Vitamin C supplementation to prevent cardiovascular disease

Background

Cardiovascular diseases (CVD) are a group of conditions affecting the heart and blood vessels. CVD is a global burden and varies between regions, and this variation has been linked in part to dietary factors. Such factors are important because they can be modified to help with CVD prevention and management.This review assessed the effectiveness of vitamin C supplementation as a single supplement at reducing cardiovascular death, all-cause death, non-fatal endpoints (such as heart attacks, strokes and angina) and CVD risk factors in healthy adults and adults at high risk of CVD .

Study characteristics

We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin C supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to May 2016.

Key results

Eight trials fulfilled our inclusion criteria. One large trial looked at the effects of vitamin C supplements on the risk of major CVD events (fatal and non-fatal) and found no beneficial effects. This trial was however conducted in middle-aged and older male doctors in the USA and so its not certain that the effects are the same in other groups of people. Seven trials looked at the effects of vitamin C supplements on CVD risk factors. We could not combine these trials as there was lots of missing information and differences between the trials in terms of the participants recruited, the dose of vitamin C and the duration of trials. Overall, there were inconsistent effects of vitamin C supplements on lipid levels and blood pressure and more research is needed. Four of the included studies did not mention sources of funding of the study, two had non-commercial (grants) funding and two had both commercial (industries) and non-commercial funding (grants).

Quality of the evidence

The evidence was of low or very low quality for major CVD events (myocardial infraction, stroke, angina and coronary artery bypass grafting), all-cause mortality and CVD mortality. The evidence was of low quality because it was not applicable to the general population (included only USA male physicians) and limited studies of vitamin C on the prevention of CVD.

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.

Read the full 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 strategy: 

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.

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