三庚酸甘油酯与三辛酸甘油酯治疗长链脂肪酸氧化障碍：一项双盲、随机对照试验。
Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial.
机构信息
Department of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
出版信息
J Inherit Metab Dis. 2017 Nov;40(6):831-843. doi: 10.1007/s10545-017-0085-8. Epub 2017 Sep 4.
BACKGROUND
Observational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs.
METHODS
A double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis.
RESULTS
Patients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups.
CONCLUSIONS
C7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC-FAODs.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov NCT01379625.
背景
观察报告表明，通过补充柠檬酸循环中间产物进行补料可以比传统的中链甘油三酯（MCT）治疗长链脂肪酸氧化障碍（LC-FAOD）具有治疗优势，但尚未报道对照试验。我们的研究目的是比较庚三酸酯（C7），一种补料七碳脂肪酸三酸甘油酯和辛三酸酯（C8），一种八碳脂肪酸三酸甘油酯，在 LC-FAOD 患者中的作用。
方法
对 32 名 LC-FAOD 患者（肉碱棕榈酰转移酶-2、极长链酰基辅酶 A 脱氢酶、三功能蛋白或长链 3-羟基酰基辅酶 A 脱氢酶缺乏症）进行了一项双盲、随机对照试验，这些患者被随机分配到含有 20%总能量的饮食中，饮食中的能量分别来自 C7 或 C8，持续 4 个月。主要结局包括总能量消耗（TEE）、超声心动图检查的心脏功能、运动耐量以及急性运动后磷酸肌酸的恢复情况的变化。次要结局包括身体成分、血液生物标志物和不良事件，包括横纹肌溶解症的发生率。
结果
C7 组患者左心室（LV）射血分数增加了 7.4%（p=0.046），而在休息时超声心动图检查中 LV 壁质量减少了 20%（p=0.041）。与服用 C8 的患者相比，他们在进行中等强度运动应激测试时，需要更低的心率来完成相同的工作量。两组之间在 TEE、磷酸肌酸恢复、身体成分、横纹肌溶解症发生率或任何其他次要结局测量方面均无差异。
结论
C7 改善了 LC-FAOD 患者的 LV 射血分数，降低了休息时的 LV 质量，并降低了运动时的心率。
临床试验注册
Clinicaltrials.gov NCT01379625。
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