背景:血清LDL-胆固醇(LDL-C)在用不饱和脂肪酸(UFA)替代饱和脂肪酸(SFA)时显示出明显的个体间差异。
目的:为了证明英国指南将膳食SFA换成UFA的有效性,降低血清LDL-C和其他CVD危险因素,并确定LDL-C反应变异性的决定因素。
方法:健康男性(n=109,平均±SD年龄48±11岁,BMI25.1±3.3kg/m2),食用高SFA/低UFA饮食4周,紧随其后的是一个等能量,较低的SFA/较高的UFA饮食4周(已达到的SFA:UFA,19.1:14.8和8.9:总能量分别为24.5%)。血清LDL-C,CVD风险标志物,外周血单核细胞(PBMC)基因表达,在基线和每次饮食结束时评估饮食摄入量。
结果:从较高的SFA/较低的UFA饮食过渡到较低的SFA/较高的UFA饮食显着降低了空腹血脂[LDL-C(-0.50mmol/L;95CI:-0.58,-0.42),HDL-C(-0.11mmol/L;95Cl:-0.14,-0.08)和总胆固醇(-0.65mmol/L;95Cl:-0.75,-0.55)]。饮食交换也降低了载脂蛋白(载脂蛋白)B,TC:HDL-C比率,非HDL-C,E-选择素(P<0.0001)和LDL亚组分[胆固醇(LDL-I和LDL-II),apoB100(LDL-I和LDL-II),和TAG(LDL-II)](P<0.01)。胆固醇肠吸收的血浆生物标志物也增加(β-谷甾醇,菜油甾醇,胆固醇),相对于较高SFA/较低UFA饮食,PBMCLDL受体mRNA表达的倍数变化(P=0.035)。观察到对这种膳食交换的血清LDL-C反应(-1.39至0.77mmol/L)变化的个体间差异。在低SFA/高UFA饮食和饮食SFA摄入量减少之前,这种变化的33.7%由血清LDL-C解释(调整后的R227%和6.7%,分别)。APOE基因型与血清LDL-C对SFA的反应无关。
结论:这些发现支持英国SFA饮食指南对整体降低血清LDL-C的功效,但显示LDL-C反应明显变化。进一步确定这种变化的决定因素将有助于靶向和提高这些指南的功效。
背景:RISSCI-1研究已在临床试验中注册。政府(没有。NCT03270527)。
BACKGROUND: Serum LDL-cholesterol (LDL-C) shows marked inter-individual variation in response to replacement of saturated fatty acids (SFA) with unsaturated fatty acids (UFA).
OBJECTIVE: To demonstrate the efficacy of UK guidelines for exchanging dietary SFA for UFA, to reduce serum LDL-C and other CVD risk factors, and to identify determinants of the variability in LDL-C response.
METHODS: Healthy males (n=109, mean±SD age 48±11 years BMI 25.1±3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4-weeks, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4-weeks (achieved intakes SFA:UFA, 19.1:14.8 and 8.9:24.5% total energy respectively). Serum LDL-C, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet.
RESULTS: Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids [LDL-C (-0.50 mmol/L; 95%CI:-0.58,-0.42), HDL-C (-0.11 mmol/L; 95%CI:-0.14,-0.08) and total cholesterol (-0.65 mmol/L; 95%CI:-0.75,-0.55)]. The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL-C ratio, non-HDL-C, E-selectin (P<0.0001) and LDL subfraction composition [cholesterol (LDL-I and LDL-II), apoB100 (LDL-I and LDL-II), and TAG (LDL-II)] (P<0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P<0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P=0.035). Marked inter-individual variation in the change in serum LDL-C response (-1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL-C before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL-C response to SFA.
CONCLUSIONS: These findings support the efficacy of UK SFA dietary guidelines for the overall lowering of serum LDL-C, but showed marked variation in LDL-C response. Further identification of the determinants of this variation will facilitate targeting and increasing efficacy of these guidelines.
BACKGROUND: The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).