Vitamin D eand vitamin C promoting healthy ageing

Overview. Both Vitamin D and Vitamin C contribute to intestinal barrier health by supporting the function of tight junctions and promoting repair. Vitamin D, through its receptor (VDR), regulates proteins that form tight junctions, which maintain barrier integrity and modulate the immune system. Vitamin C can also promote barrier repair, potentially through regulating Notch signaling pathways and by influencing the gut microbiome composition, which can further support the barrier.
Vitamin D’s Role
Tight Junctions:
The active form of Vitamin D, 1,25(OH)2D3, regulates the expression of proteins like claudins and ZO within the tight junction complex, which are crucial for maintaining and repairing the intestinal barrier.
Immune Modulation:
Vitamin D binds to VDR in immune cells and modulates immune responses, helping to protect against conditions that can compromise the barrier, like inflammatory bowel disease.
Barrier Integrity:
By binding to VDRs and affecting immune cells and epithelial cells, Vitamin D signaling helps maintain a healthy, stable intestinal barrier.
Vitamin C’s Role
Barrier Repair:
Vitamin C supplementation has demonstrated beneficial effects on the intestinal barrier, helping to repair damage.
Notch Signaling:
Combined with Vitamin D, Vitamin C may regulate the Notch signaling pathway to protect the intestinal mucosal barrier, including the expression of claudin-2.
Gut Microbiome:
Vitamin C supplementation can help balance the gut microbiota in healthy individuals with suboptimal Vitamin C levels, which may indirectly benefit the barrier by reducing the presence of potentially harmful LPS-producing bacteria.
Combined Effects
Synergistic Protection:
Research indicates that combining Vitamin C and Vitamin D may offer greater protective effects on the intestinal barrier compared to either vitamin alone, possibly through their combined influence on the Notch signaling pathway.
Therapeutic Potential:
Both vitamins are being investigated for their potential in managing intestinal diseases by enhancing barrier integrity and modulating the immune response within the gut.

Researches
1 – Gut-interplay: key to mitigating immunosenescence and promoting healthy ageing. 2025
Abstract
Background Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases.
Main text
Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health.
Conclusions
These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.
Keywords Gut microbiota, Vitamin D, Immune ageing, Immunosenescence, Healthy ageing
Gut-vitamin D interplay: key to mitigating immunosenescence and promoting healthy ageing. 2025. Hammad Ullah. https://doi.org/10.1186/s12979-025-00514-y
Hammad Ullah hammadrph@gmail.com 1 School of Pharmacy, University of Management and Technology, Lahore 54000, Pakistan

2 – Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases. Ian Richard Lucena Andriolo et al. 2024.

It is known that reactive oxygen species cause abnormal im- mune responses in the gut during inflammatory bowel dis- eases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the de- velopment of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD in- clude its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies em- ployed high doses of vitamin C and most of them did not per- form dose-response curves and neither determined the mini- mum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the ap- propriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.
Perspectives and conclusion
The pathogenesis of IBD is closely related to oxidative stress due to an intense inflammatory insult and the use of vitamin C in IBD, as well as the role of its deficiency, is currently being investigated. Therefore, this perspective reviewed the pharmacological poten- tial of this vitamin to treat and prevent these diseases. In this ap- proach, Vitamin C may help the integrity of the intestinal barrier under the inflammatory stimulus, and enhance intestinal mucosal barrier function, while reducing oxidative stress.
However, a point that is worthy of attention in non-clinical stud- ies presented here is the dose used, which must be adequate for extrapolation in humans. Studies suggest that a daily intake of vi- tamin C from 100 to 400 mg promotes 100 % of the bioavailability and reaches a maximum serum content of 70–80 µmol/L [33, 34]. In addition, when the intake of vitamin C exceeds 500 mg/day, a further increase in plasma concentration is inhibited and when doses greater than 1,000 mg of ascorbic acid are administered in a single dose the bioavailability can decrease by 30 % [34]. This oc- curs because when 500–1,000 mg of vitamin C are administered orally, the intestinal transporter quickly achieves its maximal satu- ration, while the vitamin is progressively excreted by urine [34, 35].
Another important point, which has not yet been studied, is the impact of the pH of the ascorbic acid solution used in the experi- mental studies. Since the pH of an ascorbic acid solution is very low it is expected that its administration can reduce the pH at the in- jection site, intestine, and colon if an enema was used. So, further studies need to address this bias and evaluate the use of buffered ascorbic acid solutions. Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases. Ian Richard Lucena Andriolo et al. 2024. DOI 10.1055/a-2263-1388. ISSN 2194-9379

3 – Vitamin D Receptor Influences Intestinal Barriers in Health and Disease. Jun Sun and Yong-Guo Zhang. 2022.
Abstract:
Vitamin D receptor (VDR) executes most of the biological functions of vitamin D. Beyond this, VDR is a transcriptional factor regulating the expression levels of many target genes, such as genes for tight junction proteins claudin-2, -5, -12, and -15. In this review, we discuss the progress of research on VDR that influences intestinal barriers in health and disease. We searched PubMed and Google Scholar using key words vitamin D, VDR, tight junctions, cancer, inflammation, and infection. We summarize the literature and progress reports on VDR regulation of tight junction distribution, cellular functions, and mechanisms (directly or indirectly). We review the impacts of VDR on barriers in various diseases, e.g., colon cancer, infection, inflammatory bowel disease, and chronic inflammatory lung diseases. We also discuss the limits of current studies and future directions. Deeper understanding of the mechanisms by which the VDR signaling regulates intestinal barrier functions allow us to develop efficient and effective therapeutic strategies based on levels of tight junction proteins and vitamin D/VDR statuses for human diseases.
Conclusions
The recent progress reveals a novel activity of VDR in regulation of many tight junction proteins in primate cell structure and intestinal homeostasis and diseases (as shown in the Graphic Abstract). We aim to show the current state of knowledge on this topic and its potential therapeutic applications. This knowledge can be used to develop intestinal VDR-associated TJ proteins, e.g., claudin-5 and -15, as clinical biomarkers for identifying patients who may benefit from currently available interventions and could be used for the eventual development of novel strategies for the prevention and treatment of diseases. VDR signaling is also highly significant in regulating other proliferation and anti-inflammatory pathways [74 ,157 , 162 ,174 ]. We hope to integrate our findings with other studies and, more importantly, understand how the microbiome, probiotics, and metabolites coordinate the effects of vitamin D/VDR [ 146 ]. Our long-term goal is to develop individualized therapeutic strategies based on tight junction proteins [ 175 ] and vitamin D/VDR statuses for efficient and effective prevention and treatment of chronic diseases.
Vitamin D Receptor Influences Intestinal Barriers in Health and Disease
Jun Sun 1,2,3,* and Yong-Guo Zhang 1.
1 Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; yongguo@uic.edu; 2 Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA; 3 Jesse Brown VA Medical Center Chicago (537), 820 S Damen Ave, Chicago, IL 60612, USA. Cells 2022, 11, 1129. https://doi.org/10.3390/cells11071129.

4 – Vitamin C improves gut Bifidobacteria in humans. Sabine Hazan et al. 2022.
Aims: Numerous beneficial effects of vitamin C (ascorbic acid) supplementation have been reported in the literature. However, data on its effects toward the gut microbiome are limited. We assessed the effect of vitamin C supplementation on the abundance of beneficial bacterial species in the gut microbiome. Materials and methods: Stool samples were analyzed for relative abundance of gut microbiome bacteria using next-generation sequencing-based profiling and metagenomic shotgun analysis. Results: Supplementation with vitamin C increased the abundance of bacteria of the genus Bifidobacterium (p = 0.0001) and affected various species. Conclusion: The beneficial effects of vitamin C supplementation may be attributed to modulation of the gut microbiome and the consequent health benefits thereof. Vitamin C improves gut Bifidobacteria in humans. Sabine Hazan et al. 2022. Future Microbiology, 20:7-9, 543-557, DOI: 10.2217/fmb-2022-0209

5 – Combined effect of vitamin C and vitamin D3 on intestinal epithelial barrier by regulating Notch signaling pathway. 2021. Fubin Qiu et al.
Abstract
Background: Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D 3 affects intestinal mucosal barrier stability via the Notch signaling pathway.
Methods: Intestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD3 + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD3 + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD3 + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD3 + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD3 group (0.1 μmol/L VD3); VC +VD3 group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD3).
Results: Electron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D 3 maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction.
Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D 3 were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D3 can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier.
Conclusions: We found that vitamin C combined with vitamin D 3 protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.
Keywords: Intestinal epithelial barrier, Tight junction, Inflammatory bowel disease, Vitamin D 3, Vitamin C. Combined effect of vitamin C and vitamin D3 on intestinal epithelial barrier by regulating Notch signaling pathway. 2021. Fubin Qiu, Zehui Zhang, Linxue Yang, Rui Li and Ying Ma. Nutr Metab (Lond) (2021) 18:49. https://doi.org/10.1186/s12986-021-00576-x.

Note:

1 – The Notch pathway is a cell-to-cell signaling system crucial for cell-cell communication, influencing decisions about cell fate, proliferation, differentiation, and tissue homeostasis during development and adulthood. The signal then enters the nucleus of the recipient cell to regulate the expression of target genes, controlling cellular behaviors such as self-renewal and apoptosis (the controlled process of programmed cell death).