Rezaei Ali, Hamidi Majid, Seyedmirzaei Homa, Moghadasi Abdorreza Naser
Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ann Med Surg (Lond). 2025 Apr 16;87(5):2736-2748. doi: 10.1097/MS9.0000000000003124. eCollection 2025 May.
Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of the central nervous system (CNS) with a complex and multifactorial pathophysiology. Although these mechanisms are not yet fully elucidated, it is established that oxidative stress (OS) plays a key role in driving neurodegeneration in MS. These pathological mechanisms contribute to a wide range of symptoms, including motor and sensory deficits, as well as cognitive impairment. The impairments in cognitive functions can cause a major burden for these patients and significantly affect their quality of life. For example, memory is one of the most frequently impaired cognitive domains in MS. These deficits often correlate with biomarkers of neurodegeneration and disease progression. Despite the substantial burden of cognitive impairment in MS, no established treatments currently exist to prevent or mitigate cognitive decline in these patients, aside from the disease-modifying treatments. Several clinical trials have investigated the potential of antioxidant supplementation to improve cognitive outcomes in MS patients. However, their findings are often controversial. This review discusses trials evaluating the effects of supplementation with various antioxidants, including , melatonin, omega-3 fatty acids, vitamins A, N-acetylcysteine, lipoic acid, xanthophylls, and crocin, on cognitive performance. We discuss the findings of these studies, highlight methodological limitations, and explore the underlying mechanisms by which these compounds may modulate cognition. These mechanisms range from mitigating OS, inflammation, and glutamate-induced neurotoxicity in the CNS to addressing secondary symptoms such as depression and fatigue, which are often linked to cognitive decline. By reviewing the current evidence, this review not only underscores the therapeutic potential and limitations of antioxidant supplementation but also provides guidance for future research to optimize study design and advance our understanding of cognitive preservation strategies in MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性神经炎症性和神经退行性疾病，其病理生理学复杂且具有多因素性。尽管这些机制尚未完全阐明，但已确定氧化应激（OS）在MS的神经退行性变中起关键作用。这些病理机制导致了广泛的症状，包括运动和感觉缺陷以及认知障碍。认知功能障碍会给这些患者带来重大负担，并显著影响他们的生活质量。例如，记忆是MS中最常受损的认知领域之一。这些缺陷通常与神经退行性变和疾病进展的生物标志物相关。尽管MS中认知障碍负担沉重，但除了疾病修正治疗外，目前尚无既定的治疗方法来预防或减轻这些患者的认知衰退。多项临床试验研究了补充抗氧化剂改善MS患者认知结果的潜力。然而，他们的发现往往存在争议。本综述讨论了评估补充各种抗氧化剂（包括褪黑素、ω-3脂肪酸、维生素A、N-乙酰半胱氨酸、硫辛酸、叶黄素和藏红花素）对认知表现影响的试验。我们讨论了这些研究的结果，强调了方法学上的局限性，并探讨了这些化合物可能调节认知的潜在机制。这些机制包括减轻中枢神经系统中的氧化应激、炎症和谷氨酸诱导的神经毒性，以及解决诸如抑郁和疲劳等通常与认知衰退相关的继发症状。通过回顾当前证据，本综述不仅强调了补充抗氧化剂的治疗潜力和局限性，还为未来研究提供了指导，以优化研究设计并增进我们对MS认知保护策略的理解。
