Coping With the Oxygen Paradox

June 11, 2021

Oxygen is essential to our survival, and yet this toxic, mutagenic, and highly reactive gas also has the capacity to destroy us.

The destructive side of oxygen is called oxidation. Slow oxidation turns cut apples brown and hard metal brittle with rust. Rapid oxidation destroys things more quickly, in an exothermic chemical process of combustion, otherwise known as fire.

Oxygen is a highly reactive element because it’s missing two electrons. That means it’s constantly looking to gobble up electrons from other elements, changing molecules and chemicals in the process. It’s inherently unstable, and that nature makes it both dangerous and essential.

Our cells rely on oxygen’s reactive nature to drive organic chemical reactions that create the special energy they need for everything from muscle contraction to chemical synthesis.

Just like the fire that heats our home, oxidation can go wrong in our bodies as well, and rather than providing us the heat we need to survive the winter, it can burn the things we need in order to survive.

Oxygen’s Dual Nature

When our cells get overwhelmed with oxidation, it’s called oxidative stress. The process is linked to inflammation and chronic disease.

Kelvin J. A. Davies, professor of molecular biology and biochemistry at the University of Southern California, coined the term “oxygen paradox” to describe this strange dual nature.

The oxygen paradox compels us “to look for the mechanisms by which life on earth has managed to find ways to profit from an oxygen environment without immediately falling prey to the dangers of oxidation,” Davies wrote in a journal article published in The Archives of Biochemistry and Biophysics.

Oxygen plays many roles in the body, and sometimes a role that looks like a problem is actually a solution, and other times it’s just contributing to disease formation. Oxidative stress is one example.

Oxidative Stress

According to Brian J. Day, a researcher who studies oxidative stress at National Jewish Health in Denver, our immune system purposely produces high levels of reactive oxygen molecules to kill the pathogens that cause infection: bacteria, viruses, and fungi.

“When the immune system gets going, it generates large amounts of these, much higher than the byproduct of metabolism,” Day said.

These reactive oxygen species (ROS) are created through many processes in the body and play many essential roles, including cell growth and differentiation. They’re also related to many ailments, including chronic inflammation, age-related diseases, and cancers.

During an immune response, our body uses them to launch an oxidative attack against the pathogens.

That attack is what makes us feel so lousy when we have a cold or flu. A stuffy nose, headache, and sore throat are all symptoms we suffer when we’re sick. However, they’re not generated by the infection per se, but from our immune system’s reaction to it. The genius of this strategy is that our body can recover from a short, self-inflicted surge of oxidation. Pathogens typically cannot.

“When the immune system is working properly, it goes in, does its thing, and then retreats, and the tissue remodels and heals itself,” Day said. “The immune system keeps us from being overrun by pathogens, and it has clever ways to prevent friendly fire. It fools the bugs. It can produce an oxidant that the bugs can’t metabolize, but that we have an antioxidant defense against, which is kind of cool. It’s like a smart bomb.”

Unfortunately, when this system malfunctions, it’s a major problem, because your body becomes the target of its own oxidative onslaught. In autoimmune diseases, for example, the immune system responds to the body’s own tissue as a foreign invader and uses oxidation to attack itself.

You can see this self-destruction process play out in cystic fibrosis, an inflammatory lung disease. Day said that what typically kills people with cystic fibrosis is lung failure, because these organs are subjected to high levels of oxidative stress.

“It’s due to having this immune system constantly active. It totally destroys the lung,” he said.

This is also true of many COVID-19 deaths, in which people died from an overly strong immune response known as a cytokine storm.

Oxygen’s Radical Side

Oxidative stress has become a popular buzzword in modern medicine because it promises to deliver deeper insight into degenerative disease. Researchers have linked oxidative stress to cancer, heart disease, diabetes, and other chronic conditions. But how exactly a life-giving substance can also harm us is an idea some doctors are still learning to comprehend.

“It’s complex,” Day said. “I have a hard time even getting scientists to understand it.”

Part of this complexity is due to the chemistry and scale involved. Oxidation is a process that takes place at a molecular level. And oxygen-related reactions are so varied and so widespread in the body that scientists struggle to grapple with them all.

With that said, oxidation’s destructive power becomes self-evident at times because it rapidly accelerates the aging process.

Oxidative stress is a corrosive agent at a molecular scale. It can eat away at the main constituents of a cell: fat and protein. Even if it doesn’t destroy cells outright, it can seriously warp them.

“One of the molecules that can get damaged is your DNA. If you damage your DNA oxidatively, it can cause mispairing, point mutation, band breaks, and all these things that make it very hard for your cells to replicate properly. Some of those events can lead to pre-malignant tissue,” Day said.

What makes oxygen so destructive is its radical nature. Any molecule with an unpaired electron is unstable, but oxygen has two unpaired electrons, also known as free radicals. When these free radicals steal electrons from our cellular molecules, they can leave dead and damaged cells in their wake.

And yet this destructive force can also provide the spark of life. Our cells are designed to harness oxygen’s reactive nature to give our body energy.

That process creates ATP (adenosine triphosphate), Day said.

“These are the energy currents of the mitochondria. It’s used to move your muscles, to digest food, power your brain, your heart, and lungs. This is the currency your body uses for energy.”

More Radicals

For air-breathing creatures (aerobes), oxidation is essential to life. But people today are probably subjected to more problematic forms of oxidation than those of the past. Exposure to the modern world—pollution, chronic stress, and a bad diet—can turn up the volume of bad oxidation, or impair the defense forces that help keep it in check.

Like the brick lining of a fireplace, our body has several mechanisms to manage oxygen’s reactive nature and keep oxidation in check, or active in the right reactions. But we are now bombarded with outside elements that can break those mechanisms, unleashing oxidation’s destructive potential.

Car exhaust, coal-burning power plants, or anything that creates fumes with fire generates a wealth of reactive molecules that we inevitably breathe in. Smoking is by far the worst.

“It’s probably one of the most horrific sources of oxidative stress and damage and why it produces so many diseases,” Day said of the habit. “It increases the risk of cardiovascular disease, heart attack, atherosclerosis, and COPD. And there are a lot of carcinogens in those combustion products, so they’re a large source of cancers, like oral and lung.”

Building a Better Defense System

Cleaner air can cut our exposure to some of these interfering elements, but we can’t escape them entirely. Thankfully, those internal forces that prevent oxidation from turning into oxidative stress can be supported with special agents known as antioxidants.

Antioxidants work by neutralizing reactivity. They pair free radicals up with a stabilizing proton, turning these potentially harmful molecules into something benign.

“When you have a bunch of electrons in highly reactive oxygen species and put protons onto them, you create water. You go from oxygen to water, and water is pretty harmless. This system is very efficient,” Day said.

Unfortunately, many of the touted sources of antioxidants aren’t as good as their marketing suggests, Day said.

“All the vitamins you supplement for are one-to-one. Once you oxidize them, they’re done. That’s why the vitamin C pill is so large. The reason you have to take large amounts of these antioxidants is because they are very inefficient, and they are very slow,” he said.

In other words, these pills don’t start a chain reaction that boosts our body’s ability to create more antioxidants, they just pair up with free radicals present in the body and have a limited effect on neutralizing these troublemakers.

And some of those antioxidants never get used because they pass through the body without encountering any free radicals to neutralize.

“Americans have some of the richest urine in the world because some of these antioxidants your body doesn’t store. So once it hits a certain level, you just flush it out,” Day said.

These one-to-one antioxidants are known as circumetrics. This group includes vitamins, carotenes, and glutathione. There’s another group that consists of antioxidant enzymes that are far more efficient. They can help neutralize many free radicals with greater speed and precision than circumetrics. But as a supplement, they have even larger limitations.

“Even if it really did have the enzyme in it, your digestive system would just break that down like it would a hamburger into the basic building blocks of the amino acids, and you wouldn’t get any of the benefits,” Day said. “It ends up being a very expensive protein supplement.”

Antioxidant Power Plants

So what does Day believe is the best strategy to boost your antioxidant defense? Cruciferous vegetables, such as broccoli, cauliflower, and cabbage. Other plant foods, like berries, may contain far more circumetric antioxidants. But cruciferous vegetables possess something even more valuable—constituents that trigger your body to increase its own endogenous antioxidants, both enzymes and circumetrics.

“Cruciferous vegetables have compounds in them to defend against hungry insects. It’s kind of a chemical weapon they use to try to poison them. But these are also the molecules that can turn on your antioxidant defense system,” Day said.

One major problem with supplements is that they can’t account for the myriad of responses that happen inside your body when it’s faced with oxidation. In an article on antioxidant therapeutics, Day said that most oxidant exposures evoke adaptive responses in the body that a supplemental antioxidant may block. This results in less protection from oxidative stress.

One documented example of this is seen in cigarette smokers who took beta carotene supplements. Rather than protect smokers from oxidative stress, this common antioxidant was actually shown to increase the risk of lung cancer.

But this paradoxical reaction only comes from taking isolated nutrients. Evidence shows that people who eat fruits and vegetables that contain beta carotene reduce their risk of disease.

Another problem with supplements is that they might interfere with your immune system’s ability to generate reactivity when you face an infection. Vegetables, on the other hand, can provide what your body may need at any given moment.

“Eating vegetables is a clever way to arm your immune system so it won’t hurt you,” said Day.

It turns out that just eating healthy food has the power to turn the same oxygen that could create diseases in your body into the oxygen that can protect your body from disease.


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