Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women

Abstract

Chronic low-grade inflammation is a possible risk factor for cancer that may be modifiable with long-term exercise. Very few randomized controlled trials (RCT) have studied the isolated effects of exercise on lowgrade inflammation exclusively in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial, a 2-armed RCT in healthy postmenopausal women, examined how 1 year of moderate to vigorous aerobic exercise, compared with usual inactivity, influenced circulating inflammatory markers. Baseline, 6-month, and 12-month serum was analyzed by direct chemiluminescent immunoassays to measure high sensitivity C-reactive protein (CRP) and ELISAs to measure interleukin 6 (IL-6) and TNF-a. Intention to treat analyses were conducted with linear mixed models. Statistically significant differences in CRP were observed over 12 months for exercisers versus controls (treatment effect ratio ¼ 0.87, 95% CI ¼ 0.79-0.96, P ¼ 0.005), but not in IL-6 or TNF-a. A statistically significant trend (P trend ¼ 0.021) of decreasing CRP with increasing exercise adherence and stronger intervention effects on CRP in women with higher baseline physical fitness (P heterogeneity ¼ 0.040) was found. The intervention effect on CRP became statistically nonsignificant with adjustment for dietary fiber intake change and seemed to be mediated by fat loss. Low-grade inflammation may be lowered with exercise, but confounding by dietary intake occurred and should be considered in future studies. Further trials are needed to corroborate our findings about the optimal dose of exercise required to lower CRP levels and effect modification of CRP changes by levels of body fatness and fitness. Cancer Prev Res; 5(1); 98-108. Ó2011 AACR.

Inflammatory Marker Changes in Postmenopausal Women after a Year-long Exercise Intervention Comparing High Versus Moderate Volumes

“…In our previous RCT, the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial, we demonstrated that a oneyear aerobic exercise intervention (prescribed 225 minutes/week) decreased circulating CRP, IL6, and TNFa levels compared with a usual inactive lifestyles defined as less than 90 minutes per week of physical activity (22). In an exploratory analysis, we also found that increasing exercise volume was associated with statistically significant linear trends of decreasing levels of these inflammatory markers.…”

“…The DREW trial found no direct effect of any amount of exercise on levels of CRP, IL6, of TNFa (40)(41)(42). However, three previous RCTs of exercise interventions in postmenopausal women found that an exercise or exercise and diet intervention significantly reduced levels of CRP compared with nonexercise controls: this effect was predominantly mediated by changes in adiposity (20)(21)(22). Baseline BMI was a moderator in one study as the effectiveness of the exercise intervention was only evident in obese women (BMI > 30 kg/m 2 ) at baseline (21).…”

“…Potential moderation (effect modification) of the intervention main effect was hypothesized a priori, as previously done in other analyses from the ALPHA Trial (22,36). To assess moderation, the statistical significance of the interaction term (P heterogeneity ) between intervention group assignment and each proposed moderator at baseline was evaluated.…”

“…To date, there have been four randomized controlled trials in postmenopausal women that have examined the effect of physical activity on biomarkers for cancer prevention (16)(17)(18)(19). Of these, three have examined the impact on inflammatory biomarkers and all found significant decreases in CRP levels with an exercise intervention (20)(21)(22). In addition, several recent RCTs and non-RCTs have demonstrated a decrease in inflammatory biomarkers following an exercise intervention (23)(24)(25)(26)(27); however, not all of these results were independent of dietary interventions, and some studies have shown no effect (28,29).…”

Effect of Six Months of Aerobic Exercise on Plasma Interleukin-6 and Tumor Necrosis Factor-Alpha as Breast Cancer Risk Factors in Postmenopausal Women: A Randomized Controlled Trial

“…Based on Kern et al's study (29), we can speculate that the exercise intervention favorably altered TNF-α expression, although significant changes required greater body fat loss than we observed in our study. It should be noted that in some similar RCTs, non-significant changes in the IL-6 level were reported (25,30,31), Thus, further studies are required to investigate local changes in TNF-α and IL-6 in postmenopausal women.…”