By: Neil P. Walsh Ph.D., FACSM
Research Institute for Sport and Exercise Science, Liverpool John Moores University, United Kingdom
An upper respiratory infection (URI), such as a common cold, might only present an unwelcome nuisance for many of us. However, a URI and other infections might limit an elite athlete’s availability to train and take part in major competition. (Table 1). Recent research highlights prominent risk factors for infection in elite athletes and reveals the connection between immune health and athletic performance (Table 2). (Drew et al., 2017; Hellard et al., 2015; Svendsen et al., 2016; Wentz et al., 2018).
Why Does Nutrition Influence Immunity and Infection?
The immune system’s ability to clear viruses, bacteria and other pathogens, termed “resistance,” is dependent upon an adequate supply of energy from important fuel sources including glucose, amino acids and fatty acids. In addition to fuel requirements, cell proliferation requires nucleotides for DNA and RNA synthesis and amino acids for protein synthesis. Micronutrients such as iron, zinc, magnesium and vitamins C and E play important roles in nucleotide and nucleic acid synthesis and antioxidant defenses that limit tissue damage. Antioxidant availability can be particularly important during heavy exertion or infection when oxidative stress increases.
A New Theoretical Perspective on Nutrition and Athlete Immune Health
Traditionally, immunologists have focused their efforts on understanding the immune weaponry (Figure 1) at our disposal in the fight against infectious pathogens. A new model for exercise science is presented in Figure 2 describing not only resistance but also “tolerance,” which is defined as the ability to endure a microbe (Walsh, 2019). Key to effective tolerance is a proportionate immune response; an overly exuberant immune response can cause excessive tissue damage and unnecessarily allocate energy resources away from vital functions. Vice versa, a weak immune response increases susceptibility to damage from the pathogen. Homeostasis is achieved by an appropriate balance of resistance and tolerance that allows us to fight infection — in this case, cell signals indicate that a response is necessary but also allow for maintaining a healthy relationship with the mutualistic bacteria in our gut. This new theoretical perspective may improve our understanding of how sick we will become when we have an infection (in terms of severity and duration), and more clearly elucidate a role for nutrition, particularly in terms of tolerance (Figure 2).
Nutritional Supplements for Immune Resistance: If it ain’t broke, don’t fix it!
As logic would dictate, support for nutritional supplements to improve immune resistance and thus decrease pathogen burden comes largely from studies in those with impaired immunity. This population can include the frail elderly and clinical patients, particularly in those with poor nutritional status (Bermon et al., 2017). Additionally, over the past 25 years or so, exercise immunologists have actively researched nutritional supplements to improve immune resistance in athletes (Table 3). For much of this period, there was a broad acceptance among exercise immunologists that immunity was impaired in athletes under heavy training, prompting the search for nutritional countermeasures. A more contemporary view is that the evidence supporting immuno-suppression in athletes is lacking. So it is not surprising that supplements targeted toward immune resistance show limited benefits for athlete immunity and host defense (Table 3). One exception is the therapeutic effect of zinc lozenges for treating the common cold. A recent meta-analysis showed that dissolving zinc lozenges in the mouth (75 mg/day elemental zinc) reduced URI duration by around three days when taken fewer than 24 hours after the onset of symptoms and for the duration of the illness (Hemilä, 2017).
However, in his research, Hemilä points out that the optimal zinc lozenge dosage and composition need to be determined; many over-the-counter lozenges contain too little zinc or contain substances that bind zinc. Although the exact mechanism(s) requires elucidation, zinc may act as an antiviral agent by increasing interferon gamma and decreasing the docking of common cold viruses with binding sites. The therapeutic effects of zinc lozenges for treating URI have also been ascribed to antioxidant and anti-inflammatory properties of elemental zinc in the lozenge; as such, zinc lozenges may also have tolerogenic effects on immunity.
Tolerogenic Nutritional Supplements: The New Targets
Tolerance in this model dampens defense activity yet effectively controls infection at a non-damaging level. It also facilitates homeostatic regulation of beneficial intestinal microbial communities (Figure 2). Looking through this lens, it is easy to see why studies involving nutritional supplements with tolerogenic properties have yielded some positive effects for reducing the burden of infection in otherwise healthy athletes (Table 4). Probiotics and prebiotics might have tolerogenic effects by influencing intestinal microbial communities and the common mucosal immune system. The antioxidant effects of vitamin C and the anti-inflammatory effects of vitamin D might improve tolerance, mitigating against excessive tissue damage during infection and as mentioned previously, the therapeutic effects of zinc lozenges for treating the common cold, though principally considered to reduce the pathogen burden and improve resistance, might also be attributed to antioxidant and anti-inflammatory, or tolerogenic, properties of zinc.
This new perspective sharpens the focus on nutritional supplements with beneficial tolerogenic properties that might reduce the infection burden in otherwise healthy athletes. These supplements include probiotics and vitamins C and D. Further research is required demonstrating the benefits of candidate tolerogenic nutritional supplements to reduce the infection burden in athletes — without blunting training adaptations and without side effects. When considering nutritional supplementation, athletes must check that the supplement came from a reliable source and is tested by an established quality assurance program (Walsh, 2018). Finally, to limit the infection burden and to maintain immune health, athletes should follow the simple practical recommendations in Table 5.
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