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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #328705
Title: Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

Author
item BISCHOFF-FERRARI, HEIKE - University Of Zurich
item DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ORAV, ENDEL - Harvard University
item STAHELIN, HANNES - University Of Basel
item MEYER, OTTO - University Of Zurich
item THEILER, ROBERT - University Of Zurich
item DICK, WALTER - University Of Basel
item WILLETT, WALTER - Harvard School Of Public Health
item EGLI, ANDREAS - University Of Zurich

Submitted to: Journal of the American Medical Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2015
Publication Date: 1/4/2016
Citation: Bischoff-Ferrari, H.A., Dawson-Hughes, B., Orav, E.J., Stahelin, H.B., Meyer, O., Theiler, R., Dick, W., Willett, W.C., Egli, A. 2016. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. Journal of the American Medical Association. 176(2):175-183.

Interpretive Summary: Vitamin D deficiency has been associated with poor physical performance. The goal of this study is to determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. We conducted a 1-year double-blind randomized-controlled trial conducted in Zurich, Switzerland. Participants were 200 community dwelling men and women age >/=70 with a prior fall. The study featured three study groups with monthly treatments: low dose control, high dose vitamin D3, or low dose vitamin D plus calcifediol. The primary endpoint measured was the improvement lower extremity function (short physical performance test battery) and achieving higher levels of 25(OH) at the 6 and 12 month time points. The main secondary endpoint was monthly reported falls. Analyses adjusted for age, gender and BMI. The mean age was 78 years, 67% were women, and 58% were vitamin D deficient at baseline. Intent-to-treat analyses showed that while high dose vitamin D and low dose vitamin D plus calcifediol were more likely than low dose vitamin D alone to result in increased levels of 25(OH)D levels, they were not more effective in improving lower extremity function which did not differ among treatment groups. However, over the 12-month follow-up, the incidence of falls differed significantly between treatment groups with a higher incidence both in the high dose vitamin D and low dose vitamin D plus calcifediol group, compared with low dose vitamin D alone. Although, higher monthly doses of vitamin D were effective in reaching higher levels of 25(OH)D, they had no benefit on lower extremity function and actually increased fall risk compared with low dose vitamin D alone.

Technical Abstract: Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. Interventions: Three study groups with monthly treatments including a low-dose control group receiving 24000 IU vitamin D3 (24000 IU group), a group receiving 60000 IU vitamin D3 (60000 IU group), and a group receiving 24000 IU of vitamin D3 plus 300 micrograms of calcifediol (24000 IU plus calcifediol group). Main Outcomes and Measures: The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/ml. at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. Results: The study cohort comprised 200 participants (men and women >/=70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/ml.) at baseline. Intent-to-treat analyses showed that while 60000 IU and 24000 IU plus calcifediol were more likely than 24000 IU to result in 25-hydroxyvitamin D levels of at 30 ng/ml. (P=.001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P=.26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24000 IU group (47.9%; 95% CI, 35.8%-60.3%), (P=.048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60000 IU group (mean, 1.47) and the 24000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24000 IU group (mean, 0.94) (P=.09). Conclusions and Relevance: Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/ml of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24000 IU.