Meta-analysis of Randomized Controlled Trials on Vitamins and Mineral Supplementation for CVD Prevention and Treatment

Search strategy:

A literature search of the Cochrane Library, Medline and PubMed will be conducted with the following search terms: "dietary supplements or supplement*" AND "cardiovascular disease or myocardial infarction or stroke or cardiovascular death or mortality or all-cause mortality or death." Specific searches will be conducted for individual supplements and included multivitamins, antioxidants, vitamin A, β-carotene, B1, B2, B3 (niacin), B6, B10 (folic acid), B-complex, C, D and E, calcium, iron, zinc, magnesium and selenium. The search will be limited to meta-analyses and RCTs.

Analysis:

Full article review and data extraction will be conducted by two independent investigators, with all disparities reconciled through consensus. The extracted data will include number of cases and total participants/population for the intervention and control group.

Data will be analyzed using Review Manager (RevMan) version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and publication bias will be conducted using STATA software, version 13.0 (College Station, TX, USA). Heterogeneity will be assessed using the Cochran Q statistic at p\<0.1 and quantified by the I² statistic. Publication bias will be investigated by visual inspection of funnel plots and quantitative assessment using Begg's and Egger's tests where p\<0.05 is considered evidence of small study effects. If \<10 trials are available in a meta-analysis, publication bias analysis will not be assessed due to insufficient power.

Risk of bias The Cochrane risk of bias tool which is based on randomization, allocation concealment, blinding, completeness of follow-up and intention-to-treat will be used to assess eligible RCTs.

Grading of the evidence The quality and strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Using the GRADE tool, evidence will be graded as high, moderate, low, or very low quality evidence using the following criteria: study limitations (as assessed by the Cochrane Risk of Bias Tool), inconsistency (substantial) unexplained inter-study heterogeneity, I2>50% and p\<0.1; indirectness (presence of factors that limit the generalizability of the results); imprecision (the 95% CI for effect estimates crosses a minimally important difference (MID) of 5% [RR 0.95-1.05]) from the line of unity; and publication bias (significant evidence of small-study effects).