Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study

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 PARTICIPANTSThe 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 D 3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.INTERVENTIONS Oral vitamin D 3 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 MEASURESThe 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. RESULTSOf 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.

Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease

“…Studies have not demonstrated improved cardiovascular outcomes in the general population with a therapeutic supplementation of deficient vitamins, such as vitamin D. 46 Even sparser is the evidence of cardiovascular benefit in the general population without a confirmed vitamin deficiency, other than possible theoretical benefits suggested in in vitro studies. 47,48 Furthermore, several studies demonstrated that routine vitamin and mineral supplementation in certain populations, for instance in elderly patients, could lead to a worse outcome.…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…The most recent meta-analysis on non-skeletal effects of vitamin D supplementation demonstrates that most trials have been done in subjects without low 25[OH]D levels limiting the credibility of the argument that vitamin D supplementation has no potential benefit on outcomes in people with 25[OH] D insufficiency [1]. The Vitamin D Assessment study (ViDA) in 5100 healthy subjects, aged > 50 years, recently reported that 100,000 IU oral vitamin D 3 monthly was neutral for the prevention of CV disease [49,50], with a low rate of 25[OH]D deficiency in participants (25%), a lower than expected endpoint rate and monthly doses cited as possible reasons [51]. Metaanalysis and data from ViDA and other studies describe that benefits on clinical outcomes are greatest in the most deficient, and in studies using daily dosing regimens (as in VINDICATE) rather than monthly [52][53][54][55].…”

Iron, Hematological Parameters and Blood Plasma Lipid Profile in Vitamin D Supplemented and Non-Supplemented Young Soccer Players Subjected to High-Intensity Interval Training

“…Moreover, Brøndum-Jacobsen et al (11) found that genetically reduced plasma 25-hydroxyvitamin D (25(OH)D) is not associated with increased risk of ischemic heart disease. Moreover, the results of Scragg et al's (12) randomized controlled trial (RCT) study showed no evidence that monthly high-dose vitamin D supplementation (100,000 IU a month) prevented cardiovascular diseases.…”