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在腹部肥胖患者中补充 n-3 或 n-6 多不饱和脂肪酸后脂蛋白颗粒亚类、标准脂质和载脂蛋白的变化：一项随机双盲交叉研究。

Changes in lipoprotein particle subclasses, standard lipids, and apolipoproteins after supplementation with n-3 or n-6 PUFAs in abdominal obesity: A randomized double-blind crossover study.

机构信息

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway; Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.

Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.

出版信息

Clin Nutr. 2021 May;40(5):2556-2575. doi: 10.1016/j.clnu.2021.03.040. Epub 2021 Apr 3.

DOI:10.1016/j.clnu.2021.03.040

PMID:33933722

Abstract

BACKGROUND & AIMS: Marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower circulating levels of triacylglycerols (TAGs), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) may reduce cholesterol levels. Clinical studies on effects of these dietary or supplemental PUFAs on other blood fat fractions are few and have shown conflicting results. This study aimed to determine effects of high-dose supplemental n-3 (EPA + DHA) and n-6 (LA) PUFAs from high-quality oils on circulating lipoprotein subfractions and standard lipids (primary outcomes), as well as apolipoproteins, fatty acids, and glycemic control (secondary outcomes), in females and males with abdominal obesity.

METHODS

This was a randomized double-blind crossover study with two 7-wk intervention periods separated by a 9-wk washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (TAG fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we investigated lipoprotein particle subclasses by nuclear magnetic resonance spectroscopy, as well as standard lipids, apolipoproteins, fatty acid profiles, and glucose and insulin. Data were analyzed by linear mixed-effects modeling with 'subjects' as the random factor.

RESULTS

The difference between interventions in relative change scores was among the lipoprotein subfractions significant for total very-low-density lipoproteins (VLDLs) (n-3 vs. n-6: -38%∗ vs. +16%, p < 0.001; ∗: significant within-treatment change score), large VLDLs (-58%∗ vs. -0.91%, p < 0.001), small VLDLs (-57%∗ vs. +41%∗, p < 0.001), total low-density lipoproteins (LDLs) (+5.8%∗ vs. -4.3%∗, p = 0.002), large LDLs (+23%∗ vs. -2.1%, p = 0.004), total high-density lipoproteins (HDLs) (-6.0%∗ vs. +3.7%, p < 0.001), large HDLs (+11%∗ vs. -5.3%, p = 0.001), medium HDLs (-24%∗ vs. +6.2%, p = 0.030), and small HDLs (-9.9%∗ vs. +9.6%∗, p = 0.002), and among standard lipids for TAGs (-16%∗ vs. -2.6%, p = 0.014), non-esterified fatty acids (-19%∗ vs. +5.5%, p = 0.033), and total cholesterol (-0.28% vs. -4.4%∗, p = 0.042). A differential response in relative change scores was also found for apolipoprotein (apo)B (+0.40% vs. -6.0%∗, p = 0.008), apoA-II (-6.0%∗ vs. +1.5%, p = 0.001), apoC-II (-11%∗ vs. -1.7%, p = 0.025), and apoE (+3.3% vs. -3.8%, p = 0.028).

CONCLUSIONS

High-dose supplementation of high-quality oils with n-3 (EPA + DHA) or n-6 (LA) PUFAs was followed by reductions in primarily TAG- or cholesterol-related markers, respectively. The responses after both interventions point to changes in the lipoprotein-lipid-apolipoprotein profile that have been associated with reduced cardiometabolic risk, also among people with TAG or LDL-C levels within the normal range.

REGISTRATION

Registered under ClinicalTrials.gov Identifier: NCT02647333.

CLINICAL TRIAL REGISTRATION

Registered at https://clinicaltrials.gov/ct2/show/NCT02647333.

摘要

背景与目的

海洋来源的 ω-3（n-3）多不饱和脂肪酸（PUFA），主要是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），可降低三酰甘油（TAG）的循环水平，而植物来源的 ω-6（n-6）PUFA 亚油酸（LA）可能降低胆固醇水平。关于这些膳食或补充 PUFAs 对其他血脂成分的影响的临床研究很少，且结果相互矛盾。本研究旨在确定高剂量补充高品质鱼油中的 n-3（EPA+DHA）和 n-6（LA）PUFAs 对女性和男性腹型肥胖者循环脂蛋白亚组分和标准脂质（主要结局）以及载脂蛋白、脂肪酸和血糖控制（次要结局）的影响。

方法

这是一项随机双盲交叉研究，两个 7 周的干预期之间间隔 9 周的洗脱期。女性（n=16）每天补充 3 g/d 的 EPA+DHA（TAG 鱼油）或 15 g/d 的 LA（红花油），而男性（n=23）每天补充 4 g/d 的 EPA+DHA 或 20 g/d 的 LA。在禁食血样中，我们通过核磁共振光谱法研究了脂蛋白颗粒亚组分，以及标准脂质、载脂蛋白、脂肪酸谱和葡萄糖及胰岛素。数据分析采用线性混合效应模型，以“受试者”作为随机因素。

结果

在脂蛋白亚组分中，相对于干预的差异，总极低密度脂蛋白（VLDLs）的相对变化分数具有显著意义（n-3 与 n-6：-38%* vs. +16%，p<0.001；：治疗内变化分数显著）、大 VLDLs（-58% vs. -0.91%，p<0.001）、小 VLDLs（-57%* vs. +41%，p<0.001）、总低密度脂蛋白（LDLs）（+5.8% vs. -4.3%，p=0.002）、大 LDLs（+23% vs. -2.1%，p=0.004）、总高密度脂蛋白（HDLs）（-6.0%* vs. +3.7%，p<0.001）、大 HDLs（+11%* vs. -5.3%，p=0.001）、中 HDLs（-24%* vs. +6.2%，p=0.030）和小 HDLs（-9.9%* vs. +9.6%，p=0.002），标准脂质中 TAGs（-16% vs. -2.6%，p=0.014）、非酯化脂肪酸（-19%* vs. +5.5%，p=0.033）和总胆固醇（-0.28% vs. -4.4%，p=0.042）也存在差异。载脂蛋白（apo）B 的相对变化分数也存在差异（+0.40% vs. -6.0%，p=0.008）、apoA-II（-6.0%* vs. +1.5%，p=0.001）、apoC-II（-11%* vs. -1.7%，p=0.025）和 apoE（+3.3% vs. -3.8%，p=0.028）。