Monthly high-dose vitamin D supplementation does not prevent cardiovascular diseases
Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study A Randomized Clinical Trial
Recent meta-analyses show that a low vitamin D status is associated with an increased cardiovascular disease (CVD) risk [1,2]. However, in other studies there was no or non-significant CVD risk benefit from vitamin D supplementation, which might be due to low dosing and poor adherence [3-6].
In this large randomised, double-blind, placebo-controlled ‘Vitamin D Assessment Study’, the association between a monthly high-dose vitamin D supplementation and the incidence of CVD was evaluated compared with placebo in 5108 New Zealand residents for a median of 3.3 years, in which they received an initial dose of 200 000 IU oral vitamin D3 or placebo, followed by monthly 100 000 IU. Calcium and 25 hydroxyvitamin D [25(OH)D], a metabolite of vitamin D, were measured at baseline and in 10% of random participants at 6, 12, 24 and 36 months. Primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency.
- Mean age was 65.9±8.3 years, 58.1% were male, 6.3% were smokers, 8.0% were taking vitamin D supplements within study eligibility criteria and 4.9% were taking calcium supplements.
- The mean baseline 25(OH)D concentration was 25.3 ng/mL and when corrected for seasonal variation, this was 26.5±9.0 ng/mL.
- The mean 25(OH)D concentrations were >20 ng/mL higher in the treated group compared with the placebo group at 6 months and up to 36 months of follow-up.
- The mean corrected serum calcium levels throughout the follow-up period were similar for the vitamin D vs placebo groups (9.2±0.4 vs 9.2±0.4 mg/dL at 6, 12 and 24 months and 9.6±0.4 vs 9.6±0.4 mg/dL at 36 months).
- The baseline 25(OH) concentration categories were inversely associated with the CVD risk during follow-up in the placebo group, after adjusting for demographic covariates.
- There was no significant difference in the percentage for all CVD events combined between the vitamin D (11.8%) and placebo (11.5%) groups (HR 1.02, 95% CI 0.87-1.20).
- Similar results were seen in vitamin D-deficient participants (HR 1.00, 95% CI 0.74-1.35) and when participants were categorized by previous CVD.
- No difference was found between the vitamin D and placebo groups in the time to first CVD event during follow-up or in the frequency of disease-specific secondary outcomes.
In a large randomised clinical trial, monthly high-dose vitamin D supplementation was not associated with a lower CVD risk. These findings do not support routine vitamin D supplementation as a preventive measure for CVD in the general population. However, the effects of daily or weekly dosing needs further study.