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Do You Know Your Oxidative Stress Risk Markers? Underlying Cause of Many Diseases + How to Reduce It

By Tucson Functional Medicine on September 30, 2024 0 Comments

What is Oxidative Stress?

Oxidative stress occurs when an imbalance between free radicals and antioxidants in your body can cause cell damage.

Your body produces free radicals during metabolic processes and antioxidants that neutralize them. However, when too many free radicals are produced, they can impair cell regeneration and repair, leading to accelerated aging and the development of certain diseases over time.

Oxidative stress is like the accumulation of rust on a car. This rust can make the walls of our blood vessels rough and sticky, leading to problems like atherosclerosis, where our arteries get clogged and hard. Through the years of wear and tear, rust slowly begins to show. First, a little here, then a little there. Eventually, rust begins to overtake the entire thing. 

Your cells act similarly. Researchers found early on that you begin to accumulate free radicals and other oxidants as you age. 

 

What are Free Radicals?

Essentially, free radicals are unstable molecules.

They are missing an electron from their outer shell. That makes them unstable, so they go and steal an electron from the molecules in your skin cells, your blood cells, or wherever they can. That causes damage to surrounding cells.

Those electrons usually come in even numbers. But free radicals have an odd number of electrons. Free radicals are desperately looking for electrons to get balanced and even.

This is where the benefits of “vetted” antioxidants come in.

Like free radicals, antioxidants also have an uneven number of electrons. Unlike free radicals, though, antioxidants don’t typically steal from otherwise stable molecules to keep themselves in check.

But antioxidants do happily take an unpaired electron from a free radical. That makes both molecules even.

In the absence of antioxidants, free radicals will go on war rage damaging the body leading to a host of disease.

When free radicals overwhelm antioxidant defense systems, cellular and molecular abnormalities occur. This ultimately leads to many diseases.

The Body’s Amazing Nrf2

The major activator of your antioxidant and detoxification defenses

Your body has the ability to fight oxidants and free radicals. It’s encoded directly into your DNA and more specifically your genes. These antioxidant and detoxification enzymes, however, need to be turned on in order to do their job. One of the proteins responsible for doing it is called Nrf2. 

Nrf2 has been called the “master regulator” of the antioxidant response. Nrf2 is a transcription factor that regulates the expression of antioxidants and anti-inflammatory genes. The Nrf2-ARE signaling pathway is the cell’s defense against oxidative stress, and it is triggered when free radicals increase and/or when there is reduced antioxidant capacity.

Sulforaphane and curcumin can activate the Nrf2. Broccoli extract is a source of sulforaphane. Broccoli seed extract or glucoraphanin (also known as sulforaphane glucosinolate or SGS) can increase glutathione levels.

Green tea extract, trans-pterostilbene (the primary antioxidant in blueberries), and black pepper extract work together with broccoli extract and turmeric to activate the Nrf2 genetic pathway. Typical daily doses are: 60 to 120 mg of broccoli extract, 400 to 800 mg of turmeric extract, 400 to 800 mg of green tea extract, 100 to 200 mg of transpterostilbene, and 4 to 8 mg of black pepper extract.

The take home message, in this instance, is quite simpleNrf2 is a potent modulator of antioxidant response and can rapidly target oxidative stressors. While Nrf2 responds to oxidative stress directly, certain key nutrients can improve this effect, the exact source of these nutrients varies widely but dark green and leafy vegetables (spinach, kale and broccoli, especially the seed extract), or reddy vegetables and spices (saffron, tumeric or paprika) are a particularly rich source. Importantly, these foods are also typically rich in direct antioxidants and display numerous other health benefits, so they are a great way to improve overall health.

The Causes of a Dangerous Increase of Free Radicals and Oxidative Stress

Increased free radicals can be dangerous, but antioxidants can protect against the cell damage that free radicals cause.

However, the antioxidant defense system can be weak because of disease, aging, low levels of antioxidants in food, and poor intake. Factors that increase the production of free radicals in the body can be internal or external.

Internal causes of the high free radical level in the body that can lead to cell damage and oxidative stress include:

  • Inflammation.
  • Mitochondrial activity.
  • Tissue trauma due to inflammation and injury.
  • Ischemia and reperfusion damage.
  • Stress.
  • Infectious and chronic diseases.
  • High internal toxin level.
  • Age.
  • Obesity.  

 

External causes of the high free radical level in the body that can lead to cell damage and oxidative stress include:

  • Consumption of certain foods, especially fried, refined, processed foods, trans fats, artificial sweeteners, food containing carcinogens, and certain dyes and additives.
  • Excessive exercise.
  • Smoking.
  • UV exposure and cigarette smoke.
  • Environmental toxins and pollution.
  • Radiation.
  • Exposure to chemicals, such as pesticides and drugs, including chemotherapy, and the consumption of skincare products that contain high amounts of parabens and other chemicals.
  • Industrial solvents.
  • Alcohol.
  • Some medications
  • Low levels of antioxidants in food.  

 

In conclusion, all these internal and external causes of the increased free radical level can result in cell damage and oxidative stress. 

Oxidative Stress Symptoms

Oxidative stress can cause several symptoms, including:

  • Memory loss or brain fog
  • Muscle and/or joint pain
  • Wrinkles
  • Gray hair
  • Decreased eyesight
  • Fatigue
  • Headache
  • Sensitivity to noise
  • Stiffness and discomfort associated with connective tissues
  • Susceptibility to infections 

 

Diseases Associated with Oxidative Stress

Oxidative stress and the damage of free radicals has been linked to:

  • Cancer – certain cancers are triggered by damaged cell DNA.
  • Atherosclerosis.
  • Vision loss – deterioration of the eye lens, which contributes to blindness.
  • Heart disease – increased risk of coronary heart disease since free radicals encourage low-density lipoprotein (LDL) cholesterol to stick to artery walls.
  • Arthritis – inflammation of the joints.
  • Stroke.
  • Respiratory diseases.
  • Immune deficiency.
  • Emphysema.
  • Parkinson’s disease – damage to nerve cells in the brain, which contributes to this condition.
  • Alzheimer’s disease – also damage to nerve cells in the brain.
  • Obesity.
  • Hair loss and gray hair.
  • Fast aging – acceleration of the aging process.
  • An excessive release of free iron or copper ions.
  • A disruption of electron transport chains.
  • An increase in enzymes that generate free radicals.
  • Inflammatory joint disease.
  • Asthma.
  • Diabetes.
  • Senile dementia.
  • Other inflammatory or ischemic conditions.  

Testing for Oxidative Stress Markers

Three Labs That Offer Oxidative Stress Testing

Oxidative Stress 2.0 Urine By Genova Diagnostics

Vibrant Wellness Oxidative Stress Profile

https://vibrant-wellness.com/test/OxidativeStressProfile

Precision Point Diagnostics Oxidative Stress Test

https://precisionpointdiagnostics.com/test/advanced-oxidative-stress-test-whole-blood-urine/

Watch YouTube from Precision Point Diagnostics

https://www.youtube.com/watch?v=l2Wk2d_bTgA

Assessing markers of oxidative stress is important not only for identifying the state of oxidative stress and cellular damage in a patient, but it deciding on appropriate interventions or support for that patient uniquely. Accurately measuring various oxidative stress markers is vital for crafting a personalized plan for the individual patient. 

Measuring levels of oxidative stress through Glutathione, Reduced Glutathione, 8-OHdG, and F2-Isoprostane shows how oxidative stress contributes to poor mitochondrial function and chronic disease in the patient.

Glutathione

Glutathione is critical in mitigating oxidative stress by neutralizing reactive oxygen species and maintaining cellular redox balance. Its administration, mainly via intravenous routes, has shown promise in enhancing antioxidant defenses and improving clinical outcomes in conditions characterized by elevated oxidative stress.

8-OHdg

8-OHdG (8-hydroxy-2′-deoxyguanosine) is an oxidized base that has been identified, removed from the DNA, and excreted in the urine. It is the most studied marker of oxidative DNA damage. DNA damage is a normal part of life, but chronic elevation can be a concern because it signals increased oxidative damage.

F2-isoprostane

F2-isoprostane is the oxidized degradation product of arachidonic acid, a fatty acid with significant inflammatory potential. F2-isoprostane is an oxidized lipid, pro-inflammatory, and a vasoconstrictor. Urinary F2-isoprostane is the gold standard marker of lipid peroxidation in biological specimens and has been described as areliable approach to assess oxidative stress.”

F2-isoprostane can cause vasoconstriction in the kidneys, lungs, liver, bronchi, blood and lymph vessels, uterus, and gastrointestinal tract. 

Top Causes of Oxidative Stress

  • Smoking: Smoking cigarettes and other tobacco products generates free radicals and reduces antioxidant levels in the body. 
  • Radiation: Ionizing radiation, such as x-rays, neutrons, and alpha, beta, and gamma rays, can cause oxidative stress. 
  • Pollution: Air pollution and exposure to industrial chemicals can cause oxidative stress. 
  • Toxic environmental chemicals, toxic metals, and mold
  • Excessive Exercise
  • Excess blue-green light exposure + deficient red-yellow (sun)light-Blue light can also be found in artificial sources such as computer monitors, smartphones, LED TVs, and fluorescent lights.
  • Excess UV light exposure
  • Poor diet: Diets high in fat, sugar, and processed foods can increase the risk of oxidative stress. 
  • Nutrient Deficiencies- Recommend doing a Genova NutrEval- https://www.gdx.net/products/nutreval
  • Alcohol consumption: Drinking too much alcohol can cause oxidative stress. 
  • Chronic emotional stress
  • Unhealthy microbiota
  • Poor liver and gut detoxification. 
  • Sleep deprivation
  • Chronic infections (viral, bacterial, fungal)
  • High vegetable Seed oil diet- Read my article: https://www.functionalmedicineuniversity.com/public/2051.cfm.
  • Medications: Certain medications can cause oxidative stress. 
  • Obesity: Obesity can increase the risk of oxidative stress. 
  • Vitamin B12 deficiency: A deficiency in vitamin B12 can lead to severe oxidative stress.

I strongly recommend getting a Total Tox Screen Lab Test from Vibrant Wellness

Total Tox Burden Test

https://vibrant-wellness.com/test/TotalToxBurden

Here is a sample report for your review

https://www.functionalmedicineuniversity.com/Total-Tox-Burden-Sample-Report.pdf

Toxic exposure is a reality of our daily lives, but toxic overload can stress our bodily systems and manifest in various ways. Toxins can lead to elevated oxidative stress and increase demand on the body’s detoxification pathways, particularly in the liver. When the liver can’t adequately eliminate toxins or infectious byproducts, these toxins can clog up normal detox pathways and lead to chronic inflammation symptoms. 

Practical Strategies to Reducing the Negative Impact of Oxidative Stress

While you can’t avoid oxidative stress entirely, it is critical to identify the underlying causes (see list above) and limit areas of exposure in your life 

You can’t completely stop oxidative stress. But you aren’t defenseless against free radicals, either. There are things you can do to minimize the effects on your body.

Foods to Help Reduce Oxidative Stress

Antioxidants work to deactivate free radicals by binding to oxidants. This stops the free radical damage in its tracks. Diets high in antioxidant-rich foods are linked to a reduced risk of developing heart disease. Natural antioxidants are found in foods, such as:

  • Tomatoes
  • Brussel sprouts
  • Carrots
  • Collard greens
  • Spinach
  • Beets
  • Red bell peppers
  • Dark leafy green vegetables-kale and spinach 
  • Apples
  • Mangoes
  • Blackberries
  • Raspberries
  • Strawberries
  • Blueberries
  • Dark orange, red, yellow, and green vegetables 
  • Citrus fruits
  • Goji berries
  • Amla (Emblica officinalis)
  • Figs
  • Dark chocolate  

 

Remember, always eat organic!

Supplements to “Possibly” Reduce Oxidative Stress

  • Vitamin C
  • Vitamin E 
  • Carnosine
  • Glycine
  • alpha-lipoic acid (ALA)
  • Glutathione-elevated glutathione lab results cause reductive stress
  • Curcumin
  • Acetylcysteine
  • Polyphenol
  • Selenium
  • Ubiquinone or coenzyme Q10
  • Vitamin D
  • Omega 3 Fatty Acids  

Dr. T’s Comments:

Knowing the levels of oxidative stress via lab testing is of utmost importance. With the results in hand, you now have the power to outline an effective plan to reduce oxidative stress and improve your clinical outcomes.

The answer ultimately comes down to identifying the underlying causes of oxidative stress and not simply relying on taking an excessive amount of antioxidant supplements.

NOTE: While antioxidant supplementation does have its place, there is another elephant in the room called Reductive Stress.

Oxidative and reductive stress are related to the balance of oxidizing and reducing reactions in cells, known as redox homeostasis. Oxidative stress occurs when free radicals and antioxidants are imbalanced, while reductive stress occurs when there are too many antioxidants. Both can lead to oxidative damage to macromolecules and cellular dysfunction.

Reductive stress can be dangerous and contribute to many diseases: 

Mitochondrial dysfunction

Reductive stress can disrupt mitochondrial homeostasis, increasing apoptosis and decreasing cell survival. 

Cancer

Cancer cells use reductive stress to promote growth and resist anti-cancer therapies. 

Heart disease

Reductive stress can increase the risk of cardiomyopathy, and chronic reductive stress can induce heart failure. 

Other diseases

Reductive stress may also contribute to the development of muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, and Alzheimer’s disease.

The takeaway is a good thing, as an abundance of antioxidants can be the Achilles’ heel in reducing oxidative stress.

If this appears confusing, the future of Reductive Stress is ongoing and will be discussed in more detail in a later article.

As for now, adhere to my motto: TEST DON’T GUESS.

Suppose you see elevated levels of glutathione on your oxidative stress test. In that case, NAD and glutathione may push one into a Reductive Stress pattern, and avoiding these antioxidants is best.

Here are two tests as of today to determine if you have excessive amounts of glutathione and NAD.

https://www.doctorsdata.com/Glutathione-erythrocytes

https://biostarks.com/longevity-nad-blood-test/

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