Table_1_Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis.XLSX

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.

背景：维生素C缺乏可引发疲劳、呼吸困难、水肿及胸痛，上述症状亦为心力衰竭（heart failure, HF）的典型表现。动物实验研究显示，维生素C可改善心脏收缩功能与机械效率。相较于健康人群，心力衰竭患者的血浆维生素C水平更低，且该差异无法用膳食摄入水平差异解释；病情更严重的心力衰竭患者，其血浆维生素C水平往往也更低。本荟萃分析旨在探讨维生素C对左心室射血分数（left ventricular ejection fraction, LVEF）的影响。
方法：我们检索了报道维生素C对LVEF影响的临床试验，评估了各试验的方法学质量，并采用逆方差法、固定效应模型对入选试验进行合并分析。此外，我们运用荟萃回归分析，检验维生素C对LVEF的干预效应与基线LVEF水平之间的关联。
结果：本研究共检索到15项相关试验，其中3项被排除出本次荟萃分析。在纳入的6项心脏相关试验（共246名受试者）中，维生素C可使LVEF平均提升12.0%（95%置信区间：8.1%~15.9%；P < 0.001）。在6项非心脏相关试验（共177名受试者）中，维生素C可使LVEF平均提升5.3%（95%置信区间：2.0%~8.5%；P = 0.001）。荟萃回归分析显示，基线LVEF水平最低的试验中，维生素C的干预效应最为显著，斜率检验P值为0.001。荟萃回归拟合线在基线LVEF接近70%时与无效应水平线相交，即LVEF水平越低，维生素C带来的临床获益越显著。部分纳入试验存在方法学局限性。在仅纳入4项方法学质量最优的心脏相关试验的敏感性分析中，维生素C的干预效应未发生显著改变。
结论：本项荟萃分析结果表明，无论心脏相关还是非心脏相关受试者，维生素C均可提升其LVEF水平，且维生素C的干预效应强度与基线LVEF水平呈显著负相关。未来应针对维生素C与心力衰竭开展进一步研究，尤其是针对同时存在低LVEF、低膳食维生素C摄入或低血浆维生素C水平的患者；同时还应比较不同给药剂量与给药途径的干预效果。