左旋肉碱补充对血液透析患者组织中晚期糖基化终产物的潜在抑制作用。
Potential inhibitory effects of L-carnitine supplementation on tissue advanced glycation end products in patients with hemodialysis.
机构信息
1 Division of Nephrology, Department of Medicine, Kurume University School of Medicine , Kurume, Japan .
出版信息
Rejuvenation Res. 2013 Dec;16(6):460-6. doi: 10.1089/rej.2013.1459.
BACKGROUND AND AIMS
Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether L-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency.
METHODS
This was a single-center study. One hundred and two HD patients (total carnitine levels <50 μmol/L) were enrolled and randomized to either oral administration of L-carnitine (900 mg/day) (n=51) or control (n=51). After 6 months, metabolic and inflammatory variables, including serum levels of carnitine, were measured. Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader.
RESULTS
There were no significant differences of clinical variables at baseline between the control and L-carnitine therapy group. Thirty-two patients did not complete the assessment or treatment of the study. Oral L-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol (LDL-C), triglycerides, total, free, and acyl carnitine levels, while it decreased alanine transaminase, acyl/free carnitine ratio, β₂-microglobulin, and skin AGE values. Change in total carnitine values from baseline (Δtotal carnitine) and Δfree carnitine were inversely associated with Δskin AGE levels in L-carnitine-treated patients (p=0.036 and p=0.016, respectively). In multiple regression analysis, Δfree carnitine was a sole independent determinant of Δskin AGEs (R²=0.178).
CONCLUSIONS
The present study demonstrated that oral L-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency. These observations suggest that supplementation of L-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD.
背景与目的
晚期糖基化终产物（AGEs）可导致血液透析（HD）患者发生心血管疾病。我们最近发现，在 HD 患者中，肉毒碱水平与皮肤 AGE 水平呈负相关。我们研究了肉毒碱缺乏的 HD 患者补充左旋肉碱是否能降低皮肤 AGE 水平。
方法
这是一项单中心研究。共纳入 102 例总肉碱水平<50 μmol/L 的 HD 患者，并随机分为口服左旋肉碱（900mg/d）组（n=51）或对照组（n=51）。6 个月后，检测代谢和炎症指标，包括血清肉碱水平。采用 AGE 阅读器评估皮肤自动荧光来检测皮肤 AGE 水平。
结果
对照组和左旋肉碱治疗组的基线临床变量无显著差异。32 例患者未完成研究的评估或治疗。口服左旋肉碱补充 6 个月可显著升高 LDL-C、甘油三酯、总、游离和酰基肉碱水平，同时降低丙氨酸氨基转移酶、酰基/游离肉碱比值、β₂-微球蛋白和皮肤 AGE 值。与基线相比，左旋肉碱治疗患者的总肉碱值变化（Δ总肉碱）和Δ游离肉碱与Δ皮肤 AGE 值呈负相关（分别为 p=0.036 和 p=0.016）。多元回归分析显示，Δ游离肉碱是唯一与Δ皮肤 AGEs 独立相关的因素（R²=0.178）。
结论
本研究表明，口服左旋肉碱补充可显著降低肉毒碱缺乏的 HD 患者皮肤 AGE 水平。这些观察结果提示，补充左旋肉碱可能是预防 HD 患者肉毒碱缺乏时组织 AGE 积聚的一种新的治疗策略。
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