Patients taking vitamin D in significant doses may not be doing anything to support their bone mineral density (BMD) or bone strength, according to the findings of a new randomized clinical trial. The researchers, who reported their findings in JAMA, called for future research to determine whether high-dose vitamin D could have harmful effects.
“Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day,” the study authors observed.
The double-blind, single-center study was conducted in Calgary, Canada, and spanned August 2013 through December 2017. Eligible participants were healthy adults without osteoporosis aged between 55 and 70 years. All participants had baseline 25-hydroxyvitamin D (25[OH]D) levels 30 to 125 nmol/L. Participants took daily vitamin D3 doses at 400 IU (n = 109), 4,000 IU (n = 100), or 10,000 IU (n = 102), and patients with less than 1,200 mg per day also received calcium supplementation. The primary outcome measures were total volumetric BMD at radius and tibia, and bone strength (failure load) at tibia. High resolution peripheral quantitative CT was used to measure BMD, and failure load was forecasted by finite element analysis.
In total, 311 participants (mean [SD] age, 62.2 [4.2] years; 53% were male) were randomized, of which 287 (92%) finished the trial. Levels of 25(OH)D at baseline, three months, and three years were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. After three years, the 4,000 IU group had lower radial volumetric BMD (−3.9 mg HA/cm3 [95% CI, −6.5 to −1.3]), as did the 10,000 IU group (−7.5 mg HA/cm3 [95% CI, −10.1 to −5.0]) in comparison with the 400 IU group. The mean percentage change in volumetric BMD was −1.2% in the 400 IU group, −2.4% in the 4,000 IU group, and −3.5% in the 10,000 IU group.
Compared to the 400 IU group, the tibial volumetric BMD differences in the high-dose groups were −1.8 mg HA/cm3 (95% CI, −3.7 to 0.1) in the 4,000 IU group and −4.1 mg HA/cm3 in the 10,000 IU group (95% CI, −6.0 to −2.2); the mean percent change values were −0.4% in the 400 IU group, −1.0% in the 4,000 IU group, and −1.7% in the 10,000 IU group. Changes in failure load did not largely differ (radius, P = 0.06; tibia, P = 0.12).
The authors said that their conclusions “do not support a benefit of high-dose vitamin D supplementation for bone health” and added that “further research would be needed to determine whether it is harmful.”