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Despite the null results on neuroplasticity, the observed decrease in corticospinal excitability and inhibition in the treatment group might suggest improved synaptic efficiency, warranting further investigation over longer intervention periods or with higher doses ( 3.3 Antioxidant and anti-inflammatory properties Oxidative stress and chronic low-grade inflammation are central features of brain aging and contribute to neuronal damage, reduced synaptic plasticity, and cognitive decline ( In rodent models, aging is consistently linked to cognitive deficits and heightened inflammation

Specifically, treatment with nicotinamide significantly reduced the levels of key pro-inflammatory cytokines, including TNF-, IL-1, and IL-6, alongside a marked suppression of TGF-1, a central mediator of fibrogenesis (Figure 4A) (Sani et al., 2025)

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Methylation cycle hypothesis The methylation cycle hypothesis posits that a core component of the pathophysiology of chronic fatigue syndrome involves a partial block in the methylation cycle