The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark ; Department of Internal Medicine, Gastroenterology and Hepatology, Medical Faculty, University of Nis, Niš, Serbia.
PLoS One. 2013 Sep 6;8(9):e74558. doi: 10.1371/journal.pone.0074558. eCollection 2013.
Evidence shows that antioxidant supplements may increase mortality. Our aims were to assess whether different doses of beta-carotene, vitamin A, and vitamin E affect mortality in primary and secondary prevention randomized clinical trials with low risk of bias.
The present study is based on our 2012 Cochrane systematic review analyzing beneficial and harmful effects of antioxidant supplements in adults. Using random-effects meta-analyses, meta-regression analyses, and trial sequential analyses, we examined the association between beta-carotene, vitamin A, and vitamin E, and mortality according to their daily doses and doses below and above the recommended daily allowances (RDA).
We included 53 randomized trials with low risk of bias (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta-carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose of vitamin A was significantly positively associated with all-cause mortality. Beta-carotene in a dose above 9.6 mg significantly increased mortality (relative risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I(2) = 13%). Vitamin A in a dose above the RDA (> 800 µg) did not significantly influence mortality (RR 1.08, 95% CI 0.98 to 1.19, I(2) = 53%). Vitamin E in a dose above the RDA (> 15 mg) significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I(2) = 0%). Doses below the RDAs did not affect mortality, but data were sparse.
Beta-carotene and vitamin E in doses higher than the RDA seem to significantly increase mortality, whereas we lack information on vitamin A. Dose of vitamin A was significantly associated with increased mortality in meta-regression. We lack information on doses below the RDA.
All essential compounds to stay healthy cannot be synthesized in our body. Therefore, these compounds must be taken through our diet or obtained in other ways [1]. Oxidative stress has been suggested to cause a variety of diseases [2]. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing diseases and death. Despite the fact that a normal diet in high-income countries may provide sufficient amounts of antioxidants [3,4], more than one third of adults regularly take antioxidant supplements [5,6].
有证据表明，抗氧化补充剂可能会增加死亡率。我们的目的是评估β-胡萝卜素、维生素 A 和维生素 E 的不同剂量是否会影响低偏倚风险的一级和二级预防随机临床试验中的死亡率。
本研究基于我们 2012 年的 Cochrane 系统评价，分析了抗氧化补充剂对成年人的有益和有害影响。使用随机效应荟萃分析、荟萃回归分析和试验序贯分析，我们根据β-胡萝卜素、维生素 A 和维生素 E 的每日剂量以及低于和高于推荐日摄入量 (RDA) 的剂量，研究了它们与死亡率之间的关系。
我们纳入了 53 项低偏倚风险的随机试验（241883 名参与者，年龄 18 至 103 岁，44.6%为女性），评估了β-胡萝卜素、维生素 A 和维生素 E。荟萃回归分析表明，维生素 A 的剂量与全因死亡率呈显著正相关。β-胡萝卜素剂量高于 9.6mg 时显著增加死亡率（相对风险 1.06，95%置信区间 1.02 至 1.09，I²=13%）。维生素 A 剂量高于 RDA（>800μg）时，死亡率无显著影响（RR 1.08，95%CI 0.98 至 1.19，I²=53%）。维生素 E 剂量高于 RDA（>15mg）时，死亡率显著增加（RR 1.03，95%CI 1.00 至 1.05，I²=0%）。RDA 以下剂量不影响死亡率，但数据稀少。
RDA 以上剂量的β-胡萝卜素和维生素 E 似乎显著增加死亡率，而我们对维生素 A 的信息有限。剂量与死亡率的关系在荟萃回归分析中呈显著正相关。我们对 RDA 以下剂量的信息有限。
所有保持健康所需的基本化合物都不能在我们体内合成。因此，这些化合物必须通过我们的饮食或其他方式获得[1]。氧化应激被认为会导致多种疾病[2]。因此，有人推测抗氧化补充剂可能在预防疾病和死亡方面发挥作用。尽管高收入国家的正常饮食可能提供足够的抗氧化剂[3,4]，但超过三分之一的成年人经常服用抗氧化补充剂[5,6]。
