Oxidative stress occurs when reactive oxygen species (ROS) build up in cells. ROS buildup can happen during an immune response or when the cells' mitochondria (the energy producers of the cell) are not working properly. If ROS builds up excessively inside cells, it can then be released from those cells, causing inflammation. Inflammation caused by the release of ROS could be either short-term or long-term, depending on the cause. Cells also contain other important parts inside cells like protein, DNA, and fat, which ROS buildup can damage, ultimately leading to the cell's destruction. When those cells are destroyed, they release even more ROS, causing the severity of the inflammation to worsen. Small amounts of ROS are helpful, however. They can help cells with important jobs like gene activation and waste cleanup. In the immune system, ROS helps in destroying harmful invaders like bacteria.
ROS are produced in the mitochondria during ATP production, as well as in cellular response to xenobiotics (substances not natural to the human body, such as drugs and harmful chemicals), and pathogenic organism invasions (bacteria, molds, and parasites) of the body. In simpler terms, Oxidative Stress is the imbalance caused by the excess production of harmful molecules, matched with a low amount of antioxidants that struggle to wash away those excess molecules.
As the body turns sugars, proteins, and fats into energy, the mitochondria produce the harmful molecules mentioned previously. Those molecules are the ROS, which the mitochondria's antioxidant system usually takes care of. However, if the electron transport chain (the part inside the mitochondria that creates energy) does not function properly, it causes the ROS to build up. Once it builds up too much to the point where the body can not handle it, then the mitochondria will cause the self-destruction of the cell to protect the rest of the body.
Xenobiotic production of reactive oxygen species occurs as the body attempts to detoxify these molecules. Xenobiotic chemical substances are foreign to animal life and include plant constituents, drugs, pesticides, cosmetics, flavorings, fragrances, food additives, industrial chemicals, and environmental pollutants. It has been estimated that humans are exposed to 1-3 million xenobiotics in their lifetimes.
Another cause of excess ROS buildup is pathogens, which are harmful germs. When pathogens infect your body, they damage cells. The damage and immune response cause an increase in ROS, since ROS helps in fighting off germs, but also causes inflammation in an area with germs to signal for an immune response.
Symptoms of Oxidative Stress
Oxidative stress can appear in different ways. More short-term symptoms, such as fatigue, mild inflammation, and redness and/or pain in certain areas, are normal and part of the healing process. Long-term symptoms such as chronic pain, joint pain, or memory problems can lead to chronic diseases. The way oxidative stress appears depends on the cause. For example, stress as a result of damaged mitochondria looks different than stress caused by xenobiotics.
Mitochondrial oxidative stress affects cells that require a lot of energy. Brain, heart, and muscle cells require a lot of energy, on top of being some of the most important cells in the body. Since it affects these parts of the body, mitochondrial oxidative stress can be very harmful. Here is more information on this specific type on the Mitochondrial Function Blog.
The symptoms of mitochondrial oxidative stress vary depending on the cause. It can occur during vigorous exercise, resulting in fatigue and muscle soreness, which should heal itself. The cause of mitochondrial oxidative stress during physical training is a lack of oxygen in the muscles. As muscles are trained, their ability to deliver oxygen while simultaneously producing more mitochondria in the muscle is increased.
Oxidative stress is a common issue we see in my clinic relating to the overuse of muscles due to sustained chronic postural stress. A common example is people who have desk jobs. Most people have poor posture while working at desks with computers, and that posture forces their muscles into positions that strain their muscles to compensate for their poor posture. In this case, shoulder and neck muscle strain is more common. Since poor posture is repetitive, it leaves the muscles with little time to recover and therefore creates inflammation and pain.
Any condition that creates a high demand for energy production without sufficient oxygen delivery to the cells causes oxidative stress. COPD, Asthma, rapid elevation changes, lower respiratory illness, and any cardiac insufficiency will cause increased oxidative stress from a decrease in mitochondrial oxygen delivery. The symptoms of these conditions are usually confined to the muscular system as soreness and fatigue, with slight neurologic symptoms of confusion and mental fatigue. Extreme cases of oxygen depletion, such as a stroke or heart attack, will lead to oxidative stress-induced cell destruction.
Oxidative stress in the mitochondria can also happen if the electron transport chain doesn't work properly (detailed in the previous Blog mentioned). The three weak links of the electron transport chains are CoQ-10, Cytochrome C, and cytochrome Oxidase. Firstly, CoQ-10 is a substance created by the liver that is essential for good health. CoQ-10 helps with energy production, antioxidant protection, and keeping your heart in good shape. A lack of CoQ-10 can be a result of using statin medication or having liver disease, and it leads to oxidative stress in the mitochondria. CoQ-10 is a substance created in the liver, so we hardly get any from food. When CoQ-10 is low, symptoms develop slowly and affect multiple parts of the body. When CoQ-10 is low, mitochondria try to help each other with mitochondrial fusion (the sharing of resources between mitochondria), but that alone can not compensate for a CoQ-10 deficiency, which is why it can lead to widespread problems within the nervous system and muscles over a long period.
Common side effects
Side effects can vary between different statins, but common side effects include:
- headache
- dizziness
- feeling sick
- feeling unusually tired or physically weak
- digestive system problems, such as constipation, diarrhea, indigestion, or farting
- muscle pain
- sleep problems
- low blood platelet count
Uncommon side effects
Uncommon side effects of statins include:
- being sick
- memory problems
- hair loss
- pins and needles
- Inflammation of the liver (hepatitis), which can cause flu-like symptoms
- Inflammation of the pancreas (pancreatitis), which can cause stomach pain
- skin problems, such as acne or an itchy red rash
- sexual problems, such as loss of libido (reduced sex drive) or erectile dysfunction
Rare side effects
Rare side effects of statins include:
- muscle weakness (myopathy)
- loss of sensation or tingling in the nerve endings of the hands and feet (peripheral neuropathy)
- tendon problems (tendons are tough cords of tissue that connect muscles to bones)
Most of the above side effects are the result of decreased mitochondrial function across several systems and inflammation related to oxidative stress of the entire body. Some symptoms related to cellular function deficiency (due to a lack of energy), such as hair loss, digestive issues, tendon issues, and neurological issues, should be noted because of their significant impact on CoQ-10's function. Treatment of these conditions involves restoring the liver's ability to produce CoQ-10 and oral supplementation.
Cytochrome dysfunction causes more oxidative stress than a CoQ-10 shortage, since the purpose of Cytochromes within the electron transport chain is more complex than the other structures involved. Cytochrome C controls the speed of ATP production and regulates oxidative stress in the mitochondria. It can also initiate cell destruction if reactive oxygen species are generated at a dangerous rate. Cytochrome oxidase accepts the electrons from cytochrome c and terminates the process by adding them to oxygen and safely producing water.
An interesting fact about cytochromes is that there's very little research regarding what happens if they don't work properly. Some rare genetic conditions involving cytochrome dysfunction can appear at birth and are usually fatal early in life. New theories suggest, however, that certain frequencies in the electromagnetic spectrum might either be helpful or harmful to the mitochondria. This may be because cytochromes react to different types of nonionizing energy. Cytochromes are chromophore molecules, meaning they can absorb and reflect light. They contain a structure called a heme group, which is similar to the one found in hemoglobin (the protein in red blood cells). Red light therapy has shown positive results in increasing energy production (ATP) in mitochondria and reducing harmful byproducts. This works because red light matches the natural vibration of these chromophores, helping them to work more naturally.
On the other hand, studies suggest that man-made frequencies, like those from cell phones, can disrupt this process. These low-frequency signals may interfere with how cytochromes vibrate, which can reduce energy production and increase oxidative stress in cells.
Symptoms of cytochrome problems that lead to mitochondrial oxidative stress can vary across several factors. Some people are more sensitive to nonionizing energy like radiofrequencies, and may develop symptoms known as radiofrequency illness, while others exposed to the same energy may feel normal. Genetics research doesn’t explain the difference, since mitochondrial DNA is only inherited from the mother, and studies haven’t shown a pattern of inherited sensitivity. The difference might be how well a person’s cells can produce antioxidants to fight oxidative stress. For example, two people exposed to the same 900 MHz signal might react differently because one produces more antioxidants than the other. This ability to manage oxidative stress may explain why some people are more affected than others. In future sections, we’ll also look at how things like environmental toxins or immune responses to infections can add to overall oxidative stress in the body.
Environmental toxins can induce oxidative stress in multiple ways, either directly, indirectly, or by disrupting the mitochondria. Some toxins act as oxidants, meaning they can damage cells by stealing electrons just like ROS do. As mentioned previously, our bodies use this process in a controlled way, which benefits cells. We also have the opposite process, called reduction, which adds electrons back. These reactions are called redox reactions when put together, which means they go back and forth. Redox reactions are especially important in the electron transport chain. Toxins can cause indirect damage by attaching to other substances in the body and turning them into oxidants. Xenobiotic toxicology research shows that every toxin that the body is exposed to causes some level of oxidative stress.
Oxidative stress during infection has just recently been studied extensively. The depth of the topic will not be discussed in detail in this article. What needs to be understood from this article is that during acute and chronic infections, the body is under sustained oxidative stress as a result of tissue damage release and the immune system's release to destroy the foreign invader and clean up tissue damage. Research is even discovering that the mechanisms of antibiotic medications may lie in enhancing the production of immune-mediated reactive species.
Combating Oxidative Stress
At the cellular level, oxidative stress is controlled by many mechanisms to maintain a balance between oxidative and reductive compounds. To enhance this balance, a dietary intake of natural antioxidants is your best defense. Limiting your exposure to xenobiotic toxins would also be just as if not more important. Eating a diet of non-processed foods. Wild-caught fish, grass-fed organic beef, with high-antioxidant organic produce. Limiting exposure to unnatural forms of electromagnetic energy, such as Wi-Fi, Bluetooth, and cellular phones. Setting your Wi-Fi router to turn off at night, keeping your phone away from your body, and place on airplane mode at night are good first steps. Spend time in sunlight, especially in the morning and evening, when the most beneficial electromagnetic energy is being emitted.