Background. Poor studies have evaluated
25-hydroxycholecalciferol (25(
OH)D) levels in
Down syndrome (DS). Objective. To assess in DS subjects serum 25(
OH)D value, to identify risk factors for
vitamin D deficiency, and to evaluate whether a normal 25(
OH)D value can be restored with a 400 I.U. daily supplement of
cholecalciferol in respect to controls. Methods. We have longitudinally evaluated 31 DS patients (aged 4.5-18.9 years old) and 99 age- and sex-matched healthy controls. In these subjects, we analysed
calcium, phosphate,
parathyroid hormone (PTH), 25(
OH)D concentrations, and
calcium and 25(
OH)D dietary intakes, and we quantified outdoor exposure. After 12.3 months (range 8.1-14.7 months) of 25(
OH)D supplementation, we reevaluated these subjects. Results. DS subjects showed reduced 25(
OH)D levels compared to controls (P < 0.0001), in particular DS subjects with
obesity (P < 0.05) and
autoimmune diseases history (P < 0.005). PTH levels were significantly higher in DS subjects than controls (P < 0.0001). After
cholecalciferol supplementation, 25(
OH)D levels were significantly ameliorated (P < 0.05), even if reduced compared to controls (P < 0.0001), in particular in DS subjects with
obesity (P < 0.05) and
autoimmune diseases (P < 0.001). Conclusions. Hypovitaminosis D is very frequent in DS subjects, in particular in presence of
obesity and
autoimmune diseases. In these subjects, there could be a need for higher
cholecalciferol supplementation.