High-Dose Vitamin D Supplementation May Lead to Increased Risk of Falls

Commentary

Vitamin D deficiency is common among older adults and is associated with sarcopenia, functional decline, falls, and fractures [1,2]. Prior meta-analysis has supported that supplementation with vitamin D may lead to improved outcomes in fracture prevention [3]. However, the US Preventive Services Task Force, using more recent evidence reviews and an updated meta-analysis [4], found evidence lacking regarding the benefit of supplementation with vitamin D in community-dwelling postmenopausal women at doses > 400 IU, found no benefit in this group for doses ≤ 400, and found evidence lacking for supplementation in men or premenopausal women at any dose [5]. At the same time, the USPSTF also recommends exercise or physical therapy and vitamin D supplementation (800 IU daily) to prevent falls in community-dwelling adults ≥ 65 years at increased risk for falls [6]. This is consistent with the Institute of Medicine’s recommendation of 800 IU per day for older adults [7].

The current study attempted to elucidate the potential impact of high-dose vitamin D supplementation, hypothesizing that higher doses will achieve improvement in vitamin D levels and better outcomes in terms of lower extremity function and falls. However, the investigators found that rather than lowering risk of falls, higher-dose vitamin D was associated with elevated risk of falls without the benefit of improving lower extremity function. This is not the first study that has demonstrated that higher doses of vitamin D supplementation may be associated with harm. A prior randomized controlled trial utilizing a different dosing strategy of annual high- dose vitamin D supplementation also found that higher doses were associated with increased risks of falls [8]. Nonetheless, it helps support the notion that in vitamin D supplementation, more is not necessarily better.

The study is not without its drawbacks. The sample size was relatively small and the trial may have been underpowered to detect whether there may be certain patients for whom high-dose vitamin D supplementation may have a role. Also, the study was based in Zurich, which has a relatively uniform population, and study results may not be generalizable to populations in other countries.

Applications for Clinical Practice

The study lends support to the current recommendation of the Institute of Medicine—800 IU a day—for fall prevention, which is equivalent in dose to the 24,000 IU per month utilized in the trial. One of the questions not answered by the study is whether high-dose supplementation for adults who have severe deficiency in vitamin D is beneficial or harmful when compared with lower-dose supplementation. In clinical practice, clinicians often check an initial level of vitamin D and aim for a target level with supplementation. Among those patients with extremely low baseline levels, a lower-dose regimen of 800 IU a day may not yield a normalized level of vitamin D. Further studies are needed to elucidate whether there may be a role for higher-dose supplementation in these individuals. Nonetheless, it is clear that the current evidence does not support the routine use of high-dose vitamin D supplementation; it does not lead to better lower extremity function and may cause harm.

 —William Hung, MD, MPH