Oxidative stress describes an imbalance between cell production and the excretion of by-products of oxygen degradation. Known as reactive oxygen species (ROSs), these byproducts are important for cell function, but cause damage in large quantities. ROS belong to a larger category of highly reactive chemicals called free radicals. Because cells need ROS to function, some researchers have described oxidative stress as a good thing in some contexts. Others say that oxidative stress is bad by definition.
Oxidative damage is implicated in aging and several diseases. Chemicals that inhibit oxidation and the production of ROS are called antioxidants. Some research suggests that antioxidants may help limit oxidative damage. However, it is unclear how much or with what effect.
What causes oxidative stress?
ROS are produced naturally when the body breaks down diatomic oxygen (O2) as part of cellular respiration, the process of making energy from glucose (sugar). In organisms that have one, this happens in the mitochondria, the so-called powerhouses of the cell. As part of the final stage of cellular respiration, the cell separates electrons, or negative subatomic particles, from glucose by-products. This allows the cell to make a molecule called adenosine triphosphate (ATP), its main source of energy. At the end of this process, the cell needs oxygen to take up the electrons, and most of the oxygen molecules are eventually converted into water.
However, some oxygen molecules receive fewer electrons and are instead converted into free radicals, particularly ROS. These substances’ missing electrons make them extremely reactive, and they react with many substances in the cell to gain electrons and become more chemically stable. Some common ROS are peroxides (like hydrogen peroxide), superoxide, and the hydroxyl radical.
“We’re constantly making what we call these reactive oxygen species in every cell in the body,” Ursula Jakob, a professor of molecular, cellular, and developmental biology at the University of Michigan, told Live Science. In addition to being a byproduct of respiration, ROSs are also used in cell signaling or in sending messages within or between cells.
Ursula Jakob investigates the role of oxidative stress on host defenses and aging. Her NIH-funded research has advanced to understand exactly how the physiological oxidative bleach kills bacteria and how bacterial defenses can protect against cellular stress caused by bleach. She received her doctorate in 1995 from the University of Regensburg.
Immune responses, radiation exposure, and other cellular responses to pollutants or toxic substances can also generate ROS.
However, the production of ROS alone does not cause any harm as cells need some ROS to function. Cells use antioxidants to get rid of excess ROS and limit potential damage. When the amount of ROS overwhelms the cell’s antioxidant system, ROS accumulate and create oxidative stress, Jakob said. This could be due to increased ROS production or decreased clearance from the cell.
What are the effects of oxidative stress?
Normally cells use ROSs as part of their signaling processes – sending messages to other parts of a cell or to other cells. However, excess ROS causes oxidative damage, in which parts of the cell become oxidized. Just as the oxidation of iron forms rust, this process can transform and damage the molecules that make up cells, including mutations in DNA and RNA, misfolded proteins, and other types of damage to sugars and lipids.
Cells can repair some damage, but if it’s too big, it can trigger apoptosis (programmed cell death), a type of self-destruct mechanism. In severe cases, necrosis can also occur, in which cells become so damaged that they are destroyed prematurely, leading to tissue death.
Research suggests that oxidative stress plays a role in many diseases. Some of the best established of these are type 2 diabetes, cancer (opens in new tab)and hardening of the arteries, or atherosclerosis (opens in new tab).
Oxidative stress has also been linked to various neurodegenerative diseases, including Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). This relationship was first observed in the late 1980s, according to a 2004 article published in Nature Reviews Drug Discovery (opens in new tab), with increasing evidence that oxidative stress plays a role in neurodegenerative diseases since then. A 2016 article published in Experimental Neurology (opens in new tab) reviewed evidence for the role of oxidative stress in MS as early as 1987.
“The neurons that are compromised during this [Alzheimer’s Disease]they are severely affected by every known type of oxidative damage,” said George Perry (opens in new tab), Professor of Neurobiology at the University of Texas. In Alzheimer’s and some Parkinson’s patients, Perry told Live Science, there are signs of oxidative damage in the cytoplasm, or main body, of some neurons, which are full of “mitochondrial debris” — enzymes, along with copper and iron molecules, usually only get into the mitochondria before.
Oxidative damage is clearly a part of Alzheimer’s. However, researchers have not been able to determine exactly how and to what extent oxidative stress contributes to the disease over a person’s lifetime. It’s also hard to say if it causes aging — an idea that researchers have long proposed, Jakobs said.
“Whether this is actually the case is still pending,” she said.
What are the risk factors for oxidative stress?
Smoking “can generate some of these reactive species,” Marino Resendiz said (opens in new tab), Professor of Chemistry at the University of Colorado at Denver. “So that can cause damage,” he told Live Science. “UV radiation, which can cause oxidative damage, is also linked to skin and other cancers, according to the American Cancer Society (opens in new tab).
Some weak evidence suggests that eating foods containing antioxidants might reduce oxidative stress, and therefore an antioxidant-deficient diet might be a risk factor. Some common foods that are high in antioxidants include broccoli, carrots, potatoes, spinach, and many berries.
However, the link between antioxidants and oxidative stress is not clear. For example, in a 2012 clinical study published in JAMA, consumption of antioxidant supplements did not reduce signs of oxidative stress in the brains of people with Alzheimer’s disease and was even associated with faster cognitive decline. However, a review article from 2019 (opens in new tab) found some evidence that taking a supplement of vitamin E, which is an antioxidant, may be helpful for people with Alzheimer’s, including evidence from clinical trials.
Obesity can increase oxidative stress because free radicals can bind to and damage fat. Therefore, lifestyle changes like exercise and a balanced diet could help limit oxidative stress, Jakob said.
“Obesity is a big risk factor,” she said. In a variety of model organisms, from yeast to primates, Jakob said, exercise and calorie restriction are associated with less oxidative damage to cells. But it’s not a simple effect. Although in a 2019 study published in Nature, she said that exercise and calorie restriction can actually increase oxidative stress (opens in new tab)she and other researchers found that in one species of roundworm, increased oxidative stress early in life may help protect against later oxidative damage.
Although she stressed that this research wasn’t done on humans, Jakob said it underscores the importance of ROS, at least in controlled amounts.
“It’s not like, oh, we’re removing all the reactive oxygen species and that’s healthy,” she said. “In that case, it’s actually healthy to have some higher levels of reactive oxygen species.”