维生素C在老年肌少症中的作用机制及防治潜力

Mechanism and potential of vitamin C supplementation in sarcopenia prevention and treatment

背景:维生素C作为人体所必需的营养物质,具有广泛的生物学效应并存在多种与肌少症发病机制相关的生物学功能,研究维生素C的补充应用有望成为肌少症的一种新型防治措施。目的:综述近年来有关维生素C在肌少症发病机制和治疗中应用的最新研究进展,并基于已发表的证据探讨维生素C在肌少症预防和治疗中的潜在作用及可能的机制途径。方法:由第一作者应用计算机在PubMed、Web of Science和中国知网数据库检索涉及维生素C在肌少症中的相关文献。英文检索词:“vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle”;中文检索词:“维生素C,抗坏血酸,L-抗坏血酸,抗坏血酸盐,抗氧化剂,氧化应激,肌少症,肌肉萎缩,肌肉无力,肌肉发育,骨骼肌再生,肌肉,骨骼肌”。检索时限为各数据库建库至2023年7月,经过筛选后纳入85篇文献进行综述分析。结果与结论:①保证充足的膳食维生素C摄入或维持血液循环中正常的维生素C水平将有助于减少与年龄相关的肌肉损失,降低肌少症的患病率,此外,补充维生素C对于改善骨骼肌肌肉质量、力量和躯体功能也有一定作用,并可能在肌少症患者的运动策略中发挥协同效应。②维生素C对肌少症的作用可能经由以下生物学机制:维生素C主要通过抑制骨骼肌氧化应激和炎症反应来限制泛素-蛋白酶体途径的激活,从而积极调控蛋白质代谢稳态,并可通过其抗氧化作用增强线粒体抗氧化防御能力,维持线粒体的健康功能。另外,维生素C可以影响肌细胞增殖、分化和肌管大小,主要通过增加生肌调节因子的表达和激活蛋白质合成信号通路来实现,这有助于促进肌肉发育以及修复和再生受损的肌肉组织。③对于维生素C干预肌少症所发挥的积极作用尚需开展大样本及对一些重要影响因素进行优化设计的研究,如补充剂量和补充时间的选择、维生素C联合运动干预时的运动处方设计以及对个体的氧化还原状态评估等,建议未来的研究应以维生素C状态不佳的老年肌少症患者(<50μmol/L)为研究对象,探讨长期补充1000 mg/d维生素C(6个月或更长时间)与至少两种以上多类型综合运动的联合干预效果,补充时间选择在运动结束后的1 h进行,并对运动期间产生的氧化损伤标志物如丙二醛或蛋白质羟基水平进行监测。总之,对于肌少症老年人最佳的维生素C补充剂量和时间选择还需更多探讨,同时合适的运动处方设计(特别是运动类型和强度)亦需要进一步研究确定。

BACKGROUND:Vitamin C,as an essential nutrient,has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia.Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia.OBJECTIVE:To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia,and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence.METHODS:The first author performed a computer search of PubMed,Web of Science,CNKI and other databases for relevant studies involving vitamin C in sarcopenia.The search keywords were“vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle”in English and Chinese,respectively.The search period was from each database inception to July 2023.After screening,85 articles were included for further review.RESULTS AND CONCLUSION:Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia.In addition,vitamin C supplementation is also useful for improving skeletal muscle mass,strength and physical function with potential synergistic effects in exercise strategies for sarcopenia.The effects of vitamin C on sarcopenia may be via the following biological mechanisms:vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle,thus positively regulating protein metabolic homeostasis,and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function.In addition,vitamin C affects myoblast proliferation,differentiation and myotube size,mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways,which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue.The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors,such as the choice of supplementation dose and duration,the design of exercise prescription when vitamin C is combined with an exercise intervention,and the assessment of the redox status of the individual.It is recommended that future studies should be conducted in older patients with sarcopenia(<50μmol/L)with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1000 mg/d vitamin C(for 6 months or longer)with at least two or more types of multi-type combined exercise,with supplementation timed to take place at 1 hour after the end of the exercise,and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored.In conclusion,the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more,while the appropriate design of exercise prescriptions(especially the type and intensity of exercise)needs to be further determined.