Natural supplements in MS, Review

[NHE]

Can supplementation with antioxidants improve cognitive functions in patients with multiple sclerosis? A literature review
Ann Med Surg (Lond). 2025 Apr 16;87(5):2736-2748.

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 Ginkgo biloba, 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.

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Highlights:

• Clinical studies suggest that melatonin supplementation can improve cognitive function in MS patients, especially through enhanced sleep quality, though further research is needed.

• Clinical studies on GbE supplementation in MS patients have shown mixed results, with some improvement in memory scores; however further research with longer durations and better design is needed to assess its potential therapeutic effects.

• Alpha-linolenic acid (ALA), found in plant-based sources like flaxseed and walnuts, has shown potential benefits in MS, including slower disease progression and fewer relapses, suggesting that plant-based omega-3s may be more effective than fish oil.

• LA supplementation has been shown to reduce disease activity markers (MMP-9, ICAM-1) and improve walking performance in secondary progressive MS, suggesting its role in slowing disease progression, though it does not directly improve cognition.

• Supplementation with NAC has been linked to improvements in cognitive function in MS patients, potentially through increased cerebral blood flow and enhanced cerebral glucose metabolism.

• Evidence supporting the benefit of antioxidative supplementation for cognition in PwMS is controversial, with multiple mechanisms, including controlling oxidative stress, neuroinflammation, mitochondrial function, and enhancing cerebral blood flow, influencing cognitive outcomes.

• The complex and multifactorial nature of MS pathology suggests that combining antioxidants with different mechanisms of action may offer more significant cognitive benefits, though challenges remain in designing long-term studies to demonstrate clear effects.