Oxidative Stress, Pain and Disease

“Oxidative stress” is an imbalance in the body of excessive “oxidants” (oxidizing or chemically active, agents, including free radicals obtained from the diet or produced by the body) and insufficient “antioxidants” (chemically active agents that are also obtained from the diet or produced by the body) and neutralize oxidants.

Chronic systemic inflammation and oxidative stress are two pathophysiological conditions that coexist because they can mutually induce each other. Both chronic inflammation and oxidative stress disrupt normal cellular physiology and they both contribute to the development and progression of chronic diseases including metabolic syndrome and diabetes, cardiovascular disease, cancers, neurodegenerative disorders, chronic kidney disease, liver disease, and rheumatoid arthritis.


For a more thorough introduction to oxidative stress, it is recommended that you first read the section:

Individual antioxidants:


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Oxidative Stress

“Oxidative stress” is an imbalance in the body of excessive “oxidants” (oxidizing or chemically active, agents, including free radicals obtained from the diet or produced by the body) and insufficient “antioxidants” (chemically active agents that are also obtained from the diet or produced by the body) and neutralize oxidants. This overabundance of oxidants causes damage to biomolecules, (lipids, proteins, DNA), cells and tissue, eventually contributing to aging and chronic diseases including chronic inflammation, arthritis and pain, atherosclerosis, cancer, diabetes, heart diseases and stroke.

Free radicals

Free radicals are molecules with unpaired electron in their outer orbit. This unpaired electron makes the free radical highly reactive with molecules in cells and tissues. While free radicals  have beneficial roles in some biochemical activities, excessive levels of free radicals leads to tissue damage.  People are constantly exposed to free radicals in their environment created by electromagnetic radiation, pollutants and cigarette smoke and natural sources such as radon and cosmic radiation. In addition, the human body produces free radicals and other reactive species as byproducts of numerous physiological, metabolic and biochemical processes. The most common cellular free radicals are hydroxyl (OH·), superoxide (O –·) and nitric monoxide (NO·). Other molecules like hydrogen peroxide (H2O2) and peroxynitrite (ONOO–) generate free radicals through various biochemical reactions.



Antioxidants are produced in the mitochondria within cells throughout the body and serve to detoxify free radicals and protect tissues from such damage. Another important source of antioxidants is the diet, and diets rich in antioxidants are protective against the disease processes noted above. Fruits and vegetables are especially rich in antioxidants including . vitamin E, vitamin C, vitamin A, curcumin, resveratrol, glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, and polyphenols found in tea. .Diets rich in fruits and vegetables result in high blood antioxidant capacity and reduced oxidative stress. Antioxidant activity is further supported by antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase that exert synergistic actions in removing free radicals.

Individual Antioxidants:

Beta carotene is a yellow-red-orange pigment found in plants and fruits, especially carrots and colorful vegetables. The name beta carotene comes from the Greek “beta” and Latin “carota” (carrot). 
  1. Beta carotene is converted into vitamin A, an essential vitamin
  2. Vitamin A is toxic at high levels
  3. Beta carotene is a carotenoid and an antioxidant
  4. Foods rich in vitamin A include onions, carrots, peas, spinach and squash
  5. Some evidence suggests that beta carotene might slow cognitive decline
  6. Beta carotene supplements interact with certain drugs, including statins
  7. Beta carotene might help older people retain their lung strength as they age.


Oxidative Stress and Chronic Pain


Oxidative Stress and Diabetic Neuropathy


Oxidative Stress – Fibromyalgia


Oxidative Stress and Aging


Biomarkers of Oxidative Stress

A biomarker is any measurable substance, structure, or process in the body or its products that influences or predicts the incidence ot outcome of a disease.


Reference Publications

Oxidative Stress – Overviews

  1. oxidative-stress-implications-in-the-affective-disorders-main-biomarkers-animal-models-relevance-genetic-perspectives-and-antioxidant-approaches-2016
  2. oxidative-stress-in-health-and-disease-the-therapeutic-potential-of-nrf2-activation-2011
  3. adaptive-cellular-stress-pathways-as-therapeutic-targets-of-dietary-phytochemicals-focus-on-the-nervous-system-2014
  4. oxidative-stress-a-cause-and-therapeutic-target-of-diabetic-complications-2010
  5. a-randomized-trial-of-glutamine-and-antioxidants-in-critically-ill-patients-2013
  6. Inflammation, Oxidative Stress, and Antioxidants Contribute to Selected Sleep Quality and Cardiometabolic Health Relationships – 2015
  7. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS) – 2014
  8. Oxidative Stress – Harms and Benefits for Human Health – 2017


Oxidative Stress – Aging

  1. Update on the oxidative stress theory of aging – Does oxidative stress play a role in aging or healthy aging? – 2010


Oxidative Stress – Anxiety and Depression

  1. Markers of Oxidative Stress and Neuroprogression in Depression Disorder – 2015
  2. Neuroinflammation and Depression – Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation – 2015
  3. Novel Therapeutic Targets in Depression and Anxiety – Antioxidants as a Candidate Treatment
  4. Oxidative:nitrosative stress and antidepressants: targets for novel antidepressants. – PubMed – NCBI


Oxidative Stress – Cardiovascular

  1. Impaired Oxidative Status Is Strongly Associated with Cardiovascular Risk Factors – 2017
  2. Antioxidants and Cardiovascular Risk Factors – 2018


Oxidative Stress – Diabetic Neuropathy

  1. Oxidative Stress in the Pathogenesis of Diabetic Neuropathy – 2004
  2. Neuroinflammation and Oxidative Stress in Diabetic Neuropathy – Futuristic Strategies Based on These Targets – 2014


Oxidative Stress – Fibromyalgia

  1. Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia – Coenzyme Q10 Effect on Clinical Improvement 2012
  2. Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? – PubMed – NCBI
  3. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide. – PubMed – NCBI
  4. Oxidative Stress in Fibromyalgia – Pathophysiology and Clinical Implications – 2011
  5. Oxidative Stress in Fibromyalgia and its Relationship to Symptoms – 2009
  6. Clinical Symptoms in Fibromyalgia Are Better Associated to Lipid Peroxidation Levels in Blood Mononuclear Cells Rather than in Plasma
  7. Evidence of central inflammation in fibromyalgia — Increased cerebrospinal fluid interleukin-8 levels 2012
  8. Oxidative Stress in Fibromyalgia – Pathophysiology and Clinical Implications – 2011
  9. Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients with fibromyalgia: a controlled clinical … – PubMed – NCBI
  10. Total antioxidant capacity and the severity of the pain in patients with fibromyalgia. – PubMed – NCBI
  11. Stress, the stress response system, and fibromyalgia
  12. Serum prolidase enzyme activity and oxidative status in patients with fibromyalgia. – PubMed – NCBI
  13. Serum ischemia-modified albumin and malondialdehyde levels and superoxide dismutase activity in patients with fibromyalgia. – 2014 – PubMed – NCBI
  14. Pathophysiology and antioxidant status of patients with fibromyalgia. 2011 – PubMed – NCBI
  15. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. 2015 – PubMed – NCBI
  16. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. – PubMed – NCBI
  17. Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns. 2006 – PubMed – NCBI


Oxidative Stress – Fibromyalgia & Mitochondria

  1. Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study. 2009 – PubMed – NCBI
  2. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients – implications in the pathogenesis of the disease
  3. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? – PubMed – NCBI
  4. Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia? – 2012
  5. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia – 2013 – PubMed – NCBI
  6. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS) – 2014
  7. Oxidative stress and mitochondrial dysfunction in fibromyalgia. – PubMed – NCBIOxidative-Stress-in-Fibromyalgia-and-its-Relationship-to-Symptoms-2009
  8. The-role-of-mitochondrial-dysfunctions-due-to-oxidative-and-nitrosative-stress-in-the-chronic-pain-or-chronic-fatigue-syndromes-and-fibromyalgia-patients-20131


Oxidative Stress – Mitochondria

  1. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS) – 2014
  2. The Mitochondrial Basis of Aging and Age-Related Disorders – 2017
  3. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases – 2016 no highlights
  4. Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction
  5. Mitochondrial biogenesis: pharmacological approaches. – PubMed – NCBI
  6. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. – PubMed – NCBI
  7. Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies – Toward Mitochondria-Targeted Clinical Strategies
  8. Daily Nutritional Dose Supplementation with Antioxidant Nutrients and Phytochemicals Improves DNA and LDL Stability


Oxidative Stress – Neurodegenerative Diseases

  1. Oxidative Stress and Neurodegenerative Diseases – A Review of Upstream and Downstream Antioxidant Therapeutic Options – 2009
  2. Neuroprotective Effect of Antioxidants in the Brain – 2020


Oxidative Stress – Opioids

  1. Oxidative Stress and Opioids ́ Toxicity – An Update – 2013
  2. Morphine as a Potential Oxidative Stress-Causing Agent – 2013


Oxidative Stress – Pain

  1. Roles of Reactive Oxygen and Nitrogen Species in Pain – 2011
  2. Clinical Relevance of Biomarkers of Oxidative Stress – 2015
  3. The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease – Potential Role of Autonomic Regulation and Epigenetic Mechanisms – 2020
  4. Neuropathic Pain – Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels – 2018
  5. Neuroprotective Effect of Antioxidants in the Brain – 2020
  6. Dietary Patterns and Interventions to Alleviate Chronic Pain – 2020


Oxidative Stress – Peripheral Neuropathy

  1. Oxidative stress – A cause and therapeutic target of diabetic complications – 2010

Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


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