Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial

Highlights

• One year double blind trial, 7 daily oral doses of vitamin D or placebo, on incidence Fallers.

• Faller rate was a U shaped curve, maximum decrease on doses 1600–3200 IU or serum 25OHD of 32–38 ng/ml.

• High vitamin D dose 4000–4800 IU increases Faller incidence in those with previous Fall history.

Abstract

Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD < 20 ng/ml (50 nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p = 0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p = 0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25 ng/ml (<50 nmol/L), 21% in the low middle quintile 32–38 ng/ml (80–95 nmo/L), 72% in the high middle quintile 38–46 ng/ml (95–115 nmo/L) and 45% in the highest quintile 46–66 ng/ml (115–165 nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1–14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32–38 ng/ml (80–95 nmol/L) and faller rates increase as serum 25OHD exceed 40–45 ng/ml (100–112.5 nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history.

Introduction

Falls are a serious health problem of the aging population and start to increase after age 60 years old and increasing even more in the 70′s and 80′s [1]. About 25–30% of elderly women fall at least once a year and in those with a recent fall history more than 50% will fall again during the next year [2]. Falls have many consequences; injuries and fear of falling again restricts physical activity and social activities [3]. Falls were responsible for more than 400,000 patients admitted to hospital emergency rooms in the USA, causing fractures, soft tissue injuries and open wounds in 90% of cases [4]. In the United States in the year 2000 the costs of injurious falls were estimated at 19 billion dollars [5]. Recurrent falls indicate more of a problem than single event falls because these subjects have twice the admission rate to nursing homes and twice the mortality rate [6]. The most important risk factors for falling are a previous history of falls, lower extremity weakness, poor balance and gait abnormalities, decreased muscle strength, old age, cognitive impairment, medications, orthostatic hypotension, anemia, female gender, arthritis and psychological factors [7].

Prevention of falls can be effective with individualized programs such as physical therapy, vision correction, removal of home hazards, and hypnotics. In a meta-analysis, the risk of falls was reduced with preventive measures (RR = 0.75, 95% CI: 0.58–0.99) [8]. However, these interventions are time consuming and difficult to maintain over a long time. The idea of a medical treatment that can reduce falls has appeal and Vitamin D has been the most commonly studied option. An association between low serum 25-hydroxyvitamin D (25OHD) and lower physical performance were noted in some longitudinal studies [9], [10], [11]. It is well recognized clinically that proximal myopathy and osteomalacia responds to vitamin D, but in these cases serum 25OHD levels are very low. The concept that vitamin D could improve physical performance and reduce falls has gained popularity and so far, more than 25 trials have been conducted. One of the problems in interpreting results of vitamin D on falls was the considerable variation in study design; different doses of vitamin D, type of vitamin D2 or D3, method of administration, oral or injection, frequency of administration, whether calcium was used, and length of the trial which ranged from 6 weeks to 5 years. Two meta-analyses of the effect of vitamin D on falls have been performed, one showing a significant effect of vitamin D with or without calcium with an odds ratio (OR) of 0.80 (95% CI: 0.69–0.93) [12] and the other showing a non-significant effect, (OR = 0.96; 95% CI: 0.91–1.01) [13], but most of the trials included were single dose studies. In this paper, we report the incidence of falls as a pre-specified secondary outcome of a 12-month randomized clinical trial that tested 7 doses of vitamin D along with placebo.