Vitamin D

Cholecalciferol (vitamin D₃), C₂₇H₄₄O

Evidence: Strong

Beyond its role in calcium metabolism, Vitamin D plays a significant immunomodulatory role. It influences innate and adaptive immune responses within the gut and helps maintain intestinal barrier function. Adequate Vitamin D status is increasingly linked to gut health and reduced inflammation in the digestive tract.

There are 110,523 peer-reviewed scientific studies on this ingredient.

Selected Study 1/3:

Akimbekov, N. S., Digel, I., Sherelkhan, D. K., Lutfor, A. B., & Razzaque, M. S. (2020). Vitamin D and the Host-Gut Microbiome: A Brief Overview. Acta Histochemica et Cytochemica, 53(3), 33. https://doi.org/10.1267/ahc.20011 

Study Summary:

Study type: Narrative literature review; no new human or animal participants were enrolled.

Observed benefits: The authors collate evidence that sufficient vitamin D status associates with a more diverse gut microbiota, higher proportions of beneficial genera, tighter epithelial junctions and lower markers of bowel inflammation, all of which may translate into reduced risk or severity of inflammatory bowel disease and other dysbiosis-linked disorders.

Mechanisms of action: Vitamin D, acting through the vitamin-D receptor (VDR), is reported to up-regulate antimicrobial peptides, modulate innate and adaptive immune signaling, and preserve barrier integrity; microbially derived metabolites can in turn regulate VDR expression, creating a two-way “vitamin D–microbiome axis.”

Side effects: The review does not describe adverse effects of vitamin D beyond noting that hypervitaminosis is possible at excessive supplemental intakes; no new safety data are provided.

Strength of evidence: Because conclusions rest on secondary synthesis of heterogeneous animal, cellular and small human studies, evidence is suggestive rather than definitive; the authors explicitly call for controlled human trials to confirm causality and elucidate dose-response relationships.

Selected Study 2/3:

Aggeletopoulou, I., Marangos, M., Assimakopoulos, S. F., Mouzaki, A., Thomopoulos, K., & Triantos, C. (2023). Vitamin D and Microbiome: Molecular Interaction in Inflammatory Bowel Disease Pathogenesis. The American Journal of Pathology, 193(6), 656-668. https://doi.org/10.1016/j.ajpath.2023.02.004

Study Summary:

Study type: Narrative review in American Journal of Pathology; no new participants.  

Observed benefits: Across the literature, optimal vitamin D correlates with higher abundance of anti-inflammatory bacterial taxa present in the gut microbiota, reduced pathogenic species, strengthened intestinal barrier function and dampened innate-immune activation—factors that together may slow IBD onset or flares.

Mechanisms of action: The paper describes vitamin D–VDR signaling as central to regulating tight-junction proteins, autophagy, and antimicrobial peptide release, while also shaping microbiota composition; dysregulated VDR signaling is posited as a mechanistic bridge between vitamin D deficiency, dysbiosis and chronic gut inflammation.

Side effects: No new safety signals are reported; available trials generally declare vitamin D supplementation well tolerated at standard doses.

Strength of evidence: The review integrates molecular, pre-clinical and small-scale clinical data, providing biologically plausible links but acknowledging that large, randomized supplementation trials in IBD patients remain scarce; thus current evidence is moderate and hypothesis-generating rather than conclusive.

Selected Study 3/3:

Ullah, H. (2025). Gut-vitamin D interplay: Key to mitigating immunosenescence and promoting healthy ageing. Immunity & Ageing : I & A, 22, 20. https://doi.org/10.1186/s12979-025-00514-y 

Study Summary:

Study type: Narrative review in Immunity & Ageing; no new participants.

Observed benefits: Synthesized data suggest that correcting vitamin D insufficiency and modulating the microbiome may slow immunosenescence, lower systemic low-grade inflammation, and reduce incidence of age-related chronic diseases by preserving immune resilience in older adults.

Mechanisms of action: Vitamin D influences gut microbial diversity and metabolite production, while microbiota enzymes affect vitamin D activation; the review highlights VDR-dependent enhancement of antimicrobial peptides, maintenance of mucosal integrity, repression of pro-inflammatory cytokines and support of mitochondrial function as putative pathways that jointly delay immune aging.

Side effects: No adverse events are discussed; the author simply notes standard cautions regarding hypervitaminosis D and drug interactions with high-dose supplements.

Strength of evidence: The argument rests on converging mechanistic insights and observational findings, but lacks large intervention trials in elderly cohorts; consequently, the paper frames the gut-vitamin D axis as a promising target whose clinical benefits remain to be proven in well-designed human studies.