Oxidative stress is a term frequently used in articles concerning health and nutrition, but it is not generally understood. It is important to be familiar with these concepts because oxidative stress and AGEs are major drivers of inflammation, aging, and chronic diseases, including cancer. Antioxidant-rich foods work to counteract the harmful health consequences resulting from oxidative stress and associated health issues. Note the following terms are commonly used along with oxidative stress:
- Reactive oxygen species (ROS)
- Oxidative damage
- Free radicals
- Advanced Glycation End Products (AGEs)
Oxidation: Good and Bad
Oxidation happens in all of our bodies as we process the oxygen we breathe and our cells produce the energy we need from it. It is a chemical reaction in our body that also produces free radicals–molecules that can cause damage to our cells. Free radicals are required to some degree. Causing some damage, they also stimulate repair. It is only when too many free radicals are produced, and they overwhelm the repair processes, that it results in oxidative stress.
Free radicals include reactive oxygen species and other molecules with unpaired electrons, which make them unstable and highly reactive. To become more stable, free radicals damage the molecules that make up our DNA, protein, and lipids (fats), which leads to tissue injury.
The body has innate antioxidant systems to counteract the effects of free radicals.
However, when the cell’s antioxidant system is overwhelmed by the amount of ROS and other free radicals, this is the definition of “oxidative stress.” 1 Over many years, accumulated oxidative damage to our tissues contributes to the aging of our body and diseases, such as cancer, diabetes, and heart disease.2
In addition to some free radicals being formed during cellular energy production, they also develop due to environmental influences, such as cigarette smoke and UV radiation from sun exposure. A poor diet also increases exposure to free radicals.
ROS Are Not Always Bad, and Antioxidants Aren’t Always Good
Keep in mind that oxidation reactions are part of normal healthy physiology. ROS are not all bad and even have a beneficial effect, for example, when immune cells use them as a tool to defend the body from pathogens. Conversely, taking antioxidant vitamin supplements which you would think would be good for you, like supplemental beta-carotene, vitamin A, and vitamin E in particular, do not appear to have the same beneficial effects as a high-antioxidant diet, and may actually be harmful.3,4
Example of Oxidative Damage: Oxidized LDL
A good illustration of how oxidative damage promotes disease is oxidized LDL cholesterol, which contributes to heart disease. Oxidation makes LDL cholesterol more atherogenic (promotes the formation of abnormal fatty or lipid plaque in the arterial wall) than regular non-oxidized LDL. Oxidized LDL has additional atherogenic properties, such as the attraction of inflammatory cells and toxicity to cells that line the inner wall of blood vessels.
LDL is more susceptible to oxidation in an oxidant-rich environment and less susceptible in the presence of more antioxidants. Eating high-nutrient, high-antioxidant foods and getting regular exercise helps to reduce the susceptibility of LDL to oxidation.6
Advanced Glycation End Products (AGEs)
Advanced Glycation End Products (AGEs) are formed when sugars react with and consequently alter the structure or function of proteins or fats in the body’s tissues. AGE production causes oxidative stress and inflammation, and the formation of some AGEs is caused by oxidative stress. Elevated blood glucose accelerates AGE production, contributing to blood vessel damage and diabetes complications, such as impaired wound healing, kidney damage, and atherosclerosis.1,7-10
AGEs may also come from foods. Fried foods, broiled meats, high-fat animal foods, and dry cooked starchy foods, such as fried or roasted potatoes and baked goods.11-13 Following a diet of primarily whole plant foods and using lower heat or liquid-based cooking (soups and stews, for example) reduces exposure to AGEs.
Our Natural Antioxidant Defenses
The body has ways of dealing with oxidative damage; a potent system of its own antioxidants that scavenge free radicals or convert them into less dangerous forms, slowing or stopping the damage. There are also cellular systems that repair oxidative damage and others that induce cell death if there is too much damage.14
The body’s antioxidant system gets some help from our diet. Vitamins A, C, and E in natural foods have antioxidant properties. Additional dietary antioxidants include carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, and zeaxanthin) and polyphenols (flavonoids, phenolic acids, stilbenes, and lignans).
Some dietary antioxidants are not good at scavenging free radicals once we ingest them, but have different beneficial properties. Flavonoids have strong antioxidant activity, but during digestion, they are metabolized into molecules that do not. However, they still promote health by affecting cell signaling pathways which activate the body’s natural detoxification system, make changes in gene expression that upregulate antioxidant enzymes, inhibit cancer cell growth and proliferation, and reduce inflammation.15,16
Eating plenty of colorful vegetables and fruits protects against heart disease, diabetes, and cancer. One major reason is that these foods complement the body’s natural antioxidant defenses with antioxidant vitamins, carotenoids, and polyphenols.
- Nowotny K, Jung T, Hohn A, et al. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules 2015, 5:194-222.
- Gordon MH. Significance of dietary antioxidants for health. Int J Mol Sci 2012, 13:173-179.
- Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.Cochane Database Syst Rev 2012, 3:CD007176.
- Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One 2013, 8:e74558.
- Le NA. Lipoprotein-associated oxidative stress: a new twist to the postprandial hypothesis. Int J Mol Sci 2014, 16:401-419.
- Betteridge DJ. What is oxidative stress? Metabolism 2000, 49:3-8.
- Peppa M, Raptis SA. Glycoxidation and Wound Healing in Diabetes: An Interesting Relationship. Curr Diabetes Rev 2011.
- Peppa M, Stavroulakis P, Raptis SA. Advanced glycoxidation products and impaired diabetic wound healing. Wound Repair Regen 2009, 17:461-472.
- Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006, 114:597-605.
- Yamagishi S, Matsui T. Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev 2010, 3:101-108.
- Goldberg T, Cai W, Peppa M, et al. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 2004, 104:1287-1291.
- Pruser KN, Flynn NE. Acrylamide in health and disease. Front Biosci (Schol Ed) 2011, 3:41-51.
- Uribarri J, Woodruff S, Goodman S, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010, 110:911-916 e912.
- Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol Aspects Med 2011.
- Higdon J, Drake VJ: Flavonoids. In An Evidence-Based Approach to Dietary Phytochemicals and Other Dietary Factors. New York: Thieme; 2012: 83-108
- Stoner GD. Foodstuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Prev Res (Phila) 2009, 2:187-194.