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Review
. 2017 Mar 16;3(3):CD011114.
doi: 10.1002/14651858.CD011114.pub2.

Vitamin C supplementation for the primary prevention of cardiovascular disease

Lena Al-Khudairy  1 , Nadine Flowers  1 , Rebecca Wheelhouse  1 , Obadah Ghannam  1 , Louise Hartley  1 , Saverio Stranges  1 , Karen Rees  1
Affiliations
Review

Vitamin C supplementation for the primary prevention of cardiovascular disease

Lena Al-Khudairy et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent.

Objectives: To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD.

Search methods: We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions.

Selection criteria: Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors.

Data collection and analysis: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.

Main results: We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding.

Authors' conclusions: Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 1 Major cardiovascular event.
1.2
1.2. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 2 Cardiovascular mortality.
1.3
1.3. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 3 All‐cause mortality.
1.4
1.4. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 4 Total myocardial infarction.
1.5
1.5. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 5 Self‐reported CABG/PTCA.
1.6
1.6. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 6 Self‐reported angina.
1.7
1.7. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 7 Total stroke.
1.8
1.8. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 8 Systolic blood pressure (change from baseline, mmHg).
1.9
1.9. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 9 Diastolic blood pressure (change from baseline, mmHg).
1.10
1.10. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 10 Total cholesterol (change from baseline, mmol/L).
1.11
1.11. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 11 LDL‐cholesterol (change from baseline, mmol/L).
1.12
1.12. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 12 HDL‐cholesterol (change from baseline, mmol/L).
1.13
1.13. Analysis
Comparison 1 Vitamin C supplementation versus no intervention or placebo, Outcome 13 Triglycerides (change from baseline, mmol/L).
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  • doi: 10.1002/14651858.CD011114

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