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Lamprecht M, editor. Antioxidants in Sport Nutrition. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.

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Antioxidants in Sport Nutrition.

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Chapter 11Inflammation and Immune Function

Can Antioxidants Help the Endurance Athlete?

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Endurance athletes and coaches often pose these questions: How do we maintain good health and optimise performance? Are there nutritional strategies that promote good health during periods of heavy exercise training and preparation for competition? Are diet or supplement intakes of antioxidants beneficial, and if so, which is the best strategy? Researchers and practitioners are also interested in these issues and there has been concerted effort in laboratory and field-based studies to identify the clinical and performance effects of supplementation, and the underlying physiological mechanisms.

This review examines some of the important aspects of antioxidant supplementation in endurance athletes including increases in free radical production and subsequent oxidative stress created by high endurance training loads, the impact of endurance training and oxidative stress on immune function, the impact of improving antioxidant status on factors affecting performance, recovery and adaptation, and whether the source of supplementation is best obtained directly from dietary sources or nutraceutical supplements. Two special circumstances, ultra-endurance events and altitude training, which may invoke specific oxidative stress, are also examined.


Endurance athletes, such as those competing in the individual sport of running, cycling, swimming and triathlon, undertake many hours of aerobic exercise training each week. Endurance training relies on oxygen use in skeletal muscle to provide the energy for these activities. The oxidative nature of this training may increase the production of free radicals, which are highly reactive, and antioxidant defences are necessary to protect cells from free radical damage. This potential to damage cells is described as oxidative stress and may result in an inflammatory response from the immune system to protect host tissues.

There is a substantial body of evidence that high intensity or prolonged duration endurance-training loads stimulate increased free radical production and oxidative stress (Watson et al. 2005). Endurance training yields an increased production of reactive oxygen species (ROS) (Powers and Jackson 2008) and reactive nitrogen species (Reid 2001; Powers and Jackson 2008). Superoxide and nitric oxide are the ROS most commonly produced in cells (Powers and Jackson 2008). Although oxidative stress may result in an inflammatory response, it is also possible that free radicals play an important physiological role in training adaptations. There has been considerable debate on whether excessive antioxidant intake may reduce training related adaptations (Gross et al. 2011). Achieving an appropriate balance between pro-oxidants and antioxidants may be a challenge for many endurance athletes (Atalay et al. 2006; McGinley et al. 2009).

Regular physical activity can also reduce oxidative stress and inflammation, and improve immune function (McTiernan 2008; Shanely et al. 2011). The volume, intensity and nature of the exercise activity influence this relationship. Although high-intensity endurance training can increase antioxidant enzyme activity, as well as reduce markers for exercise-induced oxidative stress (Miyazaki et al. 2001), very high training loads are associated with an acute reduction in antioxidant capacity and an increase in markers of oxidative stress (Neubauer et al. 2008). This effect has also been demonstrated in athletes competing in ultra-endurance events, including ultra-marathons and ironman triathlons (Knez et al. 2007; Neubauer et al. 2008; Turner et al. 2011). Clearly, athletes have to balance training loads to avoid a heightened risk of fatigue, illness or injury.


Antioxidants protect the body from oxidative stress, thereby preventing damage to a wide range of cell structures including lipids, proteins and DNA (Martin 2008). In the body, antioxidants are usually categorised as either endogenous or exogenous. The main endogenous antioxidants include superoxide dismutase, catalase and glutathione peroxidase enzymes and glutathione. Exogenous antioxidants are obtained from the diet and include, but are not limited to, vitamin E (tocopherols and tocotrienols), vitamin C (ascorbic acid), coenzyme q10 and carotenoids. These substances exert their effects in different biological ways, some by converting the free radicals into less reactive substances, some by protein binding to minimise availability, and others by acting as free radical scavengers (Knez et al. 2007; Powers and Jackson 2008).

Endurance training in preparation for competition places substantial acute and chronic demands on physiological, metabolic and energetic processes. Meeting the nutrient demands can be a challenge for athletes. Competition for key nutrients between the energetic and immune systems during prolonged exercise training is one explanation for the heightened risk of illness in some athletes. There are many options available to athletes wanting to increase their antioxidant intake via either dietary sources or supplements. Antioxidant supplements are increasingly promoted in the general and sporting communities with many claims relating to improved energy availability, faster recovery from exercise, and improved cardiovascular and immune health. Supplement use is common among endurance athletes with daily consumption rates of up to 90% reported in college athletes in the USA (Frioland et al. 2004).


Upper respiratory symptoms are one of the most common reasons for an elite athlete to present for medical review (Robinson and Milne 2002) and there is an established link between training load and risk of respiratory illness (Walsh et al. 2011). Some athletes experience frequent episodes of upper respiratory illness. These symptoms are consistent with an inflammatory response and until recently were assumed to be the result of upper respiratory infection. However, this is not always true and the aetiology of the airway inflammation in endurance athletes is varied (Spence et al. 2007) including infection, localised inflammation, allergy and poorly managed asthma.

Although moderate amounts of exercise are typically protective, high volumes of training can increase the risk of respiratory symptoms compared with inactive or moderately active individuals (Nieman 1994). Bouts of endurance training at high intensity, high volume or both can yield transient changes in immune cell activity, which may be responsible for a clinically significant period of increased susceptibility to infection. The risk of upper respiratory tract illness is thought to be highest during periods of overreaching or overtraining and around competition. A period of increased vulnerability, the so-called ‘window of immunosuppression’ after exercise, is based on data showing that immune perturbations can last up to 72 h after competition or a hard training session (Nieman 2007).

The changes in immune activity in the hours after intense physical exertion can be briefly summarised as follows: an acute neutrophilia and lymphopenia, a decrease in natural killer cell activity and T-cell function, a decrease in salivary IgA, and an increase in pro-inflammatory cytokines and chemokines (Nieman 2007). These changes in cellular and soluble components of the immune system have been well described. The biological regulators of these immune responses are thought to include catecholamines, cortisol, blood flow, body temperature and dehydration (Nieman 2007).

An underlying infectious cause is not always well established for the upper respiratory symptoms experienced by athletes. The notion that inflammation not associated with infection plays a significant role in many clinical presentations is well established. In a study examining the aetiology of upper respiratory symptoms in elite athletes, bacterial infections accounted for only 5% of presentations (Reid et al. 2004), with other inflammatory causes accounting for 30–40% of upper respiratory symptoms. In support of this finding, viral aetiology was identified in only 30% of athletes with illness with similar pathogens to the general community (Spence et al. 2007). Epstein–Barr virus reactivation was deemed responsible for 22% of athletes with recurrent symptoms (Reid et al. 2004). Other causes of upper respiratory illness in athletes include asthma, allergy and unresolved non-respiratory infections and autoimmune disease (Spence et al. 2007).

Athletes may also be at increased risk of airway dysfunction as a consequence of the substantial mechanical stresses on the airways, dehydration and exposure to agents capable of inducing airway injury (pollutants, irritants, allergens). These effects are largely a consequence of the large and prolonged movements of air associated with endurance training. Oxidative stress has been identified as a major factor in pollutant-induced bronchospasm but only a few studies have investigated the role of these agents in eliciting respiratory symptoms in athletes (Chimenti et al. 2009).


Antioxidant supplementation has the potential to be a useful nutritional strategy for athletes at risk of respiratory illness. Athletes on a high-antioxidant diet, or who consume antioxidant supplements, may have increased protection against both training- and pollution-induced respiratory illness; however, studies investigating these proposals are lacking. Antioxidants are known to play a role in modifying inflammation of the airways outside the athletic community. A study of asthmatic individuals in the general community examined the role of a high antioxidant diet versus low antioxidant diet (Wood et al. 2012). In this study, the low antioxidant diet led to a worsening of two commonly used measures of asthma severity (percentage of predicted forced expiratory volume in one second, and percentage of predicted forced vital capacity, increased the concentration of the inflammatory marker C-reactive protein in serum, and reduced the time to acute asthma exacerbation compared with those on the high antioxidant diet (Wood et al. 2012). Importantly, this study also demonstrated the benefit of whole-food antioxidant intakes. Increasing the intake of whole foods rich in antioxidants may be beneficial due to the synergistic effect of multiple nutrients consumed in combination. It is also possible that other, as yet unidentified, compounds present in fruit and vegetables may contribute to the beneficial effects of antioxidant-rich foods on airway inflammation.

Another study examining the effects of increasing lycopene concentrations in participants with asthma reported a substantial reduction in airway inflammation as measured by a lower concentration of sputum neutrophils in these participants. The increase in lycopene concentrations was achieved by consumption of either tomato extract or a lycopene-equivalent dose of tomato juice for a short period of only 7 days (Wood et al. 2008). Given the evidence that inflammation is implicated in a significant number of upper respiratory symptoms reported by athletes, and a substantial reduction in airway inflammation is associated with increased consumption of dietary antioxidants in non-athletic subjects, supplementing the diet with foods that are antioxidant rich may offer similar protection to athletes. Further experimental work in athletic groups is needed to confirm this hypothesis.


There is only limited evidence that respiratory inflammation including infections is associated with reduced sport performance. In elite swimmers, an episode of respiratory symptoms prior to international competitions was associated with a decrement in performance (Pyne et al. 2005). Endurance events such as a marathon, an ironman competition or triathlon can induce muscle damage and an acute inflammatory response—however, there is also an associated increase in anti-inflammatory cytokines (Suzuki et al. 2006). The balance between inflammatory and anti-inflammatory effects depends on a variety of factors. The increase in ROS produced in skeletal muscle during physical activity is dependent on the intensity and duration of the task being performed as well as the antioxidant capacity. Although low activity levels of ROS appear to improve contractility (in vitro), high levels are likely to impair function.


Several studies have attempted to attenuate the inflammatory effects of exercise using antioxidant-rich supplements. A reduction in creatinine kinase and urinary 8-hydroxy-guanosine has been reported following pre-season supplementation with a blend of antioxidants and amino acids in collegiate soccer players (Arent et al. 2010). Although no performance benefit was demonstrated in the players, this could imply a possible recovery benefit. Acute supplementation of trained cyclists 4 h prior to an exercise trial with a pine bark extract, Pyconogenol®, increased time to exhaustion, maximal oxygen uptake and economy (Bentley et al. 2012). Another study which supports the theory of increased antioxidant capacity examined the impact of cherry juice supplementation compared with an energy-matched placebo on knee extension maximum voluntary contractions (Bowtell et al. 2010). Cherry juice supplementation substantially improved post-exercise recovery of isometric strength compared with placebo. Although this study is not specific to endurance athletes, the outcomes support the concept that improved antioxidant availability can delay time to fatigue and promote muscle recovery that potentially improves performance (Bowtell et al. 2010). Blueberry consumption prior to prolonged exercise (2.5 h of running) resulted in higher post-exercise NK cell counts and an increased concentration of anti-inflammatory cytokines compared with a control group (McAnulty et al. 2011).

Quercetin is one of the few antioxidant supplements that has been examined in a number of studies and demonstrated a consistent performance benefit; however, the studies have been conducted mostly using untrained subjects. In a study of running performance in a 12-min treadmill test, a substantial improvement was observed in untrained subjects (Nieman et al. 2010). In another study, maximal oxygen uptake and cycle time to fatigue were increased following 7 days of quercetin supplementation compared to placebo (Davis et al. 2010), again in untrained subjects. It is unclear whether this benefit would be seen in highly trained athletes.

A topic of much discussion in sport nutrition is whether the use of supplements may compromise natural physiological processes. Some researchers contend that antioxidant supplementation may interfere with cellular signalling function of ROS, and therefore prevent the adaptations that are necessary for performance improvements (Gross et al. 2011). An alternate view is that dietary supplements simply augment natural antioxidant capacities in the face of very high demands associated with endurance training and the fear of physiological interference is overstated. Further studies are needed to resolve this controversy.


A perennial question for athletes is whether they can obtain adequate antioxidant intakes from normal dietary sources or nutritional supplements are needed. Evidence that supplementation with any one antioxidant is sufficient to prevent oxidative damage from free radicals produced during exercise, or prevent immune disturbances or respiratory inflammation associated with exercise, is inconclusive (Nieman 2008). Evidence to resolve this issue in athletes is lacking. However, in individuals with asthma, the view has emerged that whole foods or multi-formulation supplements that contain more than one antioxidant may be more effective in enhancing antioxidant capacity (Wood et al. 2012).

A Mediterranean diet appears to protect against oxidative stress in the general population. The ATTICA study, a large epidemiological study of 3000 residents of urban and rural areas surrounding Athens in Greece, reported significant associations between adherence to the Mediterranean diet (rich in fruit, vegetables, legumes, whole grains, fish, nuts and low-fat dairy products) and health benefits (Kontogianni et al. 2012). Better adherence to this diet was associated with higher total antioxidant capacity and reduced levels of oxidised low-density lipoprotein (LDL)-cholesterol. The reduction in LDL-cholesterol is thought to account for its protective effect on cardiovascular health. Furthermore, this study demonstrated an association between the Mediterranean diet and reductions in markers of inflammation and coagulation.

While a high antioxidant diet is associated with a reduction in airway inflammation and markers of disease severity in asthma and chronic airway disease patients (Wood et al. 2012), there is some doubt as to the benefit and even safety of supplementation with a high-dose single antioxidant. For example, studies with isolated vitamin E supplementation in the form of α-tocopherol have, somewhat counterintuitively, increased markers of oxidative stress compared with placebo during the Triathlon World Championships (Nieman et al. 2004).

A number of food-based antioxidant supplements have shown some promise in improving outcomes during exercise, including quercetin, blueberries and even cherry juice (Nieman et al. 2007, 2010; Bowtell et al. 2010; Davis et al. 2010; McAnulty et al. 2011). Multi-nutrient supplementation could be a safer choice compared with very high doses of individual antioxidants, or nutrients providing increased antioxidant defence, with fewer risks of potential harm (Atalay et al. 2006). It seems prudent to recommend a diet rich in natural antioxidants including generous quantities of a variety of fruits and vegetables.


Ultra-endurance events are one area of endurance exercise and sport that warrants specific consideration for dietary antioxidant supplementation. These events attract substantial numbers of non-elite recreational competitors as well as elite endurance athletes. The most well known of these extreme events is the ironman triathlon incorporating a 4-km swim, 180-km bike and a full 42-km marathon (Knez et al. 2007; Turner et al. 2011). A study examining the impact of full and half ironman triathlons on markers of oxidative stress reported that the ultra-endurance athletes had lower levels at rest compared with relatively inactive controls (Knez et al. 2007), but elevations post-competition indicating a marked inflammatory response. These athletes had relatively higher concentrations of erythrocyte antioxidant enzymes at rest but reductions in these enzymes post-race indicating a depletion of antioxidant defence mechanisms. Markers of oxidative stress may remain elevated for several days after a prolonged bout of physical exercise. Neubauer et al. (2008) demonstrated increases in a variety of markers of oxidative stress after an ironman triathlon event; these markers took 5 days to return to baseline after the event (Neubauer et al. 2008).

Athletes taking antioxidant supplements can have greater elevations in markers of oxidative stress after half or full iron man triathlon events than age-matched relatively inactive control subjects (Knez et al. 2007). Similarly, vitamin E (α-tocopherol) supplementation 2 months prior to an ironman event produced greater elevations in post-race markers of oxidative stress compared with placebo (Nieman et al. 2004). In another study, examining the impact of ultra-marathon swimming on oxidative stress (Kabasakalis et al. 2011), there was no significant difference observed between pre- and post-race markers of oxidative stress, possibly due to the low intensity nature of this activity compared with that examined in other sport which are at a higher average percentage of VO2 max. Another study examining oxidative stress markers in response to training efforts in swimmers found that despite higher resting levels of oxidative stress compared with inactive controls, a juice-based flavonoid supplement pre- and post-training failed to reduce post-exercise oxidative stress (Knab et al. 2013).


The impact of training at altitude warrants special consideration, as altitude exposure can increase the production of oxidative stress independent of the intensity or volume of exercise undertaken (Bakonyi and Radak 2004; Pialoux et al. 2009a,b). It, therefore, seems logical that improving antioxidant supply during this period of increased oxidative stress would benefit health and possibly exercise performance. Studies have been conducted using the ‘live high, train low’ method of altitude exposure. Endurance training with intermittent resting hypoxia resulted in a decrease in resting plasma antioxidant levels, with little change in the control group without the hypoxic exposure (Pialoux et al. 2009b). The resting hypoxia group also had a greater increase in post-training markers of oxidative stress. It appears that training with the added hypoxia yields an increase in the production of free radicals that depletes the body’s antioxidant capacity. The increased antioxidant intake during this time may assist in maintaining antioxidant levels. The depletion in the hypoxia group had not returned to baseline levels after 2 weeks of recovery (Pialoux et al. 2009a), indicating a more sustained impact on antioxidant levels. Another study reported only a trivial difference in markers of oxidative stress in the supplemented group following 2 weeks of moderate intensity exercise at high altitude (Subudhi et al. 2004). In this study, the concentration of markers of oxidative stress did not change following prolonged submaximal (55% VO2 max) cycling. The increased oxidative stress produced by altitude exposure may play an important role in adaptation, and dampening this effect with antioxidant supplementation may theoretically impair adaptation.

11.11. SUMMARY

Antioxidants can diminish the potential oxidative stress produced by high volume and intensity endurance training. However, it is not entirely clear whether an increased oxidative stress caused by training is actually harmful to the athlete. The degree that an increase in free radical production during high training loads regulates signalling required for training adaptations warrants further investigation. While these issues are being resolved, athletes should seek advice on antioxidant supplementation from their health care practitioner(s) who should be assessing individual requirements in terms of underlying health, dietary intakes and training loads.

There is some evidence that increased dietary antioxidants modify the disease pattern in illnesses with an inflammatory aetiology. It is likely that diets that increase fruit and/or vegetable intake (and therefore high in dietary antioxidants) have a number of unknown beneficial biological actions that cannot currently be identified or measured. More research is needed to determine whether dietary interventions that benefit disease groups in the general community, such as those with asthma, transfer directly to hardworking but otherwise healthy endurance athletes.

Mixed diets high in antioxidants may be safer than antioxidant supplementation and possibly confer greater benefits. Higher antioxidant intakes may help maintain a normal pro-oxidant/antioxidant balance. Endurance athletes who undertake very high levels of training, either living and/or training at moderate to high altitudes, or who participate in ultra-endurance competitions, may benefit from antioxidant supplementation.


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