Table 1. Prospective randomized trials of vitamin D supplementation and CHD events or CVD risk factors.a
DesignPrimary outcomeStudy outcomeSummary of study, sample size, patient age, and route/dose of treatmentLength and follow-upOutcomes related to CHD or CHD risk factorsPreexisting conditions or disease?Reference
DB,b PC, RCTColorectal cancer prevention studyChange in SBP and DBPBlacks (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 months6 MonthsA −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 excludedForman et al. (60)
DB, PC, RCTChanges in brachial artery FMV, carotid–femoral PWV, and aortic augmentation indexSame as primary outcomesPostmenopausal 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 daily4 MonthsVitD supplementation did not improve endothelial function, arterial stiffness, or inflammationGenerally healthy, community-dwelling, ambulatory women from Madison, WI; patients with CVD excludedGepner et al. (51)
DB, PC, RCTChange in small LDL particle numberOther lipid fractionsVitD-insufficient (25OHD ≤20 ng/mL) male and female adults (n = 151); received 50 000 IU VitD3 weekly8 WeeksVitD repletion failed to improve lipid profileIncreased risk for CVD (with at least 1 of numerous significant CVD risk factors)Ponda et al. (48)
DB, PC, RCTBP, FMV of the brachial artery, cholesterol, and other markers of vascular healthSame as primary outcomesPatients (n = 58; mean age, 67 years) received 100 000 IU oral VitD2 or placebo at baseline16 Weeks of follow-upHigh-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 studyHistory of stroke with baseline 25OHD concentrations <75 nmol/LWitham et al. (52)
DB, PC, RCTHip fracturesCAC scoreCa/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 YearsTreatment and placebo groups were not different in CAC plaque burden measured at end of trialGenerally healthy postmenopausal womenManson et al. (53)
DB, PC, RCTFasting serum lipids, BP, and oral glucose tolerance testSame as primary outcomesObese 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 study1 YearNo significant effect of VitD on glucose tolerance, BP, or serum lipidsOverweight or obese patientsJorde et al. (56)
PC, RCTGlycemic control in patients with type 2 DMSame as primary outcomesParticipants (n = 36) received VitD3 (40 000 IU/week) or placebo6 MonthsNo significant effect of VitD on glucose metabolismType 2 DM treated with metformin and bedtime insulinJorde et al. (54)
DB, PC, RCTWeight loss and traditional + nontraditional CVD risk markersSame 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 program12 MonthsNo 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 programOverweightZittermann et al. (55)
DB, PC, RCTHip fracturesIncident DMWHI Ca/D trial of postmenopausal women (n = 36 282; age, 50–79 years); received 1000 mg elemental calcium + 400 IU VitD3 daily7 Years of follow-upNo beneficial effects in reducing DM incidence or metabolic syndromeGenerally healthy postmenopausal womenDeBoer et al. (47)
DB, PC, RCTHip fracturesChange in BP and development of HTNWHI Ca/D trial of postmenopausal women (n = 36 282); received 1000 mg elemental calcium + 400 IU VitD3 daily7 Years of follow-upNo significant beneficial effect on BP or prevention of incident HTNGenerally healthy postmenopausal womenMargolis et al. (49)
DB, PC, RCTHip fracturesRisk of CHDWHI Ca/D trial of postmenopausal women (n = 36 282; age, 50–79 years); received 500 mg calcium carbonate + 200 IU VitD3 twice daily7 Years of follow-upNo beneficial CHD effects attributable to Ca/DGenerally healthy postmenopausal womenHsia et al. (50)
DB, PC, RCTSurvival rate, biochemical variables, and cytokine profileSame as primary outcomesParticipants (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 study9-Month intervention, 15 months of follow-upVitD3 reduced inflammatory milieu in CHF patients; interleukin-10 increased, but significant improvement in PTH and TNF; no difference in survival, howeverCHFSchleithoff et al. (56)
DB, PC, RCTFracture incidence and total mortality by causeSame as primary outcome; additional data assessing CVD2686 Participants (2037 men and 649 women; age, 65–85 years) randomized to receive 100 000 IU supplemental VitD3 every 4 months5 Years, BritainNo beneficial CVD effects attributable to VitDPatients recruited from the general community; excluded if history of renal stones, sarcoidosis, or malignancyTrivedi et al. (46)
DB, PC, RCTFracturesCoronary mortality327 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 placebos9 MonthsCoronary mortality higher among those taking all 3 active substances; significant increase in coronary deaths, most significantly (P < 0.001) in patients receiving VitD3 and methandienoneInkovaara 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.