Vitamin C supplementation for the primary prevention of cardiovascular disease
Vitamin C supplementation for the primary prevention of cardiovascular disease
Al-Khudairy et al., 2017 | Cochrane Database Syst Rev | Systematic Review
Citation
Al-Khudairy Lena, Flowers Nadine, ... Rees Karen. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017-Mar-16;3(3):CD011114. doi:10.1002/14651858.CD011114.pub2
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.
Key Findings
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 C
Outcomes Measured
- Requires manual extraction
Population
| Field | Value |
|---|---|
| Population | healthy participants |
| Sample Size | 15445 |
| Age Range | See abstract |
| Condition | See abstract |
MeSH Terms
- Angioplasty, Balloon, Coronary
- Ascorbic Acid
- Cardiovascular Diseases
- Coronary Artery Bypass
- Dietary Supplements
- Humans
- Male
- Middle Aged
- Myocardial Infarction
- Physicians
- Primary Prevention
- Publication Bias
- Randomized Controlled Trials as Topic
- Stroke
- Vitamins
Evidence Classification
- Level: Systematic Review
- Publication Types: Journal Article, Systematic Review
- Vertical: vitamin-c-cardiovascular
Provenance
- PMID: 28301692
- DOI: 10.1002/14651858.CD011114.pub2
- PMCID: PMC6464316
- Verified: 2026-04-09 via PubMed E-utilities API
Source extracted via PubMed E-utilities API on 2026-04-09