Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

Abstract

BackgroundVitamin C deprivation can lead to fatigue, dyspnea, oedema and chest pain, which are also symptoms of heart failure (HF). In animal studies vitamin C has improved contractility and mechanical efficiency of the heart. Compared with healthy people, patients with HF have lower vitamin C levels, which are not explained by differences in dietary intake levels, and more severe HF seems to be associated with lower plasma vitamin C levels. This meta-analysis looks at the effect of vitamin C on left ventricular ejection fraction (LVEF).MethodsWe searched for trials reporting the effects of vitamin C on LVEF. We assessed the quality of the trials, and pooled selected trials using the inverse variance, fixed effect options. We used meta-regression to examine the association between the effect of vitamin C on LVEF level and the baseline LVEF level.ResultsWe identified 15 trials, three of which were excluded from our meta-analysis. In six cardiac trials with 246 patients, vitamin C increased LVEF on average by 12.0% (95% CI 8.1–15.9%; P < 0.001). In six non-cardiac trials including 177 participants, vitamin C increased LVEF on average by 5.3% (95% CI 2.0–8.5%; P = 0.001). In meta-regression analysis we found that the effect of vitamin C was larger in trials with the lowest baseline LVEF levels with P = 0.001 for the test of slope. The meta-regression line crossed the null effect level at a baseline LVEF level close to 70%, with progressively greater benefit from vitamin C with lower LVEF levels. Some of the included trials had methodological limitations. In a sensitivity analysis including only the four most methodologically sound cardiac trials, the effect of vitamin C was not substantially changed.ConclusionsIn this meta-analysis, vitamin C increased LVEF in both cardiac and non-cardiac patients, with a strong negative association between the size of the vitamin C effect and the baseline LVEF. Further research on vitamin C and HF should be carried out, particularly in patients who have low LVEF together with low vitamin C intake or low plasma levels. Different dosages and different routes of administration should be compared.

Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial

“…However, refuting their conclusion does not explain the lack of observed benefit during the period of intravenous vitamin C administration. This is unexpected given the biological evidence and previous findings [1][2][3][4][5][8][9][10][11][12][13]. Nevertheless, there are a few potential explanations.…”

“…Vitamin C deficiency increases the risk of pneumonia and there are indications that vitamin C could be beneficial against pneumonia [ 8 ]. Sepsis is often associated with myocardial dysfunction [ 6 , 7 ], and meta-analyses indicate that vitamin C may protect the heart when under stress [ 9 , 10 ].…”

Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports

“…The classification of the remaining 24 cases is not clear. In controlled trials, vitamin C has influenced left ventricular ejection fraction (LVEF) [ 130 ], which indicates that vitamin C can have effects on LV function. Controlled trials have also shown that vitamin C can influence pulmonary function tests [ 131 , 132 ].…”

Molecular mechanisms of sacubitril/valsartan in cardiac remodeling

“…), and α-lipoic acid (0.6 g) for 30 days exerted beneficial effects on macrovascular function in patients with HFrEF ( Bunsawat et al, 2020 ). A recent meta-analysis also revealed that vitamin C administration augmented LVEF in heart failure patients ( Hemilä et al, 2022 ). The findings suggest that supplemental vitamin C may afford synergistic effects with sacubitril/valsartan if given together in patients with heart failure.…”