Antioxidant supplementation and genetics. What’s the story?

Free radicals commonly form during normal cellular activities although excess production can lead to oxidation and inflammation, characteristics typically associated with ageing and progression of multiple chronic diseases. Antioxidants limit free radical-induced tissue damage by preventing their formation through a scavenging process that promotes their breakdown. Observational studies have reported associations between circulating vitamin E and carotenoid levels with improved brain and vision health outcomes, including antioxidant, anti-inflammatory and cholesterol-lowering activities reducing morbidity and mortality, although support from randomised clinical trials has not been convincing. Despite reported associations between multiple genetic variants and antioxidant levels, their potential influence on antioxidant status and subsequent health outcomes is generally insufficiently considered in supplementation trial approaches.
The effects of polymorphisms in genes related to absorption, bioavailability and post-ingestion mechanistic effects on antioxidant levels can be potentially confounded by environmental, dietary and gene-gene interactions. Furthermore, the allele frequency for many polymorphisms differs significantly by ethnicity, meaning the significance of intervention response assessed across populations may not be consistent. Reported associations between ophthalmic disease-specific genetic risk and response to antioxidant supplementation recommendations remain largely unsubstantiated due to a lack of independent verification and validation, leading to potential misinterpretation.
Studies investigating the effects of antioxidants on inflammation and oxidative stress and subsequent health outcomes have been inconsistent. Future well-designed studies that consider genetic variation with respect to population-specific allele frequencies will better inform our understanding of antioxidant effects on inflammatory and oxidative stress biomarkers and health outcomes, particularly in response to different supplementation types and dosing regimens.