Fukami Kei, Yamagishi Sho-ichi, Sakai Kazuko, Kaida Yusuke, Yokoro Miyuki, Ueda Seiji, Wada Yoshifumi, Takeuchi Masayoshi, Shimizu Makiko, Yamazaki Hiroshi, Okuda Seiya
*Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; †Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan; ‡Division of Nephrology, Wada Cardiovascular Clinic, Tosu, Japan; §Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan; and ¶Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan.
J Cardiovasc Pharmacol. 2015 Mar;65(3):289-95. doi: 10.1097/FJC.0000000000000197.
Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue.
Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured.
Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043).
This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.
食物或补充剂来源的左旋肉碱被肠道微生物群转化为三甲胺（TMA），TMA进一步代谢为氧化三甲胺（TMAO），在动物模型中参与动脉粥样硬化的促进过程。同时，肉碱缺乏在血液透析（HD）患者加速动脉粥样硬化中起作用。然而，口服左旋肉碱补充剂对HD患者循环中TMAO水平以及血管损伤和氧化应激标志物的影响仍不清楚。在本研究中，我们解决了这个问题。
31例肉碱缺乏的HD患者接受口服左旋肉碱（900mg/d）治疗6个月。在基线和治疗后，测量临床变量，包括肉碱组分、TMA、TMAO、晚期糖基化终产物（AGE）、细胞间黏附分子-1可溶性形式（sICAM-1）、血管细胞黏附分子-1（sVCAM-1）和丙二醛（MDA）的循环水平。
口服左旋肉碱补充剂显著提高了总肉碱、游离肉碱、酰基肉碱以及血浆TMA和TMAO水平，而降低了血管损伤和氧化应激标志物，如sICAM-1、sVCAM-1和MDA水平。基线时TMA和TMAO水平相互相关，游离肉碱与TMAO水平独立相关。此外，AGE值相对于基线的变化（ΔAGE）与ΔsICAM-1呈正相关（P = 0.043），并且是ΔsICAM-1的唯一独立决定因素（R = 0.133，P = 0.043）。
本研究表明，虽然口服左旋肉碱补充剂与TMAO水平升高有关，但它可能对HD患者的血管损伤有益。HD患者补充左旋肉碱的血管保护特性可能部分归因于其对AGE的抑制作用。
