Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2017 Jun 1;2(6):608-616.
doi: 10.1001/jamacardio.2017.0175.

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial

Robert Scragg  1 , Alistair W Stewart  1 , Debbie Waayer  1 , Carlene M M Lawes  1 , Les Toop  2 , John Sluyter  1 , Judy Murphy  1 , Kay-Tee Khaw  3 , Carlos A Camargo Jr  4
Affiliations
Randomized Controlled Trial

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial

Robert Scragg et al. JAMA Cardiol. .

Abstract

Importance: Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D.

Objective: To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population.

Design, setting, and participants: The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.

Interventions: Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).

Main outcomes and measures: The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis.

Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes.

Conclusions and relevance: Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study.

Trial registration: clinicaltrials.gov Identifier: ACTRN12611000402943.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form of Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram for the Vitamin D Assessment Study
ITT indicates intention-to-treat.
Figure 2.
Figure 2.. Proportion of Participants With a Cardiovascular Disease (CVD) Event During Follow-up
Shaded areas indicate 95% CIs.
See this image and copyright information in PMC

Comment in

References

    1. Scragg R. Seasonality of cardiovascular disease mortality and the possible protective effect of ultra-violet radiation. Int J Epidemiol. 1981;10(4):337-341. - PubMed
    1. Wang L, Song Y, Manson JE, et al. . Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819-829. - PMC - PubMed
    1. Schöttker B, Jorde R, Peasey A, et al. ; Consortium on Health and Ageing: Network of Cohorts in Europe and the United States . Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656. - PMC - PubMed
    1. Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114(2):379-393. - PubMed
    1. Hsia J, Heiss G, Ren H, et al. ; Women’s Health Initiative Investigators . Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846-854. - PubMed

Publication types

MeSH terms