Vitamin D3

Signaling of Vitamin D3 includes genomic and non-genomic pathways activated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 binds to nuclear vitamin D receptor (VDR), heterodimerizes with retinoid X receptor-α (RXR-α) and recruits co-activators such as CBP/p300 and SRC-1 and displaces co-repressors such as NCoR. The RXR-VDR complex then binds with high affinity to vitamin D response elements (VDRE) located in the promoter region of target genes. VDRE binding causes chromatin remodeling, histone modification and recruitment of RNA polymerase II to regulate transcription of target genes, including genes encoding proteins related to calcium homeostasis, immune responses and cell differentiation. In addition to genomic pathways, rapid non-genomic signaling cascades activated by membrane-associated receptors such as PI3-kinase/Akt, Src kinase and MAPK pathways have also been described. In addition, the VDR-RXR complex can bind to response elements to repress transcription by displacing NFAT from the DNA. Intracrine production of 1,25(OH)2D3 has been demonstrated in osteoblasts, prostate epithelial cells and parathyroid glands, which may locally regulate calciotropic actions of Vitamin D3.

Fig. 1 Vitamin D3 intracellular signalling pathway. (Di Rosa M, et al. 2011)

Malnutrition is one of the most important nutritional issues affecting the older adult population. It can be caused by both inadequate or excessive micro and micronutrient intakes and/or physiological changes experienced with aging. For example, dysphagia is a common disorder suffered by the older adult population. Therefore, creating foods with proper consistency/viscosity is key to overcoming such diseases. From this perspective, novel functional thickened drinks have been developed and tailored for older adults using chia seed gum as a thickening agent and enriched with vitamin D3-loaded solid lipid nanoparticles (SLN). Rheological properties of different thickened drinks formulated with water, semi-skimmed milk or orange juice were optimized through a central composite rotational design. High vitamin D3 encapsulation efficiency with high concentrations (i.e., 32 IU/mg) were obtained with SLN. Furthermore, different rheological properties were attained with the different drink matrices. Higher viscosity and consistency values with the same concentration of thickening agent were observed when more complex matrices were used. An optimized formulation containing the tolerable upper intake level of vitamin D3 (ca. 4000 IU) was chosen to evaluate the vitamin D3 release and bioaccessibility using a dynamic digestion in a simulated older adults’ population. In addition, the enrichment of drinks with SLN-VitD3 did not produce any cytotoxic effects in cells.

Fig. 2 Functional thickened drinks were produced using chia seed gum and SLN-VitD3. (Fernandes J M, et al. 2025)