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Dose-dependent reductions in plasma ceramides after anthocyanin supplementation are associated with improvements in plasma lipids and cholesterol efflux capacity in dyslipidemia: A randomized controlled trial.
Zhao, Y, Xu, H, Tian, Z, Wang, X, Xu, L, Li, K, Gao, X, Fan, D, Ma, X, Ling, W, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1871-1878
Abstract
BACKGROUND & AIMS Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.
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Effects of simvastatin on white matter integrity in healthy middle-aged adults.
Vogt, NM, Hunt, JFV, Ma, Y, Van Hulle, CA, Adluru, N, Chappell, RJ, Lazar, KK, Jacobson, LE, Austin, BP, Asthana, S, et al
Annals of clinical and translational neurology. 2021;(8):1656-1667
Abstract
BACKGROUND The brain is the most cholesterol-rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol-lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol-rich brain white matter (WM) is largely unknown. METHODS We used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin-naïve, middle-aged adults during an 18-month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38). ANCOVA models (covariates: age, sex, APOE-ɛ4) tested the effect of treatment group on percent change in WM, gray matter (GM), and WM hyperintensity (WMH) neuroimaging measures at each study visit. Mediation analysis tested the indirect effects of simvastatin on WM microstructure through change in serum total cholesterol levels. RESULTS At 18 months, the simvastatin group showed a significant preservation in global WM fractional anisotropy (β = 0.88%, 95% CI 0.27 to 1.50, P = 0.005), radial diffusivity (β = -1.10%, 95% CI -2.13 to -0.06, P = 0.039), and WM volume (β = 0.72%, 95% CI 0.13 to 1.32, P = 0.018) relative to the placebo group. There was no significant effect of simvastatin on GM or WMH volume. Change in serum total cholesterol mediated approximately 30% of the effect of simvastatin on WM microstructure. CONCLUSIONS Simvastatin treatment in healthy, middle-aged adults resulted in preserved WM microstructure and volume at 18 months. The partial mediation by serum cholesterol reduction suggests both peripheral and central mechanisms. Future studies are needed to determine whether these effects persist and translate to cognitive outcomes. TRIAL REGISTRATION NCT00939822 (ClinicalTrials.gov).
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A Non-Probiotic Fermented Soy Product Reduces Total and LDL Cholesterol: A Randomized Controlled Crossover Trial.
Jung, SM, Haddad, EH, Kaur, A, Sirirat, R, Kim, AY, Oda, K, Rajaram, S, Sabaté, J
Nutrients. 2021;(2)
Abstract
Traditional Asian fermented soy food products are associated with reduced cardiovascular disease risk in prospective studies, but few randomized controlled trials have been conducted in at-risk populations. The aim of this study was to investigate the effect of a commercial non-probiotic fermented soy product on blood lipids in adults with cardiovascular risk biomarkers. In a randomized, crossover, intervention study, 27 men and women (aged 29-75 y) exhibiting at least two risk factors, consumed two packets (12.5 g each) daily of a fermented powdered soy product, or an isoenergic control powder made from germinated brown rice for 12 weeks each. The consumption of the fermented soy product resulted in a significantly greater mean change from baseline (compared to the germinated rice, all p < 0.05) in total cholesterol of -0.23 mmol/L (CI: -0.40, -0.06) compared with 0.14 mmol/L (CI: -0.03, 0.31), respectively; and low density lipoprotein (LDL) cholesterol -0.18 mmol/L (CI: -0.32, -0.04) compared with 0.04 mmol/L (CI: -0.01, 0.018) respectively. This was accompanied by an increase in high density lipoprotein (HDL) cholesterol in the germinated rice group, a decrease in apolipoprotein B (ApoB) in the fermented soy group, and a between-treatment effect in apolipoprotein A1 (ApoA1); however, the ratio of the LDL:HDL and of Apo B:ApoA1 did not differ between the groups. The ratio of total cholesterol:LDL decreased in men in the fermented soy group (p < 0.001). Twenty-four-hour urine collection at the end of each treatment period resulted in an increased excretion expressed as a ratio in μmol/d between treatments of 10.93 (CI: 5.07, 23.54) for daidzein; 1.24 (CI: 1.14, 4.43) for genistein; and, 8.48 (CI: 4.28, 16.80) for glycitein, all p < 0.05. The fermented soy powder consumed by participants in this study without implementing other changes in their typical diets, decreased the total and LDL cholesterol, and may serve as a dietary strategy to manage blood lipids. The trial was registered at ClinicalTrials.gov as NCT03429920.
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Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial.
Zhao, JV, Yeung, WF, Chan, YH, Vackova, D, Leung, JYY, Ip, DKM, Zhao, J, Ho, WK, Tse, HF, Schooling, CM
Nutrients. 2021;(8)
Abstract
Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.
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Effects of a Calorie-Restricted Mediterranean-Style Diet on Plasma Lipids in Hypercholesterolemic South Korean Patients.
Son, DH, Kwon, YJ, Lee, HS, Kim, HM, Lee, JW
Nutrients. 2021;(10)
Abstract
The objective of this randomized cross-over trial was to evaluate the short term effects of a calorie-restricted Korean style Mediterranean diet (KMD) versus a calorie-restricted conventional diet on lipid profile and other metabolic parameters in hypercholesterolemic patients. Ninety-two patients with hypercholesterolemia were randomly assigned to two groups and switched to the other group following a 4-week intervention after a 2-week washout period. While participants during KMD intervention period received home delivery of two meals daily except for weekends, those during the control group were advised to consume a conventional diet. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) significantly decreased in KMD group even after adjusting for age, sex, total energy intake changes, alcohol consumption, smoking status, and physical activity changes (all p < 0.05). Anthropometric parameters, white blood cell (WBC), fasting glucose, fasting insulin, HOMA-IR, and fatty liver index (FLI) also significantly decreased after KMD intervention (all p < 0.05). In addition, WBC, fasting glucose, total cholesterol, LDL-C and FLI were significantly decreased even after adjusting for weight reduction changes. Calorie-restricted KMD not only helps to treat dyslipidemia by improving the lipid parameters but also has beneficial effects on reducing cardiovascular risk by improving chronic inflammation, insulin resistance, and fatty liver.
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Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans.
Hyde, PN, Sapper, TN, LaFountain, RA, Kackley, ML, Buga, A, Fell, B, Crabtree, CD, Phinney, SD, Miller, VJ, King, SM, et al
Nutrients. 2021;(6)
Abstract
BACKGROUND Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate. OBJECTIVE We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition. METHODS We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution. RESULTS Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group. CONCLUSIONS These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.
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Efficacy and Safety of Lactobacillus plantarum K50 on Lipids in Koreans With Obesity: A Randomized, Double-Blind Controlled Clinical Trial.
Sohn, M, Na, GY, Chu, J, Joung, H, Kim, BK, Lim, S
Frontiers in endocrinology. 2021;:790046
Abstract
BACKGROUND Only few studies have investigated the role of probiotics in the development of obesity. We aimed to determine the efficacy and safety of an intake of Lactobacillus plantarum K50 (LPK) on body fat and lipid profiles in people with obesity. METHODS This randomized, double-blind, placebo-controlled, clinical trial involved 81 adults with a body mass index of 25-30 kg/m2 who were assigned randomly to a diet including 4 × 109 colony-forming unit of LPK or a placebo. Changes in body fat, anthropometric parameters, and biomarkers of obesity were compared using a linear mixed-effect model. RESULTS After 12 weeks of treatment, body weight, fat mass, and abdominal fat area did not change significantly in the two groups. However, total cholesterol levels decreased from 209.4 ± 34.4 mg/dL to 203.5 ± 30.9 mg/dL in the LPK group, but increased from 194.7 ± 37.5 mg/dL to 199.9 ± 30.7 mg/dL in the placebo group (P = 0.037). Similarly, triglyceride levels decreased from 135.4 ± 115.8 mg/dL to 114.5 ± 65.9 mg/dL in the LPK group, with a significant difference between groups. LPK supplementation also tended to decrease leptin levels compared with placebo. It also changed the distribution of gut microbiota significantly, with an increase in L. plantarum and a decrease in Actinobacteria, both of whose changes in abundance were correlated with changes in visceral adiposity, with borderline significance. CONCLUSION A 12-week consumption of LPK reduced the total cholesterol and triglyceride levels significantly with favorable alterations in microbiota, suggesting potential benefits for controlling blood lipid profiles.
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Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial.
van Rooijen, MA, Plat, J, Blom, WAM, Zock, PL, Mensink, RP
Clinical nutrition (Edinburgh, Scotland). 2021;(3):804-811
Abstract
BACKGROUND The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. OBJECTIVE We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. DESIGN In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. RESULTS Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14 mmol/L; p = 0.010), HDL cholesterol (-0.09 mmol/L; p=<0.001), and apoA1 (-0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p = 0.002), while in men, C-peptide concentrations were lower (-0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. CONCLUSIONS As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. CLINICAL TRIAL REGISTRY This trial was registered at clinicaltrials.gov as NCT02835651.
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Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study.
Dixon, DL, Billingsley, HE, Canada, JM, Trankle, CR, Kadariya, D, Cooke, R, Hart, L, Van Tassell, B, Abbate, A, Carbone, S
Journal of cardiovascular pharmacology. 2021;(3):407-410
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Abstract
The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (-12.5 to 19.5) mg/dL versus -8 (-19 to -1) mg/dL (P = 0.82) and triglyceride levels was -4 (-26 to 9) mg/dL and -10.5 (-50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.
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Effects of the Consumption of Low-Fat Cooked Ham with Reduced Salt Enriched with Antioxidants on the Improvement of Cardiovascular Health: A Randomized Clinical Trial.
Victoria-Montesinos, D, Arcusa, R, García-Muñoz, AM, Pérez-Piñero, S, Sánchez-Macarro, M, Avellaneda, A, López-Román, FJ
Nutrients. 2021;(5)
Abstract
The aim of the study was to analyze how cardiovascular risk factors can be modified using nutritionally improved cooked ham enriched with a pool of antioxidants to influence relevant metabolic targets. Sixty-five untreated subjects (49.2% males, 50.8% females, mean age 40.92 ± 9.03 years) with total cholesterol level ≥180 mg/dL or LDL cholesterol ≥130 mg/dL participated in a 8-weeks randomized, double-blind controlled trial. Participant in the intervention group (51.5% males, 48.5% females, mean age 41.6 ± 9.8 years and mean BMI 25.1 ± 3.6 kg/m2) consumed cooked ham enriched with antioxidants (100 g/d) and controls (49.9% males, 53.1% females, mean age 40.2 ± 8.3 years and mean BMI 26.3 ± 3.2 kg/m2) received placebo. At 8 weeks, oxidized LDL decreased significantly between experimental and placebo groups (p < 0.036). Experimental group differences were also significant (p < 0.05). Similar findings in malondialdehyde, total cholesterol, high-sensitivity C-reactive protein, and interleukin 6 were observed in the intervention group. Significant between-group differences in these variables were also found, except for total cholesterol and interleukin 6. The effects on inflammation and oxidation support the direct action of these antioxidants on the etiopathogenic factors of atheromatous plaque. We also observed an improvement in the lipid profiles among the subjects.