Effects of poly-bioactive compounds on lipid profile and body weight in a moderately hypercholesterolemic population with low cardiovascular disease risk: a multicenter randomized trial.
ABSTRACT: UNLABELLED:A dietary supplement (AP, Armolipid Plus) that combines red yeast rice extract, policosanol, berberine, folic acid, coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease (CVD) biomarkers. The aim of this study was to assess whether the intake of AP, in combination with dietary recommendations, reduces serum low density lipoprotein cholesterol (LDL-c) concentrations and other CVD biomarkers in patients with hypercholesterolemia. Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío (Sevilla); Hospital San Jorge (Huesca); Hospital San Pedro (Logroño); Hospital Gregorio Marañón (Madrid), Hospital la Fe (Valencia) and Hospital Universitari Sant Joan (Reus) as recruiting and coordinating center. 102 participants (mean age ± SD; 50.91 ± 11.61; 32 men) with low CVD, with mild-to-moderately elevated LDL-c (between 3.35 mmol/L and 4.88 mmol/L) without hypolipemic therapy were randomized in a double-blind, parallel, controlled, multicenter trial commencing January 2012 and ending December 2012. Among the exclusion criteria were any concomitant chronic disease, triglycerides (TG) >3.97 mmol/L, pregnant or lactating, and history of CVD. At 12 weeks, compared to placebo, AP reduced LDL-c by -6.9%, apolipoprotein (Apo) B-100 by -6.6% and total cholesterol/HDL-c ratio by -5.5%, the ApoB/ApoA1 ratio by -8.6%, while increasing ApoA1 by +2.5% (p<0.05). AP consumption was associated with modest mean weight loss of -0.93 kg (95%CI: -1.74 to -0.12; P = 0.02) compared with control group while dietary composition remained unchanged in the AP group. The AP product was well tolerated. In conclusion, AP, combined with dietary recommendations, reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios, while increasing Apo A1, all of which are improvements in CVD risk indicators. AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight. TRIAL REGISTRATION:ClinicalTrials.gov NCT01562080.
Project description:BACKGROUND: Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. METHODS: A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24-28, and > 28 kg/m(2); respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. RESULTS: The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.
Project description:The association of ATP-binding cassette (ABC) transporter single nucleotide polymorphisms (SNPs) and serum lipid profiles is inconsistent. The present study was undertaken to detect the association of ABCG5/G8 SNPs and several environmental factors with serum lipid levels.Genotyping of the ABCG5 (rs4131229 and rs6720173) and ABCG8 (rs3806471 and rs4148211) SNPs was performed in 719 unrelated subjects of Mulao nationality and 782 participants of Han nationality. There were no differences in the genotypic and allelic frequencies of four SNPs between the two ethnic groups besides the genotypic frequencies of rs4131229 SNP in Han. The levels of triglyceride (TG), apolipoprotein (Apo) A1, and ApoA1/ApoB ratio (rs4131229); low-density lipoprotein cholesterol (LDL-C) and ApoB (rs6720173); high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB, and ApoA1/ApoB ratio (rs3806471); and HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han were different among their genotypes (P<0.05-0.001). The levels of LDL-C (rs6720173) and ApoA1 (rs3806471) in Mulao were also different among their genotypes (P<0.05 for each). The levels of TC, TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4131229); LDL-C and ApoB (rs6720173); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs3806471); and TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han males; and ApoA1/ApoB ratio (rs4131229); LDL-C, ApoB, and ApoA1/ApoB ratio (rs3806471); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han females were different between the genotypes (P<0.05-0.001). The levels of LDL-C in Mulao females were also different between GG and GC/CC genotypes of rs6720173 (P<0.05). The correlation between serum lipid parameters and genotypes of four SNPs was observed in Han, especially in Han males. Serum lipid parameters were also correlated with several environmental factors.The associations of four ABCG5/G8 SNPs and serum lipid levels are different between the Mulao and Han populations, or between males and females, suggesting that there may be a racial/ethnic- and/or sex-specific association between ABCG5/G8 SNPs and some serum lipid parameters.
Project description:So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake correlated negatively with sdLDL constituents and positively with HDL2 components. Consumption of monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2 cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk of cardiovascular disease in men was associated with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions.
Project description:BACKGROUND/OBJECTIVES:Hypercholesterolaemic effects of saturated fatty acids (SFA) may be influenced not only by the chain length, but also by their specific location within the triacylglycerol (TAG) molecule. We examined the hypothesis that dietary fats rich in SFA, but containing mostly unsaturated fatty acids in the sn-2 position with most SFA in sn-1 and -3 (palm olein [PO] and cocoa butter [CB]) will have similar serum lipid outcomes to unsaturated olive oil (OO). SUBJECTS/METHODS:Thirty-eight participants (20-40?yr, 18.5-???27.5?kg/m2) completed a 4-week randomised 3?×?3 crossover feeding intervention, preceded by 2-week run-in and separated by 2-week washout periods. Background diet contained 35 percentage of total energy (%E) fat, 18%E protein, 48%E carbohydrates, differing in test fats only (palm olein (PO), CB, OO; 20%E). Total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio and related variables; TC, HDL-C, low density lipoprotein cholesterol (LDL-C), TAG, apoA1, ApoB, ApoA1 (apolipoprotein A1)/ApoB (apolipoprotein B), lipoprotein (a) (Lp(a)), NEFA, LDL sub-fractions, were assessed pre- and post-intervention. Data were analysed using mixed effects longitudinal models with a P-value?<?0.05 considered significant. RESULTS:Changes in plasma fatty acids (P?<?0.05) confirmed compliance; C18:1 increased with OO compared to PO and CB; C16:0 decreased with OO and C18:0 increased following CB. No differences were seen for TC/HDL-C (mean [95%CI] change for PO, 0.08[0.00, 0.15] mmol/L; CB, 0.06 [-0.05, 0.16] mmol/L; and OO, -0.01 [-0.15, 0.13] mmol/L; P?=?0.53] or any other parameter including LDL sub-fractions. OO decreased IDL-A compared to PO (-2.2 [-4.31, -0.21] mg/dL, P?=?0.03). CONCLUSION:In healthy young participants, plasma lipid responses to PO and CB, enriched in SFA but having primarily unsaturated fatty acid in the sn-2 position of TAG, did not differ from OO.
Project description:BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. METHODS:We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n?=?262) received treatment from a health coach and medical provider. A usual care (UC) group (n?=?87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P?<?0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. RESULTS:The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m-2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (-?4.9%, P?=?0.02), small LDL-P (-?20.8%, P?=?1.2?×?10-12), LDL-P size (+?1.1%, P?=?6.0?×?10-10), ApoB (-?1.6%, P?=?0.37), ApoA1 (+?9.8%, P?<?10-16), ApoB/ApoA1 ratio (-?9.5%, P?=?1.9?×?10-7), triglyceride/HDL-C ratio (-?29.1%, P?<?10-16), large VLDL-P (-?38.9%, P?=?4.2?×?10-15), and LDL-C (+?9.9%, P?=?4.9?×?10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P?<?1?×?10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased -?11.9% (P?=?4.9?×?10-5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P?=?5.3?×?10-5). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m-2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C. CONCLUSIONS:A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.
Project description:The association of ADP-ribosylation factor-like 15 (ARL15) rs6450176 single nucleotide polymorphism (SNP) and serum lipid profiles has never been studied in the Chinese population. The present study was undertaken to detect the association of ARL15 rs6450176 SNP and several environmental factors with serum lipid levels in the Jing and Han populations. Genotypes of the SNP were determined in 726 unrelated subjects of Jing nationality and 726 participants of Han nationality. The genotypic and allelic frequencies of the SNP in Jing but not in Han were different between males and females (P < 0.001 and P < 0.05; respectively). The G allele carriers in Han had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels, and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05-0.01). The G allele carriers in Jing had lower serum TC, high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB levels and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05 for all). Subgroup analyses showed that the G allele carriers had lower TC and LDL-C levels in Han males; lower LDL-C and ApoB levels in Han females; lower ApoB levels and ApoA1/ApoB ratio in Jing males; and lower LDL-C levels in Jing females than the G allele non-carriers (P < 0.05-0.01). Multiple linear regression analysis showed that serum TC, LDL-C, ApoB levels and the ApoA1/ApoB ratio in Han; and TC, HDL-C and ApoA1 levels in Jing were correlated with the genotypes of the ARL15 rs6450176 SNP (P < 0.05-0.001). Serum lipid parameters were also associated with several environmental factors in both ethnic groups. These findings indicated that there may be a racial/ethnic- and/or sex-specific association of the ARL15 rs6450176 SNP and serum lipid levels.
Project description:BACKGROUND:Dietary recommendations to limit red meat are based on observational studies linking intake to cardiovascular disease (CVD) risk together with the potential of its saturated fatty acid (SFA) content to raise low-density lipoprotein (LDL) cholesterol. However, the relation of white meat to CVD risk, and the effects of dietary protein source on lipoprotein particle subfractions, have not been extensively evaluated. OBJECTIVE:We tested whether levels of atherogenic lipids and lipoproteins differed significantly following consumption of diets with high red meat content compared with diets with similar amounts of protein derived from white meat or nonmeat sources, and whether these effects were modified by concomitant intake of high compared with low SFAs. METHODS:Generally healthy men and women, 21-65 y, body mass index 20-35 kg/m2, were randomly assigned to 1 of 2 parallel arms (high or low SFA) and within each, allocated to red meat, white meat, and nonmeat protein diets consumed for 4 wk each in random order. The primary outcomes were LDL cholesterol, apolipoprotein B (apoB), small + medium LDL particles, and total/high-density lipoprotein cholesterol. RESULTS:Analysis included participants who completed all 3 dietary protein assignments (61 for high SFA; 52 for low SFA). LDL cholesterol and apoB were higher with red and white meat than with nonmeat, independent of SFA content (P < 0.0001 for all, except apoB: red meat compared with nonmeat [P = 0.0004]). This was due primarily to increases in large LDL particles, whereas small + medium LDL and total/high-density lipoprotein cholesterol were unaffected by protein source (P = 0.10 and P = 0.51, respectively). Primary outcomes did not differ significantly between red and white meat. Independent of protein source, high compared with low SFA increased LDL cholesterol (P = 0.0003), apoB (P = 0.0002), and large LDL (P = 0.0002). CONCLUSIONS:The findings are in keeping with recommendations promoting diets with a high proportion of plant-based food but, based on lipid and lipoprotein effects, do not provide evidence for choosing white over red meat for reducing CVD risk. This trial was registered at Clinicaltrials.gov as NCT01427855.
Project description:The objective of the present study was to detect the association of the Trp316Ser variant (rs1801690) near the apolipoprotein H (?2-glycoprotein-I) gene and serum lipid levels in the Mulao and Han populations. A total of 879 subjects of Mulao and 844 subjects of Han Chinese were included. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoA1 in Mulao, and triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and the ratio of ApoA1/ApoB in Han were different among the three genotypes of the rs1801690 SNP (P < 0.05-0.01). Subgroup analyses showed that the levels of TC, TG, LDL-C, and ApoA1 in Mulao males; ApoA1 in Mulao females; TC, TG, HDL-C and ApoB and the ApoA1/ApoB ratio in Han males; and HDL-C, ApoA1 and the ApoA1/ApoB ratio in Han females were associated with the genotypes of rs1801690 (P < 0.05-0.001). Serum lipid parameters were also associated with several environmental factors (P < 0.05-0.001). The Trp316Ser variant (rs1801690) near the apolipoprotein H (?2-glycoprotein-I) gene was associated with some serum lipid parameters in the two ethnic groups, but the trends of association suggest that the Trp316Ser variant (rs1801690) near the apolipoprotein H (?2-glycoprotein-I) gene might have racial/ethnic-and/or gender-specificity.
Project description:This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva®) and the reference formulation (Lipitor®) of atorvastatin, both at a dosage of 20 mg once daily.This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated.Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (-43.9%±15.3% in the generic group, -43.3%±17.0% in the reference group, P=0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P=0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P=0.804).The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia.
Project description:Existing treatments are inadequate for patients at high risk of coronary heart disease caused by elevated levels of plasma low-density lipoprotein cholesterol (LDL-C). Bambuterol is a prodrug of ?2-agonist commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) with the advantage of once daily dosing and favorable side effect profile. The potential lipid-lowering effects of bambuterol were unclear, possibly due to the racemic bambuterol (rac-bambuterol) that was used in previous studies.The lipid-lowering effects of R-bambuterol were examined in a randomized phase I trial in 48 healthy Chinese volunteers aged 18-45 years. Participants were randomly assigned to five groups to receive a single dose (2.5 mg, 5 mg or 10 mg) or multiple doses (5 mg) of oral medications of R-bambuterol, or a single dose of rac-bambuterol (10 mg). Plasma lipid levels were measured at baseline, time to peak concentration (Tmax) and 24 h after the treatment.Administration of a single-dose of R-bambuterol resulted in dose-dependent reductions in the levels of plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) at Tmax. Levels of LDL-C exhibited the most reductions, which were statistically significant in all three single-dose R-bambuterol groups (all P values < 0.05). R-bambuterol was more potent in LDL-C lowering compared to rac-bambuterol at Tmax (P = 0.08). At 24 h after dosing, the significant lipid lowering effects of R-bambuterol sustained for LDL-C (P = 0.01), ApoB (P = 0.001) and ApoA1 (P = 0.03), but not for HDL-C. The ratio of ApoA1/ApoB was marginally increased (P = 0.06). In the multiple-dose group, LDL-C levels again were significantly reduced (all P values < 0.05), whereas the ratios of ApoA1/ApoB were marginally increased.R-bambuterol can lower the plasma levels of LDL-C, and marginally raise the ratio of ApoA1/ApoB (indicator of HDL-C/LDL-C) with both a single dose and multiple doses. R-bambuterol was more potent in LDL-C lowering than rac-bambuterol.