Is there a future for antioxidants in atherogenesis?

Area of Science:

• Biochemistry
• Molecular Biology
• Nutritional Science

Background:

• Dietary antioxidants have long been hypothesized to prevent diseases linked to oxidative stress, including cardiovascular diseases, cancer, and neurodegenerative disorders.
• Clinical trial outcomes supporting this hypothesis have been largely inconclusive, prompting a re-evaluation of their mechanisms of action.

Purpose of the Study:

• To investigate the non-antioxidative mechanisms of dietary antioxidants.
• To re-evaluate the role of antioxidants in disease prevention by considering their signaling and gene regulatory functions.
• To highlight the potential benefits of moderate oxidative stress.

Main Methods:

• Analysis of existing evidence and specific examples concerning vitamin E and selenium.
• Examination of gene regulatory functions beyond simple antioxidant activity.
• Investigation into the induction of defense mechanisms by moderate oxidative stress.

Main Results:

• Vitamin E exhibits gene regulatory functions that may be more critical in vivo than its antioxidant capacity.
• Selenium, even when incorporated into glutathione peroxidases, does not function as an antioxidant.
• Moderate oxidative stress can be beneficial by activating cellular defense systems against xenobiotics and oxidative damage.

Conclusions:

• The future of antioxidants in disease prevention lies in understanding their true mechanisms of action, which extend beyond antioxidative effects.
• Establishing appropriate read-outs and biomarkers is crucial for accurately assessing the efficacy of antioxidants.
• Non-antioxidative pathways, such as gene regulation and stress response induction, are key areas for future research in antioxidant-related health benefits.