Exercise, Weight Loss, and Effects on Inflammation Barbara J. Nicklas & Kristen M. Beavers Published online: 27 April 2010 # Springer Science+Business Media, LLC 2010 Abstract Persistent, subclinical inflammation, as indicated by higher systemic concentrations of inflammatory acute phase reactants and cytokines, is a strong risk factor for several chronic diseases. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. The efficacy of increasing physical activity for reducing the risk of chronic disease is well recognized, but its effectiveness in reducing chronic inflammation is less established. This review summa- rizes the strongest evidence (i.e., randomized controlled trial data) for a role of increasing physical activity, with and without concurrent weight loss, in the reduction of chronic inflammation. The available data do not provide strong evidence that exercise training in the absence of weight loss reduces inflammatory biomarker concentrations, except in some individuals with elevated inflammation at baseline. In fact, it appears that exercise-induced weight loss is more important than improvements in aerobic fitness for determin- ing reductions in inflammatory biomarker concentrations in response to exercise training. Keywords Inflammation . Exercise . Cytokines . Weight loss . Physical activity Introduction Inflammation is a necessary response of the immune system to infection or trauma; however, a prolonged inflammatory state has detrimental health effects and is a robust risk factor for several chronic diseases. Empirical evidence now links low- grade inflammation with disorders of several body systems and tissues, including the circulatory (atherosclerosis, heart failure), endocrine (insulin resistance, metabolic syndrome), skeletal (sarcopenia, arthritis, osteoporosis), pulmonary (chronic ob- structive pulmonary disease), and neurological (dementia, depression) systems, along with many other adverse health conditions now thought of as inflammatory disorders. To date, the acute phase reactant C-reactive protein (CRP) has been the most frequently studied circulating inflammatory biomarker with respect to prediction of disease risk. Several prospective studies now provide convincing data indicating that CRP, even when within the nonpathologic “reference range,” is a strong, indepen- dent predictor of incident cardiovascular disease (CVD) in both middle-aged and older individuals [1, 2]. Based on these data, both the Centers for Disease Control and the American Heart Association provide clinical recommenda- tions concluding that individuals with CRP values in the upper tertile of the adult population (> 3.0 mg/L) have a twofold increase in CVD risk compared with those with a CRP concentration below 1.0 mg/L [3]. Due to the ubiquitous nature of low-grade inflammation as an underlying risk factor for chronic disease, medical therapies or behavioral interventions that control or reduce inflammation could be effective in treating multiple adverse health conditions. At present, no pharmaceutical agents with anti-inflammatory effects are approved for the on- going treatment of persistent inflammation. However, lifestyle behavioral interventions, including those that B. J. Nicklas : K. M. Beavers J. Paul Sticht Center on Aging, Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA B. J. Nicklas (*) Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA e-mail: bnicklas@wfubmc.edu Curr Cardio Risk Rep (2010) 4:284–292 DOI 10.1007/s12170-010-0106-8