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Hedi Raizer

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What is oxidative stress?

Oxidative stress is a biochemical state defined by an imbalance between the production of reactive oxygen species and the capacity of antioxidant defence systems. This page outlines the formal definition, the molecular p

peptides-pro Editorial

What is oxidative stress?

Oxidative stress is formally defined as a disruption in the balance between the generation of reactive oxygen species (ROS) and the ability of biological systems to detoxify these reactive intermediates or repair the resulting damage. It is not a single molecule or a discrete pathway but a biochemical state that arises when pro-oxidant production exceeds antioxidant capacity. Synonyms include oxidant stress and redox imbalance. The term encompasses damage to lipids, proteins, and nucleic acids, and is implicated in a broad range of pathological processes.

The molecular species central to oxidative stress include superoxide anion (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and peroxynitrite (ONOO−). Endogenous antioxidant defences include enzymatic components such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and glutathione reductase, as well as non-enzymatic small molecules including glutathione (GSH), vitamins C and E, and coenzyme Q10. The work described in the evidence below centres on the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway, the PI3K/Akt signalling axis, and mitochondrial electron transport chain complexes, which are the principal regulators of cellular redox homeostasis.

Research Studies

Vitamin E and oxidative stress markers in levothyroxine-treated hypothyroidism

A clinical trial is investigating whether vitamin E supplementation, as an adjunct to levothyroxine therapy, reduces oxidative stress and improves antioxidant defence mechanisms in patients with hypothyroidism. The study aims to determine whether this combination favourably influences thyroid hormone status and to establish an evidence-based framework for integrating targeted antioxidant therapies into standard hypothyroid management [1]. The population is adults with hypothyroidism already receiving levothyroxine. The trial is registered but results are not yet available.

Zinc and insulin resistance in women with polyendocrine metabolic ovarian syndrome

Polyendocrine metabolic ovarian syndrome (PMOS) is the most common endocrinopathy in women of reproductive age and is mechanistically anchored in insulin resistance (IR), which drives hyperandrogenism, anovulation, dyslipidaemia, and long-term type 2 diabetes risk. South Asian women, including Bangladeshi women, develop IR at lower BMI thresholds than other populations and simultaneously carry a high burden of zinc deficiency (57% of non-pregnant, non-lactating women). Zinc is structurally required for pancreatic β-cell insulin synthesis, modulates insulin-receptor signalling and PI3K/Akt-mediated glucose uptake, and acts as a cofactor for Cu/Zn-superoxide dismutase. A clinical trial is evaluating the effect of zinc supplementation on insulin resistance and clinical features in this population [2]. The study is ongoing; no results are reported.

Nicotinamide riboside and walking performance in peripheral artery disease

The NICE-PAD II trial is testing whether nicotinamide riboside (NR) improves or slows decline in six-minute walk distance at six-month follow-up compared to placebo in people with peripheral artery disease (PAD) aged 50 and older. The study will randomize 250 participants to NR or placebo for six months. Secondary outcomes include Walking Impairment Questionnaire (WIQ) distance score, PROMIS Mobility score, and calf muscle perfusion measured by magnetic resonance arterial spin labelling [3]. The rationale links NR, a NAD+ precursor, to mitochondrial function and oxidative stress in ischaemic muscle. Results are pending.

N-acetylcysteine and repetitive behaviours in Cornelia de Lange syndrome

A randomized cross-over pilot trial is testing the efficacy of N-acetylcysteine (NAC) for repetitive behaviours (RB) and self-injurious behaviour (SIB) in patients with Cornelia de Lange syndrome (CdLS). NAC is described as a known anti-oxidative stress and neuroprotective agent that has been shown to decrease the occurrence of SIB such as skin picking, and has shown partial response in trials for compulsive behaviours in obsessive-compulsive disorder and related disorders in autism. CdLS is a genetic disorder with autistic features, including RBs and SIB [4]. The trial is ongoing; no efficacy data are available.

GPX4 expression after Kono-S versus conventional anastomosis in Crohn's disease

Crohn's disease is a long-term condition causing bowel inflammation, and many patients require surgery to remove damaged intestine. Disease recurrence often occurs at the anastomosis. A newer surgical approach, Kono-S anastomosis, is designed to reduce recurrence risk, but the mechanism is not fully understood. A clinical trial is exploring how the bowel heals after surgery by examining oxidative stress markers, specifically GPX4 expression, comparing Kono-S with conventional anastomosis [5]. The study is ongoing; no results are reported.

Light therapy and cellular energy in healthy adults and type 1 diabetes

A clinical trial is evaluating the effects of low-level light therapy on cellular energy and oxidative stress in healthy adults and patients with type 1 diabetes. The main questions are whether light therapy changes adenosine triphosphate (ATP) levels and cytochrome c oxidase activity in blood cells, and how it affects oxidative stress markers, specifically glutathione and malondialdehyde concentrations. Researchers will compare blood samples before and after light therapy to assess mitochondrial function, and will compare responses between healthy volunteers and diabetic patients [6]. The study is ongoing; no results are available.

Vitamin D and oxidative stress in diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is among the most common chronic complications of diabetes and a major cause of morbidity, impaired quality of life, sleep disturbance, chronic pain, and functional disability. The pathogenesis of DPN is multifactorial and involves oxidative stress, chronic inflammation, endothelial dysfunction, mitochondrial injury, and microvascular ischaemia, leading to progressive nerve damage. Despite symptomatic therapies such as gabapentin, pregabalin, and duloxetine, many patients continue to experience persistent neuropathic symptoms. A clinical trial is investigating vitamin D supplementation in this context [7]. The study is ongoing; no results are reported.

Tauroursodeoxycholate and liver-targeted therapy for diabetic macular edema

Diabetic macular edema occurs in the later stages of diabetic retinopathy. Current conventional therapies target local vascular dysfunction and provide transient visual improvement but are often uncomfortable and financially burdensome. The condition is a complication of diabetes that cannot be managed without addressing systemic inflammation. Liver metabolism and function are implicated in diabetes, and evidence suggests that hepatic metabolic dysfunctions are linked to neuroinflammation and vascular dysfunctions observed in diabetic retinopathy. A clinical trial is investigating nutraceutical supplements including tauroursodeoxycholate (a bile acid) and modified traditional Chinese medicine as liver-targeted therapies [8]. The study is ongoing; no results are available.

ALKBH5-dependent m6A demethylation in cardiac aging

Preclinical research has examined the role of N6-methyladenosine (m6A) mRNA methylation in cardiac aging. The study reports that ALKBH5 (alpha-ketoglutarate-dependent dioxygenase) promotes cardiac aging through reduction of SLC38A3 and alteration of glutamine metabolism [9]. This work was conducted in animal models and cell systems; the findings have not been validated in human clinical trials.

Coffee-derived bioactive compounds and skeletal muscle health

A scoping review examined the relationship between coffee consumption and skeletal muscle health, focusing on mechanistic pathways, preclinical evidence, and human outcomes. Coffee is a complex source of bioactive compounds including caffeine, (poly)phenols, trigonelline, and diterpenes. Although habitual coffee consumption has been associated with metabolic benefits, its relationship with skeletal muscle health remains incompletely understood [10]. The review synthesizes existing evidence but does not report new primary data.

Ergothioneine and mitochondrial redox regulation in cardiovascular disease

A review discusses ergothioneine as a diet-derived xenobiotic, its OCTN1-mediated disposition, and its role in mitochondrial redox regulation, with emerging implications for cardiovascular disease. Mitochondrial dysfunction is a convergent upstream driver of cardiovascular disease, linking energetic failure, oxidative stress, inflammation, and maladaptive remodelling. The inconsistent results of conventional antioxidant trials are likely due to multiple factors, including compound selection and dose [11]. This is a review article; no new experimental data are presented.

Samm50 downregulation and ferroptosis in ketamine-induced neurotoxicity

Preclinical research has investigated the mechanisms underlying ketamine-induced neurotoxicity and cognitive impairment. The study reports that Samm50 downregulation-driven mitochondrial dysfunction triggers ferroptosis and contributes to hippocampal damage [12]. This work was conducted in animal models; the findings have not been confirmed in human studies.

If you are reading this for personal health reasons

The compounds and interventions described on this page are sold for laboratory research use only. We do not provide dosing information, medical guidance, or treatment recommendations. If you are considering any compound for yourself, you must speak with a licensed clinician.

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