Understanding Oxidative Stress and the Role of Antioxidants

Free radicals and other reactive oxygen molecules (ROS) are a natural outcome of normal metabolic processes. The body is in a constant balancing act between free radicals and antioxidants. Free radicals roam through the body, and because they have an uneven number of electrons, they readily react to other molecules, causing damage that can lead to illness and aging.
In terms of chemistry, ROS are produced when single electrons are transferred to oxygen, leading to the generation of the superoxide radical (O2-), the more reactive hydrogen peroxide (H2O2), and the highly reactive and damaging hydroxyl radical (OH). (1)
Chronic inflammation produces lots of free radicals, which ultimately create more inflammation. This continuous vicious cycle can damage many systems in the human body. (2) The detrimental effects of free radicals causing health damages is termed oxidative stress.
If enough antioxidants are available, then free radicals are neutralized. This is because antioxidants donate electrons without themselves becoming unstable. This helps stabilize the free radicals.
Some ROS are important signaling molecules. For example, exercise can lead to oxidative stress that’s beneficial for the body as it signals to increase tissue growth and stimulate antioxidant production. Yet, overproduction of ROS molecules or pathological depletion of antioxidants can lead to oxidative stress. Oxidative stress is involved in the pathogenesis of several diseases, like Alzheimer's and Parkinson's disease, diabetes, hypertension, autoimmune disorders, or cancer. (1)
A healthy young body is equipped with natural mechanisms for neutralizing ROS. Yet defects, under-performance, or overwhelming in the ROS detoxifying machinery can also significantly contribute to the generation of oxidative stress. These can be a consequence of aging, environmental stress, or even psychological stress.
The brain, with its high oxygen consumption and a lipid-rich (i.e., fat-rich) environment, is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders, including depression, anxiety disorders, schizophrenia, and bipolar disorder, is not surprising. (3)

Increased Exposure to Free Radicals
Our current environments can lead to increased levels of free radicals. For example, exposure to pollution (including ozone), certain cleaners and pesticides, radiation (such as ultraviolet rays or UV from sunlight), and cigarette smoke all increase exposure to free radicals.
One of the biggest offenders, however, is the Standard American Diet (SAD). Eating foods high in sugars and refined fats and drinking excessive amounts of alcohol can lead to greater free radical production in the body. Typical western diets also don’t include enough fruits and vegetables, which would help provide the body with at least some of the antioxidants the body needs. (4)
The Damaging Effects of Oxidative Stress
When in balance, oxidation is a normal bodily process. However, when it gets out of balance, it can lead to oxidative stress. (5) When the body has to deal with too many free radicals, it can start damaging tissues, proteins, and even DNA in the body. (6) Over time, this oxidative stress can lead to:
Accelerated aging
Increased risk of diabetes and metabolic syndrome
Hardening of blood vessels (atherosclerosis)
Heart disease
Lung damage (7)
Increased chronic inflammation
Cataracts and age-related declines in vision
High blood pressure and heart disease
Decreased brain health, including an increased risk of neurodegenerative diseases like Alzheimer’s and Parkinson’s (8, 9)
Increased risk of cancer (10 – 13)
Specifity of Antioxidants
On the cutting edge of antioxidant research is identifying the specific target of activity. The label of a substance as “antioxidant” is a generalization that all too commonly hides the fact that different antioxidants are not equivalent, just like vitamins are not all the same in their activities.
ROS are generated in specific sites in cells. ROS production from these sites is modulated in a specific manner, and the sites are differentially accessible to antioxidants. The inhibition of ROS accumulation by different antioxidants is specific to the site of ROS generation as well as the antioxidant. (14) Therefore, it is expected that different antioxidants are effective for the prevention of different target body tissue damage.
Overcoming Oxidative Stress
No one can avoid oxidative stress altogether. It’s part of life. However, we can take steps to reduce the damaging effects of excess oxidation on the body. One of the most common ways is to increase the antioxidants available in the body. Some of the most common antioxidants include vitamins A, C, and E and glutathione. Getting plenty of fruits and vegetables (at least five servings) per day is one way to get antioxidants. Foods high in antioxidants include berries, dark leafy greens, carrots, tomatoes, fish, nuts, green tea, and spices like turmeric, ginger, and cinnamon. (4)
Unfortunately, 68% of adults don’t eat the recommended 5 servings of fruits and vegetables per day. And research on supplementing the diet with increased levels of antioxidants has been conflicting.
Other lifestyle changes can help decrease the amount of oxidative stress. These include:
Getting quality sleep
Exercising regularly
Avoiding cigarette smoke or vaping
Maintaining a healthy weight
Reducing stress
Decreasing exposure to common household chemicals from cleaners
Taking steps to reduce pollution in your community (such as by driving less)
Protecting the skin from sun damage (e.g., wearing sunscreen)
Consuming less alcohol
Avoiding overeating
While improving nutrition levels by eating foods rich in antioxidants is one well-known way to help combat the increased exposure to free radicals, there’s another lesser-known way to increase antioxidant levels in the body.
Spending time in nature and breathing antioxidant-rich air has been shown to be a more effective way to take in antioxidants. Research shows it may be up to 10 times more effective. Unfortunately, most societies have moved away from natural plant-rich environments and into more urban areas. City air is more likely to be teaming with pollution than antioxidant-rich forest air.
Research indicates that consuming foods high in antioxidants yields a mere .5 to 1% antioxidants. This is due to the natural denaturing effect of the digestive system. Breathing antioxidant-rich air, on the other hand, may lead to up to 50% bioavailability. That means antioxidants end up in the bloodstream rather than degraded by digestion.
Oxidative Stress: Takeaway
There’s no way to completely avoid free radicals or the oxidative stress and damage they can lead to. However, there are, fortunately, steps you can take to help reduce their effects to help promote greater health.
References:
1. Kreuz S, Fischle W. Oxidative stress signaling to chromatin in health and disease. Epigenomics. 2016 Jun;8(6):843-62. https://www.futuremedicine.com/doi/10.2217/epi-2016-0002
2. Biswas S, Das R, Banerjee ER. Role of free radicals in human inflammatory diseases. Aims Biophysics. 2017;4(4):596-614. https://www.aimspress.com/article/10.3934/biophy.2017.4.596
3. Salim S. Oxidative stress and psychological disorders. Current Neuropharmacology. 2014 Mar 1;12(2):140-7. https://pubmed.ncbi.nlm.nih.gov/24669208/
4. Poljsak B. Strategies for reducing or preventing the generation of oxidative stress. Oxidative Medicine and Cellular Longevity. 2011 Oct;2011. https://www.hindawi.com/journals/omcl/2011/194586/
5. Yoshikawa T, Naito Y. What is oxidative stress? Japan Medical Association Journal. 2002 Jul;45(7):271-6. https://www.med.or.jp/english/pdf/2002_07/271_276.pdf
6. Betteridge DJ. What is oxidative stress? Metabolism. 2000 Feb 1;49(2):3-8. https://pubmed.ncbi.nlm.nih.gov/10693912/
7. Suresh Y, Devi MS, Manjari V, Das UN. Oxidant stress, antioxidants and nitric oxide in traffic police of Hyderabad, India. Environmental Pollution. 2000 Aug 1;109(2):321-5. https://www.sciencedirect.com/science/article/abs/pii/S0269749199002547
8. Cobley JN, Fiorello ML, Bailey DM. 13 reasons why the brain is susceptible to oxidative stress. Redox Biology. 2018 May 1;15:490-503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881419/
9. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology. 2018 Apr 1;14:450-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680523/
10. Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, Tsouh Fokou PV, Azzini E, Peluso I, Prakash Mishra A. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Frontiers in Physiology. 2020 Jul 2;11:694. https://www.frontiersin.org/articles/10.3389/fphys.2020.00694/full
11. Knight JA. Diseases related to oxygen-derived free radicals. Annals of Clinical & Laboratory Science. 1995 Mar 1;25(2):111-21. https://pubmed.ncbi.nlm.nih.gov/7785961/
12. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. International Journal of Biomedical Science: IJBS. 2008 Jun;4(2):89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614697/
13. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. European Journal of Medicinal Chemistry. 2015 Jun 5;97:55-74. https://www.sciencedirect.com/science/article/abs/pii/S0223523415300039
14. Liu Y, Schubert DR. The specificity of neuroprotection by antioxidants. Journal of Biomedical Science. 2009 Dec;16(1):1-4. https://jbiomedsci.biomedcentral.com/articles/10.1186/1423-0127-16-98