Brass Eric P
Harbor-UCLA Center for Clinical Pharmacology, 1124 West Carson Street, Building J2, Torrance, CA 90502, USA.
Ann N Y Acad Sci. 2004 Nov;1033:67-78. doi: 10.1196/annals.1320.006.
Carnitine has important roles in skeletal muscle bioenergetics. Skeletal muscle carnitine deficiency is associated with profound impairment of muscle function. It has thus been natural to ask if carnitine supplementation can improve skeletal muscle function and athletic performance in healthy individuals. Oral carnitine doses of several grams cause no significant clinical toxicity, further encouraging the use of carnitine as a supplement. Despite this strong foundation and 20 years of research, no compelling evidence exists that carnitine supplementation can improve physical performance in healthy subjects. The available data have been reviewed in recent publications. Several key issues are relevant to a potential therapeutic benefit of carnitine supplementation, and addressing these may provide insight into trials of carnitine therapy in healthy subjects: (1) Can carnitine supplementation increase skeletal muscle carnitine content in healthy subjects? Muscle carnitine content is not easily increased with carnitine supplementation. This reflects both the systemic pharmacokinetics of carnitine and the systems controlling transmembrane transport of carnitine in skeletal muscle. (2) How much carnitine is required to support optimal metabolism in skeletal muscle? Data are not available to definitively define the relationship between muscle carnitine content and muscle metabolic function. Extrapolation of data from several models suggests that very low amounts of carnitine are required to support muscle function. (3) Does carnitine supplementation alter energy homeostasis in healthy subjects? Several, but not all, studies suggest that subjects on carnitine supplementation have altered regulation of fuel homeostasis. However, the mechanisms of these changes, the tissues affected, and the relevance of these phenomena to exercise performance are all ill defined. (4) How can changes in performance be assessed in healthy subjects? Most studies have failed to demonstrate an objective performance improvement in healthy subjects taking carnitine. However, these negative studies must be interpreted with caution. Performance studies in athletes are conducted against a background of aggressive training regimens and nutritional interventions. Small changes, which may be very important to the athlete, may be very hard to objectify in the laboratory. Assessments must differentiate between changes in maximal aerobic capacity, ability to sustain effort at varied workloads, and the subject's perception of exertion. The interaction of carnitine supplementation with exercise training may be particularly important on theoretical and experimental bases. Systematic research in each of these areas is required to better understand the physiology, biochemistry, and pharmacology of carnitine supplementation. While data do not allow a conclusion to be drawn that carnitine is beneficial, the negative has not been proven either.
肉碱在骨骼肌生物能量学中发挥着重要作用。骨骼肌肉碱缺乏与肌肉功能的严重受损有关。因此,自然而然会有人问,补充肉碱是否能改善健康个体的骨骼肌功能和运动表现。口服几克剂量的肉碱不会引起明显的临床毒性,这进一步促使人们将肉碱用作补充剂。尽管有坚实的基础和20年的研究,但尚无令人信服的证据表明补充肉碱能改善健康受试者的身体表现。近期出版物已对现有数据进行了综述。几个关键问题与补充肉碱的潜在治疗益处相关,解决这些问题可能有助于深入了解针对健康受试者的肉碱治疗试验:(1)补充肉碱能否增加健康受试者骨骼肌中的肉碱含量?补充肉碱不易增加肌肉中的肉碱含量。这既反映了肉碱的全身药代动力学,也反映了控制肉碱跨膜转运进入骨骼肌的系统。(2)骨骼肌中支持最佳代谢需要多少肉碱?目前尚无数据能明确界定肌肉肉碱含量与肌肉代谢功能之间的关系。从多个模型外推的数据表明,支持肌肉功能所需的肉碱量非常低。(3)补充肉碱是否会改变健康受试者的能量稳态?一些(但并非所有)研究表明,补充肉碱的受试者对燃料稳态的调节发生了改变。然而,这些变化的机制、受影响的组织以及这些现象与运动表现的相关性均不明确。(4)如何在健康受试者中评估性能变化?大多数研究未能证明服用肉碱的健康受试者在客观性能上有所改善。然而,对这些阴性研究的解读必须谨慎。针对运动员的性能研究是在积极的训练方案和营养干预背景下进行的。对运动员可能非常重要的微小变化,在实验室中可能很难客观化。评估必须区分最大有氧能力的变化、在不同工作量下持续努力的能力以及受试者对运动强度的感知。从理论和实验基础来看,补充肉碱与运动训练之间的相互作用可能尤为重要。需要在这些领域中的每一个进行系统研究,以更好地理解补充肉碱的生理学、生物化学和药理学。虽然现有数据无法得出肉碱有益的结论,但也尚未证明其有害。