| Design | Primary outcome | Study outcome | Summary of study, sample size, patient age, and route/dose of treatment | Length and follow-up | Outcomes related to CHD or CHD risk factors | Preexisting conditions or disease? | Reference |
|---|---|---|---|---|---|---|---|
| DB,b PC, RCT | Colorectal cancer prevention study | Change in SBP and DBP | Blacks (n = 283; 30–80 years; median, 51 years) randomized for 3 months to oral placebo, 1000, 2000, or 4000 IU/day VitD3, followed by treatment for 3 more months | 6 Months | A −1.4-mmHg change in SBP for each additional 1000 IU/day of VitD3 (P = 0.04). No significant effect on DBP. Each 1-ng/mL increase in 25OHD accompanied by a −0.2-mmHg change in SBP (P = 0.02) | Generally healthy patients. Patients with preexisting disorders of the parathyroid or calcium metabolism; patients with type I DM, sarcoidosis, malignancy, or thyroid disease excluded | Forman et al. (60) |
| DB, PC, RCT | Changes in brachial artery FMV, carotid–femoral PWV, and aortic augmentation index | Same as primary outcomes | Postmenopausal women [n = 114; mean (SD) age, 63.9 (3) years] with serum 25OHD concentrations >10 and <60 ng/mL; received 2500 IU VitD3 or placebo daily | 4 Months | VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation | Generally healthy, community-dwelling, ambulatory women from Madison, WI; patients with CVD excluded | Gepner et al. (51) |
| DB, PC, RCT | Change in small LDL particle number | Other lipid fractions | VitD-insufficient (25OHD ≤20 ng/mL) male and female adults (n = 151); received 50 000 IU VitD3 weekly | 8 Weeks | VitD repletion failed to improve lipid profile | Increased 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, and other markers of vascular health | Same as primary outcomes | Patients (n = 58; mean age, 67 years) received 100 000 IU oral VitD2 or placebo at baseline | 16 Weeks of 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 end of study | History of stroke with baseline 25OHD concentrations <75 nmol/L | Witham et al. (52) |
| DB, PC, RCT | Hip fractures | CAC score | Ca/D trial (1) nested within WHI hormonal trial (2) (estrogen among women who underwent hysterectomy). Women (n = 754; age, 50–59 years) received daily calcium carbonate (1000 mg elemental calcium) and VitD3 (400 IU) | 7 Years | Treatment and placebo groups were not different in CAC plaque burden measured at end of trial | Generally healthy postmenopausal women | Manson et al. (53) |
| DB, PC, RCT | Fasting serum lipids, BP, and oral glucose tolerance test | Same as primary outcomes | Obese or overweight patients (n = 438; 21–70 years) received VitD3 (40 000 or 20 000 IU/week) or placebo; all received 500 mg calcium daily; 330 patients completed study | 1 Year | No significant effect of VitD on glucose tolerance, BP, or serum lipids | Overweight or obese patients | Jorde et al. (56) |
| PC, RCT | Glycemic control in patients with type 2 DM | Same as primary outcomes | Participants (n = 36) received VitD3 (40 000 IU/week) or placebo | 6 Months | No significant effect of VitD on glucose metabolism | Type 2 DM treated with metformin and bedtime insulin | Jorde et al. (54) |
| DB, PC, RCT | Weight loss and traditional + nontraditional CVD risk markers | Same as primary outcomes (PTH, TG, and inflammatory markers) | Participants (n = 200; mean baseline 25OHD, 30 nmol/L) received 3320 IU/day VitD or placebo while participating in weight-reduction program | 12 Months | No adverse effect of VitD on weight loss but significantly decreased PTH, TG, TNF (although LDL increased significantly) in overweight individuals with inadequate VitD status while participating in weight-reduction program | Overweight | Zittermann et al. (55) |
| DB, PC, RCT | Hip fractures | Incident DM | WHI Ca/D trial of postmenopausal women (n = 36 282; age, 50–79 years); received 1000 mg elemental calcium + 400 IU VitD3 daily | 7 Years of follow-up | No beneficial effects in reducing DM incidence or metabolic syndrome | Generally healthy postmenopausal women | DeBoer et al. (47) |
| DB, PC, RCT | Hip fractures | Change in BP and development of HTN | WHI Ca/D trial of postmenopausal women (n = 36 282); received 1000 mg elemental calcium + 400 IU VitD3 daily | 7 Years of follow-up | No significant beneficial effect on 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 of postmenopausal women (n = 36 282; age, 50–79 years); received 500 mg calcium carbonate + 200 IU VitD3 twice daily | 7 Years of 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, and cytokine profile | Same as primary outcomes | Participants (n = 123) received 2000 IU VitD3 and 500 mg Ca/D daily (D+ group), or placebo and 500 mg Ca/D daily (D− group); 93 patients completed study | 9-Month intervention, 15 months of follow-up | VitD3 reduced inflammatory milieu in CHF patients; interleukin-10 increased, but significant improvement in PTH and TNF; no difference in survival, however | CHF | Schleithoff et al. (56) |
| DB, PC, RCT | Fracture incidence and total mortality by cause | Same as primary outcome; additional data assessing CVD | 2686 Participants (2037 men and 649 women; age, 65–85 years) randomized to receive 100 000 IU supplemental VitD3 every 4 months | 5 Years, Britain | No beneficial CVD effects attributable to VitD | Patients recruited from the general community; excluded if history of renal stones, sarcoidosis, or malignancy | Trivedi et al. (46) |
| DB, PC, RCT | Fractures | Coronary mortality | 327 Patients (57 men and 270 women >65 years; mean, 79.5 years) received daily all possible combinations of 3 g calcium carbonate, 1000 IU VitD3, 2.5 mg methandienone, and/or placebos | 9 Months | Coronary mortality higher among those taking all 3 active substances; significant increase in coronary deaths, most significantly (P < 0.001) in patients receiving VitD3 and methandienone | Inkovaara et al. (58) |
↵a Note that because this article is not an all-inclusive systematic review, this table may not list all randomized controlled trials (RCTs) reporting on vitamin D supplementation and CHD risk factors as well as CHD events.
↵b DB, double-blind; PC, placebo controlled; SBP, systolic blood pressure; DBP, diastolic blood pressure; VitD3, vitamin D3; DM, diabetes mellitus; FMV, flow-mediated vasodilation; PWV, pulse wave velocity; BP, blood pressure; CAC, coronary artery calcium; WHI, Women's Health Initiative; Ca/D, calcium and vitamin D; PTH, parathyroid hormone; TG, triglycerides; TNF, tumor necrosis factor; HTN, hypertension; CHF, congestive heart failure.