The Effects of Vitamin D Supplementation on Musculoskeletal Health: The VITAL and DO-Health Trials

Abstract

Previous clinical trials and systematic reviews on the effects of supplemental vitamin D on musculoskeletal outcomes are conflicting. In this paper, we review the literature and summarize the effects of a high daily dose of 2 000 IU vitamin D on musculoskeletal outcomes in generally healthy adults, in men (≥50 years) and women (≥55 years) in the 5.3-year US VITamin D and OmegA-3 TriaL (VITAL) trial (n = 25 871) and women and men (≥70 years) in the 3-year European DO-HEALTH trial (n = 2 157). These studies found no benefit of 2 000 IU/d of supplemental vitamin D on nonvertebral fractures, falls, functional decline, or frailty. In VITAL, supplementation with 2 000 IU/d of vitamin D did not reduce the risk of total or hip fractures. In a subcohort of VITAL, supplemental vitamin D did not improve bone density or structure (n = 771) or physical performance measures (n = 1 054). In DO-HEALTH, which investigated additive benefits of vitamin D with omega-3 and a simple home exercise program, the 3 treatments combined showed a significant 39% decreased odds of becoming prefrail compared to the control. The mean baseline 25(OH)D levels were 30.7 ± 10 ng/mL in VITAL and 22.4 ± 8.0 ng/mL in DO-HEALTH and increased to 41.2 ng/mL and 37.6 ng/mL in the vitamin D treatment groups, respectively. In generally healthy and vitamin D-replete older adults not preselected for vitamin D deficiency or low bone mass or osteoporosis, 2 000 IU/d of vitamin D had no musculoskeletal health benefits. These findings may not apply to individuals with very low 25(OH)D levels, gastrointestinal disorders causing malabsorption, or those with osteoporosis.