Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study
Jiao Luo1, Saskia le Cessie2, Diana van Heemst3
1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Insights
This study found no causal link between higher circulating antioxidant levels and reduced coronary heart disease (CHD) risk. Antioxidant supplementation is unlikely to prevent CHD.
Area of Science:
- Cardiovascular disease research
- Nutritional science
- Genetic epidemiology
Background:
- Observational studies suggest dietary antioxidants may lower coronary heart disease (CHD) risk.
- However, randomized trials have not confirmed this benefit with antioxidant supplementation.
Purpose of the Study:
- To investigate potential causal associations between circulating antioxidants and primary CHD risk.
- Utilized a 2-sample Mendelian randomization (MR) approach.
Main Methods:
- Employed single-nucleotide polymorphisms (SNPs) for circulating antioxidants (vitamins E, C, retinol, beta-carotene, lycopene) as genetic instrumental variables.
- Analyzed summary statistics from large-scale consortia (CARDIoGRAMplusC4D, UK Biobank, FinnGen) involving over 768,000 individuals.
- Performed meta-analysis of MR results across multiple databases.
Main Results:
- Genetically predicted circulating antioxidant levels showed no causal association with CHD risk.
- Odds ratios for CHD per unit increase in antioxidants ranged from 0.93 to 1.03, indicating no significant protective effect.
- No evidence of a protective effect for either absolute antioxidant levels or their metabolites.
Conclusions:
- Genetic predisposition to high dietary-derived antioxidant levels does not appear to protect against CHD.
- Clinical benefits of antioxidant supplementation for primary CHD prevention are unlikely based on these findings.
Background:
Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants 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, β-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved 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.
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
01:26Coronary Artery Disease IV: Preventive Measures
01:26Atherosclerosis III: Management
02:59Cancer Prevention
Some...
01:26Coronary Artery Disease II: Pathophysiology