Active Voice: Revising Our Outlook on Physical Activity and Systemic Inflammation in Obesity

Active Voice is an occasional column by ACSM experts. These comments do not necessarily reflect the views or positions of ACSM.

Timothy Church, M.D., Ph.D., is a 15-year member of ACSM and an expert on exercise and obesity. He has been lead researcher on several NIH-funded studies investigating physical activity and health issues. Dr. Church directs the Laboratory of Preventive Medicine at the Pennington Biomedical Research Center, Baton Rouge, Louisiana. See the April 2010 issue of Medicine & Science in Sports & Exercise® for two scientific reports from Dr. Church and his colleagues, relating to this Active Voice commentary, on findings from the INFLAME and DREW studies.

Four years of hard work by your dedicated team, and you simply do not want to believe the SAS output...the dreaded negative result. You look at the data from every angle possible but the story does not change. Despite excellent compliance and a large change in fitness, we did not see an improvement in C-reactive protein with exercise training in the INFLAME trial. We had some clue this might happen after we observed similar results from an ancillary analysis of the DREW study; however, because INFLAME was specifically designed to examine exercise and inflammation, we held out hope that the outcome might be different. This is a good example of the importance of conducting a clinical trial instead of relying on the cross-sectional epidemiology data even when the cross-sectional data is very compelling. Many groups, including ours, have reported that regular exercisers have lower levels of CRP compared to non-exercisers even when adjusting for body weight. While some smaller trials have reported exercise training to lower CRP, and other large studies have reported exercise training to have no effect on CRP, it is important to note that INFLAME is the only study to our knowledge specifically designed and conducted to examine the effect of exercise on CRP in individuals with elevated CRP.

However, not all is lost and secondary data analyses from both INFLAME and DREW revealed that exercise-induced weight loss was strongly associated with reductions in CRP. This finding confirms numerous reports from weight-loss interventions demonstrating that weight loss reduces CRP. We have multiple data sets available to us to examine CRP, and in every instance body fat is a powerful correlate with CRP. It is my belief that in normal-weight or moderately overweight individuals, exercise without weight loss may improve CRP but within obese individuals, like the participants of DREW and INFLAME, that fat mass must be reduced to improve CRP. In other words, in obese individuals, the volume of fat simply overwhelms any positive benefit of exercise training on CRP and reducing this volume of fat is critical to reducing CRP. While it is widely accepted that weight loss can reduce CRP, there remains a need for a better understanding of the dose-response relationship between changes in weight and changes in CRP. How much weight loss (fat loss) is needed to create a clinically meaningful reduction in CRP? Elevated CRP is a powerful risk factor for cardiovascular disease and currently there are few therapeutic strategies to improve it. We demonstrated that exercise in the absence of substantial weight loss is not adequate to reduce CRP in obese individuals, but there remain many important questions related to weight, diet type, and combinations of these two for treating elevated levels of CRP.