What is Oxidative Stress?
During many processes throughout the body, tiny molecules called free radicals are produced that collide and react easily with other molecules, changing their properties. These free radicals serve an important purpose, but may also cause damage. There is a dynamic balance between producing and scavenging free radicals, and the disturbance of this balance is called ‘oxidative stress’. The amount of oxidative stress (thus the amount of disturbance) determines whether it will lead to a ‘good’ or ‘bad’ response.
By exposing isolated cells to free radicals and measuring their response (called a dose-response relationship), scientists have elucidated the effect of oxidative stress. Mild levels of oxidative stress are necessary to activate adaptive responses to free radicals, such as the activation of signalling pathways which increase antioxidant defences.
However, high levels of oxidative stress can lead to excessive production of these free radicals in the absence of sufficient defences resulting in damage to proteins, lipids and DNA. This damage has been shown to be a potential mechanism behind the onset of disease states such as obesity, diabetes, and some cardiovascular diseases (through low-density lipoprotein oxidation contributing to atherosclerotic processes); alongside the ageing process.
The effects of exercise and nutrition
Exercise is a good example of how the response to oxidative stress works. Engaging in regular, moderately intense exercise increases the defence against oxidative stress (improved stress resistance) whereas a lack of, or extremely strenuous, exercise increases oxidative stress to levels that damages body cells.
Your calorie intake will also regulate the levels of oxidative stress your body experiences: Eating slightly fewer calories than required improves the defence against oxidative stress (improved stress resistance), whereas over-eating shortens longevity and has detrimental impacts on health by overproducing free radicals.
The mechanism by which exercise and caloric restriction improve the defence against oxidative stress are comparable: they trigger the mitochondria to release short and transient mild amounts of free radicals, that improve the adaptive processes within the cells. This process is called ‘mitohormesis’.
Caloric restriction and periods of fasting have indeed proved to increase longevity (within yeast, worms, mice and rhesus monkeys) alongside an increase in mitochondrial respiration and thus radical production. It also may be that caloric restriction and fasting reduce the activity of some antioxidant enzymes, leading to mild levels of radical production, activating the upregulation of oxidative stress defences.
A class of proteins called Sirtuins (SIRT) have shown to be key for the mitohormesis response. SIRT1 and SIRT3 upregulate genes for protection against oxidative stress (PGC-1, SOD2) while they suppress the activity of genes involved in producing radicals (such as nitric oxide).Thus, fasting, caloric restriction and sirtuins seem to extend longevity via oxidative stress, but more research is needed to fully determine their roles in humans.
Since ageing process has been shown to be linked to the accumulation of free radicals so it was first thought that in order to increase lifespan, preventing or lowering free radical production was key. The scavengers of free radicals, antioxidants, play an important role in reducing oxidative stress levels and inflammation.
There are endogenous and exogenous sources of antioxidants.
Endogenous antioxidants are made within the body and are enzymes involved in cell defences. Examples of these are superoxide dismutase, glutathione peroxidase and catalase. These enzymes are involved in reactions that convert free radicals such as superoxide, which can rapidly react with nitric oxide and is highly produced by the mitochondria, into less reactive molecules. As stated above, exercise training has been shown to increase these endogenous antioxidant defence mechanisms: upon exercise, for example, a 20-112% increase in the activity of superoxide dismutase has been found across studies.
Exogenous antioxidants enter the body via our diet. Natural sources found in many fruits and vegetables are the most beneficial as their antioxidants concentrations trigger an adaptive responses from radical production, without having the risk of over supplementation which inhibits the response (as said earlier, a certain amount of oxidative stress is essential for a stimulating the adaptive response).
When used incorrectly, antioxidant supplements may lead to overconsumption, attenuating the body’s mitohormesis response. Therefore, it is recommended to avoid antioxidant supplementation during exercise, with the exception being extreme and very intense sports events such as Ironman Triathlons, where the level of free radicals may reach such high levels that the body may benefit from some supplementation to raise its defence mechanisms.
Sources of natural antioxidants
- Nuts e.g. walnuts
- Dark green and brightly coloured vegetables e.g. spinach, red bell pepper
The important take home message is that low levels of oxidative stress are good as they activate adaptive processes that facilitate stress resistance, longevity, and reduced disease risks. This supports the importance of regular exercise, maintaining a healthy balanced diet that doesn’t involve over-eating and avoiding consumption of high levels of antioxidant supplements.