Department of Endocrinology and Internal Medicine (L.R., L.M.), Aarhus University Hospital, 8000 Aarhus, Denmark; Health Services Research Unit (A.A.), University of Aberdeen, Aberdeen AB24 2TZ, United Kingdom; Geriatric Medicine (T.M.), Nottingham University Hospitals, Nottingham NG1 5DU, United Kingdom; Institute of Clinical Research (T.M., K.B., B.A.), University of Southern Denmark, 5000 Odense, Denmark; Geriatric Medicine (F.A.), Developmental Origins of Health and Disease Research Division, University of Southampton School of Medicine, Southampton SO17 1BJ, United Kingdom; Division of Epidemiology (H.E.M.), Norwegian Institute of Public Health, 0456 Oslo, Norway; Department of Community Medicine (H.E.M.), University of Oslo, 0316 Oslo, Norway; NorthWest Academic Centre (K.M.S.), Department of Medicine, University of Melbourne and Western Health, Victoria 3052, Australia; Bone and Cartilage Research Unit (K.S.), University of Eastern Finland, 70210 Kuopio, Finland; Department of Orthopedics, Traumatology, and Handsurgery (K.S.), Kuopio University Hospital, 70211 Kuopio, Finland; Medical Research Council Lifecourse Epidemiology Unit (C.C.), University of Southampton and National Institute for Health Research Biomedical Research Unit in Musculoskeletal Science, University of Oxford, Oxford OX1 2JD, United Kingdom; Primary Care and Public Health (H.E.S.), Brighton and Sussex Medical School, Brighton BN19PH, United Kingdom; Mel and Enid Zuckerman College of Public Health and the Arizona Cancer Center (E.T.J.), University of Arizona, Tucson Arizona 85721; York Trials Unit (D.T.), University of York, York YO1 05DD, United Kingdom; Division of Endocrinology, Diabetes, and Metabolism (R.D.J.), College of Medicine, The Ohio State University, Columbus, Ohio 43210; Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Endocrinology (K.B.), Odense University Hospital, DK-5000 Odense, Denmark; Internal Medicine (J.A.R.), University of California Davis, Sacramento, California 95817; Institute for Ageing and Health (R.M.F.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom; and Department of Medicine F (B.A.), Copenhagen University Hospital Gentofte, DK-2900 Hellerup, Denmark.
Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.
Subjects and Methods:
Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.
The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).
Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.