Written by Tabish Mehraj, PhD. In this cross-sectional study of 2,044 participants (median age, 69 years; 61.1% women), plasma vitamin C levels were significantly and independently associated with the GMV/ICV ratio and DMN connectivity (both p < 0.001).

Vitamin C is an important nutrient that acts as an antioxidant and helps regulate communication between nerve cells. It also supports the maintenance and normal functioning of neurons, which are essential for healthy brain function. Previous studies have suggested that higher dietary vitamin C intake may be associated with a lower risk of cognitive impairment. However, less is known about whether blood vitamin C levels are associated with brain structure and interregional connections. Brain magnetic resonance imaging (MRI) can be used to assess brain volumes and structural connectivity, providing valuable information about brain health. One important brain network is the default mode network (DMN), which is involved in functions such as memory, self-referential thinking, and other cognitive processes. Changes in brain structure and connectivity may be associated with age-related cognitive decline. The association between plasma vitamin C levels and structural connectivity within the DMN has not been comprehensively examined in a large cohort of older adults living in communities.

In this cross-sectional analysis, the data was used from the population-based Iki-Iki Health Promotion Project in Hirosaki, Japan. Community-dwelling residents aged over 64 years underwent fasting blood sampling and 3-T magnetic resonance imaging. Plasma vitamin C concentration was measured using a commercially available assay. T1-weighted MRI scans were analyzed using CAT12/SPM12 to measure gray matter, white matter, and total intracranial volume, accounting for differences in head size. Researchers identified 147 patterns of gray matter distribution and, with input from two experienced neuroradiologists, selected three representing the anterior and posterior default mode networks (DMNs). Statistical models examined associations between plasma vitamin C levels and brain measures, adjusting for demographic factors, cognitive function, medical conditions, and lifestyle habits. False discovery rate (FDR) correction was applied to reduce the risk of false-positive findings across the three DMN comparisons. Voxel-based morphometry was also used to identify specific brain regions where gray matter volume was associated with plasma vitamin C levels.

Results/Key Findings

• Of 2,390 participants, 2,044 were included in the analysis. The median age was 69 years, 61.1% were women, and median plasma vitamin C was 7.38 μg/mL.
• Higher vitamin C levels were associated with greater gray matter (β = 0.076, p < 0.001) and white matter volumes (β = 0.074, p < 0.001).
• Interestingly, vitamin C showed a negative association with posterior DMN-II connectivity, a network component the authors suggest may reflect age-related structural alterations (β = 0.097) and posterior DMN-I connectivity (β = 0.082), but negatively associated with posterior DMN-II connectivity (β = −0.111; all p < 0.001)
• Higher plasma vitamin C levels were independently associated with greater global brain in several DMN-related regions, including the posterior and middle cingulate cortices, medial prefrontal cortex, and bilateral inferior temporal regions.

Vitamin C levels were not directly associated with MMSE scores, although anterior DMN and posterior DMN-I connectivity were positively associated with cognitive performance. Although statistically significant, the observed associations were modest in magnitude. There are several strengths of the study, which include a large population-based sample, standardized imaging on a single 3-T scanner, fasting biomarker assessment, head-size correction, adjustment for major demographic, clinical, and lifestyle confounders, and convergence of network-level and voxel-wise MRI analyses. The principal limitations are the cross-sectional design, which prevents causal inference; reliance on a single plasma vitamin C measurement, which may not represent long-term status; restricted generalizability because participants were older Japanese adults with relatively high educational attainment; and possible residual confounding from unmeasured dietary intake, body mass index, and socioeconomic factors. Associations were statistically robust but modest in magnitude.

In this large cohort of older adults, higher plasma vitamin C levels were independently associated with preserved global brain volume, gray matter volume in DMN-related regions, and distinct DMN structural network patterns. These findings support a potential role for vitamin C status in healthy brain aging but should be regarded as hypothesis-generating. Longitudinal studies with repeated biomarker measurements and intervention trials are needed to determine directionality, mechanisms, and clinical relevance.

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Posted October 21, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

Reference:

1. Nagaya, H., Watanabe, K., Shintaku, T., Sasaki, M., Kudo, J., Kasai, S., … & Kakeda, S. (2026). Plasma vitamin C levels are associated with brain structural networks on MRI: A large cohort study. Plos one, 21(6), e0348504.