背景:最近显示短期(4周)补充n-3多不饱和脂肪酸二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)可以剂量依赖性地改善体重正常的慢性阻塞性肺疾病(COPD)患者的蛋白质代谢。此外,EPA/DHA补充能够增加四肢瘦软组织,但不能增加肌肉功能。在慢性临床病症中没有结合n-3PUFA和亮氨酸代谢物β-羟基-β-甲基丁酸(HMB)补充剂的研究。在每天补充EPA/DHA10周时添加HMB是否会增强肌肉和大脑健康,日常功能性能,而COPD患者通过进一步改善蛋白质和氨基酸稳态来提高其生活质量仍是未知的。
方法:COPD患者(GOLD:II-IV,n=46)每天接受10周,根据随机双盲安慰剂对照三组设计,EPA/DHA(n=16),添加HMB的EPA/DHA(n=14),或安慰剂(n=16)。通过凝胶胶囊提供2.0gEPA/DHA或大豆玉米油作为安慰剂的每日剂量,和3.0g的Ca-HMB或麦芽糊精作为安慰剂作为粉末。在干预前和干预后,采用多种氨基酸的脉冲混合物来测量吸收后净蛋白质分解(netPB作为主要终点)和全身产量(WBP)以及氨基酸的转化率.作为次要终点,通过双能X线吸收法评估瘦软组织和脂肪量,通过手握和单腿等速测力计的上部和下部肌肉功能,大脑(认知,福祉)通过评估获得健康,通过测量6分钟步行距离的日常功能性能,4米的步态速度,和姿势平衡,通过问卷调查和生活质量。通过LC-MS/MS分析血浆富集和浓度,以及Luminex的全身炎症和代谢激素。
结果:HMB+EPA/DHA而不是EPA/DHA补充增加吸收后的净PB(p=0.028),和谷氨酰胺的WBP(p=0.024),牛磺酸(p=0.039),和酪氨酸(p=0.036)。EPA/DHA和HMB+EPA/DHA补充均导致苯丙氨酸的WBP增加(p<0.05)。EPA/DHA而不是HMB+EPA/DHA能够增加精氨酸的WBP(p=0.030),瓜氨酸(p=0.008),缬氨酸(p=0.038),以及瓜氨酸向精氨酸的转化(p=0.009)。仅补充HMB+EPA/DHA后,全身和四肢脂肪量减少,而瘦软组织在EPA/DHA(p=0.049)和HMB+EPA/DHA(p=0.073)后增加。没有观察到其他显著的发现。在HMB+EPA/DHA组中观察到几种促炎细胞因子的减少,包括IL-2、IL-17、IL-6、IL-12P40和TNF-β(p<0.05)。
结论:每天补充2gEPA/DHA10周足以诱导COPD患者的肌肉增加,但需要HMB来诱导脂肪减少。尚不清楚HMB是否仅对脂肪质量损失负责或与EPA/DHA具有协同作用。用HMB+EPA/DHA补充观察到的净蛋白质分解的增加可能表明与瘦软组织增加相关的有益的增强的蛋白质周转循环。
背景:ClinicalTrials.gov;NCT03796455。
BACKGROUND: Short-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions. Whether adding HMB to daily EPA/DHA supplementation for 10 weeks enhances muscle and brain health, daily functional performance, and quality of life of patients with COPD by further improving their protein and amino acid homeostasis remains unknown.
METHODS: Patients with COPD (GOLD: II-IV, n = 46) received daily for 10 weeks, according to a randomized double-blind placebo-controlled three-group design, EPA/DHA (n = 16), EPA/DHA to which HMB was added (n = 14), or placebo (n = 16). The daily dose of 2.0 g of EPA/DHA or soy + corn oil as the placebo was provided via gel capsules, and 3.0 g of Ca-HMB or maltodextrin as placebo as powders. At pre- and post-intervention, a pulse mixture of multiple amino acids was administered to measure postabsorptive net protein breakdown (netPB as primary endpoint) and whole body production (WBP) and conversion rates of the amino acids. As secondary endpoints, lean soft tissue and fat mass were assessed by dual-energy X-ray absorptiometry, upper and lower muscle function by handgrip and single leg isokinetic dynamometry, brain (cognitive, wellbeing) health by assessments, daily functional performance by measuring 6-min walk distance, 4-m gait speed, and postural balance, and quality of life by questionnaire. Plasma enrichments and concentrations were analyzed by LC-MS/MS, and systemic inflammatory profile and metabolic hormones by Luminex.
RESULTS: HMB + EPA/DHA but not EPA/DHA supplementation increased postabsorptive netPB (p = 0.028), and WBPs of glutamine (p = 0.024), taurine (p = 0.039), and tyrosine (p = 0.036). Both EPA/DHA and HMB + EPA/DHA supplementation resulted in increased WBP of phenylalanine (p < 0.05). EPA/DHA but not HMB + EPA/DHA was able to increase WBP of arginine (p = 0.030), citrulline (p = 0.008), valine (p = 0.038), and conversion of citrulline to arginine (p = 0.009). Whole body and extremity fat mass were reduced after HMB + EPA/DHA supplementation only, whereas lean soft tissue was increased after EPA/DHA (p = 0.049) and HMB + EPA/DHA (p = 0.073). No other significant findings were observed. Reductions in several proinflammatory cytokines were observed in the HMB + EPA/DHA group including IL-2, IL-17, IL-6, IL-12P40, and TNF-β (p < 0.05).
CONCLUSIONS: Ten weeks of supplementation with 2 g of EPA/DHA daily is sufficient to induce muscle gain in COPD but HMB is needed to induce fat loss. Whether HMB is solely responsible for the fat mass loss or has a synergistic effect with EPA/DHA remains unclear. The increase in net protein breakdown observed with HMB + EPA/DHA supplementation may indicate a beneficial enhanced protein turnover cycling associated with increased lean soft tissue.
BACKGROUND: ClinicalTrials.gov; NCT03796455.