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JAMA Cardiol. 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.

Author information

1
School of Population Health, The University of Auckland, Auckland, New Zealand.
2
Department of Public Health & General Practice, The University of Otago, Christchurch, New Zealand.
3
Department of Public Health, University of Cambridge, Cambridge, England.
4
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.

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.

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