Oxidative stress during exercise Exercise, especially when it is intense or prolonged and involves eccentric muscle activation (such as during running), imposes profound effects on the body. These effects often initiate beneficial adaptations that are associated with training. One particular response to intense exercise is an increase in levels of chemicals known as reactive oxygen species (ROS), sometimes called ‘free radicals’. Some of these ROS are produced as by-products by oxidative processes, those chemical reactions that are important for aerobic energy. ROS are also produced from the inflammatory chemicals that respond to muscle injury. In fact, ROS are believed to help in the initiation and progression of injury and are also produced from the inflammatory chemicals that respond to the injury. Muscle injury or damage is the disruption in muscle cell membranes or tears in the fiber, resulting from repeated intense contractions. The greatest amount of injury occurs when there is eccentric muscle activation such as during running (downhill running is a severe example of eccentric muscle activation) or intense weight lifting. When there is muscle injury, an athlete experiences reduced performance, reduced range of motion, muscle fatigue and muscle soreness. These symptoms are associated with an inflammatory response to the injury.
The other effect of ROS has to do with a reduced immune function. High intensity exercise is associated with increased risk of infection associated with suppressed immune function and it can last several hours following exercise. Stress hormones such as cortisol can also negatively affect immune function. Think of the endurance athlete who is competing or training for long hours outside. Prolonged intense exercise will produce a significant amount of ROS, induce high levels of stress hormones, and may increase exposure to pathogens through higher breathing rates. Thus, athletes may be more susceptible to upper respiratory tract infections during periods of heavy training or competition.
What they are Antioxidants are natural defenses in the body that help neutralize ROS, thus reducing the negative effects of ROS. Most ROS do not pose a problem because the body has an antioxidant defense system that is made up of a variety of compounds including vitamins A, C and E, glutathione, ubiquinone and flavonoids. But during intense exercise, ROS increases and this can create an imbalance between antioxidants and ROS. This imbalance is oxidative stress. Oxidative stress, as mentioned above, is associated with muscle injury and reduced immune function.
It would make sense that if an athlete had more antioxidants available to neutralize ROS, less oxidative stress would occur, which in turn would reduce muscle injury and decrease the suppression of immune function. It would seem logical that antioxidants would benefit the athlete by aiding in the recovery process following intense or prolonged exercise. This is where supplements come in. The most common antioxidant supplements are vitamins C and E. The most active form of vitamin E in the body is alpha-tocopherol, but there are other forms that exist. The alpha-tocopherol form can be purchased singly or in combination with these other forms. Other types of antioxidant products sold as supplements include vitamin A (or beta carotene), selenium, zinc, carnitine, flavonoids, or bovine colostrum. It should be noted that antioxidants can be found in a normal diet made up of fruits and vegetables and a few other items known to contain certain beneficial compounds like isoflavones and flavonoids. These items include red wine, green and black teas, dark chocolate and soy.
The real evidence I found a review article (Peake et al, 2007) that nicely summarized the results from several studies. The authors divided the studies into categories of exercise, and all of these studies tested the effects of either vitamin C or E, or a combination of the two. These studies included measures of chemical markers in the blood for immune function and inflammatory responses and compared levels between a placebo group (no antioxidant supplements) and a supplement group. Supplements were usually given daily for several days or weeks prior to exercise and several days following the exercise. Here is a summary of these studies:
Non-damaging exercise (5 studies, one at high altitude): Two studies found supplements to reduce the inflammatory response to 45 min of cycling and 3 hr of 2-legged knee extension exercise. The supplements supplied included a combination of vitamin C and E. One study performed at high altitude showed no effect of a combined antioxidant supplement following 3 hr of cycling. The other two studies used vitamin C supplements and found no effect following 2 ½ hr of cycling. One of these studies did show an effect with vitamin C when it was combined with carbohydrates. The lack of effect from vitamin C may be that exercise does not allow enough time for ascorbic acid (vitamin C) to take an effect.
Moderate to high-intensity running 1 ½ to 2 ½ hr (4 studies): Three studies used vitamin C supplements, one study used vitamin E. Only one of the three vitamin C studies demonstrated a positive effect from vitamin C supplementation. The difference between that study and the other two was the length of the supplementation period prior to exercise, 2 weeks vs 3 or 7 days. The vitamin E study indicated no effect from vitamin E supplements, taken over a 3-day period prior to exercise. The varying results could be due to length of the supplementation period and the dosage of supplements. Other factors include how well the vitamins are available during exercise, training status and diet. In particular, vitamin E absorption is largely dependent on dietary fat.
Downhill running (2 studies): This protocol is designed to impose greater muscle damage, thus sources of ROS will largely come from the inflammatory response to the muscle injury. Neither study demonstrated an effect from 2 weeks of vitamin C supplements or 2 weeks of a combination vitamin C and E supplementation. It may be that antioxidants are ineffective against ROS produced from muscle injury. Ultraendurance exercise (5 studies): Three studies investigated the effects of vitamin C supplements 7 days prior to the race. The results were mixed, but in summary, vitamin C supplements appear to have some effect only at high dosages, like 1500 mg a day and only when very long exercise is involved (50 miles or more). The other two studies involved vitamin E supplements for 2 months prior or combined vitamin E and C 6 weeks prior to the race. The results indicated that vitamin E actually increased levels of oxidative stress markers, this is particularly so when vitamin E is taken alone and in the form of alpha- tocopherol.
A couple other studies deserve mention. One study (Shing et al, 2007) tested the effects of bovine colostrum supplements in highly trained cyclists. Bovine colostrum is the pre-milk fluid produced by a cow a few days after giving birth. Bovine colostrum has been used in human vaccinations and is also used to treat infections because it contains several nutrients and growth and immune factors that are important to the development of the newborn’s immune system. The cyclists in this study were given a concentrated amount of bovine colostrum daily over an 8-week period prior to performing 5 days of intensified training. Following the intense training period, the investigators found an increase in T cells (immune cells) in the cyclists taking colostrum indicating that the supplement may help reduce the suppression of immune function. In fact, there was a trend (though not statistically significant) for a lower rate of upper respiratory tract infection in these cyclists following the intensified training.
Another study tested a flavonoid called quercetin. Flavonoids are a kind of polyphenol having antioxidant effects. We often hear about flavonoids associated with red wine. Most of the flavonoids ingested from a normal diet is in the form of quercetin. Participants in this study were trained cyclists given 1000 mg/day of quercetin for 3 weeks prior to engaging in intensified exercise that included 3 hr of cycling a day, 3 days in a row. The results showed a decrease in rate of upper respiratory tract infections during a 2-week period following intense exercise. 5% of participants who took quercetin reported illness, compared to 45% in the placebo group.
The bottomline There seems to be some variability in antioxidants effects on inflammatory responses; some studies showing a positive effect, others showing no effect. Further, one study demonstrated a possible pro-oxidative effect from vitamin E (alpha tocopherol) if taken in large quantities. Vitamin E’s antioxidant benefits may come with small amounts and when combined with other antioxidants. Dietary intake of antioxidants must be considered. Those getting low amounts from their diet are more likely to benefit from the supplementations. Bioavailability of antioxidants are affected by consumption of other foods and the absorption of vitamin E is dependent on dietary fat.
Although most of the research thus far has focused on vitamins C and E, new research is including other forms of antioxidants such as bovine colostrum and quercetin. Though only one study each was found here, the results look promising and warrant continued research on this topic. For an athlete who is engaging in intense, prolonged exercise for several days in a row, antioxidant supplements are likely to not be harmful and may even provide some benefits.
The final score for antioxidants out of a possible 5 points: 3
References Bloomer R. J. The role of nutritional supplements in the prevention and treatment of resistance exercise-induced skeletal muscle injury. Sports Med. 37: 519, 2007.
Nieman et al. Quercetin reduces illness but not immune perturbations after intensive exercise. Med. Sci. Sport Exerc. 39: 1561, 2007.
Nieman D.C. Is infection risk linked to exercise workload? Med Sci Sport Exerc. 32:S406-411, 2000.
Peake et al. The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise. J. Nutr. Biochem. 18: 357, 2007.
Shing et al. Effect of bovine colostrums supplementation on immune variables in highly trained cyclists. J. Appl. Physiol. 102:1113, 2007.
Written in 2007
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