Are Supra-Physiological Plant-Based Antioxidants Ready for the Clinic? A Scoping Review of Hormetic Influences Driving Positive Clinical Outcomes

Julie Wendt; Benjamin Knudsen; Leigh A Frame

doi:10.1177/27536130241231508

Are Supra-Physiological Plant-Based Antioxidants Ready for the Clinic? A Scoping Review of Hormetic Influences Driving Positive Clinical Outcomes

Glob Adv Integr Med Health. 2024 Feb 6:13:27536130241231508. doi: 10.1177/27536130241231508. eCollection 2024 Jan-Dec.

Authors

Julie Wendt¹, Benjamin Knudsen², Leigh A Frame^{1

3}

Affiliations

¹ Department of Clinical Research and Leadership, George Washington School of Medicine and Health Sciences, Washington, DC, USA.
² George Washington School of Medicine and Health Sciences, Washington, DC, United States.
³ Department of Physician Assistant Studies, George Washington School of Medicine and Health Sciences, Washington, DC, USA.

Abstract

Background: A pro-inflammatory metabolic state is key to the chronic disease epidemic. Clinicians' ability to use nutrients to balance inflammation via oxidant homeostasis depends on the quality of antioxidants research. Understanding the intersection of two prominent theories for how antioxidants quell inflammation-nutritional hormesis and oxidant scavenging-will enable therapeutic antioxidant use in clinical practice. Purpose: We sought to survey the literature to answer the question: has the hormetic response of exogenous antioxidants been studied in humans and if so, what is its effect Research Design: This review investigates the less well-established theory, nutritional hormesis. To understand the state of hormetic response research, we conducted a literature review describing the relationship between exogenous antioxidants, hormesis, and chronic disease. We used an adaptive search strategy (PubMed and Scopus), retrieving 343 articles, of which 218 were unique. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were in humans. Results: Given the limited robust evidence, clinicians lack research-based guidance on the appropriate therapeutic dose of exogenous antioxidants or, more concerning, supra-physiological dosing via supplements. A critical hurdle in searching the literature is the lack of standardized nomenclature describing the hormetic effect, challenging the ability of clinicians to make informed decisions. Conclusion: Non-human research shows a biphasic, hormetic relationship with antioxidants but observational studies have yet to translate this into the complexities of human biochemistry and physiology. Therefore, we cannot accurately translate this into clinical care. To remedy this insufficiency, we suggest: (1) Improved data collection quality: controlled diet, standardized antioxidant measurements, bioavailability assessed via biomarkers; (2) Larger, harmonized datasets: research subject transparency, keyword standardization, consensus on a hormesis definition.

Keywords: antioxidants; clinical trials; dietary antioxidants; free radicals; hormesis; nutritional hormesis; oxidative stress; plant-derived antioxidants; polyphenols; reactive oxygen species.