Bibliographic reference
The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults. A Response-Adaptive, Randomized Clinical Trial. Lawrence J. Appel, MD, MPH; Erin D. Michos, MD, MHS; Christine M. Mitchell, ScM; Amanda L. Blackford, ScM; Alice L. Sternberg, ScM; Edgar R. Miller III, MD, PhD; Stephen P. Juraschek, MD, PhD; Jennifer A. Schrack, PhD, MS; Sarah L. Szanton, PhD, ANP; Jeanne Charleston, BSN, RN; Melissa Minotti, MPH; Sheriza N. Baksh, PhD, MPH; Robert H. Christenson, PhD; Josef Coresh, MD, PhD; Lea T. Drye, PhD; Jack M. Guralnik, MD, PhD; Rita R. Kalyani, MD, MHS; Timothy B. Plante, MD, MHS; David M. Shade, JD; David L. Roth, PhD; and James Tonascia, PhD for the STURDY Collaborative Research Group.
Summary
According to previous research, taking vitamin D supplements may reduce the risk of falls in elderly people. The current data is inconsistent, however, because different supplementation regimens were used. This study experiments with different Vitamin D schedules and tests the effects. Subjects receiving 1000 IU/day do not show a decreased risk of falling with respect to the control group who receives lower doses (200 IU/day). The administration of higher doses (2000 IU/day or 4000 IU/day) was considered potentially dangerous (with a higher number of adverse events) and was therefore discontinued.
Context and starting point
The issue of falls among older adults is a very serious one and carries a substantial socio-economic burden. Many studies have suggested that vitamin D supplements might reduce the risk of falls in older adults, potentially by improving the skeletal muscle function. That said, the evidence has been inconsistent, which is possibly due to differences in vitamin D doses and modes of administration. Indeed, while in early trials vitamin D supplements seemed to reduce fall risk by approximately 20%, later studies documented no effects, and 1 study found that vitamin D administered in an annual bolus dose (500 000 IU) might increase fall risk. In 2013, the National Institute on Aging (NIA) funded the STURDY (Study To Understand Fall Reduction and Vitamin D in You) trial to assess the dose-response relationship and potential efficacy of vitamin D supplementation at preventing falls, comparing the effects of 4 different doses of vitamin D.
The characteristics of the study
The trial was structured in two phases. The first phase aimed at identifying the optimal vitamin D dosage for fall prevention among the following three: 1000, 2000 and 4000 IU/day; the second phase compared the effectiveness of the identified dose compared to the control dose (200 IU/daily). The control dose was calculated based on the idea that, when added to the amount of Vitamin D consumption from normal food intake, it would be under a cumulative daily dose of 800 IU (the recommended amount for that age group). The trial recruited 688 people dwelling in the Hagerstown and Woodlawn communities of Maryland. They were all aged 70 years or older, with elevated fall risk and low serum 25-(OH)D. Elevated fall risk was defined by the presence of one or more of the following criteria: two or more falls or at least one injurious fall in the past year, fear of falling due to balance or walking problems, difficulty maintaining balance, and use of an assistive walking device. Low serum 25-(OH)D (25 to 72.5 nmol/l) was measured by calibrated high-performance liquid chromatography and tandem mass spectrometry. Of the 688 persons trial participants, the mean age at entry was 77.2 years, 56.4% were men, and 18.2% were African-American; the mean total 25-(OH)D level was 55.3 nmol/l. Exclusion criteria included: cognitive impairment; hypercalcemia; kidney, bladder, or ureteral stones; and use of supplemental vitamin D in doses higher than 1000 IU/d or calcium in doses higher than 1200 mg/d. Persons using 1000 IU/d or less of supplemental vitamin D had to agree to maintain this dosage. The primary outcome was the time until the first fall, or death, within 2 years. Rates of serious events potentially related to vitamin D supplementation (such as falls causing a fracture, or dislocation, or resulting in hospitalization) were examined for safety. The participants reported primary outcomes through monthly calendars, quarterly contacts, and ad hoc telephone reports.
The results achieved
Of the 688 subjects recruited, 667 participants completed the trial; among them, 423 falls and 10 deaths were recorded. The mean time of observation was 22 months. 21 participants (3.1%) left the trial early without having a primary outcome. During the dose-finding stage, patients were randomly assigned to receive 1 of 4 supplemental vitamin D doses: 200 IU/day (control group) or 1000, 2000, or 4000 IU/day. Upon finding a higher risk for adverse events in subjects who were administered 2000 and 4000 IU/day regimens, the dose of 1000 IU/day was declared the best one. All the participants previously receiving 2000 or 4000 IU/day were then assigned to the 1000 IU/day regimen. At the end of the observation period, patients receiving higher vitamin D doses (1000 IU/day) did not show any advantage with respect to control group (200 IU/day).
The limitations of the study
- The control group received 200 IU of vitamin D per day, not a placebo pill. Whether 200 IU/day has any effect on fall risk is uncertain.
- Persons receiving up to 1000 IU of vitamin D supplements per day were recruited even though they had low baseline 25-(OH)D levels.
- The primary outcome was self-reported; however, monthly calendars, quarterly contacts, and ad hoc telephone reports are an accepted standard approach to ascertaining falls.
- All the participants were aged 70 years or older and at high risk for falls. Results may not be generalizable to other populations.
What’s new
The results obtained from the trial have several implications. First of all, the finding of a greater number of adverse events associated with administering a high dose of vitamin D helps explain the heterogeneity of the results that emerged from previous trials. This finding also leads to advice against vitamin D supplementation for preventing falls in elderly people without osteoporosis or vitamin D deficiency. Furthermore, evidence shows that taking a supplement of 1000 IU/day of vitamin D, for elderly people with a high risk of falling and low serum 25-(OH)D levels, does not show a higher efficacy than supplementing with 200 IU/day. This conclusion should lead to a revision of what is considered the safest vitamin D dose, given the widespread use of vitamin supplementation at a dosage of 1000 IU/day or higher.
Edited by Dr. Francesco Murano
