Oxidative stress: Functional Blood Chemistry Clues
Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
Oxidative stress affects many different cells and tissues, contributing to a wide variety of diseases. The presence of underlying oxidative stress may be revealed in commonly available blood chemistry panels in which biomarker fluctuations may provide clues to the presence of this underlying “smoldering ember.”
Clinical assessment of oxidative stress risk should begin with a comprehensive history that can reveal exposure to major risk factors including
- Alcohol consumption
- Chemotherapy drugs
- Cigarette smoke (contains more than 7000 chemicals)
- Plastics, phthalates
- Toxic heavy metals, cadmium, lead, manganese, mercury
A detailed history should help provide a general picture of antioxidant capacity by reviewing diet and supplement intake (e.g. vitamins A, C, E, selenium, phytonutrients, glutathione precursors, etc.). Comprehensive blood chemistry panels should then be reviewed and assessed within the framework of the patient’s exposure, history, and current clinical picture.
Recognizing oxidative stress early in its pathological course can help reduce associated tissue damage and dysfunction and add a valuable tool to every clinician’s toolbox.
General indicators of oxidative stress on a blood chemistry test may include:
- Decreased albumin
- Decreased cholesterol
- Decreased lymphocytes
- Decreased platelets
- Increased globulin
- Increased uric acid
- Increased bilirubin
- Increased LDL
- Increased ferritin
- Increased inflammatory markers
- Serum albumin of less than 3.2 g/dL (32 g/L) was associated with increased oxidative stress and markers of inflammation including CRP, IL-6, thiol oxidation, and protein carbonyl production in hemodialysis patients.
- Total antioxidant status and albumin levels were significantly lower, and oxidative stress was significantly higher, in a group of 55 chronic ischemic heart failure patients.
- Albumin can account for up to 70% of the antioxidant capacity in the blood and a low level is associated with inflammation, malnutrition, liver and kidney disease. Mortality risk increased by 50% for each 0.25 g/dL (2.5 g/L) reduction in serum levels.
- As a potent antioxidant compound, albumin possesses 3-7 times the antioxidant potential of vitamin C, vitamin E, and bilirubin. Therefore, lower albumin can mean reduced antioxidant potential.
- Intercepts oxidants and produces oxysterol compounds
- Oxidative damage can, in turn, deplete cholesterol and disrupt cell membrane function.
- Hypocholesterolemia (total cholesterol below 160 mg/dL) can reflect malnutrition
- style="color: #222222;" style="color: #222222; background-color: white;"Low HDL-C permits excess oxidative stress
- HDL-C exerts important antioxidant, anti-inflammatory, and anti-atherogenic properties activities that protect against cardiovascular disease.
- Lymphocytes are susceptible to oxidative damage and increased cell death in the absence of adequate antioxidant protection.
- Lymphocytes represent a double-edged sword because they produce damaging pro-inflammatory and pro-oxidant compounds needed to fight pathogens yet they in turn need adequate antioxidant protection to survive.
- Research on older (41-60 years) versus younger subjects (11-40 years) indicates that antioxidant reserves of reduced glutathione within lymphocytes declines with age, make them even more susceptible to oxidative damage.
- Oxidative stress can increase platelet activation and platelet clearance and decrease serum platelet levels.
- Oxidative stress may be a cause or trigger of platelet depletion in immune thrombocytopenia (ITP).
- An increase in reactive oxygen species and platelet activation can lead to a prothrombotic state.
- Chronic spontaneous urticaria was associated with increased platelet oxidative stress evidenced by significantly elevated plasma levels of the oxidative stress marker malondialdehyde (MDA), hs-CRP, and IL-6, as well as significantly reduced levels of platelet superoxide dismutase and glutathione peroxidase.
- Oxidative stress experienced by and perpetrated by platelets is believed to play a role in the pathogenesis of cardiovascular disease and type 2 diabetes.
- Antioxidants such as vitamin C and melatonin were found to inhibit platelet activation following exposure to oxidative stress from ischemia/reperfusion in an in vitro study using blood donated by healthy volunteers.
- Evaluation of significantly increased globulin levels may be used to assess an oxidative stress-induced inflammatory response in human studies.
- Increased serum globulin was associated with oxidative stress in hyperthyroid subjects.
- Animal studies also observe increased globulin levels with exposure to oxidative stress, inflammation, and toxins. 
- Research suggests that increasing uric acid is an important oxidative stress marker.
- In response to oxidative stress, compounds such as uric acid may increase to counter reactive oxygen species and enhance antioxidant potential of the blood.
- Uric acid may act as an antioxidant in the plasma but may become a pro-oxidant within the cell.
- Bilirubin, produced from the breakdown of heme in red blood cells, may be toxic at high levels but possesses antioxidant properties at physiological levels. 
- Accumulating research suggests that bilirubin may protect against oxidative damage and can contribute significantly to the antioxidant potential of the blood.
- As a lipophilic antioxidant, bilirubin may protect against atherosclerosis, as suggested in a meta-analysis of 11 studies.
- When LDL cholesterol is modified by oxidative stress, it becomes atherogenic. 
- Increased LDL-cholesterol was associated with increased levels of the oxidative stress marker malondialdehyde which, in turn, correlated with an increased atherogenic index and risk of atherosclerosis.
- An LDL cholesterol above 132 mg/dL (3.42 mmol/L) was associated with oxidative stress in young adults.
- Interestingly, one study noted that consumption of red wine enriched with resveratrol with a high-fat fast food meal reduced the oxidative damage to LDL-cholesterol. Therefore, I think we can conclude that we do have a creative and enjoyable way to counter oxidative stress.
- Oxidative stress is believed to be proinflammatory and can be associated with markers of inflammation.
- The term oxi-inflamm-aging reflects the close association between oxidative stress, inflammation, and aging. Oxidative stress sets off a perpetual inflammatory response from the immune system, compounding its negative effects on the body. 
- A cross-sectional study of 126 CHD-free adults revealed that the oxidative stress marker free oxygen radical test (FORT) was significantly associated with higher levels of hs-CRP.
- Frail and pre-frail elderly were found to have elevated C-reactive protein and elevated F2-IsoPs, reflecting increased inflammation and oxidative stress. Elevations in IL-6 are also observed in disorders associated with oxidative stress including Alzheimer’s, COPD, and biliary cirrhosis. 
- Ischemic stroke is associated with increased oxidative stress and inflammatory markers (e.g. hs-CRP), and decreased erythrocyte glutathione peroxidase and superoxide dismutase activity.
- Synthesis of ferritin is increased during oxidative stress and correlates with a variety of oxidative stress markers including malondialdehyde and isoprostanes.
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