Vitamin D, the Osseous System and NAFLD
Besides its role in calcium and bone metabolism, vitamin D exerts multiple pleiotropic effects in many tissues (e.g. antiproliferative, prodifferentiative and immunomodulatory actions). In addition, vitamin D receptors are present in several cell types, including pancreatic beta cells. The main source of vitamin D is endogenous generation of cholecalciferol (vitamin D3) from 7-dehydrocholesterol in skin keratinocytes through exposure to medium-wavelength ultraviolet light (UVB) from the sun. Some vitamin D also derives from dietary intake and vitamin D supplements. Vitamin D is either stored in adipose tissue or converted to 25-hydroxyvitamin D (25(OH)D or calcidiol) in the liver. The serum concentration of 25(OH)D, the major circulating form of vitamin D, is considered to reflect the total production of vitamin D from both endogenous and exogenous sources and constitutes the best clinical measure of vitamin D stores. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D or calcitriol), is primarily generated in the kidney from 25(OH)D. 1,25(OH)2D functions as a steroid hormone regulating the transcription of numerous genes. A number of clinical studies have shown that vitamin D deficiency can play a role in a number of different metabolic derangements, including type-1 and type-2 diabetes, obesity, dyslipidemia, hypertension and the MS. Recent years have also witnessed a significant scientific interest into the potential role played by vitamin D in liver pathophysiology and NAFLD. An experimental study by Nakano et al. showed that phototherapy may be a good complementary therapy for NASH because of its regulation on vitamin D3. Roth et al. recently reported that vitamin D deficiency in obese rats exacerbates NAFLD and increases the hepatic expression of genes involved in inflammatory pathways. With regard to clinical studies, Targher et al. reported that NAFLD patients have a marked reduction in serum 25(OH)D levels compared with controls; this decrease was closely associated with the histopathological features of NAFLD. These results were independently confirmed by Barchetta et al., who showed that low 25(OH)D levels were associated with the presence of ultrasound-diagnosed NAFLD independently from metabolic syndrome, diabetes and insulin resistance. However, Katz et al. did not confirm an independent association between vitamin D status and suspected NAFLD after adjusting for obesity in adolescents. Future studies are needed to clarify whether the vitamin D status should be routinely checked in NAFLD patients and deficiency corrected if present. In addition, the consequences of addressing hypovitaminosis D on both liver histology and bone health in this group of patients need to be determined in longitudinal clinical trials.