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Antioxidant Vitamins, Immunity, and Endurance Exercise
By Dónal P. O'Mathúna, PhD, Dr. O'Mathúna is a lecturer in Health Care Ethics, School of Nursing, Dublin City University, Ireland; he reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
The value of exercise for health is commonly recognized, even if recommendations are not always acted upon. But could the old adage that "too much of a good thing is bad for you" apply to exercise? Some evidence appears to indicate so, leading to suggestions that athletes require additional vitamin intake. Prolonged exercise and heavy training impact an athlete's immune system, both acutely and chronically.1 Endurance athletes have been shown in some studies, but not all, to be more susceptible to infections, especially upper respiratory tract infections (URTI), shortly before and immediately after marathons and ultra-marathons.2
Of even greater concern is a small number of epidemiological studies that have compared all-cause mortality with physical activity levels measured as energy expenditure.3 As expected, those expending the least energy through aerobic exercise had the highest death rates. Mortality rates decreased with increasing weekly energy expenditure. But then the trend reversed itself somewhat for the group with the highest energy expenditure (> 10,000 kJ/week).3 This would be roughly 4 hours/week running at 10 miles/hour. Endurance athletes are known to have higher oxidative stress, which is associated with a number of diseases. Because antioxidants counteract oxidative stress, dietary antioxidant vitamin supplementation has been suggested to benefit endurance athletes.
Mechanism of Action
The benefits of aerobic exercise arise, in part, from increased oxygen consumption. Most of this oxygen is reduced to water and safely eliminated. However, about 4-5% is incompletely reduced to form reactive oxygen species (ROS), the best known of which are free radicals. These ROS are unstable and highly reactive, making them potentially harmful to living cells. The body therefore counteracts ROS through an elaborate antioxidant system consisting of endogenous and exogenous antioxidants. Vitamins C and E are included in the latter group. However, if the ROS levels are elevated beyond what the antioxidants can neutralize, oxidative stress results. The latter has been associated with a number of diseases, including atherosclerosis, diabetes, Parkinson's disease, Alzheimer's disease, and cancer.3
Oxidative stress is also believed to contribute to muscle fatigue and damage.4 Exercise-induced muscle and lymph tissue inflammation and damage are associated with free-radical mediated processes.5 For these reasons, supplementation with antioxidant vitamins, most commonly vitamins C and E, has also been recommended to counteract muscle fatigue and injury associated with endurance exercise.
The connection between exercise and immune dysfunction is less well understood. ROS have a direct inhibitory effect on neutrophils and other cells of the immune system. In addition, acute exercise releases a number of stress hormones such as adrenaline and cortisol.1 Elevated levels of these compounds are associated with reduced levels of several components of the immune system. Although numerous studies document an exercise-induced immune depression, the link between this and increased incidence of illness has been difficult to establish. However, because several vitamins are essential for normal immune function, vitamin supplementation is also recommended to counteract this aspect of endurance training. Vitamins A, C, and E are most commonly recommended here.
A review published in 2006 found 41 original studies of the impact of dietary antioxidant supplementation on exercise-induced oxidative stress.3 Although almost all were randomized and double-blind, a variety of antioxidants were used at different doses and in different regimens. The most commonly used compound was vitamin E, used in 28 of the studies (given alone in 16). Overall, the results were equivocal, with 20 studies showing that the antioxidants reduced oxidative stress, 23 studies showing no effect, and four showing increased oxidative stress. Some other observations made by the reviewers: the form of vitamin E used (whether natural or synthetic) did not impact outcomes; no association was found between outcomes and the dose of vitamin E (which ranged between 300 mg/d and 1200 mg/d); and the duration of supplementation had a significant impact. Studies which found that antioxidants significantly reduced oxidative stress assigned participants to an average of eight weeks of supplementation, while studies that found no change in oxidative stress gave the supplements for an average of four weeks.
Clinical research with vitamin E and immunity is even less clear. The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study was conducted with 50- to 69-year-old male smokers, a population very different from endurance athletes. People were randomly assigned to receive either alpha-tocopherol (vitamin E, 50 mg/d), beta-carotene (a precursor to vitamin A, 20 mg/d), both, or a placebo.6 While the primary endpoints being studied involved cancer prevention, supplementation did not impact the incidence of the common cold when sedentary men were compared to those whose employment involved significant physical exercise, or those who exercised vigorously during leisure time.
A small number of studies have shown reduced levels of exercise-induced immunodepression after vitamin E supplementation, but the results have not been consistent. A recent randomized controlled trial assigned 20 men to receive either placebo or vitamin E (400 IU/d) and vitamin C (1 g/d) for 28 days.7 Participants cycled on an exercise bicycle for 2.5 hours and had immunological analysis carried out on blood samples collected immediately before and after exercising. While the supplement group showed less of an increase in cortisol levels after exercise, no significant differences were seen in interleukin-6 or neutrophil levels, nor in oxidative stress.
Vitamin C has generated the most interest as an essential nutrient that influences the immune system.5 A number of cells in the immune system store vitamin C in high concentrations.8 Vitamin C is involved in a number of metabolic reactions activated during exercise, leading to suggestions that prolonged exercise may deplete vitamin C and lead to higher dietary requirements. Three controlled trials of short duration found that vitamin C supplementation (0.5-1.0 g/d for 7-14 days) did not impact immune changes after intensive exercise for 1-2.5 hours.5
Two other studies examined the elevated levels of several interleukins (signaling compounds important to proper immune system function) present in runners who completed a 90 km ultramarathon. The levels were significantly less elevated in those who took 1.5 g/d vitamin C for seven days prior to the competition compared to those who took 0.5 g/d vitamin C or placebo.9 However, neither study randomly assigned participants. In a brief, randomized controlled study, 1.5 g/d vitamin C for seven days prior to an 80 km ultramarathon did not impact immune or oxidative stress levels following the event.5
A meta-analysis of vitamin C for the common cold found no evidence of benefit in reducing the incidence in the general population.10 However, a sub-group analysis was conducted on six studies involving participants under heavy acute physical stress. These included marathon runners, skiers, and soldiers on sub-arctic exercises. The meta-analysis found the incidence of colds reduced by half among those taking vitamin C. Doses of vitamin C ranged from 250 mg/d to 1,000 mg/d for up to two months prior to the endurance exercise.
A small number of studies have examined the use of vitamins as ergogenic aids: to improve sports performance. A 1988 study of 30 competitive male runners used a placebo-controlled crossover design with each runner taking a multivitamin and mineral supplement for a three-month period.11 Performance was measured in a 15 km time trial, a treadmill run to exhaustion, peak running speed, and with metabolic markers. None of these differed significantly during the supplementation period. In another double-blind study, 22 physically active men were randomly assigned to either placebo or a multivitamin and mineral supplement for 90 days.12 No significant differences occurred between the two groups for performance in a 90-minute run, muscle strength, or metabolic markers of fitness. A more recent 2006 study likewise found no ergogenic benefit with anaerobic exercise from a multivitamin and mineral supplement.13 For athletes consuming an adequate diet, vitamin supplements are unlikely to have a direct effect on athletic performance.
The International Olympic Committee (IOC) has warned that large doses of some essential nutrients may be harmful, but does not reference the evidence to support that claim.14 A very small number of studies (four out of 41 reviewed) found that antioxidant supplementation increased oxidative stress.3 Direct negative effects of supplementation were not reported in other studies. Athletes should be cautious in purchasing vitamins because, as dietary supplements, there may be significant variability in their quality.
Another problem for those taking dietary supplements is the wide variety of formulations available, often combining different supplements in different ratios.3 There is practically no evidence available on the best formulations or doses.
The literature on vitamins and exercise is clear that neither long-term nor short-term supplementation has an impact on exercise performance, aerobic performance, or muscle strength.15 Whether supplementation has a more subtle effect on exercise performance by reducing the incidence of infections or lowering oxidative stress is less clear. Research is presently inadequate to completely address concerns regarding excessive exercise that arose from the epidemiological studies noted at the beginning of this article.
While some studies find a beneficial impact for endurance athletes on biomedical markers associated with disease after supplementation, an almost equal number of studies have not found such benefits. This has been the case with vitamin C and vitamin E taken alone or in combination. Some of this variability may arise because of differences in dosage regimens, exercise protocols, study duration, or fitness levels of the participants. The only clear benefit demonstrated in studies is reduced incidence of colds after prolonged acute exercise when people took vitamin C supplements beforehand. At the moment, however, available evidence does not support the general use of antioxidant vitamin supplementation in endurance athletes.
National Dietary Guidelines take into account everyone's need for antioxidants, including antioxidant vitamins. These are most readily available by consuming a diet rich in fruit and vegetables. However, these guidelines were developed with an average energy expenditure in mind and to prevent deficiency states, but not necessarily to optimize health or performance.3 Athletes, especially endurance athletes, will likely have higher energy expenditure. This should lead to endurance athletes increasing the amount of fruit and vegetables in their diet, and taking a general multivitamin. Elite athletes, or those undertaking prolonged endurance training, should consider consulting a qualified sports nutritionist to ensure they are meeting their dietary requirements. At this point, there is insufficient evidence to recommend that endurance athletes consistently take high doses of antioxidant vitamin supplements.
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4. Barclay JK, Hansel M. Free radicals may contribute to oxidative skeletal muscle fatigue. Can J Physiol Pharmacol 1991;69:279-284.
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13. Fry AC, et al. Effect of a liquid multivitamin/mineral supplement on anaerobic exercise performance. Res Sports Med 2006;14:53-64.
14. International Olympic Committee. IOC consensus statement on sports nutrition 2003. Available at http://multimedia.olympic.org/pdf/en_report_723.pdf. Accessed April 30, 2007.
15. Evans WJ. Vitamin E, vitamin C, and exercise. Am J Clin Nutr 2000;72:647S-652S.