Table 1:
Recent major RCTs of vitamin D and CVD events or CVD risk factors
| Trial name | Population | Intervention | Follow-up | Outcomes and main findings | Year | Ref |
|---|---|---|---|---|---|---|
| The VITAL (Vitamin D and Omega-3) trial | 25 871 men 50 years or older and women 55 years or older | Vitamin D3 (cholecalciferol) 2000 IU per day and omega-3 1g per day or placebo | Median 5.3 years | Vitamin D did not lower incidence of major cardiovascular events or incidence of invasive cancer compared to placebo | 2018 | 109 |
| The ViDA (Vitamin D Assessment) trial | 5110 community-resident adults, aged 50 to 84 years | Vitamin D3 (200 000IU), followed a month later by monthly 100 000 IU or placebo | Median 3.3 years | Monthly high-dose vitamin D supplementation did not prevent incident CVD and death compared to placebo | 2017 | 108 |
| The effect of vitamin D statues on endothelial function trial | 114 post-menopausal women with 25D concentrations between 10 and 60ng/mL | Vitamin D3 2500 IU or placebo | 4 months | No significant differences between groups in changes in brachial artery flow-mediated vasodilation (FMD), pulse wave velocity (PWV), augmentation index (AI) or CRP. | 2012 | 67 |
| The effect of vitamin D repletion on small low density lipoprotein (LDL) particle number in subjects at elevated cardiovascular risk trial | 151 adults with 25D concentrations < 20 ng/mL | Vitamin D3 50 000 IU weekly or placebo | 8 weeks | Vitamin D repletion did not change small low-density lipoprotein (LDL) levels, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) or triglyceride levels compared to placebo | 2012 | 144 |
| Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative (WHI) trial | 754 women aged 50 to 59 | Calcium carbonate (1000mg elemental calcium) + vitamin D3 400 IU daily or placebo nested within WHI trial of estrogen among women who underwent hysterectomy | 7 years | Treatment with vitamin D3 and calcium did not alter coronary artery calcification (CAC) measurements as assessed by cardiac CT compared to placebo | 2010 | 145 |
| Vitamin D Effects in Overweight Patients (SMART) trial | Healthy overweight subjects (n=200) with mean 25D concentration of 30 nmol/L | Vitamin D preparation (Vigantol oil, Merck) 83μg per day or placebo | 12 months | Weight loss was not affected by vitamin D supplementation. Vitamin D group had lower PTH, triglyceride and TNF-α levels compared to placebo. | 2009 | 147 |
| Calcium/vitamin D supplementation and cardiovascular events in the Women’s Health Initiative (WHI) trial | 36,282 women aged 50 to 79 | Calcium carbonate (1000mg elemental calcium) + vitamin D3 400 IU daily or placebo | 7 years | Vitamin D3 and calcium supplementation did not increase or decrease coronary or cerebrovascular risk in healthy postmenopausal women | 2007 | 97 |
| Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure | 93 patients with congestive heart failure (CHF), New York Heart Association class ≥ 2 | Vitamin D3 50μg daily + 500mg calcium or placebo + 500mg calcium | 9 months | Pro-inflammatory cytokine TNF-α increased in the placebo group but remained constant in the vitamin D3 treatment group. There was no change in survival rate between the two groups. | 2006 | 146 |
| Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community | 2686 adults aged 65–85 years | Vitamin D3 100 000 IU or placebo every four months | 5 years | There was no significant difference in all-cause mortality or cardiovascular disease between the two groups. | 2003 | 148 |
| Vitamin D and the health of blood vessels in kidney disease trial | 119 patients eGFR 15–45 ml/min/1.73m2 | Calcifediol 5000 IU, calcitriol 0.5μg or placebo thrice weekly | 6 months | PWV decreased in the calcifediol group, remained unchanged in the calcitriol group and increased in the placebo group. | 2017 | 101 |
| The OPERA trial (Effect of Paricalcitol on Left Ventricular Mass and Function in CKD) trial | 60 patients with stage 3–5 CKD | Paricalcitol 1μg per day or placebo | 52 weeks | Paricalcitol significantly reduced PTH, alkaline phosphatase levels, and cardiovascular-related hospitalizations compared to placebo. There was no change in LV mass index as determined by cardiac MRI | 2014 | 134 |
| The PRIMO (Paricalcitol Capsule Benefits in Renal Failure– Induced Cardiac Morbidity) study | 227 CKD patients with mild to moderate LVH and preserved EF | Paricalcitol 2μg per day or placebo | 48 weeks | Paricalcitol reduced PTH levels within 4 weeks. At 48 weeks, there was no difference in left ventricular mass index compared to placebo as determined by cardiac MRI | 2012 | 133 |
| Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes study | 281 type-2 diabetic patients receiving RAAS inhibitor | Paricalcitol 1μg or 2μg per day, or placebo | 24 weeks | Addition of 2μg per day to RAAS inhibition lowered residual albuminuria in patients with diabetic nephropathy | 2010 | 99 |