Efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular disease : a meta-analysis of randomized controlled trials

다국어 초록 (Multilingual Abstract)

Introduction Randomized controlled trials have reported inconsistent findings regarding the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. The current study aimed to investigate the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases by using a meta-analysis of randomized controlled trials.

Methods We searched PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov in June and additionally November 2012. Two of the authors independently reviewed and selected eligible randomized controlled trials, based on pre-determined selection criteria. A meta-analysis of randomized controlled trials was performed.

Results Out of 2,240 articles retrieved from databases and relevant bibliographies, a total of 50 RCTs, which involved 294,478 participants (156,663 intervention and 137,815 control groups), were included in the final analyses. In a fixed-effect meta-analysis of 50 RCTs, supplementation with vitamins and antioxidants did not reduce the risk of major cardiovascular events (relative risk [RR], 1.00; 95% confidence interval [CI], 0.98-1.02; I2 = 41.6%). Overall, no beneficial effect of those supplements was observed in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, supply source for supplement, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation marginally increased the risk of angina pectoris, while low-dose vitamin B6 supplementation slightly decreased the risk of major cardiovascular events. However, in the subgroup meta-analysis of high-quality RCTs within each category, those beneficial or harmful effects disappeared. Also, even though vitamin B6 supplementation decreased the risk of cardiovascular death in high-quality trials, and vitamin E supplementation decreased the risk of myocardial infarction, those beneficial effects were only shown in RCTs supplied with supplements by pharmaceutical industry.

Conclusion Our meta-analysis found that there is no evidence to support the use of vitamin and antioxidant supplements in the prevention of cardiovascular diseases.

목차 (Table of Contents)

• CONTENTS
• Abstract i
• Contents iii
• List of tables and figures ⅳ
• List of abbreviations ⅴ
• Introduction 1
• Methods 3
• Literature search 3
• Selection criteria 3
• Selection of relevant trials 3
• Assessment of methodological quality 4
• Main and subgroup analyses 4
• Statistical analysis 5
• Results 7
• Selection of trials 7
• General characteristics of trials 8
• Efficacy of vitamin or antioxidant supplements on cardiovascular disease in all 50trials 35
• Efficacy of vitamin or antioxidant supplements on cardiovascular disease in subgroup meta-analysis by various factors 47
• Discussion 82
• References 89
• Abstract in Korean 102
• LIST OF TABLES AND FIGURES
• Tables
• Table 1. Characteristics of trials included in the final meta-analysis
• (n = 50) 9
• Table 2. Methodological quality of trials based on the Jadad Scale
• (n = 50). 50
• Table 3. Efficacy of vitamin or antioxidant supplements in the prevention of the major cardiovascular events in subgroup meta-analyses by type of prevention and type of supplement 58
• Table 4. Efficacy of vitamin or antioxidant supplements in the prevention of the major cardiovascular events in subgroup meta-analyses by type of cardiovascular outcome 63
• Table 5. Efficacy of vitamin or antioxidant supplements in the prevention of the major cardiovascular events in subgroup meta-analyses by type of study design, methodological quality, duration of treatment, funding source, supply source for supplements, type of control, and number of participants in each trial. 72
• Table 6. Efficacy of vitamin and antioxidant supplements given singly or in combination with other vitamin or antioxidant supplements in the prevention of the major cardiovascular events in subgroup meta-analyses. 75
• Figures
• Figure 1. Flow diagram for identification of relevant clinical trials 7
• Figure 2. Efficacy of vitamin and antioxidant supplements in the prevention of the major cardiovascular events in a meta-analysis of randomized controlled trials sorted in ascending order by the number of participants (n = 50) 36
• Figure 3. Efficacy of vitamin and antioxidant supplements in the prevention of the major cardiovascular events in subgroup meta-analysis of randomized controlled trials by type of supplements 37-41
• Figure 4. Efficacy of low-dose vitamin B6 supplements in the prevention of the major cardiovascular events in subgroup meta-analysis of randomized controlled trials by study quality 42-43
• Figure 5. Efficacy of vitamin E supplements in the prevention of myocardial infarction in subgroup meta-analysis of randomized controlled trials by supply with supplements from pharmaceutical industry 44-45
• Figure 6. Begg’s funnel plots and Egger’s test for identifying
• publication bias 46