Oxidative Stress
1. Root Cause Overview
Oxidative stress occurs when the production of reactive oxygen species (ROS) overwhelms the body's antioxidant defence systems, leading to oxidative damage of lipids, proteins, and DNA. It is a central mechanism in ageing, cardiovascular disease, neurodegeneration, cancer, and metabolic syndrome. Key drivers include mitochondrial dysfunction, chronic inflammation, environmental toxin exposure, poor diet, smoking, and nutrient deficiencies in antioxidant cofactors (glutathione, CoQ10, vitamins C/E, selenium).
2. Common Signs & Symptoms
- Premature ageing: wrinkles, grey hair, reduced skin elasticity
- Chronic fatigue and post-exertional malaise
- Cognitive decline, brain fog, poor memory
- Elevated GGT, ALT/AST on standard labs
- Elevated urinary 8-OHdG (oxidative DNA damage marker)
- Recurrent infections (impaired immune defence)
- Cardiovascular risk markers: oxidised LDL, elevated hs-CRP
- Muscle weakness and poor exercise recovery
- Inflammatory skin conditions
- Sensitivity to environmental chemicals or fragrances
3. Labs to Consider
hs-CRP, GGT, ALT/AST, fasting glucose/insulin, lipid peroxidation/oxidised LDL when available, urinary 8-OHdG when available.
Choose the lab option based on what you want to assess within this root cause.
Oxidative Stress 2.0 Urine
Genova Diagnostics
4. Clinical Priorities
Assess for potential drivers of oxidative stress, which may include toxin exposure, poor diet quality, smoking, chronic infection, hyperglycaemia, high training load, medication effects, or inadequate antioxidant capacity. Correct foundational nutrient insufficiencies first (for example glutathione precursors, vitamins C/E, selenium, and zinc), and use functional lab testing to quantify oxidative burden and monitor response over time.
Where to Start: Top 2 Supplements
The most direct and cost-effective way to raise intracellular glutathione — the body's master antioxidant. Addresses the root of oxidative stress rather than just scavenging ROS downstream. Well-evidenced, safe, and broadly applicable.
Unique dual water- and fat-soluble antioxidant that regenerates glutathione, vitamin C, and vitamin E simultaneously. Provides mitochondrial antioxidant protection where oxidative stress originates. Synergistic with NAC.
5. Diet Strategy
Maximise dietary antioxidant density: deeply coloured vegetables and fruits (berries, leafy greens, cruciferous vegetables), green tea, dark chocolate (≥70% cacao), turmeric, and extra-virgin olive oil. Ensure adequate sulphur-containing foods (garlic, onions, cruciferous vegetables) to support glutathione synthesis. Minimise fried foods, processed meats, refined carbohydrates, and alcohol — all of which generate ROS. Prioritise protein adequacy to supply cysteine and glycine for glutathione production.
6. Lifestyle Strategy
Regular moderate exercise upregulates endogenous antioxidant enzymes (SOD, catalase, GPx); avoid excessive high-intensity training without recovery. Eliminate tobacco. Reduce environmental toxin exposure (plastics, pesticides, heavy metals). Optimise sleep — oxidative stress markers rise significantly with sleep deprivation. Manage chronic stress (cortisol drives ROS production). Sauna use (3–4×/week) has been shown to upregulate heat-shock proteins and antioxidant pathways.
7. Supplement Strategy
Full supplement list below. See Section 4 (Clinical Priorities) for the recommended Top 2 starting supplements. Add additional supplements based on lab results and clinical response at 4–6 week reassessment.
| Supplement | Dosage | Indication | Evidence | Key Results | Example |
|---|---|---|---|---|---|
| Alpha-Lipoic Acid (ALA) [1] Mild GI upset; hypoglycaemia risk in diabetics — monitor blood glucose | 300–600 mg/day | Glutathione regeneration; mitochondrial antioxidant defence | Animal and human studies | Increased tissue glutathione levels; improved antioxidant enzyme activity (SOD, catalase, GPx) | Klaire Labs Alpha Lipoic Acid |
| N-Acetyl Cysteine (NAC) [2] Nausea, vomiting at high doses; caution in patients with cystinuria | 600–1,800 mg/day in divided doses | Glutathione precursor; direct ROS scavenging | In vitro and clinical studies | Increased intracellular glutathione in lymphocytes; enhanced antioxidant capacity | Thorne NAC |
| Vitamin C (Ascorbic Acid) [3] Loose stools at high doses (>2 g/day); oxalate kidney stones with chronic megadosing | 500–2,000 mg/day in divided doses | Aqueous-phase antioxidant; glutathione regeneration; collagen synthesis | Randomised controlled trial | Significantly elevated red blood cell glutathione levels in healthy adults | Pure Encapsulations Vitamin C |
| Glutathione (Liposomal or S-Acetyl) [4] Generally well tolerated; theoretical concern with high-dose use in cancer patients | 250–500 mg/day | Master endogenous antioxidant; detoxification; immune modulation | Clinical review and RCT evidence | Increased plasma glutathione levels; improved oxidative stress markers; immune enhancement | Quicksilver Scientific Liposomal Glutathione |
| CoQ10 (Ubiquinol form) [5] Mild GI upset; may reduce warfarin efficacy — monitor INR | 100–300 mg/day with meals | Mitochondrial electron transport; lipid-phase antioxidant; cardiac protection | Randomised, double-blind, placebo-controlled trial | Improved mitochondrial function and antioxidant status; reduced oxidative damage markers in cardiac patients | Jarrow Formulas QH-absorb Ubiquinol |
8. Safety Notes
High-dose antioxidant supplementation may paradoxically blunt adaptive exercise responses — avoid megadosing around training sessions. NAC is contraindicated in patients with active peptic ulcer disease. Do not use high-dose vitamin C in patients with G6PD deficiency or haemochromatosis. CoQ10 may interact with warfarin. Always identify and address the root oxidative driver; supplements alone are insufficient.
9. Citations & References
- [1]Alpha-Lipoic Acid (ALA)Khanna S, Atalay M, Laaksonen DE, Gul M, Roy S, Sen CK. Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise. J Appl Physiol. 1999;86(4):1191–1196.View source
- [2]N-Acetyl Cysteine (NAC)Yim CY, Hibbs JB Jr, McGregor JR, Galinsky RE, Samlowski WE. Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2. J Immunol. 1994;152(12):5796–5805.View source
- [3]Vitamin C (Ascorbic Acid)Johnston CS, Meyer CG, Srilakshmi JC. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr. 1993;58(1):103–105.View source
- [4]Glutathione (Liposomal or S-Acetyl)Pizzorno J. Glutathione! Integr Med (Encinitas). 2014;13(1):8–12.View source
- [5]CoQ10 (Ubiquinol form)Rosenfeldt F, Marasco S, Lyon W, et al. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue. J Thorac Cardiovasc Surg. 2005;129(1):25–32.View source
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