血清中的谷固醇/胆固醇比值可预测植物固醇摄入对胆固醇降低的反应：一项双中心、随机、单盲、安慰剂对照试验。

Lathosterol-to-cholesterol ratio in serum predicts cholesterol-lowering response to plant sterol consumption in a dual-center, randomized, single-blind placebo-controlled trial.

机构信息

From the Richardson Centre for Functional Foods and Nutraceuticals (DSM, PKE, and PJHJ) and the Departments of Food Science (PJHJ) and Human Nutritional Sciences (DSM, PKE, and PJHJ), University of Manitoba, Winnipeg, Manitoba, Canada, and the USDA, Agricultural Research Service, Beltsville Human Nutrition Research Center, Beltsville, MD (SKG and DJB).

出版信息

Am J Clin Nutr. 2015 Mar;101(3):432-9. doi: 10.3945/ajcn.114.095356. Epub 2015 Jan 14.

DOI:10.3945/ajcn.114.095356

PMID:25733626

Abstract

BACKGROUND

Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with nonresponse to PS consumption; however, prospective studies that show this association have yet to be conducted.

OBJECTIVE

The goal was to test whether the lathosterol-to-cholesterol ratio (L:C ratio), a surrogate marker of endogenous cholesterol synthesis, serves as an a priori predictor of cholesterol lowering in response to PS consumption.

DESIGN

Sixty-three mildly hypercholesterolemic adults who were preselected as possessing either high endogenous cholesterol synthesis [HS; n = 24; L:C = 2.03 ± 0.39 μmol/mmol (mean ± SD)] or low endogenous cholesterol synthesis (LS; n = 39; L:C = 0.99 ± 0.28 μmol/mmol) on the basis of baseline L:C consumed 2 g PS/d or a placebo for 28 d with the use of a dual-center, single-blind, randomized crossover design. Plasma lipid and noncholesterol sterol concentrations were measured at the end of each phase.

RESULTS

PS consumption lowered total cholesterol (TC; -0.25 ± 0.05 mmol/L; P < 0.0001) and LDL cholesterol (-0.17 ± 0.04 mmol/L; P < 0.0001) overall. Specifically, LS individuals responded to PS treatment with a reduction in TC (-0.40 ± 0.07 mmol/L; P < 0.0001) and LDL cholesterol (-0.29 ± 0.05 mmol/L; P = 0.0002), whereas HS individuals failed to show cholesterol lowering (TC: -0.09 ± 0.09 mmol/L; P = 0.2843; LDL cholesterol: -0.05 ± 0.07 mmol/L; P = 0.4917). The odds of LS participants responding to PS consumption with cholesterol lowering better than the mean cholesterol lowering in all participants were 4.25 (95% CI: 1.242, 14.556; P = 0.0211) for TC and 3.36 (95% CI: 1.112, 10.161; P = 0.0317) for LDL cholesterol, which was higher than for HS participants.

CONCLUSIONS

The L:C ratio predicts the extent of reduction in circulating TC and LDL cholesterol in response to PS consumption. Cholesterol synthesis assessment may thus have a use in identifying responders and nonresponders to PS therapy.

摘要

背景

植物固醇（PS）降胆固醇的益处因个体间疗效的巨大差异而受到影响。用氘掺入法测量的高分数胆固醇合成与对 PS 消费的无反应有关；然而，尚未进行前瞻性研究表明这种关联。

目的

本研究旨在检验内源性胆固醇合成的替代标志物——羊毛固醇/胆固醇比值（L:C 比值）是否可作为 PS 消费降低胆固醇反应的先验预测指标。

设计

63 名轻度高胆固醇血症成年人在基线时根据 L:C 比值（高内源性胆固醇合成[HS]组：n = 24；L:C = 2.03 ± 0.39 μmol/mmol（平均值 ± SD）；低内源性胆固醇合成[LS]组：n = 39；L:C = 0.99 ± 0.28 μmol/mmol）分为 HS 或 LS 亚组，在双中心、单盲、随机交叉设计下，分别摄入 2 g PS/d 或安慰剂 28 天。在每个阶段结束时测量血浆脂质和非胆固醇甾醇浓度。

结果

PS 摄入可降低总胆固醇（TC；-0.25 ± 0.05 mmol/L；P < 0.0001）和 LDL 胆固醇（-0.17 ± 0.04 mmol/L；P < 0.0001）。具体而言，LS 个体对 PS 治疗的 TC（-0.40 ± 0.07 mmol/L；P < 0.0001）和 LDL 胆固醇（-0.29 ± 0.05 mmol/L；P = 0.0002）降低有反应，而 HS 个体则未显示胆固醇降低（TC：-0.09 ± 0.09 mmol/L；P = 0.2843；LDL 胆固醇：-0.05 ± 0.07 mmol/L；P = 0.4917）。LS 参与者对 PS 消费降低胆固醇的反应优于所有参与者平均胆固醇降低的可能性是 HS 参与者的 4.25 倍（95%CI：1.242，14.556；P = 0.0211）（TC）和 3.36 倍（95%CI：1.112，10.161；P = 0.0317）（LDL 胆固醇），高于 HS 参与者。