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

Abstract

This randomized dose comparison trial examined if higher exercise volume decreased inflammatory biomarkers, associated with postmenopausal breast cancer risk, more than moderate exercise volume. The Breast Cancer and Exercise Trial in Alberta was a two-center, two-armed randomized trial in 400 inactive, healthy, postmenopausal women, aged 50 to 74 years, with a body mass index of 22 to 40 kg/m 2 . Participants were randomized to high (300 minutes/week) or moderate (150 minutes/ week) volumes of aerobic exercise while maintaining usual diet. Fasting blood concentrations of C-reactive protein (CRP), IL6, and TNFa were measured at baseline, 6 and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. ITT analyses of 386 (97%) participants showed no statistically significant group differences for changes in biomarker levels at 6 and 12 months. In addition, we did not observe any modification of this effect by baseline characteristics of participants. In post hoc analyses based on self-selected exercise level (measured in minutes/week), CRP decreased by 22.45% for participants who exercised >246 minutes/week (highest quintile) and increased by 0.07% for those who exercised <110 minutes/week (lowest quintile, P trend ¼ 0.04), adjusted for baseline covariates. When this analysis was restricted to include exercise time in the target heart rate zone only, statistically significant trends were observed for both CRP (P < 0.01) and IL6 (P ¼ 0.04). Prescribing 300 minutes/week of moderate-to-vigorous aerobic exercise did not improve inflammatory markers compared with 150 minutes/week in postmenopausal women. Decreases in CRP were observed with higher self-selected exercise volume.Cancer Prev Res; 9(2); 196-203. Ó2015 AACR.

Impact of aerobic exercise on levels of IL‐4 and IL‐10: results from two randomized intervention trials

“…2 The those with chronic conditions, and thus less adaptive response to the exercise-induced anti-inflammatory effects in respect to enhanced basal levels. As reported elsewhere, the median baseline CRP levels for ALPHA [18] and BETA [19] were ≤1.90 mg/L among the four intervention groups, below the 3.0 mg/L threshold considered high risk for diabetes and cardiovascular disease [57 58]. The RCTs [40,43,44,48,59,60,61] or intervention trials (all without a comparison/control group) [41,45,46,49,62] examining the effects of regular physical activity regimens on circulating anti-inflammatory cytokines have been primarily conducted in patients or individuals with specific chronic diseases (i.e., diabetes or cardiovascular diseases).…”

“…The lack of an effect in the present studies of a 1‐year, aerobic exercise intervention on circulating IL‐4 and IL‐10 may reflect an overall normal metabolic and inflammatory profile in healthy individuals, compared to those with chronic conditions, and thus less adaptive response to the exercise‐induced anti‐inflammatory effects in respect to enhanced basal levels. As reported elsewhere, the median baseline CRP levels for ALPHA and BETA were ≤1.90 mg/L among the four intervention groups, below the 3.0 mg/L threshold considered high risk for diabetes and cardiovascular disease [].…”

“…Particularly, high circulating C-reactive protein (CRP), as a nonspecific marker of systemic inflammation, is a putative risk factor for postmenopausal breast cancer [11][12][13]. Substantial evidence from observational studies and randomized controlled exercise intervention trials (RCTs) collectively demonstrate the beneficial effects of physical activity on chronic inflammation through a reduction in circulating proinflammatory biomarkers [14][15][16][17][18][19][20]. It is plausible that physical activity offers protection against chronic inflammation, and thereby chronic disease and breast cancer development, by exerting systemic anti-inflammatory effects mediated through the production of myokines via contracting skeletal muscles with a subsequent increase in anti-inflammatory cytokines [21][22][23][24].…”

Long-term Effects of Moderate versus High Durations of Aerobic Exercise on Biomarkers of Breast Cancer Risk: Follow-up to a Randomized Controlled Trial

“…Yet estradiol and hs-CRP concentrations increased significantly and SHBG decreased significantly between 0 and 24 months, consistent with higher breast cancer risk. Because there was no evidence of a group effect (MODERATE vs. HIGH) immediately after the intervention (15)(16)(17), it was not surprising to find no group effect on biomarker concentration changes over the long term. Exploratory analyses found a possible subgroup effect of exercise adherence during the BETA trial, and secondary analyses by fat mass loss between 0 and 12 months revealed the importance of fat mass loss in breast cancer risk reduction.…”

“…On average (n ¼ 382 to n ¼ 386) for insulin and glucose (15), high sensitivity C-reactive protein (hs-CRP; ref. 16), estradiol, estrone, and SHBG (17), there were no statistically significant dose effects (i.e., no difference between the 0-12-month biomarker changes in the MODERATE vs. HIGH groups). We have previously reported on the exercise dose effects on body fat at 24 months after randomization (14).…”