Table 1. Characteristics of the Involved Trials.
| Source | Year | Patients, No. | Study Period | Vitamin D Type and Dosage | Study Follow-up, y | Country | Major Inclusion Criteria | Primary Outcome | |
|---|---|---|---|---|---|---|---|---|---|
| Vitamin D | Placebo | ||||||||
| Aloia et al25 | 1988 | 12 | 15 | NA | Vitamin D3, 400 IU/d | 2 | United States | Women who were postmenopausal and aged 50-80 y, with osteoporosis (diagnosed by the presence of ≥1 nontraumatic vertebral compression fracture) | Bone mineral measurements and fracture incidence |
| Ott et al23 | 1989 | 43 | 43 | NA | Vitamin D3, 1000 mg/d | 2 | United States | Women who were postmenopausal, aged 50-80 y, and ambulatory, with ≥2 compression fractures (>15% reduction in anterior height) and without history of serious trauma or current medications for osteoporosis (except calcium supplements in some cases) | Total body calcium, change in bone mineral density, and fracture rate |
| Komulainen et al29 | 1999 | 112 | 115 | 1989-1991 | Vitamin D3, 300 and 100 IU/d | 5 | Finland | Women in early postmenopause who were nonosteoporotic | Lumber and femoral neck bone mineral density |
| STOP IT/Gallagher et al34 | 2001 | 245 | 244 | NA | Calcitriol, 0.25 μg twice daily | 3 | United States | Women aged 65-77 y with femoral neck density in normal range (SD, ≤2) for their age | Change in bone mineral density of the femoral neck and spine |
| Trivedi et al35 | 2003 | 1345 | 1341 | 1996-1997 | Vitamin D3, 100 000 IU/4 mo | 5 | United Kingdom | Participants aged 65-85 y | Fracture incidence and total mortality by cause |
| RECORD/Grant et al32 | 2005 | 2649 | 2643 | 1999-2002 | Vitamin D3, 800 IU daily | Median (IQR), 3.8 (3.1-4.3) | United Kingdom | Participants aged ≥70 y who had had a low trauma, osteoporotic fracture in the previous 10 y | The incidence of new low-energy fractures |
| Brazier et al33 | 2005 | 95 | 97 | NA | Vitamin D3, 400 IU twice daily | 1 | France | Ambulatory women aged >65 y | Vitamin D treatment–associated adverse events |
| WHI/Jackson et al27 | 2006 | 18 176 | 18 106 | 1995 and 2000 | Vitamin D3, 400 IU/d | 12 | United States | Women aged 50-79 y with no evidence of a medical condition associated with anticipated survival <3 y and no safety, adherence, or retention risks | Total number of fractures |
| Schleithoff et al30 | 2006 | 61 | 62 | 2002-2003 | Vitamin D3, 2000 IU/d | 1.3 | Germany | Participants with New York Heart Association functional class ≥II | Survival rates and biochemical variables, such as natriuretic peptides and cytokines |
| Berggren et al28 | 2007 | 102 | 97 | 2000-2002 | Vitamin D3, 800 IU/d | 1 | Sweden | Participants aged ≥70 y who had femoral neck fractures | Total number of falls |
| Zhu et al22 | 2008 | 39 | 81 | 1998 | Vitamin D3, 1000 IU/d | 5 | Australia | Women aged 70-80 y who were ambulatory | Change in hip bone mineral density, plasma 25-hydroxyvitamin D, biomarkers of bone turnover, parathyroid hormone, and intestinal calcium absorption |
| Prince et al20 | 2008 | 151 | 151 | 2003 - 2004 | Vitamin D3, 1000 IU/d | 1 | Australia | Women aged 70-90 y who were ambulatory | Number of falls |
| Vital D/Sanders et al24 | 2010 | 1131 | 1125 | 2003-2005 | Vitamin D3, 500 000 IU/y | Median (IQR), 2.96 (2.92-3.00) | Australia | Community-dwelling women aged ≥70 y at high risk of fracture (defined by criteria such as maternal hip fracture, past fracture, or self-reported fall) | Number of falls and fractures |
| Lehouck et al31 | 2012 | 91 | 91 | 2008-2009 | Vitamin D, 100 000 IU/mo | 1 | Belgium | Current or former smokers aged ≥50 y who had a chronic obstructive pulmonary disease per diagnosis Global Initiative for Chronic Obstructive Lung Disease definition (postbronchodilator ratio of first second of forced expiration to the forced vital capacity _0.7) and a first second of forced expiration <80% anticipated | Incidence of chronic obstructive pulmonary disease exacerbations |
| VITDISH/Witham et al21 | 2013 | 80 | 79 | 2009-2001 | Vitamin D3, 100 000 IU/3 mo | 1 | United Kingdom | Participants aged ≥70 y with isolated systolic hypertension (supine systolic blood pressure, >140 mm Hg; supine diastolic blood pressure, <90 mm Hg) and baseline 25-hydroxyvitamin D levels <30 ng/mL | Difference in in-office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and B-type natriuretic peptide level |
| OPERA/Wang et al26 | 2014 | 30 | 30 | 2008-2010 | Paricalcitol, 1 μg/d | 1 | Hong Kong | Participants with stages 3-5 chronic kidney disease and left ventricle hypertrophy | The change in left ventricle mass index measured by cardiac magnetic resonance imaging |
| Baron et al19 | 2015 | 1130 | 1129 | 2004-2008 | Vitamin D3, 1000 IU\day | 3 | United States | Participants aged 45-75 y who had ≥1 colorectal adenoma removed within 120 d before enrollment and no remaining polyps after a complete colonoscopy | Incidence of colonic adenoma |
| EVITA/Zitterman et al15 | 2017 | 199 | 201 | 2010-2013 | Vitamin D3, 4000 IU/d | 3 | Germany | Participants aged 18-79 y who were classified as having New York Heart Association functional class ≥II | All-cause mortality |
| VIDA/Scragg et al16 | 2017 | 2558 | 2550 | 2011-2015 | Vitamin D3, Initial 200 000 IU, then 100 000 IU/mo | Median (IQR), 3.3 (2.5-4.2) | New Zealand | Participants aged 50-84 y | Incident cardiovascular disease and death |
| J-DAVID/Shoji et al14 | 2018 | 488 | 476 | 2011-2015 | Alfacalcidol, 0.5 μg/d | Median (IQR), Vitamin D: 4.0 (2.6-4.0)a; Placebo: 4.0 (3.5-4.0) | Japan | Participants aged 20-80 y who were receiving maintenance hemodialysis; had calcium ≤10.0 mg/dL, phosphate ≤6.0 mg/dL, and intact parathyroid hormone ≤180 pg/mL, and were not taking any vitamin D receptor activations at randomization | Composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb owing to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization |
| VITAL/Manson et al13 | 2018 | 12 927 | 12 944 | 2011-2014 | Vitamin D3, 2000 IU/d | Median (IQR), 5.3 (3.8 to 6.1)a | United States | Participants had no history of cancer (except nonmelanoma skin cancer) or cardiovascular disease at trial entry | Incidence of invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) |
Abbreviations: EVITA, Effect of Vitamin D on All-Cause Mortality in Heart Failure patients; IQR, interquartile range; J-DAVID, Japan Dialysis Active Vitamin D; OPERA, Oral Paricalcitol in Retarding Cardiac Hypertrophy, Reducing Inflammation and Atherosclerosis in Stage 3-5 Chronic Kidney Disease; RECORD, Randomized Evaluation of Calcium or Vitamin D; STOP IT, Estrogen and Calcitriol in the Prevention of Age-Related Bone Loss; VIDA, Vitamin D Assessment; VITAL, Vitamin D and Omega-3 Trial; VITDISH, Vitamin D in Isolated Systolic Hypertension; WHI, Women’s Health Initiative.