In athletics, coaches and athletes are continually striving to find optimal conditioning regimens to ensure maximum performance. Using the progressive overload theory, coaches create training programs to overload athletes in hopes of adaptation, resulting in gains in aerobic and anaerobic power. Progressive overload makes use of Selye's (44) theory of general adaptation, providing the basis for training. Identifying positive and negative stress is critical to the success of the conditioning program with the former improving and the latter decreasing positive training adaptations. Unfortunately, continually pushing the envelope during training in an attempt to make greater gains can result in excess overload, which is often referred to as overtraining syndrome (OTS). OTS occurs during periods of intense training and promotes fatigue and staleness, both physiologically and psychologically (12,47).
In several ways, the effects of exercise on the immune system display hormetic effects, which have been defined by a dose-dependent relationship in which a low dose of a substance is stimulatory and a high dose is inhibitory (16). Moderate exercise has been reported to produce an anti-inflammatory environment and thus reduce the risk of infection (16,35,37,41,49). Conversely, intense exercise may increase the inflammatory responses and the risk for infection (24,36,52). Nieman (23) has described this relationship as the “J” curve in which the risk of upper respiratory tract infection (URTI) may decrease below that of a sedentary person, but risk will most likely rise with excessive high-intensity exercise (Figure 1). If the intense exercise continues for an extended period, an athlete may develop OTS, a clinical designation that can result in physiological, psychological, biochemical, and immunological disturbances, including a persistent change in mood, performance decrements, and increased susceptibility to infection (12,47).
The immune system response to exercise cannot be viewed in isolation. Several factors (Figure 2) including stress, injury, environmental exposures, and nutritional status have been associated with immune depression (14). An increased risk of infection as a result of immune depression may concurrently be a risk for reduced training and decreased performance in competition. Because of the importance of proper health during training and competition, it may prove beneficial for athletes and coaches to have at least a cursory understanding of the immune system and the challenges to the system encountered during training and competition. The aim of this article is to review possible nutritional strategies to prevent immune dysfunction and symptoms of OTS.
IMMUNE FUNCTION AND OTS
The human immune system is a complex system that consists of 2 primary subsystems: the innate defenses (also known as nonspecific type) and the adaptive defenses (also known as specific type). The innate immune system refers to those immune processes that are present at birth and do not need further development by encountering a foreign substance. The inflammatory response or “inflammation” is a key component to properly functioning innate immunity (3). Inflammation can be described as the accumulation of fluid accompanied by swelling; redness; and pain produced by activated immune cells such as macrophages, cytokines, chemokines, and other proteins that influence the innate immune response (54). The process of inflammation typically follows strenuous exercise, especially exercise eliciting significant muscle damage. Thus, the immune system and inflammation are intricately linked. This linkage is important to understand for the coach and athlete to systematically organize training and implement successful recovery strategies to help improve performance and limit the occurrence of training-induced illness and injury.
There appears to be a link among the immune system, the brain, and skeletal muscle that if not well understood and monitored can cause decreased performance, possible psychological depression, and increased susceptibility to illness. The link may lie in cytokines, as OTS is often accompanied by increased concentrations of circulating cytokines (45). Cytokines are signaling molecules that play a large role in regulating the immune response. In addition to their role as chemical messengers in immune function, cytokines also play a role in glucose homeostasis, lipid metabolism, and brain function (35). Cytokines are also linked to muscle damage and are regulated in part by oxidative stress. Cytokines, specifically interleukin (IL)-6, have been shown to be produced not only in adipose tissue and skeletal muscle (35) but also in peritendinous tissue (19) and the brain (32).
Because cytokines can access the brain via several routes (35,47), it has been proposed that they may be able to produce the physical, psychological, and immune decrements associated with OTS (47). It is possible that cytokines are hormetic in nature as well. Perhaps, some levels of proinflammatory and anti-inflammatory cytokines are necessary for proper muscular regeneration after exercise, but chronically high levels result in OTS symptoms. In general, during and immediately after strenuous exercise, proinflammatory cytokines, such as tumor necrosis factor alpha, IL-1β, and “inflammation-responsive” IL-6, are released and then followed by regulatory or anti-inflammatory cytokines (e.g., IL-4, IL-10, and IL-1ra) (33). Normally, homeostasis is maintained as proinflammatory cytokine levels are counterbalanced by anti-inflammatory cytokine levels; however, if proinflammatory cytokines are unrestrained, risk for postexercise infection may occur (33).
NUTRITION AND IMMUNE FUNCTION
Nutritional deficiencies of certain macro- and micronutrients can play a major role in the immune dysfunction of athletes. Nutritional deficiencies often occur in sports in which body mass is thought to be an inhibiting factor for performance, in exhaustive endurance sports, or other activities that require many hours of training per day. Athletes should aim to maintain proper hydration and consume a balanced diet that provides adequate nutrients and energy to increase performance and prevent immune dysfunction. Inadequate macronutrient intake can have a detrimental effect on immune function. Protein deficiency, for example, can also have profound effects on immune system functioning in susceptibility to infection (6).
On encountering an infection, the body's demand for substrates increases to account for increased need for synthesis of cells and molecules such as antibodies. However, data concerning protein supplementation in athletes without deficiencies are limited and there is no data to suggest that dietary protein can act as an immunoenhancer in these athletes. In animal studies, excessive protein (60% or greater) may impair optimal immune function (4). In addition to the effects of protein deficiency, under consumption of animal protein is associated with low levels of iron, zinc, and vitamin B12. Although necessary for optimal immune function, excessive intake of iron and zinc from nonfood sources have negative effects on the immune system and should only be supplemented under a physician's supervision (4,15).
Extensive efforts have mostly been made to investigate the role of nutrition on immune depression. At this point, carbohydrate (CHO) supplementation seems to have the greatest effect on markers of inflammation, but a direct link to rates of infection is yet to be established. One study does, however, suggest that the use of CHO supplementation before, during, and after exercise in endurance athletes can reduce the risk of infection by attenuating the reduction in salivary immunoglobulin A (IgA) antibodies after intense exercise (28).
CHO appears to improve many markers of inflammation, immune function, and oxidative stress after exercise. Primarily, research has been conducted using endurance training modes of exercise. CHO has been reported to reduce T-lymphocyte apoptosis (17), leukocytosis (43), neutrophil and monocyte oxidative burst activity (31), and cytokine increase (18,22,26,43,48). In addition, CHO supplementation has been reported to increase blood neutrophil and monocyte concentration (27). Unlike the literature regarding endurance training, the usefulness of CHO has been reported to offer no protection for decreases in salivary IgA or muscle damage because of 2 hours of resistance training (20,25) or 100 eccentric quadriceps contractions (53). It is possible that CHO supplementation is less effective in resistance training settings, as there is generally a lesser degree of glycogen depletion than that observed with aerobic exercise.
It has been reported that exercise-induced immune dysfunction is primarily related to stress hormones, such as cortisol (13). Although CHO has been shown to attenuate the cortisol increase after exercise (31,43), conflicting results have been reported as to whether cortisol levels are related to CHO-derived immune improvements (9,17,43). At this point, CHO supplementation is advisable for aerobic activity to reduce the inflammatory effects of the exercise and possibly reduce the risk of infection. It appears that supplementing with at least a 6% CHO solution will positively affect the inflammatory response (31,43) and that it is beneficial to supplement before, during, and after exercise for maintaining muscle glycogen and blood glucose levels (9,25,31,48). Ingestion of approximately 4 ml/kg of a 6% CHO solution every 15 minutes during continuous moderate-intensity exercise appears to be a sound method of reducing the local inflammatory response after exercise (31). At this point, it still appears that CHO is the most effective supplement at preventing immune compromises.
In recent years, research has begun investigating the roles fatty acids may have on immune function. It has been determined that the intake of n-3 polyunsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play an important role in optimal immune function. Adequate intake of EPA and DHA promotes the resolution of inflammatory responses in the body (7). These n-3 PUFAs may decrease cytokine and inflammatory progesterone response within the body (50). Future investigations are needed to determine the roles PUFA intake may have on OTS.
Difficulty lies in examining the effects of antioxidant supplementation in athletes as multitudes of different combinations and dosages have been used. Several studies have reported results of antioxidant supplementation that were neither beneficial nor harmful. Petersen et al. (38) reported no effect on any inflammatory markers after strenuous downhill running after 2 weeks of supplementation with 500 mg of vitamin C and 400 mg of vitamin E per day. Nieman et al. (30) and Palmer et al. (34) each reported that ingestion of 1,500 mg/d of vitamin C did not act as a countermeasure for increases in cytokines or salivary IgA.
Other investigations have reported a beneficial effect of using antioxidant supplements. Phillips et al. (40) reported that a combination of antioxidants attenuated rises in markers of inflammation. In addition, Bryer and Goldfarb (5) reported that 3 g/d of vitamin C supplementation reduced muscle soreness, creatine kinase increase, and blood glutathione oxidation without influencing muscular force loss after 70 eccentric elbow extensions. Nieman et al. (29) reported that quercetin supplementation did not alter measured immune markers after 3 days of intense exercise, but it did significantly reduce URTIs. At this point, taking mega doses of vitamins is not recommended as they can potentially act in a proinflammatory manner to induce greater muscle damage and possibly lower immune cell function. However, because deficiencies are detrimental, it is recommended that athletes consult with a sports nutritionist to determine the levels of nonenzymatic antioxidants in their diet and adjust intake accordingly. A balanced diet is recommended and should provide ample antioxidant nutrients to the body.
Many other nutritional supplements have been studied in terms of their effect on immune, inflammatory, and muscle damage in response to exercise. Supplements studied include dehydroepiandrosterone sulfate (39), caffeine (51), n-3 fatty acids (6), N-acetylcysteine (24), glutamine (8), Immunoferon (10,11), and l-cysteine (24), and oat β-glucan (21). None of these have been studied thoroughly enough to warrant supplementation at this point, but some do show promise. Immunoferon is a polysaccharide/protein compound that is a commercially available immunoenhancer. It has been reported to prevent increases in creatine kinase and cytokine response associated with strenuous exercise (10,11). Although thought to be beneficial, caution is advised until further research delineates the effects of blunting the inflammatory response.
In conclusion, proper nutrition is critical for proper immune function in athletes, yet at this time, supplements recommended to possibly enhance this function are limited. At this point, much remains to be investigated in terms of the immune function of athletes and the proper nutritional strategies to prevent immune dysfunction and symptoms of OTS.
The following are general recommendations for minimizing the immune disturbance that may occur with extremely high-intensity exercise continuously undertaken over the course of a competitive season.
* Focus on maintaining proper levels of hydration especially during periods of heavy training. Simple measures of hydration status include body weight loss and darkening of urine color after exercise. It is recommended that athletes replenish each pound of body weight lost with 20-24 oz of water, and urine color is light yellow (2,46).
* Consume adequate calories daily to support the energy demands of the particular training program. This diet should consist of a variety of foods, being sure to focus on eating ample fruits and vegetables. Simple calculations based on gender and activity level can be used to estimate energy needs (42).
* More is not always better in terms of consuming antioxidant supplements such as vitamins. Vitamins and minerals should optimally be consumed through the diet. Individual supplementation of vitamins and minerals should be under medical supervision.
* Consume adequate protein. Daily protein requirements are generally suggested to be 1.2-2.0 g/kg of body weight for athletes (1). Recent evidence suggests that strength/power athletes consume a postworkout nutrient mixture of 2 parts CHOs and 1 part protein, endurance athletes consume a mixture of 4:1, and team sport athletes a 3:1 mixture. The protein dose for this mixture should be 0.25-0.50 g/kg of body weight. This postworkout CHO-protein mixture should be consumed every 1-2 hours after exercise for 6 hours (55). Vegetarians, older athletes, and those going through puberty may need slightly increased protein intakes.
* CHO intake should be between 6 and 10 g/kg of body weight per day for energy, with many athletes continually participating in very-intense long-duration activity consuming close to the 10 g/kg recommendation. However, CHO intake may need to be decreased below 6 g·kg−1·d−1 for athletes with lower total caloric intake needs. For these athletes, consuming approximately 60% of calories from CHOs is likely sufficient.
* CHO intake is recommended before exercise at levels tolerable to the athlete's digestive system. At present, it appears that a 6% CHO liquid solution can be given every 15 minutes during long-duration moderate-intensity activity to aid in recovery and attenuate the local inflammatory response. Postexercise CHO should be consumed quickly after exercise to both reduce the inflammatory response and maximize the glycogen synthesis. An intake of 1.5 g/kg of body weight of CHO immediately after exercise or 0.6-1.0 g/kg of body weight within the first 30 minutes and again every 2 hours for 6 hours has been shown to maximize glycogen synthesis (1).
* Approximately, 20-25% total caloric intake should be from fat (1). Consumption of a minimum of 2 servings of fatty fish (8 oz) per week is recommended. Salmon, trout, halibut, sardines, anchovies, and herring are good sources of n-3 PUFAs.
* At present, the nonmacronutrient supplements most likely to aid an athlete's immune system appear to be those derived from the polyphenolic group known as flavonoids. Quercetin, found in foods such as apples and onions, has been shown to reduce incidence of URTIs. Flavonoids found in tea and berry products may be beneficial as well.
* Other products show potential, but the market is saturated with products claiming to boost the immune system. Further research on these products is needed before recommendation.
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