Research evidence has been accumulating that damage to cell components by oxygen free radicals (also known as "reactive oxygen species" or ROS) is an important mechanism of aging, with oxidative damage playing a role in various diseases, such as arthritis, diabetes, and arteriosclerosis.
Oxidative stress is the term used to describe the rate at which oxidative damage is occurring in living organisms and the organisms' ability to protect against such damage. KSL attempts to assess oxidative stress status by measuring various endogenous and exogenous “protection factors” (antioxidants) in serum as listed in the Oxidative Stress Protection Panel below; along with the Comprehensive Oxidative Stress Damage Panel in urine. For the damage panel, LC/MS/MS methodology is used to measure DNA/RNA, lipid, and protein oxidation products. LC/MS/MS has been recognized as the gold standard in this field. Direct damage factors include oxidized lipid molecules (8 isoprostanes including: 8-iso-prostaglandin F2a (iPF2α-III); 2,3-dinor-iPF2α-III; iPF2α-VI; and 8,12-iso-iPF2α-VI); an important DNA damage adduct (8-hydroxy-2'-deoxyguanosine and uridine) and an RNA damage product (8-oxo-guanosine); several protein oxidation products (di-tyrosine, nitro-tyrosine, and Cl-tyrosine.) in serum, plasma and urine; and leukotriene E4. Taken together, these assays give a reasonably complete assessment of an individual’s oxidative stress status.
Oxidative Stress Protection - Serum (Code 10190)
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Bilirubin, indirect
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Iron Binding Capacity, total (TIBC)
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Bilirubin, total
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Iron Binding Capacity, unsaturated (UIBC)
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Coenzyme Q10
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Copper
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Ferritin
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Uric Acid
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Oxidative Stress Damage Panel - Urine (Code 10195)
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DNA Damage
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Protein Oxidation
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Isoprostanes
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8-hydroxy Guanosine
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Dityrosine
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8-iso-Prostaglandin F2α (iPF2α–III)
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8-Hydroxy-2-deoxy Guanosine
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Nitrotyrosine
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iPF2α - VI
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Leukotriene Panel
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2,3-dinor-8-iso Prostaglandin F2α
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Leukotriene E4 (LTE4)
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8,12-iso-iPF2α VI
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Individual Damage Panels - Urine
DNA Damage (Code 9565)
Isoprostanes (Code 9920)
Dityrosine & Nitrotyrosine (Code 9648)
Leukotrienes (Code 9980)
Factors Related to Oxidative Protection
Albumin – a protein that performs many important functions including control in scavenging free radicals.
Ascorbate – Vitamin C; has been shown to promote arterial relaxation and diminish the oxidation of LDL, the harmful form of cholesterol that causes disease.
Bilirubin – is known to act as an antioxidant that provides protection against oxidative stress.
Coenzyme Q10 – in addition to its cardiovascular effects, this vitamin provides valuable antioxidant protection, particularly in the mitochondria, or energy factories, of every living cell.
Glutathione – Glutathione is among the body’s most important free radical scavengers.
Homocysteine – an important free radical scavenger.
Iron Binding – these measurements include UIBC and total iron binding capacity (TIBC). Iron binding proteins function in the body to store iron and keep it from exerting its harmful, pro-oxidative effects.
Total Carotenoids – this KSL panel measures eight different carotenoids, which together provide valuable information regarding the oxidative protection offered by this important class of antioxidants. Included are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, retinol, retinyl palmitate and zeaxanthin.
Total Tocopherols – the most important tocopherols in human antioxidant protection include alpha, which plays a very important role in preventing LDL oxidation, and gamma, most commonly available in food. Most over-the-counter dietary supplements consist solely of alpha-tocopherol. This KSL assay allows physicians to assess levels of both of these important tocopherols.
Uric acid – elevated uric acid levels appear to correlate well with improved oxidative stress protection.
Factors Related to Oxidative Damage
Ceruloplasmin – a protein much like ferritin; binds iron and copper. Although these metals are required in small amounts, high levels can cause oxidative harm to the body.
Copper – a trace metal that the body requires in small amounts for important metabolic functions. Increased amounts of copper are potent pro-oxidants and facilitate oxidative damage.
Ferritin – a protein that binds iron; although it has protective qualities it is a measure of overall iron load. Excess Iron causes oxidative stress.
Glucose – elevated glucose levels are diagnostic of diabetes mellitus, one of the most prevalent pro-oxidant conditions.
Hemoglobin A1c – HbA1c is formed as hemoglobin is gradually glycosylated throughout the 120-day lifespan of red blood cells. Therefore, the amount of HbA1c in the blood provides a good measure of the average blood glucose level over the past two months. It is, perhaps, the best indicator of overall blood glucose control. Since HbA1c is an indication of glycoxidation of bodily proteins, blood levels should be as low as possible.
Iron – a powerful pro-oxidant; has a strong role in promoting the oxidation of lipids. Oxidized lipids lead to arterial inflammation and blockage.
Isoprostanes – indicators of oxidative damage that have been shown to be associated with risk of cardiovascular disease. They are formed by the free radical catalyzed non-enzymatic peroxidation of arachidonic acid in cellular membranes and lipoproteins. (iPF2-alpha-III, iPF2-alpha-VI, 2,3-dinor-PGF2-alpha)
DNA Damage – oxidative damage to DNA may be an important contributor to aging and degenerative disease. 8-Hydroxy-2-deoxyguanosine (8OhdG) reflects the patient’s potential for cell mutation and, therefore, cancer risk. 5-Hydroxymethyl-2-deoxyuridine (5OhmU), in conjunction with 8OhdG, is a useful marker of oxidative damage status.
Protein Oxidation
Research has shown that dityrosine and nitrotyrosine as potential biomarkers in acute respiratory distress syndrome, Alzheimer’s disease, ALS, asthma, atherosclerosis, cardiovascular disease, COPD, chronic renal failure, coronary artery disease, cystic fibrosis, diabetes, lung cancer, lung injury, MS and rheumatoid arthritis.
Leukotrienes (LTE4)
LTE4 is most often used as an indicator of asthma and other diseases. Cysteinyl-leukotrienes have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, urticaria and end-stage renal disease.
KS Articles
Heward C, & Su Y. Oxidative Stress Assessment at Kronos Science Laboratory (read article)
Critical Reviews of Oxidative Stress and Aging: Advances in Basic Science, Diagnostics and Intervention. Chapter 81: Database Analysis of Human Intervention Studies (The Kronos Longitudinal Study of Aging and Anti-aging Interventions). World Scientific Publishing Co. Pte. Ltd. Singapore 596224. © 2003. (read article)
S. Mitchell Harman, Christopher Heward. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 6th Edition. Chapter 15: Anti-Aging Interventions. Elsevier Science Limited, London. © 2003. (read article)
Liang Y, Wei P, Duke RW, Reaven PD, Harman SM, Cutler RG, Heward CB. Quantification of 8-Iso-Prostaglandiin-F(2alpha) and 2,3-Dinor-8-Iso-Prostaglandin-F(2alpha) in Human Urine Using Liquid Chromatography-Tandem Mass Spectrometry. Free Radic Bil Med. 2003 Feb 15;34(4):409-18. (read article)
Harman SM, Liang L, Heward CB, Reaven P, Ping W, Cutler RL, Duke R. Comparisons of Urinary Excretion of Three DNA Oxidation Adducts and Isoprostane F2a Measured by Liquid Chromatography-Mass Spectrometry in Smokers, Ex-smokers, and Non-smokers. Free Rad Biol Med 35:1301-9, 2003. (read article)
Nieman DC, Henson DA, McAnulty SR, McAnulty LS, Morrow JD, Ahmed A, Heward CB. Vitamin E and Immunity after the Kona Triathlon World Championship. Medicine and Science in Sports and Exercise. 2004 Aug;36(8):1328-35. (read article)