, fasting insulin, and homeostasis model assessment (HOMA). An intention-to-treat strategy was not followed, and the final number of subjects in the analysis was 22 (14 in the TLM group and 8 in the control group). RESULTS After a 4-week TLM program, MCP-1, fasting insulin, and HOMA were significantly decreased in the TLM group compared to those in the control group (all p < .05). CONCLUSIONS We conclude that a short-term TLM program could be effective for improving inflammatory state and IR, which are significant preceding biomarkers for cardiovascular complications in subjects with metabolic syndrome.
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10.
Effects of margarines and butter consumption on lipid profiles, inflammation markers and lipid transfer to HDL particles in free-living subjects with the metabolic syndrome.
Gagliardi, AC, Maranhão, RC, de Sousa, HP, Schaefer, EJ, Santos, RD
European journal of clinical nutrition. 2010;(10):1141-9
Abstract
OBJECTIVE Our purpose was to examine the effects of daily servings of butter, no-trans-fat margarine and plant sterol margarine, within recommended amounts, on plasma lipids, apolipoproteins (Apos), biomarkers of inflammation and endothelial dysfunction, and on the transfer of lipids to HDL particles in free-living subjects with the metabolic syndrome. METHODS This was a randomized, single-blind study where 53 metabolic syndrome subjects (62% women, mean age 54 years) received isocaloric servings of butter, no-trans-fat margarine or plant sterol margarine in addition to their usual diets for 5 weeks. The main outcome measures were plasma lipids, Apo, inflammatory and endothelial dysfunction markers (CRP, IL-6, CD40L or E-selectin), small dense LDL cholesterol concentrations and in vitro radioactive lipid transfer from cholesterol-rich emulsions to HDL. Difference among groups was evaluated by analysis of variance. RESULTS There was a significant reduction in Apo-B (-10.4 %, P=0.043) and in the Apo-B/Apo-A-1 ratio (-11.1%, P=0.034) with plant sterol margarine. No changes in plasma lipids were noticed with butter and no-trans-fat margarine. Transfer rates of lipids to HDL were reduced in the no-trans-fat margarine group: triglycerides -42.0%, (P<0.001 vs butter and sterol margarine) and free cholesterol -16.2% (P=0.006 vs sterol margarine). No significant effects were noted on the concentrations of inflammatory and endothelial dysfunction markers among the groups. CONCLUSIONS In free-living subjects with the metabolic syndrome consumption of plant sterol and no-trans-fat margarines within recommended amounts reduced, respectively, Apo-B concentrations and the ability of HDL to accept lipids.