Preparatory work for the update of the tolerable upper intake levels for vitamin D

This technical report describes the collection of data and appraisal of scientific evidence in relation to the assessment of Tolerable Upper Intake Levels (UL) for vitamin D. Five systematic reviews (SR) were conducted following a tailored literature search, data extraction, evidence appraisal (i.e., risk of bias (RoB) assessment) and evidence synthesis. Narrative reviews were conducted to gather contextual evidence relevant to the interpretation of the main body of evidence (BoE). In the SR on bioavailability of calcidiol compared to native vitamin D3, 4304 records were identified and reduced to 12 individual records after screening for eligibility. The evidence appraisal revealed an overall low to high RoB of the individual studies. The available BoE demonstrated higher relative bioavailability of calcidiol compared to native vitamin D3 with a conversion factor of about 2 across baseline 25(OH)D concentrations of 30 to 55 nmol/L. In the SR on hypercalcaemia and hypercalciuria, 8277 records were identified and reduced to 37 individual records after screening for eligibility. The evidence appraisal revealed an overall low to high RoB of the individual studies. The available evidence demonstrated that occurrence of persistent hypercalcemia and hypercalciuria with high doses of vitamin D supplementation was rare. Nevertheless, increased risk of persistent hypercalciuria was observed with 250 μg/d of vitamin D supplementation. In the SRs on bone fractures, falls, bone mineral density (BMD), bone mineral content, and bone strength, 15 541 records were identified and reduced to 20 individual records after screening for eligibility. The evidence appraisal revealed an overall low to moderate RoB of the individual studies. No clear signs of adverse effects of high vitamin D intake were found in relation to bone fractures, falls, or areal BMD, but volumetric BMD was reduced with 100 and 250 μg/d of vitamin D.