The regulatory and pleiotropic role of vitamin D

Abstract

Vitamin D is a multifunctional secosteroid compound that plays a key role in maintaining systemic homeostasis in humans and animals. Its active form, 1,25-dihydroxyvitamin D3 (calcitriol), acts as an endocrine and autocrine modulator, influencing the expression of hundreds of genes that regulate metabolism, immune response, cell proliferation, and antioxidant protection. In recent years, a significant amount of evidence has been accumulated indicating the pleiotropic nature of vitamin D: it is involved not only in phosphorus-calcium metabolism, but also in the regulation of the NF-κB, PI3K/Akt/mTOR, and Wnt/β-catenin signaling cascades, which control cell survival, apoptosis, inflammatory response, and aging processes. It has been proven that adequate levels of 25(OH)D in blood plasma reduce the risk of developing autoimmune, metabolic, cardiovascular, and oncological diseases. Calcitriol inhibits excessive NF-κB activation, reducing the production of pro-inflammatory cytokines IL-6, TNF-α, and IL-17; at the same time, it activates AMPK and PTEN, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy. By inhibiting β-catenin, vitamin D blocks the transcription of proto-oncogenes, preventing excessive proliferation. Due to its effect on these signaling systems, vitamin D acts as a universal integrator of cellular responses to stress, oxidative disturbances, and inflammatory stimuli. Particular attention is paid to its effect on the antioxidant and excretory systems, where vitamin D enhances the expression of antioxidant enzymes, reduces lipoperoxidation, and promotes the normalization of renal tubule function. In addition, epidemiological and clinical studies confirm the inverse relationship between vitamin D deficiency and the incidence of cancer, especially breast, prostate, and colon cancer. Vitamin D should be considered as a systemic regulator that integrates immune-endocrine, antioxidant, and metabolic processes, ensuring the stability of the body's functional systems. Its pleiotropic effect opens up new opportunities for the development of personalized approaches to the prevention and treatment of chronic diseases.