Exercise and chronic inflammation

Nutrition Research Newsletter, April, 2004

Increasing amounts of epidemiologic data show that persistent, low-grade inflammation is an independent predictor of ischemic heart disease, stroke, diabetes and all-cause mortality. In addition, experimental evidence shows that markers of chronic inflammation, such as proinflammatory cytokines [interleukin 6 (IL-6) and tumor necrosis factor (TNF-)] and the acute-phase reactant C-reactive protein (CRP) play a direct role in the etiology of atherosclerosis and insulin resistance. Given these widespread deleterious health effects of an augmented inflammatory state, the identification of therapies that reduce chronic inflammation is essential.

Some studies have shown that a few pharmacologic interventions (such as statin use) decrease inflammation, as evidenced by decreased CRP levels. Other promising data suggest that decreasing energy intake and increasing physical activity could be effective in reducing overall inflammation. However, these previous studies of the effect of diet-induced weight loss and exercise training on inflammatory markers were limited by sample sizes, by the lack of randomization to treatments, or by the lack of a control group. In addition, no prior study compared diet and exercise interventions alone with a combination of these treatments. Therefore, the intention of the present study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation by using a randomized controlled intervention trial.

Three hundred and sixteen older (aged >60 years), overweight or obese (BMI >28), sedentary men and women with radiographic evidence of knee osteoarthritis were randomly assigned to four 18-month treatments. The groups were a healthy lifestyle control, diet-induced weight loss (WL), exercise (EX) and diet plus exercise (WL EX). The goal of the dietary weight-loss intervention was to produce and maintain an average weight loss of 5% of baseline body weight and consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake. The three-day/ week exercise program consisted of an aerobic and a resistance-training phase. Body weight was measured and blood was collected at baseline and after six and 18 months of intervention. Fasting serum concentrations of IL-6, TNF-, and CRP were measured.

Subjects in the WL group lost 5.7% of their baseline body weight and reduced their BMI by 2.0, whereas subjects in the WL EX group lost 4.4% of their baseline body weight and reduced their BMI by 1.48. Body weight did not change significantly in the EX group relative to the control group. The diet-induced weight loss intervention resulted in significantly greater reduction in CRP, IL-6 and soluble TNF- receptor 1 concentration than did no weight loss treatment. Changes in soluble tumor necrosis factor receptor 1 but not in CRP or IL-6 correlated with changes in body weight. Reductions in CRP were greater in men than in women, and IL-6, TNF-, and their soluble receptors decreased more in African Americans than in whites. Exercise training did not have a significant effect on these inflammatory biomarkers, and there was no significant interaction between weight loss and exercise training.

The results of this randomized controlled trial provide evidence that a dietary intervention designed to elicit weight loss reduces overall inflammation in older, obese persons. However, no statistically significant effect of exercise on these inflammatory biomarkers was found. In addition, although the study was not powered to detect whether there were sexual or racial differences in the inflammatory responses, the data suggest that this may be the case. These effects were independent of treatment assignment, so additional research is needed to determine whether the magnitude of a weight-loss induced reduction in chronic inflammation differs by sex or race. It would also be useful to have more data on the effects of different modes and intensities of exercise on inflammation.

Barbara J. Nicklas, Walter Ambrosius, Stephen P. Messier, et al. Diet-induced weight loss, Exercise, and chronic inflammation in older, obese adults: A randomized controlled clinical trial. Am J Clin Nutr 79: 544-551 (March 2004) [Address reprint requests to B. J N.icklas, Section on Gerontology arid Geriatric Medicine and Center for Human Genomics, Wake Forest University Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail: bnicklas@wfubmc.edu]