High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients

High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients
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DOI:
10.2215/cjn.04150415
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发表时间:
2016-07-01
影响因子:
9.8
通讯作者:
Ikizler, T. Alp
Ikizler, T. Alp
中科院分区:
医学1区
文献类型:
--
作者:
Deger, Serpil Muge;Hung, Adriana M.;Ikizler, T. Alp

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背景与目的维持性血液透析(MHD)患者普遍存在蛋白质能量浪费和全身炎症。Omega-3(omega-3)脂肪酸具有抗炎特性,并已被证明可以改善蛋白质动态平衡。我们假设,服用高剂量(2.9g/d)omega-3将与减少患有全身炎症的MHD患者的肌肉蛋白质分解有关。设计、设置、参与者和测量这是一项随机、安慰剂对照研究的子研究(NCT00655525)。患者是在2008年9月至2011年6月之间招募的。主要纳入标准包括慢性炎症症状(连续三次测量的平均C反应蛋白mg/L),无活动性感染性或炎症性疾病,在研究前1个月内没有住院,以及没有接受类固醇(>5 mg/d)和/或免疫抑制剂。主要结果是干预前后前臂肌肉和全身蛋白质的分解和合成。患者接受omega-3(n=11)和安慰剂(n=9)治疗12周。用协方差分析比较12周时的结果变量。结果与安慰剂相比,补充omega-3 12周时肌肉蛋白分解显著减少(-31,[四分位数范围,-98-13]比26[四分位数范围,13-87],mug/100ml/min;P=0.01),经多因素调整后仍显著(-46,[95%可信区间,102-1]mU g/100ml/min)。补充omega-3导致前臂肌肉蛋白质合成减少,而安慰剂组的比例增加;然而,经多因素调整后,骨骼肌蛋白质合成或净蛋白质平衡不再有统计学意义。补充omega-3对全身蛋白质合成或分解的影响无统计学意义。结论MHD全身炎症患者补充大剂量omega-3超过12周与前臂肌肉蛋白质分解的减轻有关,但不影响骨骼肌蛋白质合成、骨骼肌净蛋白平衡或全身蛋白质平衡的任何成分。考虑到这两个群体的不平衡和干预持续时间较短,对这些结果的解读应该谨慎。
Background and Objectives Protein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (omega-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) omega-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.Design, setting, participants & measurements This is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (>5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received omega-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics.Results Compared with placebo, omega-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87], mu g/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, 102 to 1] mu g/100 ml per min). omega-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of omega-3 supplementation on whole body protein synthesis or breakdown.Conclusions High-dose omega-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention.