Summary:
This study is a cross‑sectional analysis of more than 2,000 adults, which looked at whether blood vitamin C levels were linked to brain structure and connectivity, focusing particularly on the default mode network (DMN). The DMN is the brain’s idle mode that’s activated when you’re not doing a task. This network switches on and supports memory, self‑reflection, and planning. Vitamin C is known to be highly concentrated in the brain and acts as a major antioxidant involved in neurotransmission, enzyme activity and hormone regulation. Experimental work shows extremely high vitamin C levels inside neurons, and human research has also linked higher vitamin C intake with lower Alzheimer disease risk. Vitamin C has also been investigated for potential roles in neurodegenerative and psychiatric conditions. Despite this, very few studies have examined how circulating vitamin C relates to brain integrity, and almost none have explored its relationship with brain networks such as the DMN. In this study, lower plasma vitamin C levels were associated with reduced gray matter volume relative to head size and with weaker DMN connectivity. The study also found that different DMN components showed opposite patterns: vitamin C was positively associated with DMN subsystems that typically decline with age, and negatively associated with a subsystem that increases abnormally with aging. This suggests vitamin C may help maintain normal network integrity while limiting age‑related structural changes. Overall, these findings suggest that vitamin C status is related to the structural health of key brain regions and networks. Because humans cannot synthesize vitamin C and rely entirely on dietary intake, maintaining adequate vitamin C levels may support healthy brain aging.
Read the Complete Article >
Abstract:
Background: Neurodegenerative diseases significantly impact brain health in older adults, and although dietary vitamin C intake has been associated with a reduced risk of cognitive impairment, it remains unclear whether plasma vitamin C levels independently affect brain structure and neural connectivity. This study aimed to investigate whether plasma vitamin C levels were independently associated with brain volume and default mode network (DMN) connectivity in older adults. Methods: All participants underwent 3T magnetic resonance imaging (MRI). Total intracranial volume (ICV), gray matter volume (GMV), and white matter volume (WMV) were calculated using CAT 12 in SPM 12. DMN connectivity was assessed using independent component analysis, based on shared GMV variance across voxels, and quantified by the loading coefficients. Multiple regression analysis was used to investigate the associations among brain volume, DMN connectivity measurements, and plasma vitamin C levels. These analyses were adjusted for potential confounders (age, sex, Mini-Mental State Examination score, diabetes, hypertension, hyperlipidemia, and education levels), and lifestyle factors (smoking history, drinking history, and physical activity). GMV/ICV ratio and WMV/ICV ratio were calculated to adjust for individual differences in head size. Results: This cross-sectional study included 2,044 participants (median age, 69 years; females, 61.1%). Low plasma vitamin C levels were significantly and independently associated with the GMV/ICV ratio (p < 0.001) and DMN connectivity (p < 0.001). Conclusions: In conclusion, our findings demonstrate that plasma vitamin C levels are positively associated with the structural integrity of the gray matter and DMN connectivity, generating the hypothesis that vitamin C may play a role in brain health.
Article Publication Date: 10/06/2026
DOI: 10.1371/journal.pone.0348504
