Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine.
Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine.
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DOI：
10.1016/j.ymgmr.2018.04.005
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发表时间：
2018-06
影响因子：
1.9
通讯作者：
Horvath G
中科院分区：
文献类型：
--
作者：
Vallance HD;Koochin A;Branov J;Rosen-Heath A;Bosdet T;Wang Z;Hazen SL;Horvath G
口服补充左旋肉碱是一种常见的治疗方式线粒体疾病，尽管有限的证据的效力。最近，许多研究表明，肠道微生物依赖的代谢产物左旋肉碱，氧化三甲胺（TMAO），是一个独立的和剂量依赖性的心血管疾病（CVD）的危险因素。鉴于有限的数据证明口服左旋肉碱治疗的疗效和新提出的潜在危害的问题，我们评估了血浆TMAO水平与线粒体疾病患者口服左旋肉碱补充剂和不补充。招募了9名受试者并完成了研究。基线时9名受试者中有8名的血浆TMAO浓度<第97.5百分位数（<15.5 μM）。1例3期肾病受试者的血浆TMAO显著升高（治疗前33.98 μm vs治疗后101.6 μm）。补充左旋肉碱至少3个月后（1000 mg/d）时，9例中有7例血浆TMAO水平明显升高;总的来说，血浆TMAO显著升高11.8倍（p < 0.001）从基线中值水平3.54 μm（四分位距（IQR）2.55-8.72）至补充后43.26 μ m（IQR 23.99-56.04）。这项研究的结果表明，长期口服左旋肉碱补充剂显着增加线粒体疾病的受试者血浆TMAO水平。进一步的研究，以评估口服左旋肉碱补充治疗线粒体疾病的疗效和长期安全性是必要的。
Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO), is an independent and dose-dependent risk factor for cardiovascular disease (CVD). Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed plasma TMAO levels in patients with mitochondrial disease with and without oral l-carnitine supplementation. Nine subjects were recruited and completed the study. Eight out of 9 subjects at baseline had plasma TMAO concentrations <97.5th percentile (<15.5 μM). One subject with stage 3 renal disease, had marked elevation in plasma TMAO (pre 33.98 μm versus post 101.6 μm). Following at least 3 months of l-carnitine supplementation (1000 mg per day), plasma TMAO levels were markedly increased in 7out of 9 subjects; overall, plasma TMAO significantly increased 11.8-fold (p < 0.001) from a baseline median level of 3.54 μm (interquartile range (IQR) 2.55–8.72) to 43.26 (IQR 23.99–56.04) post supplementation. The results of this study demonstrate that chronic oral l-carnitine supplementation markedly increases plasma TMAO levels in subjects with mitochondrial disorders. Further studies to evaluate both the efficacy and long term safety of oral l-carnitine supplementation for the treatment of mitochondrial disorders are warranted.
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影响因子：
8.8
作者：
Schugar RC;Shih DM;Warrier M;Helsley RN;Burrows A;Ferguson D;Brown AL;Gromovsky AD;Heine M;Chatterjee A;Li L;Li XS;Wang Z;Willard B;Meng Y;Kim H;Che N;Pan C;Lee RG;Crooke RM;Graham MJ;Morton RE;Langefeld CD;Das SK;Rudel LL;Zein N;McCullough AJ;Dasarathy S;Tang WHW;Erokwu BO;Flask CA;Laakso M;Civelek M;Naga Prasad SV;Heeren J;Lusis AJ;Hazen SL;Brown JM
通讯作者：
Brown JM
DOI：
10.1056/nejmoa1109400
发表时间：
2013-04-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tang WH;Wang Z;Levison BS;Koeth RA;Britt EB;Fu X;Wu Y;Hazen SL
通讯作者：
Hazen SL
DOI：
10.1123/ijsnem.15.4.386
发表时间：
2005-08-01
影响因子：
2.5
作者：
Abramowicz, WN;Galloway, SDR
通讯作者：
Galloway, SDR
DOI：
10.1123/ijsnem.15.6.665
发表时间：
2005-12-01
影响因子：
2.5
作者：
Broad, EM;Maughan, RJ;Galloway, SDR
通讯作者：
Galloway, SDR
影响因子：
5.8
作者：
Stephens, Francis B.;Constantin-Teodosiu, Dumitru;Greenhaff, Paul L.
通讯作者：
Greenhaff, Paul L.