Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study

Abstract

Background: Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants (抗氧化剂) and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.

Objectives: The purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).

Methods: Single-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol (视黄醇；维生素A), β-carotene (胡萝卜素), and lycopene (番茄红素)), assessed as absolute levels and metabolites, were retrieved (恢复；重新取回；补偿) from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.

Results: Among an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for β-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for γ-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.

Conclusions: Evidence from our study did not support a protective effect of genetic predisposition to high dietary-derived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD.

临床上的随机对照实验表明，补充抗氧化剂并不能保护降低冠心病风险。本文使用两样本孟德尔随机化的方法探究膳食来源的循环抗氧化剂和原发性冠心病风险之间可能的因果关系。本文研究的证据并不支持高饮食来源抗氧化剂水平（遗传易感性）对冠心病风险的保护作用。因此，服用抗氧化剂来增加血液抗氧化剂水平不太可能对预防原发性冠心病有临床益处。

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