Regular daily physical activity is among the most effective lifestyle factors for improving cardiovascular and metabolic health, fitness, mood, and cognitive function while reducing all-cause mortality [1–5]. However, the effects of physical activity on the metabolic activity of organs and tissues other than the musculoskeletal system remain unclear. Traditional, additive models of activity and expenditure assume that physical activity does not affect metabolic energy expenditure in other physiological systems . However, work in recent decades has demonstrated effects of physical activity throughout the body, including immune function and inflammation [4, 7–9], stress physiology [4, 10], glucose trafficking [11, 12], and even on the central nervous system [5, 13]. Many of these studies have examined exercise or exercise interventions, or have focused on athletes [4, 14]. Those that have investigated the impact of daily physical activity in large, representative samples of adults have typically relied on self-reported activity , and none to our knowledge have examined thyroid hormones, which are important mediators of metabolic activity throughout the body. In this paper, we examine the association between daily physical activity and both thyroid hormone levels and immune system biomarkers in a large sample of adult men and women.
One framework for understanding the impact of physical activity on other physiological systems is the Constrained Energy Expenditure hypothesis proposed by Pontzer, which posits that increased physical activity leads to reductions in the activity of other (i.e., non-musculoskeletal) systems [15–18]. This suppression could be evident in global (i.e., whole-body) mediators of metabolic activity, such as thyroid hormone. Results from studies examining the effects of chronic exercise on resting levels of thyroid hormones have been mixed. In animal models, sustained exercise results in lower levels of T4, T3, and TSH [19–21]. Krogh et al. found sled dogs had significantly decreased levels of all three thyroid hormones after four months of vigorous physical activity . In humans, Pakarinen et al.  reported a reduction in resting T4 levels in response to 24 weeks of intense weight lifting, but these levels returned to pre-training values when training ceased. One study of female collegiate long distance runners reported lower levels of T4, T3, and TSH than non-athletes but no differences in measurements taken before versus after competition season . Female rowers in a 20-week training program showed mixed responses in TSH, T3, and T4 . However, we note that human studies to date examining thyroid responses to exercise have general lasted less than 6 months. Measures of morning testosterone levels in male endurance runners suggest endocrine adjustment to physical activity may occur over longer time periods, perhaps several years .
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Physical activity-induced suppression could also affect specific physiological systems, such as immune function . Immune function, particularly inflammation and other innate immune system activity, is a compelling target for exercise-induced metabolic suppression because it is energetically costly and potentially labile [26, 27]. During exercise and immediately afterward, inflammation increases in proportion with exercise intensity [7, 28]. However, regular exercise leads to lower baseline inflammation levels and is associated with lower levels of white blood cells (WBC), neutrophils, and lymphocytes [7, 8] and a lower risk of clinical elevation in C-reactive protein (CRP) and fibrinogen (indicators of chronic inflammation), and WBC . There is also evidence that, when the energetic demands of physical activity are sufficiently high, exercise-induced immune suppression can be harmful. Intense exercise workloads such as those in elite athletes increase the risk of clinically significant suppression and functional impairment collectively referred to as overtraining syndrome or relative energy deficit syndrome [7, 8, 25, 29, 30].
In this study, we examine the association between daily physical activity and both thyroid hormones and immune system activity in a large representative sample of U.S. men and women from the National Health and Nutrition Examination Survey (NHANES). Daily physical activity was measured by accelerometry or accelerometry-validated questionnaire responses. We tested the prediction that greater daily physical activity is associated with reduced immune activity and lower thyroid hormone levels. We also investigated whether daily physical activity was associated with lower prevalence of clinically elevated immune cell counts and inflammatory cytokines.