McComsey G A, O'Riordan M, Setzer B, Lebrecht D, Baron E, Walker U A
Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Eur J Clin Nutr. 2008 Aug;62(8):1031-7. doi: 10.1038/sj.ejcn.1602793. Epub 2007 May 30.
Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy.
Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial.
Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry.
In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.
尿苷可消除脂肪细胞培养中核苷类逆转录酶抑制剂的线粒体毒性。我们旨在研究补充尿苷对人类免疫缺陷病毒(HIV)脂肪萎缩患者的人脂肪细胞线粒体DNA(mtDNA)水平的影响。
招募了16名接受含司他夫定抗逆转录病毒治疗的脂肪萎缩患者,给予NucleomaxX,这是一种尿苷生物利用度高的膳食补充剂(每隔一天36克,每日三次,共16周)。然后让患者停用尿苷再随访16周。在试验期间高效抗逆转录病毒治疗保持不变。
14名患者完成了研究。两名受试者在第4周前因与研究无关的原因退出。在整个研究过程中未观察到不良事件。HIV-1 RNA、CD4细胞计数、肝酶和血红蛋白保持不变。体重指数、乳酸、血脂、胰岛素和胰岛素抵抗的稳态模型评估未改变。脂肪、外周血和单核细胞的mtDNA水平彼此不相关,且在整个研究过程中未显示变化。与研究开始时相比,患者和医生评估的脂肪萎缩评分在第16周和第32周时显著改善。
在这项初步研究中,NucleomaxX是安全的,耐受性良好,对HIV指标没有明显有害影响。与体外数据相反,NucleomaxX并未导致脂肪或血液mtDNA水平的变化。