xercise increases reactive oxygen species and impairs antioxidant defence systems. The generation of oxygen free radicals is increased during exercise as a result of increases in mitochondrial oxygen consumption and electron transport flux, including lipid peroxidation. Exercise also activates primary messengers and secondary messengers such as activated protein kinase (AMPK) and p38 mitogen activated protein kinases, that can lead to acute changes in mRNA transcription. This means that exercise affects not only how our body changes energy states, but also affects our genes. And vice-versa, our genes also affect how we exercise.
Dietary antioxidants are essential to detoxify peroxides produced during exercise, which would otherwise result in lipid peroxidation, and that they are capable of scavenging peroxyl radicals and therefore prevent muscle damage.
The nuclear factor erythroid 2-related factor (Nrf2) is encoded by the NFE2L2gene, and is known as the master regulator of antioxidant defences which regulates more than 200 cytoprotective genes. There is now clear evidence that Nrf2 signalling plays a key role in how oxidative stress mediates the benefits of exercising. Exercise induces creation of reactive oxygen species (ROS) through oxidation of cysteine residues which can be damaging to the body. However, once we start exercising for the first time the acute exercise stimulates Nrf2 activation which leads to greater upregulaton of endogenous antioxidant defences.
Studies have shown that gene expression of Nrf2 and other antioxidant defence genes were significantly increased in skeletal muscle of young fit males when partaking in exercise lasting more than 90 minutes. However in participants who had never exercised continuously there were no effects on gene expression of Nrf2 (1). The more we exercise, the greater this response comes, and like everything, our body adapts to higher levels of stimulation to produce antioxidants, so naturally our body produces more even when at rest.
It has been known that Nrf2 levels decrease with age, therefore elderly generations should supplement with Nrf2 compounds. Given the premise of the role of oxidative stress in aging, exogenous antioxidant supplementation should slow aging, or at minimum slow the rate of ROS derived cellular damage and age-related pathology by reducing free radicals prior to contact with cellular components and promoting a more balanced cellular redox environment.
Antioxidants increase expression of genes which encode Phase II detoxification enzymes. Induction of these enzymes is regulated at the transcription level by the Antioxidant Response Element (ARE). Nrf2 also interacts with the ARE to increase levels of antioxidants in response to oxidative stress.
There have been identified certain phytonutrients which activate Nrf2, possibly through modification of cysteine residues, but these phytonutrients offer a way for the body to absorb exogenous antioxidants and even to create more endogenous antioxidants. Thus, this gives our bodies better protection against oxidative stress damage.
Coenzyme q-10 and cordyseps sinesis are potent activators of NRf2 and phase 11 detoxifying enzymes.
Sulphoraphane is a powerful activator of Nrf2, a study using rat models and exercise showed that rats who were made to exercise for long periods of time, and had never done so before elicited no Nrf2 gene activation. However, when the same rats were given sulphoraphane prior to exercise, there were significant increases in Nrf2 activation (2).
A diet too high in antioxidants, and a diet too low in antioxidants can have negative effects, too little Nrf2 leads to a loss of cytoprotection diminished antioxidant capacity and lowered β-oxidation of fatty acids. On the contrary, too much Nrf2 activity causes a favour in reduction of oxidative stress by overproduction of glutathione causing epitheliall cell hyperplasia and failure of certain cell types to differentiate correctly.
Cytochrome P4501A1 (the protein made by the CYP1a1 gene) is part of the xenobiotic metabolising enzymes. Xenobiotics are compounds which are foreign to the body, such as drugs and some medicines. These xenobiotics can induce expression of phase I and phase II detoxifying enzymes that are needed to avoid accumulation of toxic reactive intermediates by activating CYP1A1. Polymorphisms in this gene can reduce this and cause negative issues in the body as they affect the way the body processes xenobiotic. One important SNP includes the A-G transition resulting in higher hydrocarbon enzyme activity which may cause increased rates of carcinogen activation.
Strenuous exercise causes the oxidation of glutathione, release of enzymes and other metabolic intermediates that cause cell damage. Xanthine oxidase is just one of the ROS that is produced and generates superoxide’s associated with exercise. Exercise not only produces these, but also triggers antioxidant defences. Exercise causes activation of MAPkinases which in turn activate the NF-κB, Nrf2 and other important genes which stimulate the production of phase I and phase II detoxifying enzymes (3). Exercise in itself, is considered to be an antioxidant.
Figure1: Exercise increases ROS production and Nrf2 stimulation. When diet is high in antioxidants, modulation of Nrf2 increases Phase II antioxidant gene expression which increases endogenous Antioxidant defences in the body.
- Ballmann C., McGinnis G., Peters B., Slivka D., Cuddy J., Hailes W., Dumke C., Ruby B., Quindry J. Exercise-induced oxidative stress and hypoxic exercise recovery.Eur. J. Appl Physiol.2014;114(4):725–733.
- Malaguti M., Angeloni C., Garatachea N., Baldini M., Leoncini E., Collado P.S., Teti G., Falconi M., Gonzalez-Gallego J., Hrelia S. Sulforaphane treatment protects skeletal muscle against damage induced by exhaustive exercise in rats.J. Appl Physiol. 2009;107(4):1028–1036
- Cabrera MC., Domenech E., Vina J. 2008. Moderate exercise is an antioxidant. Upregulation of antioxidant genes by training. Free Radicals in Exercise. 44(2): 126-131