Effectiveness and Safety of a High-Dose (20,000 IU) Weekly Vitamin D Protocol in Older Adults in Residential Care.

Abstract

To the Editor: We are concerned about the following conclusions by Feldman et al.: “Twelve months after implementation of a 20,000-IU/wk vitamin D protocol for older adults in residential care, mean 25OHD concentrations were high, and there was no evidence of poor vitamin D status,” and “One year after commencement of a 20,000 IU vitamin D per week protocol, vitamin D insufficiency was virtually nonexistent.”1 Because there was no control group, and baseline 25-hydroxyvitamin D (25OHD) levels were not obtained in this study, one cannot ascertain the magnitude of change in serum levels as a result of vitamin D supplementation. The results of this study merely support the notion that supplementation with vitamin D may result in high serum concentrations of the surrogate marker, 25OHD, but the results do not prove causation. The more important question is not whether vitamin D supplementation corrects vitamin D levels but whether correcting vitamin D levels with supplementation leads to a lower risk of falls in elderly institutionalized adults without a corresponding increase in risk of other harms.2 The clinical significance of correcting 25OHD levels in isolation is unclear. According to the Cochrane handbook, surrogate outcome measures “can be misleading and should be avoided or interpreted with caution as they may not predict clinically important outcomes accurately.”3 When the more clinically significant question, what is the effect of vitamin D supplementation on the risk of falls in elderly institutionalized adults, was examined, the following was found. A Cochrane review from 2012 that included studies of elderly institutionalized adults showed that vitamin D supplementation alone had no significant effect on rate of falls (rate ratio = 0.55, 95% confidence interval (CI) = 0.19–1.64) or the risk of experiencing a fall (risk ratio = 0.80, 95% CI = 0.38–1.71). The addition of vitamin D to calcium supplementation only reduced the rate of falling (rate ratio = 0.71 95% CI = 0.56–0.90) but had no effect on the risk of experiencing a fall (risk ratio = 0.85 95% CI 0.69–1.05) or fracture.4 A recent systematic review published in the British Medical Journal found that there was no significant effect of vitamin D supplementation on the odds of falling (odds ratio = 0.97 95% CI = 0.84–1.11) or the rate of falls in older adults (rate ratio = 0.55 95% CI = 0.19–1.64).5 A meta-analysis of randomized controlled trials found no significant difference in falls for vitamin D monotherapy (relative risk = 0.95, 95% CI = 0.89–1.02) or vitamin D plus calcium (relative risk = 0.95, 95% CI = 0.89–1.03).6 Feldman et al.1 conclude that high doses of vitamin D may not be safe given the vitamin D levels achieved and will consider lower doses in the future. This is troubling. Regardless of the dose, the evidence does not support the use of vitamin D monotherapy for reduction of clinical outcomes. The protocol at Feldman et al.'s institution has recently been revised to reduce the dose to 10,000 IU of vitamin D weekly. What is the scientific basis for the new recommended dose? Several contradictory statements were also made in the article. Specifically, it mentions that, in previous studies, mortality tended to increase with higher serum 25OHD levels—with a need for randomized controlled trials to demonstrate this causality—and that “collectively, these studies suggest that high 25OHD concentrations are not beneficial and could have adverse effects. The relevance of this in residential care needs to be established.” But in the conclusion, they state that the “Fraser Health Protocol of giving 20,000 IU of vitamin D weekly to older adults living in residential care facilities is feasible and safe and appears to have virtually eliminated vitamin D insufficiency. Serum 25OHD concentrations were higher than expected, with more than half the residents surveyed having a 25OHD concentration >100 nmol/L.” If someone were to read just the abstract or conclusion, they might miss the crucial point related to the known safety concerns regarding high 25OHD serum concentrations. The use of this protocol should be reconsidered, or at the very least, residents and clinicians should be informed that the efficacy and safety of high-dose vitamin D supplementation in terms of falls and fractures is unknown. Conflict of Interest: Aaron M. Tejani has received Canadian Institutes of Health Research research and knowledge translation grants, has been hired as part of the plaintiff team for multidistrict litigation versus Boehringer Ingleheim and Dabigatran, has served as coordinator for clinicians who participated in the readjudication on case report forms on the RELY trial, has received honoraria for presentations from various clinician groups for which the money came from members and not pharmaceutical industry sponsors. Author Contributions: All authors contributed equally to the concept, analysis, and preparation of the letter. Sponsor's Role: Not applicable.