Vitamin D as a Systemic Regulatory Axis: From Homeostasis to Multiorgan Disease.

Background/Objectives: To critically evaluate the current scientific literature on the physiological and preventive functions of vitamin D, with special emphasis on its possible involvement in multi-organ pathologies, and to assess the effectiveness of supplementation strategies for maintaining homeostasis. Methods: A review of the literature was conducted following a methodological approach in accordance with the PRISMA 2020 statement for systematic reviews. The bibliographic search was carried out in the PubMed, Scopus, and Web of Science databases, using controlled terms and Boolean operators. Rigorous inclusion and exclusion criteria were applied in three phases: blind search, selection by title/abstract, and full-text evaluation. Articles published in first quartile journals (JCR 2023) were prioritized. The search was complemented with targeted strategies such as consulting ORCID profiles, using the Jábega tool, and tracking cross-references. Results: The selected studies reinforce that vitamin D acts as a transcriptional modulator with effects beyond the skeletal system, including immunomodulatory, neuroprotective, and antitumor functions. Associations were identified between low levels of 25(OH)D and a higher prevalence of autoimmune, neurodegenerative, and metabolic diseases, as well as certain types of cancer. However, evidence of causality is still limited, and clinical trials have shown mixed results regarding its preventive efficacy. Supplementation strategies are useful in vulnerable populations, although their indiscriminate use without a documented deficiency is not recommended. Conclusions: Vitamin D is emerging as a potentially relevant agent in preventive medicine. While its benefits extrapolated from bone metabolism still require robust clinical validation, current findings support its role in regulating key systemic functions. A balanced approach combining sun protection, health education, food fortification, and targeted supplementation, tailored to the clinical context of each individual, is recommended.