Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training

Abstract

Review SynthèseT he biologic cascade of events that form the body's natural defenses against injury or infection is a vital part of the immune system. Ordinarily, this process is an acute response resulting in rapid, major increases in inflammatory mediators released into the circulation. 1,2 In healthy, lean, non-elderly people, for example, blood concentrations of the acute-phase reactant C-reactive protein (CRP), which are normally less than 2 mg/L in men 3 and less than 2.5 mg/L in women, 4 can increase more than 1000-fold in response to infection or trauma. 2,5,6 Typically, a CRP value of 10 mg/L or more is considered indicative of clinically significant inflammation. 7 However, recent evidence indicates that persistent elevations in circulating markers of inflammation, even when within the clinically normal range, are risk factors for cardiovascular disease in both middle-aged [8][9][10][11][12][13] and older [14][15][16][17][18][19] people. Recently, the US Centers for Disease Control and Prevention and the American Heart Association have stated that people with CRP values in the upper tertile of the adult population (> 3.0 mg/L) have a risk of cardiovascular disease that is double that of people whose CRP concentrations are less than 1.0 mg/L. 20In addition to CRP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), along with several other acutephase reactant proteins, cytokines and cytokine-soluble receptors, are strongly associated with increased risk for several chronic diseases, including cardiovascular disease, 12,17,21,22 diabetes mellitus 23,24 and disability. 25,26 IL-6 and TNF-α are both stimulators of CRP release from hepatocytes.27,28 It is not yet known which of these factors might be the most robust indicator of underlying inflammation, or whether the effects of these biomarkers are additive for risk prediction.As illustrated in Figure 1, behavioural factors are associated with chronic, low-grade states of inflammation (as measured by slightly elevated inflammatory biomarkers), and therefore with the several chronic diseases that are associated with inflammatory states. Since the risk estimates associated with elevated inflammation appear to be linear (e.g., the CRP category cut-offs for assessment of cardiovascular disease risk 20 are low risk < 1.0 mg/L, medium risk 1.0-3.0 mg/L and high risk > 3.0 mg/L), behavioural interventions that produce even slight reductions in inflammation may have clinically significant benefits. A few pharmacologic interventions such as use of angiotensin-converting-enzyme inhibitors and statins decrease inflammation, as evidenced by lowered CRP concentrations in prospective clinical trials. [29][30][31][32] Moreover, there are very promising data suggesting that decreasing body weight and increasing physical activity are just as effective as medication for reducing overall inflammation. The published effects of behavioural interventions involving weight loss and exercise training on inflammatory markers are reviewed here. Role of adiposity and weigh...

Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study

“…Since subclinical inflammation increases the risk of cardiovascular disease, disability, neurodegenerative disorders and cancers [20][21][22][23][24], it is important to identify efficient ways to modulate low-grade immune activation. Lifestylebased interventions are one option as they have been proved to exert anti-inflammatory effects in many studies [17,32]. The decrease in CRP and IL-6 levels in response to lifestyle intervention in the Finnish DPS reported here is Data are for intervention and control groups combined, n=406 Correlations are given as (partial) Spearman correlation coefficients, r E%, proportion of total energy derived from the nutrient in question similar to the effects observed in other studies.…”

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

“…already been shown in the literature (45,46), although concurrent roles for fat-independent mediators remain plausible. The decrease in cancer risk that might result from the CRP changes experienced in the ALPHA trial is unknown.…”

“…Although there is convincing evidence that obesity creates an inflammatory state (44) and that weight loss decreases circulating CRP levels in adults (45,46), controversy surrounds the role of exercise that may occur independently of weight loss; it is postulated that the relative contributions from "fitness" versus "fatness" on inflammatory markers may depend on gender, age, and disease status (47). In this group of disease-free postmenopausal women, the effect of our intervention on CRP levels seemed to have been The TER was calculated from a general linear model for each biomarker, estimating a parameter with anti-logarithm corresponding to the ratio of adjusted geometric means for the exercise intervention group over the control group; this ratio was assumed to be common at 6 months and 12 months postrandomization.…”

“…In the fourth RCT of postmenopausal women, in which CRP decreased independently of weight loss (suggesting the involvement of a fatindependent mechanism), an average of only 1.3 kg of body fat was lost in the exercise group (26). Among the proposed mechanisms relating CRP changes to exercise (46)(47)(48), loss of body fat predominates and, for women in the ALPHA Trial, seems the most plausible. The infiltration of inflammatory cells into adipose tissue ultimately increases circulating CRP levels (46) by producing TNF-a and IL-6 (18,44).…”

Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women

“…Although the MHO individuals' clinical markers did not reflect the beneficial effects of weight loss in the present study, these results should not persuade us to underestimate the positive effects of lifestyle modifications, including weight loss, on MHO individuals. According to a recently published review by Nicklas et al, 28 weight loss has a direct effect on adipose tissue, which not only decreases the production of proinflammatory mediators such as IL-6 and TNF-a, but also increases the production of anti-inflammatory mediators such as IL-10 and IL-1 receptor antagonist. In the present study, we cannot exclude the possibility that MHO individuals might experience weight loss-induced improvement in their anti-inflammatory profiles during intervention, although the improvement in proinflammatory profiles was not evident in this study.…”