General Precision Point Diagnostics February 1, 2024

Cellular therapy is hot right now. Every attentive medical professional, health-minded individual, athlete, and person wanting to age well is aware of antioxidants, free radicals, the importance of cellular health, and their importance to a healthy body, rejuvenation, and anti-aging. The cellular level is where all of our energy is made. Each cell determines how long an organ is going to live, and how well it will function. Understanding the cell gives us another window into metabolism, nutrition, and longevity. With improvements in science, we are able to test and identify issues right down to a cellular level and build health from the ground floor up. Cells are what produce our energy, regulate our immune system, and control every function in our body. Cellular health depends upon all kinds of factors, and figuring those factors out that affect each of us specifically is key to crafting a plan to combat the oxidation going on in YOUR cells. 

When a cell oxidizes, it begins to malfunction, produce less cellular energy, and eventually die. That process can be hastened by Reactive Oxygen Species (ROS)- a group of chemical compounds that can damage cells by donating oxygen to other substances. These compounds are usually discussed as free radicals, while antioxidants are discussed as substances that combat the process of oxidation by donating oxygen atoms to free radicals, making them more stable and thus less reactive. It might seem like oxygen would be good for our cells, since it’s so important to life on earth, but there is a big difference between an oxygen molecule (O2), and ozone (O3) the number of oxygen atoms in each molecule can profoundly alter what effect it will have on the body and its health. Free radicals have the power to form long-chain compounds that can damage cell function through oxidation. Oxygen itself is a powerful catalyst and even solvent. Rust, the browning of an apple, tarnish on silver, bleaching, and decomposition are all examples of oxidation. In the human body, we break down food by oxidizing it and antiseptics like hydrogen peroxide can kill bacteria through oxidation for example. When it comes to cells, though, oxidation is usually a bad thing- essentially rusting or decomposing them. This general negative oxidation of cells is usually combatted by a healthy body through antioxidants. These antioxidants can be absorbed from food that contains vitamins C and E, flavonoids, carotenoids, and tannins. So lots of fruits, vegetables, nuts and seeds, tea, coffee, wine, chocolate, and some spices. You can also increase antioxidants through supplementation. The lack of enough antioxidants in the body to combat the damaging effects of free radicals causes oxidative stress- an assault on the cells via oxidation.

Why should we be concerned about oxidative stress? What are the potential harms to the body from cellular damage caused by free radicals? Left unchecked, oxidation of cells can potentially lead to cancer, heart disease, neurodegenerative diseases, diabetes, cholesterol removal issues, Alzheimer’s, autoimmune diseases, inflammation, and plenty more. Cellular damage from ROS accumulates as we age- you might even say that cellular oxidation is a hallmark of aging. Damage to your DNA, fatty tissues, and proteins are common locus points. The ways in which oxidative stress can cause damage are myriad, as are the specific pathways. Your cells have a number of defense mechanisms that can help clear free radicals and boost antioxidants.

Two systems in particular are important for the proper removal of ROS. One is intracellular reduced glutathione, the primary antioxidant found within cells. The other is the superoxide dismutase (SOD) family, the main enzymes which remove ROS from the cell and mitochondria. When these antioxidants do not function normally, free radicals accumulate, which leads to cellular damage including DNA, protein, and lipid membrane dysfunction. Glutathione is the most abundant intracellular antioxidant and is critical for defending the cell against oxidative stress. Glutathione (also known as GSH) neutralizes free radicals and conjugates toxins for removal from the body, thereby protecting cells from oxidative stress and toxins. GSH is important for mitochondrial function is involved in cell proliferation, apoptosis, autophagy, and gene expression, and is involved in the regulation of Nrf2- which is important as a controller of the entire system of antioxidants and inflammatory control. 

Total glutathione includes both reduced and oxidized glutathione levels. Glutathione is constantly undergoing oxidation and reduction and therefore exists in two forms, reduced and oxidized. The reduced form of glutathione is the radical scavenger (or antioxidant). Oxidized glutathione is the “used up” form of glutathione. Oxidized glutathione has already contributed its antioxidant potential and then must be recycled to the reduced form of glutathione to be useful once again. Total glutathione levels can indicate the body’s total reserves of glutathione for removing harmful free radicals and toxins. Total glutathione may be low due to genetic variation in enzymes involved in glutathione production, nutritional insufficiency, or exposure to reactive chemicals or medicines. Levels of reduced glutathione are useful to determine a person’s current antioxidant potential. Levels of oxidized glutathione are important as to their ratio to reduced glutathione as a measurement of how efficient a person’s system is at scavenging oxidized glutathione and the overall health of the glutathione cycle. 

SOD1 is a marker of cellular health overall, and SOD2 is a marker of mitochondrial health. Good levels of these markers are achieved when glutathione levels are also at peak, and especially when the ratio of reduced glutathione to oxidized glutathione is in a healthy range. A high level of SOD1 protects the cell from damage, and a high level of SOD2 protects the mitochondria from oxidant damage. Mitochondria show improved activity with higher glutathione levels. Since SOD levels are directly tied to glutathione, testing the various modes of glutathione is of higher importance. What else can be tested to determine cellular health? How? How can we know what adjustments to make to our antioxidant systems?

The Precision Point Diagnostics Advanced Oxidative Stress Test offers the most comprehensive examination of an individual’s cellular health. This panel uses whole blood and urine samples from a patient to test for total glutathione, percent reduced glutathione (which determines the ratio between reduced glutathione and oxidized glutathione),  F2-isoprostane, and 8-hydroxy-2’-deoxyguanosine (8-OHdG). We’ve already discussed the importance of testing for, and regulating total and percent reduced glutathione. Let’s take a look at why testing for and regulating F2-isoprostane and 8-OHdG are also important.

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. Testing urinary levels of F2-isoprostane is the gold standard marker of lipid peroxidation in biological specimens. What does this mean? Since F2-isoprostane can cause inflammation while also constricting blood vessels, it has been suggested as an indicator of cardiovascular disease, including high blood pressure. It can constrict blood vessels in primary organs including the kidneys, lungs, liver, bronchi, blood and lymph vessels, uterus, and gastrointestinal tract. F2-isoprostanes are associated with an increased perception of pain and are elevated in acutely hyperglycemic diabetics. On a cellular level, cellular and mitochondrial membranes with elevated levels of F2-isoprostane suggest oxidized, unhealthy fatty acids in the lipid bilayer of those membranes. Oxidized fatty acids in the cell membranes essentially “clog up” the cell walls. This low membrane fluidity decreases cell and mitochondrial membrane health, contributing to cell dysfunction. This acceleration of cell damage contributes to premature aging and inflammation in the body.

 8-OHdG is part of a DNA base pair that exists in the body to repair DNA strands by becoming oxygenated (much like an antioxidant works) and is then flushed in the urine. It is the most studied marker of oxidative damage to DNA. DNA damage is a normal part of life, but chronic elevation can be a concern because it signals increased oxidative damage. High levels of 8-OHdG in the urine indicate that this DNA repair mechanism might be working overtime to contain DNA damage- an indication of higher rates of DNA decay than should be occurring. While 8-OHdG is not a diagnostic marker of cancer, it has been widely used as a marker of oxidative stress, and degenerative diseases, and is considered a risk factor for certain cancers. In general, high levels of 8-OHdG indicate poor mitochondrial and DNA health. Oxidative stress as evidenced by high 8-OHdG has been found in depression, fatigue, diabetes, extreme exercise, neurodegenerative disease, toxicity, and other conditions. High urinary 8-OHdG was found in patients with major depression and chronic fatigue syndrome. There was a correlation between 8-OHdG levels and scores for sadness and flu-like malaise. It has also been found to be markedly higher after courses of antibiotic treatment and also of chemotherapy. DNA damage has been shown to correlate with Alzheimer’s disease, and 8-OHdG levels have been found to be elevated in the cerebrospinal fluid of patients with Alzheimer’s and are correlated with the duration of illness.

High levels of F2-Isoprostane and/or 8-OHdG, low levels of total glutathione, and especially, percent reduced glutathione all indicate cell damage and accelerated aging. Testing to find which mechanisms or pathways are involved specifically in a person’s cell health is important so that you can identify lifestyle changes and treatments specific to that cause of damage. It’s not enough just to take a random selection of antioxidants, you have to know how to formulate a plan specific to YOU! The only way to do that is to engage in comprehensive testing of your cell health to begin the process of healing, rejuvenation, and anti-aging. 

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