Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level

Background: The Food and Nutrition Board of the National Academy of Sciences states that 95 mug vitamin D/d is the lowest observed adverse effect level (LOAEL). Objective: Our objective was to assess the efficacy and safety of prolonged vitamin D-3 intakes of 25 and 100 mug (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D-3; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios. Design: Healthy men and women (n = 61) aged 41 +/- 9 y ((x) over bar +/- SD) were randomly assigned to receive either 25 or 100 mug vitamin D-3/d for 2-5 mo, starting between January and February. Serum 25(OK)D was measured by radioimmunoassay. Results: Baseline serum 25(OH)D was 40.7 +/- 15.4 nmol/L ((x) over bar +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-mug/d group and at 96.4 +/- 14.6 nmol/L in the 100-mug/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D-3 were 46.7 +/- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 mug vitamin D-3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study. Conclusions: The 100-mug/d dosage of vitamin D-3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 mug vitamin D-3/d to be a safe intake.