Gut microbiota links vitamin C supplementation to enhanced mental vitality in healthy young adults with suboptimal vitamin C status: A randomized, double-blind, placebo-controlled trial

The intricate relationship between nutrition, gut microbiome, and mental health has gained increasing attention. We aimed to determine how vitamin C supplementation improves mental vitality through the gut microbiome and associated neurological and immunological changes. We used 16S rRNA sequencing to analyze gut microbiota profiles of participants from our previous trial, in which healthy young adults (20–39 years) with inadequate serum vitamin C levels (< 50 μM) received 500 mg vitamin C or a placebo twice daily for 4 weeks (vitamin C, n = 21; placebo, n = 19). We examined whether changes in gut microbiota correlated with previously determined mental vitality indices, including Stroop test performance, work engagement, and serum brain-derived neurotrophic factor (BDNF) levels. Serum concentrations of microbial-derived molecules, cytokines, and neurotransmitters were analyzed using enzyme-linked immunosorbent assay, electrochemiluminescence-based immunoassay, or ultra-high-performance liquid chromatography–mass spectrometry. Monocyte subpopulations in peripheral blood were quantified using fluorescence-activated cell sorting analysis. Vitamin C supplementation increased the relative abundance of Bacillaceae and Anaerotruncus, while decreasing Desulfovibrio, with the Desulfovibrio reduction correlating with Stroop test performance. Moreover, participants showing a substantial Desulfovibrio reduction (“responders”) demonstrated greater BDNF increases and stronger correlations between serum L-DOPA levels and work engagement scores than did non-responders. In addition, vitamin C supplementation suppressed inflammatory responses with concurrent reduction in serum lipopolysaccharide levels, and responders showed greater decreases in IL-10 levels and classical monocyte frequencies than non-responders. In conclusion, vitamin C supplementation modulates gut microbiota composition, particularly by reducing Desulfovibrio abundance, with the extent of reduction correlating with mental vitality improvements and decreased inflammation. This study provides insights into vitamin C supplementation as a critical dietary intervention, as it may modulate mental health through its influence on the gut-brain-immune axis.