A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D(3) Supplementation

We aimed to determine whether a cumulative dose of vitamin D(3) produces the same effects on the serum concentration of 25(OH)D(3) if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D(3) daily or 50,000 IU monthly. The same cumulative dose of vitamin D(3) was given to each treatment group (150,000 IU). The 25(OH)D(3) serum concentrations from baseline to day 75 were 14.3 ± 3.7 to 27.8 ± 3.9 ng/mL in the monthly group and 14.1 ± 3.4 to 28.8 ± 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D(3), as expected, serum 25(OH)D(3) and 1,25(OH)(2)D(3) increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D(3) provides an effective tool for a rapid normalization of 25(OH)D(3) in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL.