Hugh Sinclair Unit of Nutrition, School of Chemistry, Food Biosciences and Pharmacy, University of Reading, Reading, UK.
Atherosclerosis. 2010 Mar;209(1):104-10. doi: 10.1016/j.atherosclerosis.2009.08.024. Epub 2009 Aug 21.
To investigate the impact of apolipoprotein E (apoE) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) intervention in humans.
38 healthy normolipidaemic males, prospectively recruited on the basis of apoE genotype (n=20 E3/E3 and n=18 E3/E4), completed a double-blind placebo-controlled cross-over trial, consisting of 3 x 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3g EPA/day) or DHA-rich oil (DRO, 3.7g DHA/day) in random order, separated by 10 week wash-out periods. A significant genotype-independent 28% and 19% reduction in plasma triglycerides in response to ERO and DRO was observed. For total cholesterol (TC), no significant treatment effects were evident; however a significant genotype by treatment interaction emerged (P=0.045), with a differential response to ERO and DRO in E4 carriers. Although the genotype x treatment interaction for LDL-cholesterol (P=0.089) did not reach significance, within DRO treatment analysis indicated a 10% increase in LDL (P=0.029) in E4 carriers with a non-significant 4% reduction in E3/E3 individuals. A genotype-independent increase in LDL mass was observed following DRO intervention (P=0.018). Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins (VLDL) from the human trial, indicated that following DRO treatment, VLDL(2) fractions obtained from E3/E4 individuals resulted in a significant 32% (P=0.002) reduction in LDL uptake relative to the control.
High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.
研究载脂蛋白 E（apoE）基因型对人体摄入二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）后血浆脂蛋白谱应答的影响。
38 名健康的血脂正常男性，根据 apoE 基因型（n=20 E3/E3 和 n=18 E3/E4）前瞻性招募，完成了一项双盲安慰剂对照交叉试验，包括 3 个 4 周干预期，分别接受对照油、富含 EPA 的油（ERO，每天 3.3g EPA）或富含 DHA 的油（DRO，每天 3.7g DHA），随机顺序排列，每个干预期之间间隔 10 周洗脱期。观察到 ERO 和 DRO 可使血浆甘油三酯分别显著降低 28%和 19%，且这种降低与基因型无关。对于总胆固醇（TC），未观察到明显的治疗效果；然而，出现了基因型与治疗的显著相互作用（P=0.045），E4 携带者对 ERO 和 DRO 的反应不同。虽然 LDL-胆固醇的基因型与治疗的相互作用（P=0.089）未达到显著水平，但 DRO 治疗分析表明，E4 携带者的 LDL 增加了 10%（P=0.029），而 E3/E3 个体的 LDL 减少了 4%。DRO 干预后观察到 LDL 质量的基因型独立增加（P=0.018）。在 HepG2 细胞中进行的血浆极低密度脂蛋白（VLDL）的竞争摄取研究表明，在 DRO 治疗后，从 E3/E4 个体获得的 VLDL(2) 部分导致 LDL 摄取显著减少 32%（P=0.002），与对照相比。
高剂量 DHA 补充与 E4 携带者总胆固醇的增加有关，这似乎是由于 LDL-C 的增加引起的，并且可能在一定程度上抵消了 DHA 在该人群亚组中的心脏保护作用。
