ReviewFree radical biology & medicine2014
How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo.
Review in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 284 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
284 citing papers in PubMed, 3 syntheses or guidelines pooled it, 671 citations in OpenAlex.
- Effects of Anthocyanin-rich Berries on the Risk of Metabolic Syndrome: A Systematic Review and Meta-analysis.The review of diabetic studies : RDS · 2022Pooled it
- Flavonoid Containing Polyphenol Consumption and Recovery from Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis.Sports medicine (Auckland, N.Z.) · 2021Pooled it
- The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials.Molecular biology reports · 2021Pooled it
- Polyphenols increase circulating lipids but improve LDL particle quality and reduce LDL oxidation in postmenopausal women: metabotype- and age-dependent effects in a randomised, placebo-controlled crossover trial.European journal of nutrition · 2026Trial
- Therapeutic role of fucoidans against oxidative stress: recent developments, translational challenges, and future directions.Archives of toxicology · 2026Review
- Hydrogen peroxide sensing and signaling in physiology and disease: implications for therapy.Signal transduction and targeted therapy · 2026Review
- Review
- Combined Protective Effects of Raffinose and Isoflavones Against High-Fructose-Induced Liver Damage via Improved Bioavailability and Metabolic Regulation.Foods (Basel, Switzerland) · 2026Article
- Interpreting the Evidence on Wine Consumption and Health: A Narrative Review of the J-Shaped Association and Contemporary Alcohol Guidelines.Nutrients · 2026Review
- Interactions Between Antioxidants: How Useful Are In Vitro Studies for Understanding the Action of Antioxidants in Complex Systems?International journal of molecular sciences · 2026Review
- Isoflavone-Rich Fraction of Traditional Thai Fermented Soybean (Thua Nao) Protects Dermal Fibroblasts from Photoaging by Modulating MAPK and Akt Signaling Pathways.International journal of molecular sciences · 2026Article
- IMD-1 Protects SH-SY5Y Cells Against HNeurochemical research · 2026Article
- Genistein Protects Against Lead-Induced Cognitive Impairment Through a Glutathione-Dependent Redox-Mitochondrial Apoptosis Axis.Molecules (Basel, Switzerland) · 2026Article
- Urate as a COAntioxidants (Basel, Switzerland) · 2026Article
- Tuning the Fire: Context-Dependent Mitochondrial ROS Signaling, Mitohormesis, and Redox-Modulating Interventions.Biomolecules · 2026Review
- (Poly)phenols: Mechanisms of action and efficacy of contemporary supplements for exercise recovery and performance.Experimental physiology · 2026Review
- Low Brain Levels of Dietary Polyphenols and Their Conjugates: Reassessing Mechanisms of Alzheimer's Disease Prevention.Journal of dementia and alzheimer's disease · 2026Article
- Transcriptomic and Proteomic Analysis of the Skeletal Muscle Revealed the Effects and Mechanism of Mulberry Leaf Flavonoids on Alleviating Exercise-Induced Muscle Damage in Mongolian Horses.Animals : an open access journal from MDPI · 2026Article
- Update: Is exercise-induced oxidative stress a friend or foe?Sports medicine and health science · 2026Review
- Antioxidants and Exercise: A Redox-Informed Framework for Training Adaptation, Performance, and Recovery.Antioxidants (Basel, Switzerland) · 2026Review
224 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of nonradical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of "nucleophilic tone," by a mechanism that can be called "para-hormesis," provides a means for regulating physiological nontoxic concentrations of the nonradical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.