The Constant Relationship: Balancing Oxidative Stress and Building Antioxidant Health
Updated: Oct 23, 2021
Any discussion here would be remiss if we don't discuss this topic first. What is Oxidative Stress? Why is it so important to address, when it comes to health and wellness?
Essentially, our bodies are always trying to maintain balance, homeostasis. Homeostasis is a balance between biochemical processes, that sustain life while supporting the body's ability to detoxify those processes. We are combating oxidative stress every microsecond, every second, of every day. Our relationship with Oxygen is one of the most complex relationships we have biologically since it is a source that sustains life. However, its effects can also be destructive when an imbalance occurs. Since we are made up of about 65% of Oxygen, it’s a pretty significant relationship.
Oxidative stress takes place at the cellular level and is the result of an imbalance when a net excess of production vs. destruction occurs. The imbalance occurs when the cell's mechanism of detoxification is unable to detoxify excess reactive oxygen species (ROS) quickly enough, in order, to restore cellular balance. Reactive Oxygen Species is a broad description of highly reactive molecules and free radicals.
These molecules and free radicals are produced during aerobic respiration, as a byproduct of enzymatic response to electron activity, while moving down the electron transport chain (ETC). Oxygen is highly susceptible to producing these molecules and free radicals due to its unpaired electrons, in separate orbits, on the outer shell. All aerobic organisms are at the mercy of this process, since the utilization of oxygen is paramount, to sustaining life.
Reactive Oxygen Species are not all detrimental, in fact, at a low threshold Reactive Oxygen Species are essential for cellular health. They are responsible for cell signaling, gene expression, and activation of cell signaling pathways. They are also responsible for maintaining immunity, redox balance, and eventually signaling apoptosis (if need be). When there is an excess amount of Reactive Oxygen Species, there is significant damage that can occur; to proteins, nucleic acids, lipids, cell membranes, and organelles which essentially leads to the activation of apoptosis. Apoptosis is cell destruction and cell death.
This is a failed switch mechanism of the cell, when mutations or pathogens accumulate in the cell, apoptosis is activated, to stop the possibility of compromised cells invading healthy cells. Reactive Oxygen Species are responsible for cell signaling pathways to apoptosis which starts at the mitochondria, death receptor, and the endoplasmic reticulum (ER).
Though, Reactive Oxygen Species are both beneficial and harmful. When in balance, or at a nominal level of balance, they are beneficial for maintaining important pathways that maintain cellular health. However, when there is an excess, they can become harmful, causing oxidative stress to occur.
The balance of Reactive Oxygen Species within the cell is maintained by an integrated antioxidant defense system, that consists of both enzymatic and non-enzymatic antioxidants. The antioxidant defense mechanisms have three lines of defense, the first is preventative, followed by repair, and the last is inactivation. The first line of defense involves enzymatic antioxidants that strive to neutralize hydrogen peroxide, yielding water and oxygen molecules. These enzymatic antioxidants are superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and peroxiredoxins (Prxs).
The non-enzymatic substances are preventative antioxidants in blood plasma, these proteins inhibit the formation of Reactive Oxygen Species binding to transition metal ions like iron and copper. These antioxidants are ceruloplasmin, ferritin, transferrin, and albumin. In fact, many of these proteins are important as biomarkers in blood serum tests, as they measure iron levels without blood clotting factors or blood cells. Albumin is the main carrier protein to measure the function of the liver.
Many enzymatic antioxidants that exist to counterbalance oxidative stress, are primarily located in areas containing type I collagen fibers, such as those surrounding pulmonary and systemic vessels. A large percentage of enzymatic antioxidants are in the bronchial epithelium and alveolar epithelium, which can be found in pulmonary (lung) tissue. Obviously, this is beneficial to the body since this is a predominant site where gas exchange occurs. It is also a site that is highly susceptible to inhalation of irritants, toxins, and allergens. In addition, the lungs are the primary staging area for the process of cellular respiration, in that, it is the mode of oxygenation and gas exchange. For this reason, physiologically it makes sense for the greatest percentage of antioxidant defenses to existing here.
Some literature states antioxidant supplementation does not necessitate better outcomes. Researchers in Slovenia have been exploring this very topic, by focusing on whether Synthetic Antioxidants are useful in combating oxidative stress.  Research showed that a significant issue around Reactive Oxygen Species is due to difficulties around detection. Thus monitoring or recognizing Reactive Oxygen Species at excess has been difficult to measure. There are no viable or reliable measuring tools for Reactive Oxygen Species detection, whether in excess or at optimal levels. In addition, Reactive Oxygen Species at "optimal levels" is a relative term, since Reactive Oxygen Species production happens rapidly within microseconds, which makes measuring them even more difficult.
However, as the authors state "oxidative stress is involved in over 100 diseases, as their cause of consequence" (Poljisak, 2013, 1). Some conditions that are contributed to, by oxidative stress, include, "cancer, some neurological disorders, atherosclerosis, hypertension, ischemia/perfusion, diabetes, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and asthma" Therefore, oxidative stress and the impact of Reactive Oxygen Species, in excess, is not completely benign. Its effects are important for cell balance and ultimately overall health and wellness. Since oxidative stress is inevitable, by the mere relationship we have with oxygen, its effects increase with age. This is due to both environmental factors such as environmental and lifestyle choices, and due to the plasticity of our cells through the lifespan.
Of course, the most readily applied utilization of synthetic antioxidants is in food products as an application of nanotechnology in nutritional science. The reason, most cited, is the modulating capabilities of polyphenols. Due to its potential synergistic abilities to work with the antioxidant defenses predominantly present in pulmonary tissue.
Nevertheless, the main objective of synthetic antioxidants, being petroleum-based, is to inhibit lipid oxidation. It strives to maintain the integrity of the lipids in the food products and the possible oxidative effects of fat/lipids when exposed to heat, during the cooking process, or when used for packaging purposes to prevent rancidity due to exposure to air (oxygen).
Therefore, you will find many synthetic antioxidants in the form of baked goods, emulsifier stabilizers, chewing gum base, dehydrated food products like potato flakes, etc. It is also found in many foods to prevent rancidity such as prepackaged meat products, like pre-formed burger patties. Therefore, synthetic antioxidants already exist in many of our food products.
However, studies have shown that synthetic antioxidants in food product may not be beneficial, as they disrupt humoral immunity, mostly through the disruption of cell signaling that occurs when a nominal level of Reactive Oxygen Species are present. This disrupts the signaling for apoptosis to occur, which is a crucial mechanism for delineating healthy cells from unhealthy or pathogen compromised cells. In addition, synthetic antioxidants may speed up the production of cancerous cells, rather than prevent it. There is a narrow window in which cells can respond. Therefore, shows the difficulty, in determining, the optimal level of ROS for cell health and ROS excess that causes oxidative stress.
Antioxidants also exist naturally in fruits and vegetables. Many common vegetables and fruit contain antioxidant compounds like α-tocopherol (lipid-soluble Vitamin E), ascorbic acid (Vitamin C), or β-carotene (Retinol- Vitamin A). But some researchers states that they only make a minuscule impact or lessen the effects of oxidative stress. While vegetables and fruit that are more uncommon that contain a larger amount of non-vitamin antioxidants like polyphenols and anthocyanin are more potent in reducing or neutralizing free radicals.
Researchers also found that the greatest effect of antioxidants, obtained through fruit and vegetables, worked best to combat oxidative stress in synergy. Such as the combination of tocopherols (vitamin) and polyphenols (non-vitamin), or any of the other combinations of vitamin and non-vitamin antioxidants, such as ascorbic acid and beta carotene. Generally, there are three types of tocopherols- alpha, beta, and gamma.
The main dietary sources of alpha-tocopherols are found in sunflower and olive oil. In addition, polyphenols are readily available in many vegetables, berries, fruits, seeds/nuts, and spices/herbs. Some popular foods you can find polyphenols in are spinach, olives (black and green), red onion, red chicory, chestnuts, hazelnuts, dried sage and rosemary, spearmint, black chokeberry, black elderberry among others.
A good example of synergy is a spinach salad with red onions topped with grapes and almond slices, with a cold preparation of a rosemary olive oil vinaigrette. Another example of a dish, that works in synergy, is sliced grilled peaches over a bed of spinach and sliced avocado salad, dressed with a light lemon vinaigrette and topped with nuts/seeds. Olive oil is best consumed as cold preparation, as cooking degrades the oil and its benefits, therefore causing oxidative stress to occur. The antioxidant potential of dishes in synergy is truly antioxidant potent.
It’s safe to state that the consumption of antioxidant-rich fruits and vegetables is the safest and most beneficial way to combat the adverse effects of oxidative stress. The danger in synthetic antioxidants occurs mostly from the potential for toxicity and dosing, even in a food product, especially in food product form. The antioxidant potential is best gleaned from a combination of vegetable and fruit sources between non-enzymatic and enzymatic forms to increase synergy and antioxidant potency.
Especially, if the enzymatic antioxidant source is rare or uncommon. However, there is still a body of research about antioxidant efficacy, within the body, in terms of metabolism and what is the most therapeutic level to attain too.
Though the body is equipped with integrated antioxidant defenses, the consumption of rich antioxidant fruits and vegetables will help aid those defenses; by aiding in suppressing, the constant effects of oxygen degradation in the body. Therefore, quell the development of oxidative stress and its resulting cause of consequence towards the development of chronic diseases. Currently, this is the most conservative and effective way to combat oxidative stress.
 Birben, Esra et al. (2012). Oxidative Stress and Antioxidant Defense. World Allergy Organization, 9-19.
 Poljsak, Borut et al. (2013). Achieving the Balance between ROS and Antioxidants: When to Use Synthetic Antioxidants. Oxidative Medicine and Cellular Longevity, 2013: 1-8.
 Skimsted, Leif H. (2012). Vitamin and Non-Vitamin Antioxidants and Their Interaction in Food. Journal Food and Drug Analysis, 20: 355-358.