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Vitamin C, gut bacteria, and mental vitality: early findings

February 23, 2026
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Mental vitality, a part of mental wellbeing, is the capacity to engage in daily tasks with sufficient mental energy. It includes things like staying motivated, maintaining focus, thinking clearly, adapting to change and coping with stress (Logvinov & Loerzel, 2026).

Mental vitality can be influenced by a range of bio-psycho-social factors including diet (Jongeneelen et al., 2025), and micronutrients, such as vitamin C, have been linked to aspects of it (Das et al., 2025). Individuals who are deficient in vitamin C may experience fatigue, reduced motivation, cognitive impairment and low mood (Plevin & Galletly, 2020), whereas supplementation can improve some of these symptoms (Yosaee et al., 2021). This has sparked scientific interest in the role of vitamin C supplementation in improving mental vitality.

Vitamin C is a water-soluble vitamin that cannot be made by or stored in the human body, so it can only be obtained through dietary sources such as fruits and vegetables, or supplements. Vitamin C is known for its antioxidant properties that help protect cells from free radical damage, contribute to immune defence and support neurotransmitter production that aid nerve cell communication.

Beyond these functions, vitamin C may play a role in the gut–brain–immune axis, an intricate network of interactions between the gut, brain and immune system (Clarke G, 2023; Robinson S, 2025). Our diet shapes the bacteria that lives in our gut, and these in turn can affect the types of microbial metabolites (chemical messages) sent from our gut to our bodily systems, like the brain and immune system. On the other hand, the types of bacteria that live in our gut and how they function can also affect the way we respond to diet. This highlights the possibility of using tailored gut-focused approaches to enhance mental well-being. However, this relationship has not yet been clearly established in the context of vitamin C.

Sim and colleagues (2025) conducted a randomised, double-blind, placebo-controlled trial to investigate whether supplementing vitamin C in healthy young adults with suboptimal levels (< 50 μM) can enhance mental vitality and whether this is accompanied by changes in the gut microbiome, neural signalling and immune response. They also explored whether the extent of gut microbiome changes might help explain the observed effects and identify responders and non-responders to vitamin C supplementation.

Vitamin C may play a role in the gut–brain–immune axis and this study explored whether supplementing vitamin C in healthy young adults could enhance mental vitality.

Vitamin C may play a role in the gut–brain–immune axis and this study explored whether supplementing vitamin C in healthy young adults could enhance mental vitality.

Methods

Healthy adults aged 20-39 years old who had vitamin C levels below 50umol/L, no acute or chronic diseases, and were not taking vitamin C supplements were recruited. Participants were randomly allocated to consume 500mg of vitamin C twice daily in the form of a 100ml drink, or a placebo of the same volume, colour and flavour, for 4 weeks. A medium navel orange typically contains 70mg of vitamin C.

Participants attended two study visits, the day before starting supplementation (baseline) and the day after completing supplementation (week 4). During these visits, participants completed questionnaires to assess mental vitality, which include subjective attention and fatigue (Checklist Individual Strength), work engagement (Utrecht Work Engagement Scale) and cognitive performance (Stroop color-word test.) Participants also provided stool and fasted blood samples.

The authors examined between-group differences in change in neuroplasticity-related markers and assessed whether changes in mental vitality differed according to microbiome differences. Participants in the vitamin C group were classified based on changes in gut microbial features that significantly correlated with mental vitality indices. The threshold for classification was set at a 1.5-fold decrease or increase compared to the mean fold change observed in the placebo group.

Results

Among the 46 participants who completed the study, 40 (21 = vitamin C; 19 = placebo) were included in the analyses. All participants who received the vitamin C intervention achieved adequate levels of serum vitamin C at week 4.

Vitamin C on mental vitality outcomes

Participants supplemented with vitamin C demonstrated enhancement in mental vitality. Specifically, significant improvements in attention, work absorption and cognitive performance were found, and near-significant improvements in fatigue and work engagement as compared to placebo.

Vitamin C on gut outcomes

Vitamin C supplementation did not significantly alter microbiome diversity, but there were significant changes in specific bacteria taxa. In particular, relative abundance of Bacillaceae and Anaerotruncus (generally beneficial bacteria) increased whereas Desulfovibrio (potentially harmful bacteria) decreased. Vitamin C supplementation also altered the gut microbial activity (i.e. what the microbes do) and circulating levels of relevant metabolites (i.e. what the microbes produce). Reduced activity was observed across two microbial metabolic pathways (the polyamine and Entner–Doudoroff pathways), along with corresponding decreases in serum spermidine and lipopolysaccharide-binding protein (LBP). There were significant correlations between changes in microbial pathways and changes in metabolite levels, which may indicate that microbiome function is altered by vitamin C.

Vitamin C on immune outcomes

Vitamin C also suppressed inflammatory cytokine responses. In the vitamin C group, anti-inflammatory IL-10 levels remained stable while pro-inflammatory TNF-α significantly decreased.

Vitamin C and the gut-brain-immune relationship

Changes in the relative abundance of Desulfovibrio and microbial metabolic pathways significantly correlated with reaction times in the Stroop test. Moreover, changes in Desulfovibrio abundance were significantly correlated with IL-10 levels. This may reflect a connection between the gut microbiota, cognitive functioning and the immune system, which can be influenced by vitamin C supplementation.

Responders vs non-repsonders

As Desulfovibrio reduction was the only microbial feature that significantly correlated with mental vitality indices, responders were classified as individuals who had at least 1.5-fold reduction in the abundance of Desulfovibrio compared to the mean fold change in placebo. Individual variability in physiological responses (neural and immune) was found based on the magnitude of Desulfovibrio reduction. Vitamin C responders showed a significant increase in brain-derived neurotrophic factor (BDNF), stronger positive correlations between changes in serum L-DOPA levels (dopamine precursor) and work engagement scores, and experienced greater reduction in some immune markers (classical monocyte frequencies and IL-10) compared with non-responders.

Vitamin C supplementation was linked to improvements in attention and work absorption, alongside specific microbial and immune changes.

Vitamin C supplementation was linked to improvements in attention and work absorption, alongside specific microbial and immune changes.

Conclusions

This study suggests that vitamin C supplementation can modulate gut microbiota composition, particularly by reducing Desulfovibrio abundance, with the amount of reduction correlating with mental vitality improvements and decreased inflammation. Vitamin C supplementation may be a promising approach to improve mental vitality in healthy individuals with suboptimal Vitamin C status.

The authors concluded that their results provide:

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.

Vitamin C supplementation may modulate mental health through its influence on the gut-brain-immune axis.

Vitamin C supplementation may modulate mental health through its influence on the gut-brain-immune axis.

Strengths and limitations

Strengths

The authors employed a rigorous study design with appropriate blinding procedures and adherence monitoring. They investigated the effect of vitamin C supplementation on key biological mechanisms (i.e. the gut-brain-immune axis) that are linked to mental well-being. The authors included both subjective assessments and objective biomarkers to help explain the effects observed in the study. Comprehensive and complementary analyses were used to explore the relationship, including analytical techniques such as 16S rRNA sequencing, functional pathway prediction and biomarker validation.

Limitations

The short intervention duration of four weeks limits our understanding of the long-term effects of vitamin C supplementation on changes in mental health and the microbiome due to their dynamic nature.

Secondly, the small sample size of 40 participants and the narrow population characteristics consisting of healthy young adults ages 20-39 with suboptimal vitamin C status, in which 85% are university students, limits the generalisability of findings. Individuals of older age, or those who have been diagnosed with medical conditions may respond differently to a vitamin C intervention due to physiological differences such as immune profile, gut microbiota composition and function, or medication use.

Not all potential confounding variables that can influence the results were measured (e.g. sleep, use of other supplements or medication) or discussed (e.g. diet or physical activity), which may affect the interpretation of the results. For instance, without capturing medication or supplement use other than vitamin C, it is challenging to ascertain whether the observed changes in the gut microbiome were truly caused by vitamin C supplementation. In addition, even though the researchers instructed participants to maintain their physical activities, activity levels were only measured at baseline, hence it is unclear whether participants adhered to these instructions. Furthermore, the 2-day dietary record at baseline and end of study may be too short to capture day-to-day variation in habitual food and nutrient intake.

Lastly, even though the authors were rigorous in using subjective and objective markers to measure associations, mechanistic studies are still needed to better understand causal effects of microbiome changes with mental health outcomes. The technical limitations of 16sRNA may also be problematic as it provides an idea of which species of bacteria is there, but not the specific strains and what they do. In addition, the responder classification of 1.5-fold appears arbitrary and will require validation in larger cohorts.

This was a well-controlled trial with rich biological measures, but its findings are limited by size, duration and generalisability.

This was a well-controlled trial with rich biological measures, but its findings are limited by size, duration and generalisability.

Implications for practice

The study suggests that vitamin C supplementation may improve aspects of mental vitality through its effect on the gut-brain-immune axis. However, it is important to note that the study was conducted in generally healthy young adults with no medical conditions who are solely deficient in vitamin C. This means that while vitamin C may be relevant for at-risk but otherwise healthy groups (e.g. those with poor diet quality and are struggling with low energy, motivation, or focus), the findings should not be generalised to older adults or individuals with physical or mental health conditions due to likely differences in dietary requirements, physiological responses or microbiome composition.

Targeting the gut-brain-immune pathway may be a promising approach, and clinicians should consider using nutritional strategies that targets this pathway as part of a holistic lifestyle approach to support mental well-being. This study also highlights the importance of evaluating dietary adequacy, monitor nutrient status and supplement where necessary to adequate levels. However, over-supplementation should be avoided to prevent potential adverse effects.

Future research should validate these findings in broader populations (e.g. larger and more diverse samples) and employ different outcome assessment tools that incorporate both patient-rated and clinician-rated measures to capture multiple perspectives on mental vitality. Moreover, mechanistic studies and advanced techniques like shotgun metagenomics, metabolomics and neuroimaging could be used to gain deeper insights into the relationship between diet, mental vitality and the gut-brain-immune axis. More research on personalised nutrition based on gut microbiome profiles would also be valuable in considering what dietary strategies may or may not be effective for different populations.

arly evidence suggests vitamin C can improve attention and energy in some young adults, though broader clinical application is not yet established.

Early evidence suggests vitamin C can improve attention and energy in some young adults, though broader clinical application is not yet established.

Statement of interests

Delyse Tien’s PhD is supported by a Co-funded Monash Graduate Scholarship (CF-MGS).

Editor

Edited by Éimear Foley. AI tools assisted with language refinement and formatting during the editorial phase.

Links

Primary paper

Minju Sim,  Sehwa Hong,  Min Ho Jung, Eun Young Choi, Geum-Sook Hwang, Dong-Mi Shin,  Chong-Su Kim. (2025). 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. Brain, Behavior, and Immunity, 128, 179–191. https://doi.org/10.1016/j.bbi.2025.03.032

Other references

Clarke, G. (2023). Gut microbiome disruptions in depression: shifting the focus to metabolic signatures in blood. The Mental Elf.

Das, S., Banerjee, P., Jana, S., & Mondal, H. (2025). Unveiling the mechanistic nexus: How micronutrient enrichment shapes brain function, and cognitive health. Frontiers in Molecular Biosciences, 12, 1623547. https://doi.org/10.3389/fmolb.2025.1623547

Jongeneelen, M. E., Wieringa, C. H. L. A., den Elzen, W. P. J., Langeveld, K., Gussekloo, J., & Drewes, Y. M. (2025). The definition of vitality—The perspectives of Dutch older persons. BMC Public Health, 25, 383. https://doi.org/10.1186/s12889-025-21458-4

Logvinov, I. I., & Loerzel, V. (2026). Vitality in older adults: A state-of-the-science review. Archives of Gerontology and Geriatrics, 141, 106072. https://doi.org/10.1016/j.archger.2025.106072

Plevin, D., & Galletly, C. (2020). The neuropsychiatric effects of vitamin C deficiency: A systematic review. BMC Psychiatry, 20(1), 315. https://doi.org/10.1186/s12888-020-02730-w

Robinson, S. (2025). Is it a gut feeling? How the microbiome may shape perinatal mental health in women with higher body weight, The Mental Elf.

Yosaee, S., Keshtkaran, Z., Abdollahi, S., Shidfar, F., Sarris, J., & Soltani, S. (2021). The effect of vitamin C supplementation on mood status in adults: A systematic review and meta-analysis of randomized controlled clinical trials. General Hospital Psychiatry, 71, 36–42. https://doi.org/10.1016/j.genhosppsych.2021.04.006

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