Monthly high-dose vitamin D supplementation does not prevent cardiovascular disease (CVD), a large University of Auckland randomised trial found.
Studies have reported increased incidence of CVD among individuals with low vitamin D status. To date, randomised clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D.
Dr Robert Scragg, of the University of Auckland, New Zealand, and colleagues randomly assigned adults (age 50 to 84 years) to receive oral vitamin D3 (n = 2,558; an initial dose of 200,000 IU, followed a month later by monthly doses of 100,000 IU) or placebo (n = 2,552) for a median of 3.3 years.
Of the 5,108 participants included in the primary analysis, the average age was 66 years; 25% were vitamin D deficient. Cardiovascular disease occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group.
Similar results were seen for participants with vitamin D deficiency at study entry and for other outcomes such as heart attack, angina, heart failure, hypertension and stroke.
The authors write that the results of this study do not support the use of monthly high-dose vitamin D for the prevention of CVD. “The effects of daily or weekly dosing on CVD risk require further study.”
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 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.
Robert Scragg; Alistair W Stewart; Debbie Waayer; Carlene MM Lawes; Les Toop; John Sluyter; Judy Murphy; Kay-Tee Khaw; Carlos A Camargo Jr