A problem in a number of the RCTs is that falls rather than fallers are analyzed; consequently, individuals who fell more than once were also counted more than once in the primary outcome analysis. The studies generally did not have the statistical power to detect a significant difference in the number of fallers but relied on repeat fallers to achieve the desired number of total falls. Moreover, the meta-analyses described above combined data from the few trials in which fallers were counted with data from trials in which falls were the outcome. By comparison, the U.S. Food and Drug Administration (FDA) mandated primary outcomes in osteoporosis and cardiovascular trials are the number of individuals with fractures or cardiovascular events rather than the number of events. It remains uncertain whether a reduction in the number of falls can be used to infer that the number of fallers would be significantly reduced.
The committee’s review of the available evidence, including the results from RCTs and observational associations between vitamin D with or without calcium and risk for falls and poor physical performance, indicates a lack of sufficiently strong evidence to support DRI development. A limited review of observational data outside of the AHRQ reviews found some support for an association between 25OHD levels and physical performance. However, high-quality observational evidence from large cohort studies was lacking. Additionally, although the cross–sectional studies were more supportive of an association between high serum 25OHD levels and reduced risk for falls, evidence from RCTs in particular showed outcomes that varied in significance and thus did not support the observational findings or a causal relationship. The evidence was also not consistently supportive for a role for vitamin D combined with calcium in reduction of risk for falls.
Overall, data from RCTs suggest that vitamin D dosages of at least 800 IU/day, either alone or in combination with calcium, may confer benefits for physical performance measures. Although high doses of vitamin D (i.e., ≥ 800 IU/day) appear to provide greater benefit for physical performance than low doses (i.e., 400 IU/day), evidence is insufficient to define the shape of the dose–response curve for higher levels of intake. Thus, the outcome of physical performance is appropriate for identifying Estimated Average Requirements (EARs) of vitamin D, with or without calcium, in adults above the age of 50, but cannot be used to define the shape of the dose–response curve at higher levels of intake.
Vitamin D has been reported to modulate immune functioning in cell culture and animal models. Vitamin D, specifically its active form, calcitriol,