Department of Internal Medicine Section of Gerontology and Geriatrics Leiden University Medical Center Leiden The Netherlands.
Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands.
J Am Heart Assoc. 2021 Dec 7;10(23):e022567. doi: 10.1161/JAHA.121.022567. Epub 2021 Nov 19.
Background Dietary intake and blood concentrations of vitamins E and C, lycopene, and carotenoids have been associated with a lower risk of incident (ischemic) stroke. However, causality cannot be inferred from these associations. Here, we investigated causality by analyzing the associations between genetically influenced antioxidant levels in blood and ischemic stroke using Mendelian randomization. Methods and Results For each circulating antioxidant (vitamins E and C, lycopene, β-carotene, and retinol), which were assessed as either absolute blood levels and/or high-throughput metabolite levels, independent genetic instrumental variables were selected from earlier genome-wide association studies (<5×10). We used summary statistics for single-nucleotide polymorphisms-stroke associations from 3 European-ancestry cohorts (cases/controls): MEGASTROKE (60 341/454 450), UK Biobank (2404/368 771), and the FinnGen study (8046/164 286). Mendelian randomization analyses were performed on each exposure per outcome cohort using inverse variance-weighted analyses and subsequently meta-analyzed. In a combined sample of 1 058 298 individuals (70 791 cases), none of the genetically influenced absolute antioxidants or antioxidant metabolite concentrations were causally associated with a lower risk of ischemic stroke. For absolute antioxidants levels, the odds ratios (ORs) ranged between 0.94 (95% CI, 0.85-1.05) for vitamin C and 1.04 (95% CI, 0.99-1.08) for lycopene. For metabolites, ORs ranged between 1.01 (95% CI, 0.98-1.03) for retinol and 1.12 (95% CI, 0.88-1.42) for vitamin E. Conclusions This study did not provide evidence for a causal association between dietary-derived antioxidant levels and ischemic stroke. Therefore, antioxidant supplements to increase circulating levels are unlikely to be of clinical benefit to prevent ischemic stroke.
饮食摄入和血液中维生素 E 和 C、番茄红素和类胡萝卜素的浓度与缺血性中风的风险降低有关。然而，这些关联并不能推断出因果关系。在这里，我们通过分析血液中遗传影响的抗氧化剂水平与缺血性中风之间的关联，使用孟德尔随机化来研究因果关系。
对于每一种循环抗氧化剂（维生素 E 和 C、番茄红素、β-胡萝卜素和视黄醇），我们根据早期全基因组关联研究（<5×10），选择了独立的遗传工具变量，这些变量被评估为绝对血液水平和/或高通量代谢物水平。我们使用来自 3 个欧洲血统队列（病例/对照）的单核苷酸多态性-中风关联的汇总统计数据：MEGASTROKE（60341/454450）、英国生物银行（2404/368771）和芬兰基因研究（8046/164286）。使用逆方差加权分析对每个暴露于每个结果队列的暴露进行孟德尔随机化分析，然后进行荟萃分析。在 1058298 名个体（70791 例病例）的综合样本中，没有一种遗传影响的绝对抗氧化剂或抗氧化剂代谢物浓度与缺血性中风的风险降低有因果关系。对于绝对抗氧化剂水平，比值比（ORs）的范围为维生素 C 的 0.94（95%CI，0.85-1.05）至番茄红素的 1.04（95%CI，0.99-1.08）。对于代谢物，ORs 的范围为视黄醇的 1.01（95%CI，0.98-1.03）至维生素 E 的 1.12（95%CI，0.88-1.42）。
本研究没有提供饮食来源的抗氧化剂水平与缺血性中风之间存在因果关系的证据。因此，增加循环水平的抗氧化补充剂不太可能对预防缺血性中风具有临床益处。
