Vitamin D supplementation and falls: a trial sequential meta-analysis

Background Vitamin D supplementation is often recommended to prevent falls, although vitamin D trials and meta-analyses of these trials have reported conflicting results for this outcome. We aimed to assess if there was a need for further research. Methods We explored the value of doing further randomised controlled trials assessing the effects of vitamin D supplements on falls with trial sequential analysis with a risk reduction threshold of 15%. All analyses were done using the numbers of participants who had a fall in intention-to-treat analyses. Trial sequential analysis performs a cumulative meta-analysis, but reduces the risk of false-positive results from repetitive statistical testing by maintaining the overall risk of type 1 error at 5%. Findings In 20 existing randomised controlled trials (n=29 535), the effect estimate for vitamin D with or without calcium on falls lay within the futility boundary, providing evidence that vitamin D supplementation does not alter the relative risk by 15% or more. In a sensitivity analysis using a risk reduction threshold of 10%, the effect estimate also lay within the futility boundary. In subgroup analyses using a risk reduction threshold of 15%, the effect estimate also lay within the futility boundary for trials of vitamin D supplementation (16 trials, n=22 291) and trials of vitamin D with calcium (six trials, n=9919). Interpretation In pooled analyses, supplementation with vitamin D, with or without calcium, does not reduce falls by 15% or more. Future trials with similar designs are unlikely to alter these conclusions. At present, there is little justification for prescribing vitamin D supplements to prevent falls.