Redox Paradox of Polyphenols: Bioavailability, Hormesis, and Safety Concerns
Stanislava Vrankova1,2, Martina Cebova1,2, Jana Klimentova1
1Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Phytotherapy Research : PTR
|February 16, 2026
Summary
Polyphenols offer health benefits at dietary levels but can be harmful at high doses, exhibiting hormetic dose-response behavior. Understanding this dual effect is crucial for safe and effective polyphenol use.
Area of Science:
- Nutritional Biochemistry
- Toxicology
- Pharmacology
Background:
- Polyphenols are known for antioxidant and anti-inflammatory effects.
- Evidence suggests a paradoxical, dose-dependent biological activity of polyphenols.
Purpose of the Study:
- To review the dual effects of polyphenols, focusing on hormesis and context-dependent outcomes.
- To highlight adverse effects and mechanistic pathways of high-dose polyphenol intake.
Main Methods:
- Literature review of experimental and clinical studies on polyphenol biological activity.
- Analysis of mechanistic pathways including redox modulation, enzyme interactions, and reactive intermediate formation.
Main Results:
- Dietary polyphenols promote beneficial effects via redox homeostasis and signaling pathways.
- High-dose polyphenols can induce pro-oxidant activity, enzyme inhibition, endocrine disruption, and organ toxicity (carcinogenicity, hepatotoxicity, nephrotoxicity).
- Mechanisms include metal chelation, CYP450 interference, and glutathione depletion.
Conclusions:
- Polyphenols exhibit hormetic dose-response behavior, with both beneficial and adverse effects.
- A nuanced understanding beyond antioxidant properties is needed for safe polyphenol application.
- Future research should focus on dose-response, mechanisms of toxicity, and long-term safety for optimized dosing strategies.
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