Table 1.
Prospective randomized trials of Vitamin D supplementation and CHD events or CVD risk factors*
| Design | Primary Outcome |
Study outcome |
Summary of study, sample size, patient age, & route/ dose of Rx |
Length & Follow- up |
Outcomes related to CHD or CHD risk factors |
Preexisting conditions or disease? |
Reference |
|---|---|---|---|---|---|---|---|
| DB, PC, RCT | Colorectal cancer prevention study | Change in SBP & DBP | 283 blacks age 30 to 80 years (median age of 51) randomized for 3 months of oral placebo, 1000, 2000, or 4000 IU/d vitD3 followed by 3 additional months off of treatment. | 6 months | A −1.4 mm Hg change in SBP for each additional 1000 IU/d of vitD3 (P=0.04). No significant effect on DBP. For each 1 ng/ml increase in 25OHD there was a −0.2 mm Hg in SBP (P=0.02) | Generally healthy patients. Patients with pre-existing disorders of the parathyroid or calcium metabolism, Type I DM, sarcoidosis, malignancy, or thyroid disease were excluded. | Forman JP, et al.60 |
| DB, PC, RCT | Changes in brachial artery FMV, carotid-femoral PWV, and aortic augmentati on index | Same as primary outcomes | 114 postmenopausal women with mean age (63.9+/−3) and with serum 25OHD concentrations >10 and <60 ng/mL, received VitD3 (2,500 IU) or placebo, daily for 4 months | 4 months | VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. | Generally healthy, community-dwelling, ambulatory women from Madison, Wisconsin. Patients with CVD were excluded. | Gepner et al..51 |
| DB, PC, RCT | Change in small LDL particle number | Other lipid fractions | 151 VitD insufficient male and female adults (25OHD ≤ 20ng/ml), received 50,000 IU VitD3 weekly × 8 weeks | 8 weeks | VitD repletion failed to improve the lipid profile. | Elevated risk for CVD (with at least 1 of numerous significant CVD risk factors). | Ponda et al. 48 |
| DB, PC, RCT | BP, FMV of the brachial artery, cholesterol, & other markers of vascular health | Same as primary outcomes | 58 patients with mean age of 67 years received 100,000 units of oral VitD2 or placebo at baseline | 16 weeks follow-up | High dose oral VitD supplementation did not improve BP but produced short-term improvement in endothelial function in stroke patients with well-controlled baseline BP, which was not sustained by the end of the study. | History of stroke with baseline 25OHD concentrations <75 nmol/L | Witham MD, et al.52 |
| DB, PC, RCT | Hip fractures | coronary artery calcium (CAC) score | WHI CaD trial (1) nested within WHI hormonal trial (2) (estrogen among women who underwent hysterectomy) 754 women aged 50 to 59 years received calcium carbonate (1,000 mg of elemental calcium daily) plus VitD3 (400 IU daily) | 7 years | CAC plaque burden measured at the end of the trial did not differ between treatment and placebo groups. | Generally healthy postmenopausal women. | Manson JE, et al. 53 |
| DB, PC, RCT | Fasting serum lipids, BP, & oral glucose tolerance test | Same as primary outcomes | 438 obese or overweight patients, 21-70 years old, received VitD3 (40, 000 IU per week, 20 000 IU per week, or placebo) and all received 500 mg calcium daily. 330 patients completed the study. | 1 year | No significant effect of VitD on glucose tolerance, BP or serum lipids. | Overweight or obese subjects | Jorde R, et al.56 |
| PC, RCT | glycemic control in subjects with type 2 DM | Same as primary outcomes | 36 subjects received cholecalciferol (40,000 IU per week) versus placebo | 6 months | VitD had no significant effect on glucose metabolism | Type 2 DM, treated with metformin and bed-time insulin | Jorde R, et al. 54 |
| DB, PC, RCT | weight loss & traditional & Nontraditio n al cardiovasc ular disease risk markers | Same as primary outcomes (parathyroid hormone, triglyceride levels, and inflammatory y markers). | 200 subjects with mean baseline 25OHD concentrations of 30nmol/L received VitD 3320 IU/d or placebo while participating in a weight-reduction program. | 12 months | VitD did not adversely affect weight loss and was able to significantly decrease PTH, TG, TNF (although LDL increased significantly) in overweight subjects with inadequate VitD status, while participating in a weight-reduction program. | Overweight | Zittermann A, et al.55 |
| DB, PC, RCT | Hip fractures | Incident DM | WHI Ca/D trial, 36,282 postmenopausal women, 50-79 years old received 1,000 mg elemental calcium + 400 IU VitD3 daily | 7 years follow-up | No beneficial effects in reducing incidence of DM or the metabolic syndrome | Generally healthy postmenopausal women. | DeBoer et al.47 |
| DB, PC, RCT | Hip fractures | Change in BP and the Developme nt of HTN | WHI Ca/D trial, 36,282 postmenopausal women received 1,000mg elemental calcium +400 IU VitD3 daily | 7 years follow-up | No significant beneficial effect in BP or prevention of incident HTN. | Generally healthy postmenopausal women. | Margolis, et al.49 |
| DB, PC, RCT | Hip fractures | Risk of CHD | WHI Ca/D trial, 36,282 postmenopausal women ages 50–79 received 500mg calcium carbonate +200 IU VitD3 Bid | 7 years follow-up | No beneficial CHD effects attributable to Ca/D | Generally healthy postmenopausal women. | Hsia, et al.50 |
| DB, PC, RCT | survival rate, biochemical variables, & cytokine profile | Same as primary outcomes | 123 subjects received 2,000 IU/d of VitD3 plus 500 mg Ca/D [D(+) group] or placebo plus 500 mg Ca/d [D(−) group] for 9 mo. 93 patients completed the study. | 9 months intervene tion, 15 months follow-up | VitD3 reduced the inflammatory milieu in CHF patients. While interleukin-10 increased, there was a significant improvement in PTH and TNF. However, there was no difference in survival. | Congestive heart failure | Schleithoff SS, et al.56 |
| DB, PC, RCT | Fracture incidence & total mortality by cause | Same as primary outcome. Additional data assessing CVD. | 2,686 people (2,037 men and 649 women), 65-85 year old randomized to receive 100,000 IU of supplemental VitD3 every 4 months for 5 years. | 5 years, Britain | No beneficial CVD effects attributable to VitD. | Patients recruited from the general community. Excluded if there was a hx of renal stones, sarcoidosis, or malignancy. | Trivedi DP, et al.46 |
| DB, PC, RCT | Fractures | Coronary mortality | 327 patients (57 men & 270 women) over 65 (mean age 79.5) years received all possible combinations of calcium carbonate 3 g, VitD3 1000 IU, methandienone 2.5 mg and/or placebos daily for 9 months. | 9 months | Coronary mortality was higher among those taking all three active substances. A significant increase in coronary deaths was seen, most significant (P < 0.001) in those receiving VitD3 & methandienone | Inkovaara J, et al.58 |
DB, double-blind; PC, placebo controlled; RCT, randomized clinical trial; N/A, not addressed; Hx, History; CVD, Cardiovascular disease; CHD, Coronary heart disease; HTN, hypertension; Vit, Vitamin; WHI, Women’s Health Initiative; Ca/D, Calcium and Vitamin D; DM, diabetes mellitus; FMV, flow-mediated vasodilation; PWV, pulse wave velocity; BP, blood pressure (SBP, systolic BP and DBP, diastolic BP); PTH, parathyroid hormone; TG, tryglyceride; TNF, tumor necrosis factor; LDL, low density lipoprotein cholesterol; IU, international unit; d, day.
*
Of note, because this is not an all-inclusive systematic review, this table may not list all RCTs reporting on vitamin D supplementation and CVDrisk factors as well as CVD events.