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Neuroprotective synergy of vitamin D and exercise: A narrative review of preclinical and clinical evidence on aging-related neuroplasticity and cognitive health
This review examines the potential synergistic effects of vitamin D and physical exercise on neurobiological and cognitive outcomes related to healthy brain aging. While both factors have been independently linked to neuroprotection and anti-aging, their combined impact remains inadequately explored. The review synthesizes findings from preclinical and clinical studies, emphasizing mechanisms pertinent to older adults, such as neurotrophic signaling (e.g., BDNF, IGF-1) and inflammatory pathways (e.g., VEGF, cytokines). Recent randomized controlled trials (RCTs), including SYNERGIC, DO-HEALTH, and PONDER, alongside large-scale epidemiological studies, suggest that vitamin D and exercise may converge on biological pathways that mitigate oxidative stress, regulate inflammation, and promote neurogenesis. While some animal studies suggest that combined interventions enhance neuroprotection and cognitive function, human trials reveal that aerobic-resistance exercise with or without cognitive training yields improvements in cognitive scores among older adults with mild cognitive impairment. In contrast, vitamin D supplementation alone appears to have limited efficacy. Observational studies indicate that higher serum levels of vitamin D and regular physical activity are associated with delayed biological aging, both independently and in conjunction. However, the current evidence for clinically significant synergy between vitamin D and exercise remains inconclusive due to variability in study design, population characteristics, and intervention methodologies. Thus, while the biological plausibility is supported by selective findings, definitive conclusions regarding their synergistic effects on brain aging in older adults have yet to be established. Future research should prioritize at-risk populations, standardized intervention frameworks, and mechanistic investigations to assess the combined efficacy of these interventions as cost-effective preventive strategies in aging. [NPID: vitamin D, inflammation, oxidative stress, neurogenesis, exercise]
Year: 2025
