The realization that lifestyle factors such as exercise, nutrition, sleep, and stress can optimize the immune system seems to have captured the attention of the medical community. Since the inception of the International Society of Exercise and Immunology in the early 1990’s, exercise immunology as a science has revealed some fascinating statistics. In this article, we will delve into how physical activity is associated with fewer infections, fosters the exchange of immune cells between the bloodstream and cellular tissues, and discuss how exercise can improve immune markers across multiple disease states, including cancer.
Debunking the Immune Suppression Theory
Undeniably, acute, vigorous exercise profoundly affects the composition and functional capacity of the immune system. Indeed, the behavior of almost all immune cell populations in the bloodstream changes in some way during and after exercise, improving immune competency across the lifespan. However, for decades, it has been widely accepted that these changes result in a temporary decline in immune competency in the hours following exercise. Scientists note that during vigorous aerobic exercise, the functional capacity of the body’s lymphocytes, the white blood cells that work with the immune system to fight foreign invaders such as bacteria and viruses, dramatically increases. This knowledge led to the notion that exercise can actually “stimulate” the immune system. On the other hand, in the hours following exercise, total peripheral blood lymphocyte frequency—and the functional capacity of these lymphocytes—drops below pre-exercise levels, leading some to propose that exercise induces a short-term window of immune suppression (termed the “open-window” hypothesis). Still, experts deem it a misconception that this process reflects immune suppression; rather, they emphasize that during this post-exercise period, the body functions in a heightened state of immune surveillance and regulation.
Higher Activity = Better Immune Response
A recent study from Sweden, involving over 1,500 mixed-gender subjects aged 20 to 60, demonstrated that higher levels of physical activity were associated with a reduced incidence of upper respiratory tract infections. In addition, the data revealed that men who led high-stress lifestyles appeared to benefit more from participation in physical activity than individuals with lower stress levels.
A much smaller but highly detailed analysis of illness records kept by 11 elite endurance athletes over a period of 3–16 years showed that total annual training hours were inversely correlated with the number of reported sick days. Studies of ultramarathon runners, who undertake the greatest exercise volume among athletes, have shown that these individuals report fewer days missed from school or work due to illness than the general population.
Amplifying the Vaccination Response
The novel topic of studying the effects of exercise on antibody responses in older adults—who typically exhibit impaired or attenuated immune systems—has received considerable attention in recent years. One study found that antibody responses in women aged 55–75 years improved significantly when they engaged in moderate-intensity aerobic exercise immediately prior to vaccination. At least eight additional studies have corroborated these heightened vaccination responses in physically active adults aged over 60 years.
A study on influenza cases categorized adults aged 62 years or older into one of three groups: those participating in at least 20 minutes of vigorous exercise three or more times per week, moderately active individuals engaging in exercises of lower intensity, frequency, and/or duration, or a control group comprised of non-exercisers. Two weeks after receiving influenza vaccinations, the most active subjects had higher serum anti-influenza IgG and IgM titers, as well as stronger mononuclear cell responses to antigen-specific stimulation.
Older Adults Reap the Best Exercise-Induced Immunity Boost
The beneficial effects of exercise on immune function seem greatest for elderly people who more often than not tend to experience age-associated deterioration of immune competency, also referred to as immunosenescence. Even more encouraging, preliminary evidence suggests that routinely participating in structured exercise may limit or delay immunological aging.
As the human body ages, scientists see profound changes in the numerical, phenotypic, and functional capacity of almost all immune cells, resulting in altered immune responses. Findings from recent studies examining relationships between an active lifestyle and the characteristics of the T cell pool—strong biomarkers of immunosenescence—support the notion that other measures of immune competency, which typically decline with age, can likewise improve with physical activity.
Exercise and Immunometabolism
Physical activity can recalibrate immune differentiation and function through convergent immune-metabolic pathways. This intracellular metabolic network in immune cells changes during activation, dictating the manner in which six of the major metabolic pathways function: glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism. Scientists have only scratched the surface in this arena, but what has clearly emerged reflects the complex interplay between metabolic reprogramming and immunity, which in turn promotes a better understanding of the human immune system, health, and disease.
Cells within the immune system seem to share several characteristics. An enhanced process of glycolysis fosters cellular activation in the immune system; scientists now believe that this upregulation of glycolysis supports the rapid energy demand during immune activation, similar to the increased glucose demand witnessed within muscle tissue during maximal exercise.
Long-Term Physical Activity Lessens Risk of Breast and Other Cancers
Substantial scientific evidence indicates that exercise and physical activity can reduce incidence and improve outcomes in cancer patients, as the immune system appears highly responsive to exercise. A single dynamic exercise event results in abundant mobilization of disease-fighting white blood cells with increased functional capacity into the circulation.
As personal trainers, we know that lifelong exercise habits lead to higher physical fitness, including greater cardiorespiratory function and/or muscle strength and endurance. Today, we see growing evidence that physical activity reshapes the human immune system in ways relevant to tumor initiation, progression, and metastasis, and can modulate responsiveness to anti-cancer therapies, including immunotherapy. Across a multitude of studies, exercise consistently aligns with lower cancer risk while also enabling cancer patients to better tolerate treatments and improve their survival rates.
Doctors who study breast cancer found that long-term habitual activity led to a reduction in cancer diagnoses. Women who engage in 6 or more hours per week of high-intensity exercise throughout adulthood experience a 23% lower breast cancer risk. Colorectal cancer, too, has provided some of the most promising clinical evidence that structured exercise improves patients’ health outcomes. Future clinical work will benefit from specification of exercise doses, such as modality, duration, recovery, and frequency, with the goal of clarifying which patients and tumor contexts benefit most.
Nutritional Molecules Also Affected by Exercise
A fairly new term in the exercise science world, metabolomics encompasses the study of small-molecular-weight molecules: amino acids, lipids, carbohydrates, vitamins, and minerals. Exercise seems to induce significant positive changes in lipid-related metabolites, including post-exercise increases in medium-chain fatty acids, long-chain fatty acids, and ketones. Proteins, too, experience positive immune-related variances in response to heavy exercise. Studies show that blood concentrations of several proteins increase during prolonged exercise, many of which function in regulating immune responses. Some proteins increase chronically following intense training bouts, and they are incorporated into what scientists term the “acute phase” responses, a systemic reaction to stress that muscle-damaging exercise brings about. The acute phase response involves the production of many proteins; their levels remain elevated in the bloodstream for several days following stressful exercise.
The G.I. Microbiome Changes in Response to Exercise
The human gastrointestinal system, colonized by trillions of microbes and bacterial cells, comprises what we know as the microbiome. In 2018, several exercise studies demonstrated the effects of physical activity on the microbiome. Over a 6-week period, scientists observed significant differences in microbial species in the gut of previously sedentary adults who engaged in 6 weeks of physical exercise. While a number of laboratories have demonstrated that various exercise modalities can have profound effects on the microbiome, experts still do not have a definitive grasp on the mechanisms behind these changes.
Muscle, Myokines and Immune Response
In addition to rendering our bodies stronger, healthier and more sculpted, muscle serves as a major secretory organ, releasing as many as 300 different proteins, which in turn regulate a variety of physiological processes daily.
Researchers classify many of these proteins as myokines, or muscle-derived cytokines. In addition to supporting glucose metabolism, these myokines foster a better-functioning immune system. The most prominent myokines relevant to supporting both muscle and immune health, various interleukins (IL-4, IL-6, and IL-8, among others), are released when muscles contract. Their presence in the bloodstream rises exponentially with increasing exercise intensity and duration, sometimes reaching nearly 100X baseline plasma levels.
The immune system responds positively to exercise, with the extent and duration of the response reflecting the workload. Each bout of exercise promotes the recirculation of key immune cells. Over time, regular exercise training mediates an anti-inflammatory state, though the specific mechanisms by which the body achieves this still remain elusive, as mentioned above. Ideally, future research will help elucidate how these exercise-induced, immune-related effects help counter immunosenescence and the development of chronic diseases.
As science advances toward the emerging practice of precision medicine, the medical community hopes to unravel the mysteries of how exercise affects immunity at a personalized level, accounting for variations in genetic, environmental, and lifestyle factors. In so doing, perhaps we will come to understand the implications of lifelong training on the make-up of one’s immune system and how these implications might benefit athletic performance.
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