什么是左旋肉碱？

左旋肉碱是人体所需的天然能量。

左旋肉碱用于治疗肉碱缺乏症。

左旋肉碱也可用于本用药指南中未列出的目的。

重要信息

遵循药品标签和包装上的所有说明。告诉您的每个医疗保健提供者所有您的医疗状况，过敏和您使用的所有药物。

在服药之前

为确保左旋肉碱对您安全，请告知您的医生是否患有：

• 肾脏疾病（或正在透析）；

• 癫痫病史；要么

• 如果您使用血液稀释剂（华法令，香豆素，扬托芬），并且进行了常规的“ INR”或凝血酶原时间检测。

左旋肉碱不会伤害未出生的婴儿。告诉医生您是否怀孕或计划怀孕。

尚不知道左卡尼汀会进入母乳中还是会损害哺乳婴儿。使用左旋肉碱时，请勿哺乳。

我应该如何服用左旋肉碱？

遵循处方标签上的所有指示。不要以更大或更小的量服用该药，也不要服用超过建议的时间。

使用提供的剂量注射器或专用的剂量测量勺或药杯测量液体药物。如果您没有剂量测量装置，请向您的药剂师咨询。

液体药物可以单独服用，也可以与饮料或软食品混合服用。慢慢喝或吃混合物。

左旋肉碱应每3或4小时均匀间隔服用一次。如果您在用餐时或饭后30分钟内服用此药，效果最好。

使用左旋肉碱时，您可能需要经常进行血液检查。

存放在室温下，远离湿气和热源。

如果我错过剂量怎么办？

记住时，请立即服用错过的剂量。如果快到下一次预定的时间了，请跳过错过的剂量。不要服用多余的药物来弥补错过的剂量。

如果我服药过量怎么办？

寻求紧急医疗护理或致电1-800-222-1222，拨打毒药帮助热线。

服用左旋肉碱应该避免什么？

关于食物，饮料或活动的任何限制，请遵循医生的指示。

左旋肉碱的副作用

如果您有以下任何过敏反应迹象，请寻求紧急医疗救助：呼吸困难；脸，嘴唇，舌头或喉咙肿胀。

如果您有以下情况，请立即致电您的医生：

• 抽搐（抽搐）。

常见的副作用可能包括：

• 肚子痛;

• 恶心，呕吐;要么

• 腹泻。

这不是副作用的完整列表，并且可能会发生其他副作用。打电话给您的医生，征求有关副作用的医疗建议。您可以通过1-800-FDA-1088向FDA报告副作用。

哪些其他药物会影响左旋肉碱？

其他药物可能会与左卡尼汀相互作用，包括处方药和非处方药，维生素和草药产品。向您的每个医疗保健提供者告知您现在使用的所有药物以及您开始或停止使用的任何药物。

版权所有1996-2018 Cerner Multum，Inc.版本：1.03。

注意：本文包含左旋肉碱的副作用信息。此页面上列出的某些剂型可能不适用于商标名称L-肉碱。

对于消费者

适用于左卡尼汀：胶囊剂，溶液剂，片剂

需要立即就医的副作用

除左旋肉碱（左旋肉碱中的活性成分）外，还有可能产生一些不良作用。尽管并非所有这些副作用都可能发生，但如果确实发生了，则可能需要医疗护理。

服用左卡尼汀时，如有任何下列副作用，请尽快与您的医生联系：

比较普遍;普遍上

• 高血压

不常见

• 快速的心跳
• 发热

罕见

• 癫痫发作

不需要立即就医的副作用

左卡尼汀可能会发生一些通常不需要医疗的副作用。随着身体对药物的适应，这些副作用可能会在治疗期间消失。另外，您的医疗保健专业人员可能会告诉您一些预防或减少这些副作用的方法。

请咨询您的医疗保健专业人员，是否持续存在以下不良反应或令人讨厌，或者是否对这些副作用有任何疑问：

比较普遍;普遍上

• 腹部或腹部绞痛
• 腹泻
• 头痛
• 恶心或呕吐

不常见

• 腹部不适
• 体味
• 萧条
• 头晕
• 视力受损
• 食欲不振或体重减轻
• 手，小腿和脚肿胀
• 刺痛感
• 弱点

对于医疗保健专业人员

适用于左卡尼汀：注射液，口服胶囊，口服溶液，口服片剂

胃肠道

非常常见（10％或更多）：腹泻（35％），腹痛（21％），呕吐（21％），恶心（12％）

常见（1％至10％）：便秘，消化不良，胃肠道疾病，黑便

非常罕见（少于0.01％）：腹部绞痛^[参考]

神经系统

非常常见（10％或更多）：头痛（37％），头晕（18％），感觉异常（12％）

常见（1％至10％）：高渗，眩晕，味觉变态

未报告的频率：癫痫发作（有或没有先发癫痫发作活动），癫痫发作频率和/或严重程度增加^[参考]

新陈代谢

有临床试验报告称，向尿毒症透析患者服用高剂量左旋肉碱（左旋肉碱中的活性成分）（3克/天）会引起明显的高甘油三酸酯血症。 ^[参考]

非常常见（10％或更多）：高钙血症（15％），高血容量（12％）

常见（1％至10％）：厌食症，高钾血症^[参考]

其他

非常常见（10％或更多）：疼痛（35％），流感综合征（29％），胸痛（15％），意外伤害（12％），乏力（12％），发烧（12％）

常见（1％至10％）：周围水肿，体重减轻，体重增加

非常罕见（小于0.01％）：体臭，国际标准化比率（INR）增加^[参考]

本地

很常见（10％或更多）：注射部位反应（38％） ^[参考]

肌肉骨骼

在慢性血液透析患者中​​，左旋肉碱（左旋肉碱中的有效成分）与安慰剂治疗相关的肌肉骨骼副作用包括乏力（8％至12％vs 8％）和腿抽筋（4％至8％vs 13） ％）。接受D，L-肉碱（而非左卡尼汀）的尿毒症患者发生轻度肌无力。 ^[参考]

血液学

来自临床试验的报告表明，给予血液透析患者的高剂量左卡尼汀（左卡尼汀中的活性成分）（3克/天）与血小板聚集显着增加有关。 ^[参考]

非常常见（10％或更多）：贫血（12％） ^[参考]

肾的

常见（1％至10％）：肾衰竭（慢性血液透析患者） ^[参考]

内分泌

常见（1％至10％）：甲状旁腺疾病^[参考]

呼吸道

非常常见（10％或更多）：咽炎（27％），咳嗽增多（18％），呼吸困难（11％），鼻炎（11％）

常见（1％至10％）：支气管炎，鼻窦炎^[参考]

皮肤科的

常见（1％至10％）：瘙痒，皮疹^[参考]

眼科

常见（1％至10％）：弱视，眼疾^[参考]

泌尿生殖

常见（1％至10％）：尿路感染^[参考]

心血管的

非常常见（10％或更多）：高血压（21％），低血压（19％）

常见（1％至10％）：心房颤动，心律不齐，心血管疾病，心电图异常，心，心动过速，血管疾病^[参考]

过敏症

常见（1％至10％）：过敏反应^[参考]

精神科

常见（1％至10％）：抑郁，焦虑，药物依赖性，失眠^[参考]

免疫学的

很常见（10％或更多）：感染（24％） ^[参考]

某些副作用可能没有报道。您可以将其报告给FDA。

常见的成人肉碱缺乏症剂量

代谢性疾病：
原发性或继发性肉碱缺乏症：
口服液：
初始剂量：每天口服1克，均分剂量（每3-4小时）
维持剂量：每天口服1至3克，均分剂量（每3至4小时）

口服片剂：
每天990毫克口服1至3次，具体取决于临床反应

静脉注射液：
50 mg / kg缓慢的2到3分钟推注或通过输注，每天一次
-在严重的新陈代谢危机中，可以给予负荷剂量，然后在接下来的24小时内每3至4小时（但不少于每6小时）给予等效剂量
-随后的日剂量应在50 mg / kg范围内或根据治疗需要
-最高给药剂量为300 mg / kg。


血液透析终末期肾病患者
静脉内解决方案：
初始剂量：10至20 mg / kg，在每次透析后以缓慢的2至3分钟推注方式注入静脉回流管
-考虑透析前血浆谷氨酸水平低于正常水平（40至50微摩尔/升）的疗法。
-剂量调整应以透析前左卡尼汀低谷水平为指导。
-可以在治疗的第三或第四周进行剂量下调。

评论：
-缓慢增加剂量，同时评估耐受性和治疗反应。
-定期监测血液化学，生命体征，血浆肉碱浓度和整体临床状况。
-谨慎使用较高剂量，并且仅在临床和生化考虑因素可能使较高剂量有益时才使用。
-在某些患者中，尤其是那些患有心肌病的患者，补充药物可以迅速缓解体征和症状。
-治疗应包括患者状况所指示的支持疗法和其他疗法。

用途：
-原发性全身肉碱缺乏
-急性和慢性治疗先天性代谢错误导致继发性肉碱缺乏
-预防和治疗接受透析的终末期肾病患者的肉碱缺乏症（仅静脉注射）

儿科肉碱缺乏症的常用剂量

代谢性疾病：
口服液或片剂：
初始剂量：50 mg / kg /天，均分口服
维持剂量：每天50至100 mg / kg /天，均分剂量
最大剂量：每天3克

静脉注射液：
50 mg / kg缓慢的2到3分钟推注或通过输注，每天一次
-在严重的新陈代谢危机中，可以给予负荷剂量，然后在接下来的24小时内每3至4小时（但不少于每6小时）给予等效剂量
-随后的日剂量应在50 mg / kg范围内或根据治疗需要
-最高给药剂量为300 mg / kg。


血液透析终末期肾病患者
静脉内解决方案：
初始剂量：10至20 mg / kg，在每次透析后以缓慢的2至3分钟推注方式注入静脉回流管
-考虑透析前血浆谷氨酸水平低于正常水平（40至50微摩尔/升）的疗法。
-剂量调整应以透析前左卡尼汀低谷水平为指导。
-可以在治疗的第三或第四周进行剂量下调。

评论：
-缓慢增加剂量，同时评估耐受性和治疗反应。
-定期监测血液化学，生命体征，血浆肉碱浓度和整体临床状况。
-谨慎使用较高剂量，并且仅在临床和生化考虑因素可能使较高剂量有益时才使用。
-在某些患者中，尤其是那些患有心肌病的患者，补充药物可以迅速缓解体征和症状。
-治疗应包括患者状况所指示的支持疗法和其他疗法。

用途：
-原发性全身肉碱缺乏
-急性和慢性治疗先天性代谢错误导致继发性肉碱缺乏
-预防和治疗接受透析的终末期肾病患者的肉碱缺乏症（仅静脉注射）

肾脏剂量调整

肾功能不全的患者尚未评估安全性和疗效。
-对肾功能严重受损的患者或透析终末期肾脏疾病的患者进行慢性高剂量口服给药可能会导致潜在毒性代谢产物的积累。

肝剂量调整

数据不可用

透析

血液透析：参见成人或儿童常用剂量
腹膜透析：无可用数据

其他的建议

行政建议：
-口服溶液可以单独食用，也可以溶于其他饮料或流质食品中以减轻口感疲劳。
-缓慢服用口服溶液，并在一整天均匀地分配剂量，以最大程度地提高耐受性。
-饭后或饭后服用是优选的。

监控：
-定期监测血液化学，生命体征，血浆肉碱浓度和整体临床状况。

动物研究

对老年大鼠大脑的生化和电子显微镜研究表明，乙酰基左旋肉碱（ALC）可以抵抗与年龄有关的组织衰老，并提高脂肪酸利用率。但是，由于电子流量增加，它也可能导致氧化应激增加。已显示与抗氧化剂（例如α-硫辛酸）组合使用ALC可调节氧化效果。 12 ， 13当组合，ALC加导致与线粒体膜电势，氧的消耗年龄相关下降，以及众多的辅因子，矿物质和与线粒体功能和细胞呼吸相关的酶的部分改进硫辛酸给药。但是，单独使用ALC时，线粒体膜电位（线粒体功能的关键指标）的改善更大。 13 ， 15

与未经治疗的老年大鼠的大脑相比，ALC加α-硫辛酸处理的老年大鼠大脑中的神经元线粒体显示线粒体结构评分（ P = 0.02）和完整的线粒体数量（ P <0.001）有显着改善；治疗后，老年大鼠的线粒体超微结构模式与年轻大鼠（治疗和未治疗）相似。 13这些结果类似于在老年和年轻大鼠的肝细胞线粒体活性研究中发现的结果，其中ALC（第1至4周）和硫辛酸（第3至4周）的组合改善了与年龄相关的氧化应激增加（ P = 0.0001），并减少线粒体代谢的下降（ P = 0.02）。处理过的老大鼠的氧化应激水平与未处理过的年轻大鼠的氧化应激水平没有显着差异。另外，与未处理的老年大鼠相比，经处理的老年大鼠的活动能力下降了3倍（ P = 0.03），表明代谢活动的生理参数得到了改善。对于大龄大鼠，ALC加硫辛酸的剂量分别约为0.75和0.075 g / kg /天，对于小龄大鼠，其剂量分别为1.2和0.12 g / kg /天。 15

临床资料

衰老过程是帕金森氏病发展的最大风险因素。在正常的衰老组织中也发现了一些与帕金森病有关的中枢神经系统变化（即，多巴胺减少，谷胱甘肽减少，氧化应激标记增加，α突触核蛋白，淀粉样蛋白，线粒体DNA缺失）。营养补品（包括乙酰基左旋肉碱）处理这些衰老危险因素的能力通过抗氧化剂响应元件Keap / Nrf2途径的基因表达以及调节能量代谢，线粒体生物发生的基因表达调控的转录共激活因子来支持。 ，以及线粒体的结构完整性–过氧化物酶体增殖物激活受体gamma共同激活剂1 alpha。 12进行了一项随机，双盲，安慰剂对照的2期研究，以确定L-肉碱对70名100-106岁的西西里百岁老人的生理和心理疲劳以及认知功能的功效，并随机接受口服左旋肉碱2克/天或安慰剂，持续6个月，并另外随访6个月。补充左旋肉碱可改善总脂肪量，总肌肉量，血浆总肉碱，血浆长链和短链酰基肉碱，总胆固醇，步行6分钟的运动后的身体疲劳，精神疲劳，疲劳严重程度，日常活动评估，以及迷你精神状态检查。两组之间的尿肉碱水平没有差异。左旋肉碱耐受性良好； 1名患者因腹泻的不良影响退出治疗组。 16

抗氧化剂

动物研究

因为补充乙酰基-L-肉碱已经显示出增加的ATP线粒体电子转运活性和生产，事件可能增加氧化应激， 12给药通常以组合进行与抗氧化剂（即，硫辛酸）。 12 ， 13 ， 15

临床研究

一项台湾冠状动脉疾病且至少一条大动脉狭窄程度为50％的台湾患者的单盲，随机，安慰剂对照试验（N = 47）显示，氧化应激的生物标志物有所改善，并且抗氧化酶的数量增加了每天两次，补充12周500毫克左旋肉碱。这些数据建立在较早的临床试验的基础上，表明较高剂量的左旋肉碱（至少2,000 mg /天）对患有心肌缺血的患者的心脏代谢和功能具有保护作用。没有观察到严重的不良事件。 2

恶病质

一项前瞻性，多中心，双盲，随机，对照试验比较了左旋肉碱和安慰剂对72例IV期胰腺癌患者恶病质的影响（CARPAN试验）。每天口服4克左旋肉碱补充剂可使肉碱血清血浆水平在第6周增加至基本值的60％，而在安慰剂组中则略有下降。与左旋肉碱组的基线相比，在第12周时，BMI，身体细胞质量和体脂增加；而安慰剂组的BMI降低。与安慰剂组相比，接受左旋肉碱的患者的认知功能，整体健康状况和胃肠道症状均有改善。但是，两组之间在疲劳，生存获益或住院时间方面均未见差异。左旋肉碱耐受性良好，两组之间的不良反应没有差异。 56

心血管的

临床研究

截止到2013年11月，对随机对照试验（RCT）进行了系统回顾和荟萃分析，评估了心肌梗塞情况下左旋肉碱的各种剂量。五项试验（N = 3,108）符合纳入标准；所有试验均质量好，异质性低。每日维持剂量为2至6克口服左旋肉碱，给药期最长为12个月； 3个试验在5到7天内使用了6或9 g /天的口服或IV负荷剂量。在报告特定心血管事件（即不稳定）的研究中，使用4种每日口服维持剂量（2、3、4、6 g）的受试者之间或使用2和6 g /日剂量的受试者之间，没有观察到全因死亡率的差异。心绞痛，心力衰竭，心肌梗塞）。参与者之间的微不足道的趋势倾向于每天3 g的剂量。 3

在双盲，交叉试验（N = 36）中，与α-硫辛酸联合使用，ALC的使用显着降低了患有稳定冠心病的至少55岁成年人的动脉张力（ P = 0.008）。但是，只有收缩压（SBP）高于中值（大于135 mm Hg）的亚组和代谢综合征的亚组在治疗后SBP有所改善（两者均为P = 0.01）。终止治疗后，导致2名患者退出的不良反应（瘙痒性皮疹和恶心）得以解决。 17

在严格的审查中，评估了ALC和PLC在治疗心血管疾病中的有效性。 PLC被认为可有效治疗周围动脉疾病的间歇性lau行，尤其是与运动，脉冲性肌肉加压疗法和其他策略相结合时。在9项评价PLC间歇性lau行的临床试验中，最大的一项是对485例接受口服PLC 2 g /天治疗1年的患者进行的；与安慰剂组相比，基线最大步行距离严重受限（小于250 m）的患者有明显改善（分别为87％和46％； P <0.01）。 ALC或PLC对缺血性心脏病（心肌缺血）的治疗效果尚不明确，可能有利于预防而不是治疗。同样，支持在患有脑缺血或PLC的充血性心力衰竭患者中使用ALC的临床数据也不充分。 18对18项研究进行了系统评价，以评估补充肉碱对改善间歇性lau行患者的步行性能的作用。大多数试验表明，步行性能有小到中等的提高。在测试前和测试后，平行RCT和交叉RCT中，无痛步行距离分别从74提升至157 m，31提升至54 m和23提升至132 m。每个研究设计中还证明了最大步行距离的改善，分别从71到135 m，9到86 m和104 m。测试前和测试后的试验使用口服或静脉内PLC的剂量为300至2,000 mg /天，持续10至90天，而平行和交叉RCT主要使用PLC，但也使用左旋肉碱，剂量为600至3,000 mg /天，共21天。 1至1天和300至6,000 mg /天，分别为4至21天。结果大部分与证据的水平或质量无关，一些数据支持通过口服静脉内给药。 19

在患有CVD的患者中，较高的口服左旋肉碱剂量（每天超过3 g）增加了动脉粥样硬化和心血管疾病的风险。在进行心脏评估的患者中，血浆左旋肉碱水平与冠状动脉和周围动脉疾病的风险以及整体CVD风险之间存在正相关，呈线性，剂量依赖性。 2013年的一项研究发现，肉碱衍生物（乙酰基和棕榈酰-L-肉碱）的含量较高，导致全因死亡率和心脏移植的发生率增加。 3

肉碱缺乏症，小学和中学

尽管与先天性代谢错误有关的遗传性疾病表现为多种症状，通常在出生时或出生后不久开始出现，但直到成年后症状才变得明显。错误的转运蛋白或酶中的缺陷会导致蛋白质，碳水化合物或脂肪的合成和代谢异常以及有毒代谢产物的积累。 20 ， 21 ， 22 L-肉碱是由FDA批准用于原发性系统性肉碱缺乏症的治疗批准，以及用于在患者的短期和长期治疗继发肉碱缺乏症与代谢的或终末期肾脏疾病的先天性障碍谁正在透析。先天性代谢错误的两个例子包括戊二酰辅酶A脱氢酶缺乏症和脂肪酸氧化紊乱。在前者中，L-赖氨酸，L-羟基赖氨酸和L-色氨酸的分解代谢受到影响，如果不加以治疗，可能导致神经系统疾病。治疗包括限制赖氨酸饮食和补充左旋肉碱。推荐的补充剂量最初是口服左旋肉碱100 mg / kg /天，但后来进行调整以维持正常的游离左旋肉碱水平，通常在6岁以上的患者中口服50 mg / kg /天是可能的。 21饮食中的脂肪限制和左旋肉碱的补充都被认为是特定中，长链脂肪酸疾病以及线粒体三功能蛋白缺乏症的治疗考虑因素。但是，临床试验并未显示出肉碱补充的主要益处，而且潜在的不良心脏影响是接受调查的医疗服务提供者所关注的问题。 22对肉碱补充的先天性错误进行的Cochrane荟萃分析未发现可比较儿童或成人肉碱与安慰剂的RCT或准RCT。 20

糖尿病

动物研究

PLC对胰岛素抵抗的影响的第一份报告发表于2009年，并在肥胖Zucker大鼠（肥胖和胰岛素抵抗的动物模型）中注意到。接受PLC的大鼠体重和食物摄入量增加，肥胖，血清胰岛素，胰岛素抵抗模型指数和三酰甘油肝含量提高。 18在80只Sprague Dawley大鼠的随机对照试验中，与2型糖尿病大鼠相比，补充L-肉碱加胆钙化固醇可以改善空腹血糖，与糖尿病对照组相比或单独使用任一药物的结果（ P <0.001）。与糖尿病对照组和左旋肉碱组相比，该组合还改善了空腹血浆胰岛素（ P <0.001），并且与单独使用任何一种药物相比，胰岛素抵抗也得到了改善（ P <0.001）。 23

临床研究

2000年发表了第一份显示ALC的抗糖尿病作用的报告。与安慰剂相比，静脉推注的剂量为5 mg / kg，然后以0.025、0.1或1 mg / kg恒定输注。与安慰剂组相比，接受ALC的2型糖尿病患者（N = 18）表现出剂量依赖性更高的组织葡萄糖摄取。 18一项2010年的随机，双盲，对照比较研究纳入了258名肥胖的白人患者（体重指数[BMI]至少为30），患有非控制性2型糖尿病（糖基化血红蛋白[HbA _1c ]大于8％）；在整个试验过程中，患者均接受了多种抗糖尿病药物治疗。患者被随机分配接受或不接受左旋肉碱的奥利司他（每天3次，每次120毫克）（每天2次，每次2克），并接受饮食和锻炼计划。两组的体重，BMI，HbA _1c ，空腹血糖，低密度脂质（LDL）-胆固醇和胰岛素抵抗均得到改善。然而，在12个月时，左旋肉碱加奥利司他组的患者比单独接受奥利司他的患者有更大的改善（每个P <0.05）。没有不良反应的报道。 24 2010年另一项具有相同设计的研究在2型糖尿病患者（N = 254）中进行了比较，将西布曲明（10 mg /天）与左旋肉碱和不加左卡尼丁（2 g /天）进行了1年比较。尽管两组的大多数参数在12个月后都有改善，但添加L-肉碱后，体重，HbA _1c ，胰岛素抵抗，空腹血浆胰岛素和其他胰岛素抵抗参数（即视黄醇结合蛋白4）显着改善（每个P <0.05）。然而，仅在左旋肉碱加西布曲明组中，甘油三酸酯和炎性标志为visfatin改善（ P <0.05）。 25

2013年的系统综述和荟萃分析评估了安慰剂对照试验，以评估补充左旋肉碱在2型糖尿病中的代谢作用。有4项试验（N = 284）符合纳入标准，其中1项给药3 g /天，而其他3项试验给药2 g /天。尽管未发现对甘油三酸酯，脂蛋白（a），HbA _1c或总胆固醇有显着影响，但口服左旋肉碱（12至52周内每天2或3 g）可改善空腹血糖（ P = 0.002），LDL-胆固醇（ P <0.0001），载脂蛋白AI（ P = 0.008）和载脂蛋白B100（ P = 0.013）。当排除每天3 g的研究时，每天2 g的合并效应不再显着。异质性不显着。 26还显示静脉内施用L-肉碱4 g /天，连续7天，可以减轻空腹引起的饥饿感并改善空腹引起的疲劳，胆固醇异常（总胆固醇和LDL-胆固醇），肝代谢变化（AST，ALT，γ一项小型（N = 30）单盲随机，安慰剂对照先导研究中的代谢综合征患者的体重减轻和体重减轻。 27

血脂异常

临床研究

一项2010年的随机，双盲，对照比较研究纳入了258名肥胖的高加索白种人病患者（BMI≥30），患有2型糖尿病（HbA _1c > 8％）。在整个试验过程中，患者服用了多种抗糖尿病药物。患者被随机分配接受或不服用左旋肉碱的奥利司他（120 mg，每天3次）（每天2g，一次），并按饮食和运动计划进行治疗。在研究期间，两组在体重，BMI，HbA _1c ，空腹血糖和胰岛素抵抗方面均表现出显着改善。 LDL-胆固醇也显着降低。然而;在12个月时，左旋肉碱加奥利司他组的结果优于单独使用奥利司他的结果（每个P <0.05）。没有重大不良事件的报道。 24

高甘油三酸酯血症在社会经济地位低至中等的黎巴嫩男性中非常普遍（52％），这与谷物含量高而动物产品含量低的饮食有关。在一项为期12周的随机，安慰剂对照试验（N = 85）中，社会经济地位低，甘油三酯血症高（TG> 150 mg / dL）的成年黎巴嫩男性接受了赖氨酸（1 g /天），维生素B6（50 mg /天），赖氨酸加维生素B6或肉碱（1克/天）补充剂，以确定对血糖和脂质的影响。补充维生素B6可以改善总胆固醇和高密度脂蛋白（HDL）胆固醇，但肉碱或赖氨酸组未见变化。 28

对来自12个RCT的数据进行了荟萃分析，以确定补充L-肉碱对血液透析患者血脂水平的影响（N = 391）。大多数研究质量低下。左旋肉碱的总剂量为1.5克/周至3克/天，持续约12周至6年。根据8个报告LDL-胆固醇的试验的数据，补充左旋肉碱与LDL-胆固醇的改善有关，尤其是在使用静脉内给药超过16周的研究中。但是，未发现对甘油三酸酯，总胆固醇，HDL或极低密度脂蛋白胆固醇有影响。基于地理位置的亚组分析表明，在每个研究的国家中都没有差异。 29

左旋肉碱（每天两次，每次500 mg）治疗12周可显着改善HDL-胆固醇（平均值，+ 0.18 mmol / L； P = 0.03）和载脂蛋白A1（平均值，+ 0.12 g / L； P = 0.02）。以及在冠心病患者进行的单盲，随机，平行，安慰剂对照研究（n = 47）中，与安慰剂相比，抗氧化酶的活性有所改善。排除对象包括但不限于患有糖尿病，肝脏或肾脏疾病的患者，或接受大剂量他汀类药物治疗的患者。没有观察到甘油三酸酯（TG），总胆固醇，LDL-胆固醇或载脂蛋白B（apo-B）的显着变化。发现左旋肉碱水平与TG之间以及超氧化物歧化酶活性与TG，总胆固醇和载脂蛋白B之间存在显着的负相关。 64

运动表现/不宽容/疲劳

临床资料

一项双盲，安慰剂对照，剂量反应，交叉研究评估了L-肉碱3和4 g剂量对26位健康男性运动员耐力表现的短期影响。在乳酸水平为2至4 mmol / L的情况下，左旋肉碱剂量为3 g和安慰剂的运行速度存在显着差异。左旋肉碱4 g剂量和安慰剂在乳酸水平3.5和4 mmol / L时也发现了显着差异。在两个补充组中发现的差异表明，体育锻炼前服用3或4克左旋肉碱会延长疲劳程度。此外，与安慰剂相比，左旋肉碱组的乳酸和跑步速度心率均得到改善。在两个测试组中，测试期间每次速度增加之前对困难的主观感觉也有所改善。 4

疲劳是多发性硬化症（MS）最令人衰弱的症状，据报道，多达40％的患者患有疲劳。 2012年的Cochrane干预审查发现，有2个RCT评估了MS患者的左卡尼汀。在审查时唯一完成的研究中，一项交叉试验中，36例患有复发缓解型和继发性进行性MS的成年人接受乙酰基-L-肉碱2 g /天治疗3个月，然后金刚烷胺200 mg /天治疗3个月后3个月的淘汰期。对MS相关疲劳的影响尚不清楚。没有严重不良反应的报道。 30

在补充左旋肉碱的癌症患者中，疲劳也是最常见的症状。癌症相关的疲劳会严重削弱人的活力，休息通常无法缓解。 31 ， 32 A 4周，3期临床试验随机分配L-肉碱2克/天或安慰剂至367名癌症患者的侵入性恶性肿瘤和疲劳;然而，无论基线肉碱水平如何，治疗组和安慰剂组之间的不良反应（即疲劳，抑郁，疼痛）在统计学上均无显着差异。 31 2015年的Cochrane综述和对包括癌症在内的晚期疾病患者的姑息治疗疲劳治疗的荟萃分析发现，有限证据支持任何特定治疗的建议。具体与左旋肉碱有关的证据薄弱且无定论。 32综合肿瘤学会关于在乳腺癌患者中采用综合疗法作为支持治疗的临床实践指南（2014年）不建议使用乙酰基L-肉碱来治疗疲劳，原因是缺乏疗效（中等到高）。 33 2018年，美国临床肿瘤学会（ASCO）批准了综合肿瘤学会（SIO）循证指南，对乳腺癌治疗后使用综合疗法进行了指导，指出不应建议使用乙酰基L-肉碱来改善治疗期间疲劳（D级）。 68

间歇性lau行引起的运动能力有限在周围动脉疾病患者中很常见。运动引起的短暂性缺血会导致肉碱代谢的改变，并导致肉碱水平和骨骼肌能量供应的消耗。对18项研究的数据进行系统回顾，评估了补充肉碱在改善间歇性lau行患者的步行性能中的作用。大多数试验表明，步行性能有小到中等的提高。在测试前和测试后，平行RCT和交叉RCT中，无痛步行距离分别从74至157 m，31至54 m和23至132 m改善。每个研究设计中的最大步行距离也分别从71 m提升至135 m，9 m提升至86 m和104 m。试验前和试验后口服或静脉PLC的剂量为300至2,000 mg /天，范围为10至90天；平行和交叉RCT主要使用PLC，也使用左旋肉碱，剂量分别为600至3,000 mg /天（21天至1年）和300至6,000 mg /天（4至21天）。结果大部分与证据的水平或质量无关，一些数据表明与口服相比，静脉给药更具益处。 19顾问公司和Sigma-Tau公司（PLC的制造商和主要开发商）的雇员对使用口服PLC评估间歇性lau行患者的步行性能的影响进行了系统的回顾和荟萃分析。在6项Sigma-Tau 3期研究（N = 867）的初步分析中，与安慰剂相比，采用2 g / day PLC的峰值步行距离净提高了16 m，与之相比，结果相似（净提高了45米）荟萃分析包括另外7个RCT（总共13项研究；总共1,854例患者）。 6到12个月的剂量范围为1-4克/天（中值2克/天），耐受性良好，PLC干预组与安慰剂/比较组之间无治疗相关差异。死亡发生率分别为1.6％和1.4％。作者否认有任何行业，机构和公共资金来源。 34美国心脏病学会基金会/美国心脏协会针对外周动脉疾病的治疗指南指出，PLC在改善间歇性lau行患者步行距离方面的有效性尚未确立（证据水平：有限）。 35

运动不耐受也是线粒体肌病（MM）患者的主要症状，最常见的表现为慢性进行性外眼肌麻痹（CPOE;眼睑下垂），伴有相对较低的劳累水平的过度疲劳。一项随机，双盲，安慰剂对照的交叉试验，对12位MM和CPOE患者以及10位年龄和性别相匹配的健康对照进行了研究，记录了补充L-肉碱的MM患者运动耐受性和耗氧量的改善（3 g /天）与接受安慰剂的人相比。与对照组相比，MM患者的平均外周肌力量，身高，体重和无脂肪量较低。 36

血液学疾病

一项前瞻性，随机，开放标签的试验招募了69位慢性丙型肝炎成人，以评估4克/天左旋肉碱与不治疗对药物性贫血的影响；两组患者均接受标准α-干扰素联合利巴韦林治疗。 12个月后，接受左旋肉碱的患者的肝酶参数（即AST，ALT），病毒血症，血红蛋白和血细胞计数（即红细胞，白细胞，血小板）均有改善。左旋肉碱组的持续病毒学应答和复发率也有所改善。两组均未发现严重不良事件。 57在接受维持性血液透析的肾功能不全患者中，接受乙酰-L-肉碱至少2周的患者与接受安慰剂的患者之间的血红蛋白，血细胞比容或促红细胞生成素之间没有差异，对49项RCT进行系统回顾和荟萃分析（ N = 1,734）。 53

由于证据不足（非常低），KDIGO慢性肾脏病贫血临床实践指南（2012年）不建议使用左旋肉碱作为辅助疗法。 55

肝毒性

过量的丙戊酸不会产生容易识别的氧化反应，但可能会耗尽肝左旋肉碱的储存，从而削弱线粒体通过肉碱穿梭的运输。因此，尽管数据有限，但左旋肉碱被认为是恢复线粒体功能，减少有毒代谢产物的产生以及抵消或逆转丙戊酸毒性作用的潜在解毒剂。一项系统的审查仅鉴定了成人和儿童中丙戊酸急性暴露的8例（7种单一疗法，1种多药），以及1篇报道674名患者安全性数据的文章。静脉内给药是首选方法，因为左旋肉碱的口服生物利用度低。此外，大多数用药过量的患者都会服用活性炭，这会使口服左旋肉碱无效。根据这些病例的数据和毒理学参考资料，最常用的负载剂量是左旋肉碱100 mg / kg。建议每8小时服用50 mg / kg的维持剂量（最大3 g /剂量）以治疗由于丙戊酸持续或延迟吸收引起的毒性。尽管数据有限且怀疑存在出版偏倚，但作者认为左旋肉碱的给药对表现出意识水平下降的急性药物过量患者是合理的。 10还有一个病例报道，使用L-肉碱成功治疗PEG-天冬酰胺酶诱导的急性淋巴细胞白血病患者的肝毒性。 58

一项双盲，随机，安慰剂对照试验评估了口服肉碱在预防新诊断，初治的伊朗结核病患者中抗结核药引起的肝毒性（ATDH）的潜在益处（N = 182）。发现结核病（TB）患者中的肉碱缺乏症比健康对照者更为普遍。所有结核病患者均按方案接受一线抗结核治疗方案（异烟肼，利福平，乙胺丁醇，吡嗪酰胺），并随机分配给左旋肉碱2 g /天，共4周或安慰剂。在为期2.5年的研究期内，发生过ATDH的25％的患者中，左旋肉碱组为16.7％，而安慰剂组为32.3％（ P = 0.049）。基于多元逻辑回归的ADTH易感因素包括年龄大于35岁的糖尿病，HIV感染和安慰剂治疗的患者。 59

不孕症

氧化应激被认为在男性不育症中起重要作用，并且已经表明，成熟的，形态学上正常的精子比未成熟的形式产生的活性氧种类（ROS）少。在附睾，精浆和精子中都发现了酶促（例如谷胱甘肽过氧化物酶，超氧化物歧化酶）和非酶促（例如肉碱，谷胱甘肽，类胡萝卜素）的抗氧化活性。在正常条件下，这些氧化和抗氧化过程保持平衡，但是过量的ROS会导致广泛的精子功能障碍和DNA结构破坏。与减少摄入量相比，增加饮食中的抗氧化剂摄入量可以改善精液质量。 37 ， 38在子宫内膜异位症，在卵泡液ROS可能影响胚胎的质量和发育以及卵母细胞，其是对氧化应激极为敏感的减数分裂纺锤体的结构。 39 2014年Cochrane对男性不育症中使用的抗氧化剂的系统评价和荟萃分析得出的结论是，仅有异质性低的肉碱的唯一数据可以通过分析得出与肉碱（即乙酰基-L-肉碱，乙酰基-肉碱，左旋肉碱）和与安慰剂相比在6个月时的有益精子浓度（2个试验，116名男性）。数据不适合总结对精子活力的影响。 65岁

实验数据

在一项实验研究中，探讨了抗氧化剂，L-肉碱和N-乙酰半胱氨酸（NAC）在预防由轻度子宫内膜异位症的不育女性的卵泡液引起的减数分裂卵母细胞损伤中的潜在保护作用。从BMI小于30，年龄38岁以下，患有子宫内膜异位相关性不育症（n = 11，测试组）或输卵管或男性因素相关性不育症的妇女中收集卵泡液（FF）样品（N = 22） （n = 11，控制）。与无FF或对照FF中成熟的卵母细胞产生的百分比相比，子宫内膜异位FF中牛卵母细胞的体外成熟产生的减数分裂正常卵母细胞的百分比更低（中期II中存在正常的纺锤体）。当评估抗氧化剂单独使用或与0.6 mg / mL左旋肉碱组合使用对子宫内膜异位症-FF成熟的卵母细胞的作用时，与不添加左旋肉碱的卵母细胞相比，左旋肉碱产生的正常卵母细胞百分比更高（80.61％vs 51.35 ％），与无FF组（86.36％）和对照组FF（83.52％）相似。与单独使用左旋肉碱相比，添加NAC（1.5 mmol / L）和左旋肉碱加NAC的组合所产生的正常成熟百分比略低（分别为62.22％和61.40％）。 39

动物资料

在一项评估L-肉碱对环磷酰胺引起的不育症的保护作用的实验研究中，雄性大鼠接受IP环磷酰胺（CP）35 mg / kg，CP加L-肉碱21 mL / kg /天或盐溶液（对照）。治疗3周后，与CP组相比，给予L-肉碱的大鼠精子活动力，活力和睾丸激素水平增加。与CP组相比，L-肉碱组的睾丸凋亡细胞也减少。 Immunohistochemistry revealed nearly normal seminiferous tubules with the quality of spermatogenic cells improved with L-carnitine supplementation. 40

Clinical data

A systematic review of 17 randomized trials (N = 1,665 men) assessed the effects of oral antioxidants, including carnitine, on sperm quality in infertile men and pregnancy rates in partners; heterogeneity in clinical methods prevented a meta-analysis from being performed. Over 50% of studies used a combination of antioxidants (vitamin C and E, zinc, selenium, folic acid, carnitine, N-acetyl-cysteine, astaxanthin); monotherapy with carnitine was most frequently studied, with 4 studies that enrolling 365 patients with asthenozoospermia or oligoasthenozoospermia. Although some benefit has been reported, clinical data are lacking. Supplementation with carnitine 2 g/day, L-carnitine 2 to 3 g/day, and/or acetyl-L-carnitine 0.5 to 3 g/day for up to 26 weeks resulted in improvements in sperm motility in 3 studies, improved pregnancy rates in 2 studies, and improved sperm concentration and morphology in 1 study. 41 A randomized, double-blind, controlled trial (N = 52) in Iran compared the effects of L-carnitine with clomiphene citrate, an anti-estrogen commonly prescribed for male infertility, on idiopathic male infertility. Patients received either clomiphene citrate 25 mg/day or L-carnitine 2 g/day for 3 months. Compared with baseline, semen volume, sperm count, and motility improved with L-carnitine. Compared with clomiphene citrate, L-carnitine resulted in increased semen volume and equal improvements in sperm motility, but not sperm morphology. 38 L-carnitine 1 g/day was used as a positive control in a 12-week, RCT that evaluated the effects phosphodiesterase-5 inhibitors on Leydig cell secretory function in men with oligoasthenospermia (N = 75). Although mean sperm concentration, percent motile spermatozoa, percent morphologically normal spermatozoa, and insulin-like 3 peptide levels were improved after treatment with vardenafil or sildenafil, no differences were seen with the positive control (L-carnitine) or negative control (untreated infertile men with oligoasthenospermia). 37

Migraine prophylaxis

Because mitochondrial phosphorylation potential was reduced between headaches in migrainous patients, a single-blind, randomized, controlled clinical trial was conducted to investigate the effects of L-carnitine 500 mg/day and/or magnesium oxide 500 mg/day on migraine prophylaxis (N = 133). Conventional treatment and migraine elimination diet were continued throughout the study. After 12 weeks, L-carnitine supplementation produced the highest reductions in mean migraine days/month and the magnesium supplemented group produced the most improvements in the mean number of frequency, severity, and index. Overall, the effects of magnesium on all migraine indicators were more than those of L-carnitine, and the effects of routine treatments on all migraine indicators were more than those of the supplements. 60

Muscle cramps

A prospective uncontrolled, nonrandomized study evaluated the effects of 2 doses of L-carnitine to reduce muscle cramps in cirrhosis patients; patients with ongoing symptoms of painful, involuntary contraction of skeletal muscles at rest or that woke them from sleep at least 3 times in the previous month were included. L-carnitine 300 mg 3 times daily (900 mg/day) or 4 times daily (1,200 mg/day) was provided for 8 weeks. Muscle cramp frequency and duration was assessed with questionnaires and severity was assessed by visual analog scale (VAS). Overall, 88.1% of patients experienced a reduction in cramping and 28.6% had complete elimination of cramps; mean VAS scores improved from 69.9 at baseline to 26.2 by the end of the study. A dose-response was observed, with 43.5% compared with 10.5% experiencing fewer cramps in the 1,200 mg/day and 900 mg/day groups, respectively. The higher dose also resulted in improved VAS scores (mean 9.9 vs 39.6, respectively).没有不良反应的报道。 61

神经病学

中枢神经系统

Animal data

Animal studies have demonstrated improved antioxidant activity of acetyl-L-carnitine over L-carnitine in the brain. Although L-carnitine and acetyl-L-carnitine both increased ambulatory activity, carnitine plasma levels, and brain levels in older rats, acetyl-L-carnitine provided greater improvements in biomarkers of oxidative damage (lipid peroxidation, hippocampal and cortical oxidized nucleotides, as well as hippocampal and white matter nitrotyrosine) in older rat brains compared with L-carnitine. 6 The combination of acetyl-L-carnitine plus N-acetyl-cysteine also delayed degeneration of sensory neurons, reduced early retrograde death of spinal motor neurons, attenuated neuroinflammation, promoted axonal sprouting in injured cord segment, and produced an anti-apoptotic effect in segments rostral to injury sites. 42

Clinical data

Neuronal loss and brain atrophy are hallmarks of AIDS-related dementia complex. Treatment strategies target the reduction of glutamate levels in the brain, which appears to be involved in the pathogenesis. In a small experimental study (N = 12) conducted in male AIDS patients with higher mean glutamate levels than those of controls, administration of IV acetyl-L-carnitine 3 g/day for 4 weeks reduced mean levels of glutamate compared with baseline (137 vs 246 micromol/L, respectively). A case of improved memory and attention after 12 weeks with acetyl-L-carnitine supplementation was also reported in a 37-year-old female AIDS patient admitted with abrupt onset of cognitive and motor symptoms associated with a fall in blood (201 to 41 micromol/l) and CSF (60 to 11 micromol/L) glutamate levels. 43 A systematic review of 7 RCTs (N = 660) evaluated the effect of acetyl-L-carnitine in patients with hepatic encephalopathy. Administration of acetyl-L-carnitine 2 g/day was consistently associated with improvement in serum ammonia levels compared with those of placebo; however, heterogeneity was found among studies. 44

The American Academy of Neurology (AAN) practice parameter for the management of dementia (2001) found the evidence to be incomplete or conflicting for the use of acetyl-L-carnitine as a cognitive-enhancing agent in patients with Alzheimer disease or mixed dementia. 66

Because bipolar depression may also be associated with mitochondrial dysfunction, 40 patients with bipolar depression with incomplete responses to standard therapy were enrolled in a 12-week, double-blind, randomized, placebo-controlled, parallel-group, flexible-dose study of acetyl-L-carnitine (1 to 3 g/day) plus alpha-lipoic acid (0.6 to 1.8 g/day) as adjunctive therapy. Although supplementation reduced phosphocreatine levels in the parieto-occipital cortex, no differences were found between groups in depression scores compared with baseline in any outcome measure. Adverse effects were generally minor with diarrhea, foul-smelling urine, rash, constipation, and dyspepsia reported more frequently with supplementation than with placebo. 45

The Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder (MDD) in adults (2016) recommend acetyl-L-carnitine as third-line monotherapy for mild to moderate MDD (Level 2). 67

In a double-blind, randomized clinical trial comparing the effect of oral ALC 1 g 3 times daily to fluoxetine 20 mg/day in 80 elderly patients with dysthymic disorder, ALC resulted in improved depression scores (Hamilton depression, Hamilton anxiety, Beck depression inventory) and attention performance scores. The latter did not reach significance in the fluoxetine group. ALC achieved a higher tolerance profile than that of fluoxetine. 46

周边设备

Animal data

Acetyl-L-carnitine has been shown to virtually eliminate sensory neuronal death and possibly improve regeneration after primary nerve repair. Enhanced regenerative capacity of neurons that survive peripheral nerve trauma has been demonstrated in animal studies. Rats treated with a 6-week regimen of 50 mg/kg/day acetyl-L-carnitine after unilateral sciatic nerve graft repairs were performed, increasing the total area of regenerating nerve fibers (2,242% increase) and Schwann cells (722% increase) in the grafts. 47 Similarly, faster recovery of regenerated axons as well as increased number and diameter of resulting myelinated fibers were observed with supplementation of acetyl-L-carnitine in a rat sciatic nerve regeneration model. 8

Clinical data

An analysis of 2 multicenter, double-blind, randomized, placebo-controlled trials evaluated the effects of 2 doses of acetyl-L-carnitine (1.5 and 3 g/day) administered over 1 year on clinical diabetic neuropathy in adults with type 1 and 2 diabetes (N = 1,346). Centers in the US and Canada (USC) participated in one study while those in the US, Europe, and Canada (USEC) participated in the second study. Demographic differences were evident among the 2 studies: weight and BMI were higher in the UCS group, while the UCES group included primarily white participants with a larger proportion of type 1 diabetic patients and a longer disease duration. Compared with the placebo group, sural nerve fiber numbers and regenerating clusters increased in patients receiving 1.5 g/day (500 mg 3 times daily) but not in the 3 g/day (1 g 3 times daily) group. Vibration perception improved in the fingers in both groups and in the toes of those receiving 3 g/day. Significantly greater reductions were also seen in UCS subgroups of patients younger than 55 years who had a BMI less than or equal to 30, type 2 diabetes, and HbA _1c less than 8.5%. Mean clinical scores of both groups were improved compared with those of the placebo group, but not among groups. No differences were found in electrophysiological parameters. The greatest pain reduction was observed with 3 g/day after 1 year in type 2 diabetic patients with adequate drug compliance and HbA _1c greater than 8.5%. Fewer patients taking 3 g/day reported pain, paresthesia, and hyperesthesia compared with those taking placebo; no other differences were observed in adverse events among groups. 48 Data from the patients in these 2 studies was retrospectively examined to identify risk factors associated with sural nerve degeneration. Three risk groups were created based on the change in myelinated fiber density: "regenerators" (top 16 percentiles), "degenerators" (bottom 16 percentiles), and intermediate. Baseline HbA _1c was the only factor that differed across the 3 groups with a mean of 8.3% (± 1.6%) for regenerators and 9.2 (± 1.8%) for degenerators. 49

A systematic review was conducted to evaluate the potential use of nutraceuticals, including acetyl-L-carnitine, as adjuvant cancer therapy for treatment or prophylaxis of chemotherapy-induced peripheral neuropathy (CIPN). A total of 24 randomized, controlled, open-label, and retrospective trials were identified and results were equivocal. Insufficient data were available to recommend any of the 10 nutraceuticals reviewed. Acetyl-L-carnitine was reported as a possible treatment option for paclitaxel- and cisplatin-induced peripheral neuropathy based on data from 2 open-label studies, while a phase 3 trial demonstrated no positive prophylactic benefit. Adverse events were only reported for acetyl-L-carnitine and included mild nausea and insomnia. 50 A negative effect of 3 g/day acetyl-L-carnitine was demonstrated at 24 weeks, but not at 12 weeks, on CIPN in women with a history of stage I to III breast cancer undergoing taxane-based treatment in a double-blind, randomized, placebo-controlled trial (N = 409). Grade 3 to 4 neuropathy was reported in 8 cases in the acetyl-L-carnitine group and 1 case in the placebo group ( P = 0.46). 51

The Society for Integrative Oncology clinical practice guidelines for the use of integrative therapies as supportive care in patients treated for breast cancer (2014) recommends against the use of acetyl-L-carnitine for the prevention of neuropathy in breast cancer patients due to adverse events (moderate to high). 33 In 2018, the American Society of Clinical Oncology (ASCO) endorsed the Society for Integrative Oncology (SIO) evidence-based guideline for the use of integrative therapies after breast cancer treatment, stating that acetyl-L-carnitine is not recommended for the prevention of chemotherapy-induced peripheral neuropathy in patients with breast cancer due to potential harm (Grade H). Lyman 2018 The ASCO clinical practice guidelines for prevention and management of CIPN in survivors of adult cancers (2014) strongly advised against the use of acetyl-L-carnitine for the prevention of CIPN in patients undergoing treatment with neurotoxic agents. An increase in incidence of CIPN has been documented at 24 weeks in a phase 3 trial in women with breast cancer receiving acetyl-L-carnitine versus placebo (high-quality evidence; strong recommendation). No recommendation could be made regarding use of acetyl-L-carnitine for treatment of CIPN based on inconclusive data (low-quality evidence, inconclusive). 52

Renal disease

Clinical data

A systematic review and meta-analysis was conducted to confirm or refute previous data indicating the beneficial effect of L-carnitine on hemoglobin and erythropoietin dose in maintenance hemodialysis patients. A total of 49 RCTs (N = 1,734) comparing acetyl-L-carnitine with placebo or no treatment for at least 2 weeks were included; those that compared different doses, routes, or durations were excluded. Although LDL-cholesterol and C-reactive protein improved by L-carnitine supplementation, no significant differences were identified in any other lipid parameters, hemoglobin, hematocrit, albumin, or the required erythropoietin dose. The improvement in LDL-cholesterol was not considered to be clinically important.没有不良反应的报道。 53 Because approximately 95% of hemodialysis patients have been found to have carnitine deficiency, L-carnitine supplementation is used frequently as adjuvant therapy. However, because its use is controversial, another meta-analysis sought to assess the clinical benefit of L-carnitine on hemodialysis patients. The 25 eligible RCTs spanned more than 20 years, with sample sizes ranging from 10 to 113 patients (N = 1,172) and study durations ranging from 3 weeks to 36 months. Both oral and IV routes were used at doses ranging from 1 to 3 g/day and 10 to 20 mg/kg/hemodialysis treatment. L-carnitine supplementation was not associated with changes in any of the inflammation, oxidative stress, nutrition, anemia, dyslipidemia, or quality of life outcomes measured. 54

The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for the anemia in chronic kidney disease (2012) does not recommend use of L-carnitine as adjuvant therapy due to insufficient evidence (very low). 55

加药

Oral carnitine supplements are metabolized by microbiota prior to absorption; bioavailability of 1 to 6 g doses ranges from 5% to 18%. Certain gut microbiota species (eg, Gammaproteobacteria, Betaproteobacteria, and Firmicutes, including Acinetobacter species) can adversely affect the bioavailability of L-carnitine supplementation. The dynamics of skeletal muscle carnitine may also influence the metabolism of L-carnitine supplementation. 3

Anemia, drug-induced

Improvements in hemoglobin, blood cell counts, viremia, and liver enzymes were achieved with supplemental L-carnitine 2 g twice a day for 12 months in a small study of patients with chronic hepatitis C treated with standard interferon-alfa plus ribavirin receiving. 57

Cachexia

An oral liquid dose of L-carnitine 4 g/day for 12 weeks increased BMI, body cell mass, and body fat in patients with cachexia and stage IV pancreatic cancer (CARPAN trial). 56

Cardiovascular disease, secondary prevention

L-carnitine 2 to 6 g/day oral maintenance doses for up to 12 months have been used in clinical studies with some trials administering oral or IV loading doses of 6 or 9 g/day for 5 to 7 days. An insignificant trend favored the 3 g/day dose in terms of all-cause mortality. Doses higher than 3 g/day oral L-carnitine are not recommended; higher doses of carnitine derivatives (acetyl- and palmitoyl-L-carnitine) have been shown to increase atherogenesis, CVD risk, all-cause mortality, and heart transplantations in patients with CVD. 3 L-carnitine is often used in combination with an antioxidant, such as alpha-lipoic acid.

Carnitine deficiency, primary and secondary

L-carnitine is approved by the FDA for treatment of primary systemic carnitine deficiency, and for short- and long-term treatment of patients with an inborn error of metabolism or with end-stage renal disease on dialysis that results in a secondary carnitine deficiency. Maintenance doses for adults range from 1 to 3 g/day given as a once or twice daily divided dose. Refer to prescribing information for specific dosing recommendations.

Type 2 diabetes mellitus

Administration of L-carnitine 2 g once daily for 1 year to patients also receiving either orlistat or sibutramine demonstrated greater improvements in body weight, BMI, HbA _1c , plasma glucose, LDL-cholesterol, and insulin resistance compared with antidiabetic medication alone. 24 , 25

Acetyl-L-carnitine also improved tissue glucose uptake as a 5 mg/kg IV bolus loading dose followed by 0.025, 0.1, or 1 mg/kg constant infusion in a small group of type 2 diabetic patients. 18岁

血脂异常

The addition of L-carnitine 2 g once daily to orlistat in adults with type 2 diabetes resulted in lower LDL-cholesterol than did either drug alone; however, other studies failed to find an effect on lipid parameters or triglycerides. 24 , 28 , 29

Dysthymic disorder

Oral acetyl-L-carnitine 1 g 3 times daily administered for 7 weeks to patients over the age of 65 years with dysthymic disorder resulted in improved depression scores and attention performance. 46

Fatigue

Limited data show use of a 3 or 4 g dose of L-carnitine prolonged time to exhaustion in 26 healthy male athletes. 4

L-carnitine 3 g once daily for 2 months improved limits of tolerance, oxygen consumption, and constant work rate in a small group (N = 12) of patients with mitochondrial myopathy. 30

Effects on multiple sclerosis-related fatigue are unclear. 30

The Society for Integrative Oncology clinical practice guideline for the use of integrative therapies as supportive care in patients treated for breast cancer does not recommend the use of acetyl-L-carnitine for the treatment of fatigue. 33

Hepatotoxicity, drug-induced

Data are limited on the use of L-carnitine as a valproic acid overdose antidote. A systematic review identified only 8 cases of acute exposure to valproic acid (7 monotherapy, 1 polydrug) in adults and children. Intravenous administration is the preferred route. A loading dose of L-carnitine 100 mg/kg was most commonly used; a maintenance dose of 50 mg/kg (to a maximum of 3 g/dose) administered every 8 hours was recommended to treat toxicity due to ongoing or delayed absorption of valproic acid. 10

Carnitine deficiency was found to be more prevalent in TB patients than in healthy controls. Adjunctive administration of oral carnitine (1 g twice daily for 4 weeks) was used to reduce antituberculosis drug-induced hepatotoxicity resulting from first-line, anti-TB regimen (isoniazid, rifampin, ethambutol, pyrazinamide). 59

Infertility, male

Carnitine 2 g/day, L-carnitine 2 to 3 g/day, acetyl-L-carnitine 0.5 to 3 g/day for up to 26 weeks has been used successfully to improve sperm parameters and fertilization in men with oligoasthenozoospermia or asthenozoospermia. 38 , 41

Intermittent claudication, treatment

Propionyl-L-carnitine 2 g once daily is likely effective for treatment of intermittent claudication in patients with peripheral artery disease, especially when combined with exercise and other strategies. Administration for up to 1 year was most effective in patients with severely limited baseline maximum walking distance (less than 250 m). 18 Dosages of propionyl-L-carnitine 300 mg/day to 2 g/day of PLC orally or IV ranging from 10 to 90 days, and L-carnitine at dosages of 300 mg/day to 6 g/day for 4 days to 1 year have improved walking distance, with some data supporting more benefit with IV administration compared with oral. 19 The American College of Cardiology Foundation/American Heart Association guideline for the management of peripheral artery disease states that the effectiveness of propionyl-L-carnitine as a therapy to improve walking distance in patients with intermittent claudication is not well established. 35

Migraine prophylaxis

Compared with magnesium, oral L-carnitine 500 mg/day for 12 weeks produced the highest reductions in mean migraine days/month. The magnesium-supplemented group experienced the most improvements in migraines for the mean number of frequency, severity, and index. Overall, the effects of magnesium on all migraine indicators were higher than those of L-carnitine, and the effects of routine treatments on all migraine indicators were higher than those of supplements. 60

Muscle cramps

L-carnitine 300 mg 3 times daily (900 mg/day) or 4 times daily (1,200 mg/day) for 8 weeks was administered to patients with cirrhosis and ongoing symptoms of painful, involuntary contraction of skeletal muscles at rest or that woke them from sleep at least 3 times in the previous month. A dose-response was observed with 43.5% compared with 10.5% experiencing fewer cramps in the 1,200 and 900 mg/day groups, respectively. The higher dose also resulted in improved VAS scores (mean 9.9 vs 39.6, respectively). 61

Neuropathy, central

Neuronal loss and brain atrophy are hallmarks of AIDS-related dementia complex. Administration of IV acetyl-L-carnitine 3 g/day for 4 weeks reduced mean levels of glutamate compared with baseline in a small experimental study (N = 12). A case report also documented improvement in memory and attention after 12 weeks of acetyl-L-carnitine supplementation in a 37-year-old female AIDS patient, subsequently diagnosed with AIDS dementia, who was admitted with abrupt onset of cognitive and motor symptoms associated with decreased blood (201 to 41 micromol/l) and CSF (60 to 11 micromol/L) glutamate levels. 43

Acetyl-L-carnitine 1 to 3 g/day plus alpha-lipoic acid 0.6 to 1.8 g/day as adjunctive therapy for 12 weeks failed to improve depression scores compared with baseline in a small (N = 40) study of patients with bipolar depression. 45

Neuropathy, peripheral

Acetyl-L-carnitine 1.5 and 3 g/day administered over 1 year to treat diabetic neuropathy in adults with type 1 and 2 diabetes (N = 1,346) increased in sural nerve fiber numbers and regenerated clusters in patients receiving 1.5 g/day (500 mg 3 times daily) but not in those receiving 3 g/day (1 g 3 times daily) compared with the placebo group. Vibration perception improved in the fingers in both treatment groups and in the toes of those receiving 3 g/day. Greater reductions were seen in the US-Canada subgroups of younger than 55 years and who had a BMI less than or equal to 30, type 2 diabetes, and HbA _1c less than 8.5%. The greatest pain reduction was observed with 3 g/day after 1 year in type 2 diabetic patients with adequate drug compliance and HbA _1c greater than 8.5%. Fewer patients taking 3 g/day reported pain, paresthesia, and hyperesthesia compared with those receiving placebo. Baseline HbA _1c was the only factor that identified "regenerators" and "degenerators." 48 ， 49

The Society for Integrative Oncology clinical practice guidelines for the use of integrative therapies as supportive care in patients treated for breast cancer do not recommend use of acetyl-L-carnitine for the prevention of neuropathy in breast cancer patients due to harm (moderate to high). 33

The American Society of Clinical Oncology clinical practice guidelines for prevention and management of CIPN in survivors of adult cancers strongly advise against the use of acetyl-L-carnitine for the prevention of CIPN in patients undergoing treatment with neurotoxic agents. An increase in incidence of CIPN has been documented at 24 weeks in a phase 3 trial in women with breast cancer receiving acetyl-L-carnitine vs placebo (high-quality evidence; strong recommendation). No recommendation could be made regarding use of acetyl-L-carnitine for treatment of CIPN based on inconclusive data (low-quality evidence, inconclusive). 52

Pregnancy / Lactation

避免使用。 L-carnitine is assigned the pregnancy Category B by the FDA; L-carnitine supplementation in breast-feeding mothers has not been clinically studied.

Reproductive studies have been performed in rats and rabbits at doses of up to 3.8 times the human dose on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to L-carnitine.

Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased following exogenous administration of levocarnitine.

由于动物繁殖研究并不总是能够预测人的反应，因此只有在明确需要的情况下，才应在怀孕期间使用这种药物。 In breast-feeding mothers receiving levocarnitine, any risks to the child need to be weighed against the benefits of levocarnitine supplementation to the mother. 62 Discontinuation of levocarnitine in breast-feeding mothers should be considered.

Interactions

Carbamazepine, phenobarbital, phenytoin, and valproic acid may decrease blood concentrations of carnitine in children treated for convulsions. 1 , 63

Pivampicillin and other pivalate-conjugated antibiotics may decrease blood concentrations of carnitine and limit fatty acid oxidation. 1

不良反应

Nausea, vomiting, abdominal cramps, diarrhea, and a "fishy" body odor can occur with doses of about 3 g/day. Less common adverse effects have included pruritic rash, muscle weakness in uremic patients, and seizures in patients with seizure disorders. Administering the daily dose in 3 divided doses may help reduce some adverse effects, such as nausea and vomiting. 1 , 2 , 17 Some evidence suggests that intestinal bacteria metabolize carnitine to form trimethylamine-N-oxide, a substance that may increase cardiovascular risk, particularly in omnivores who consume meat versus in vegans or vegetarians. 1

A systematic review of nutraceuticals used for chemotherapy-induced peripheral neuropathy identified 2 open-label studies and a phase 3 trial that investigated the use of acetyl-L-carnitine. Mild nausea (n = 2) and insomnia (n = 1) were reported in 2 trials (N = 52). 39 In a fatigue treatment trial, adverse events including insomnia and nervousness led to withdrawal of 1 patient with multiple sclerosis who received acetyl-L-carnitine 1 g twice/day for 3 months. 32

In patients with cardiovascular disease, higher oral doses of L-carnitine (more than 3 g/day) increased the risk of atherogenesis and CVD. A linear, dose-dependent association was found between plasma L-carnitine levels and risks of coronary and peripheral artery disease, as well as overall CVD risk in patients undergoing cardiac evaluation. A 2013 study also found increased rates of all-cause mortality and heart transplantation with higher levels of carnitine derivatives (acetyl- and palmitoyl-L-carnitine). 3

Toxicology

The IV median lethal dose (LD ₅₀ ) of levocarnitine in rats is 5.4 g/kg, and the oral LD ₅₀ of levocarnitine in mice is 19.2 g/kg. There have been no reports of a levocarnitine overdosage; however, large doses may cause diarrhea. 62

参考文献

已知总共有2种药物可与L-肉碱（左肉碱）相互作用。

• 2中度药物相互作用

在数据库中显示所有可能与左卡尼汀（左卡尼汀）相互作用的药物。

检查互动

输入药物名称以检查与L-肉碱（左卡尼汀）的相互作用。

已知与左旋肉碱（左卡尼汀）相互作用的药物

注意：仅显示通用名称。

• 双香豆酚
• 华法林