Kristen M. Beavers

Effect of exercise training on chronic inflammation.

Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.

Associations between body composition and gait-speed decline: results from the Health, Aging, and Body Composition study

BACKGROUND In older adults, every 0.1-m/s slower gait speed is associated with a 12% higher mortality. However, little research has identified risk factors for gait-speed decline. OBJECTIVE We assessed the association between several measures of body composition and age-related decline in gait speed. DESIGN Data were from 2306 older adults who were participating in the Health, Aging, and Body Composition cohort and were followed for 4 y (50% women; 38% black). Usual walking speed (m/s) over 20 m was measured in years 2 through 6, and the baseline and changes in several measures of body composition were included in mixed-effects models. RESULTS Gait speed declined by 0.06 ± 0.00 m/s over the 4-y period. Baseline thigh intermuscular fat predicted the annual gait-speed decline (±SE) in both men and women (-0.01 ± 0.00 and -0.02 ± 0.00 m/s per 0.57 cm(2), respectively; P < 0.01). In men, but not in women, this relation was independent of total body adiposity. In longitudinal analyses, changes in thigh intermuscular fat and total thigh muscle were the only body-composition measures that predicted gait-speed decline in men and women combined. When modeled together, every 5.75-cm(2) increase in thigh intermuscular fat was associated with a 0.01 ± 0.00-m/s decrease in gait speed, whereas every 16.92-cm(2) decrease in thigh muscle was associated with a 0.01 ± 0.00-m/s decrease in gait speed. CONCLUSIONS High and increasing thigh intermuscular fat are important predictors of gait-speed decline, implying that fat infiltration into muscle contributes to a loss of mobility with age. Conversely, a decreasing thigh muscle area is also predictive of a decline in gait speed.

Is lost lean mass from intentional weight loss recovered during weight regain in postmenopausal women

BACKGROUND Despite the well-known recidivism of obesity, surprisingly little is known about the composition of body weight during weight regain. OBJECTIVE The objective of this study was to determine whether the composition of body weight regained after intentional weight loss is similar to the composition of body weight lost. DESIGN The design was a follow-up to a randomized controlled trial of weight loss in which body composition was analyzed and compared in 78 postmenopausal women before the intervention, immediately after the intervention, and 6 and 12 mo after the intervention. RESULTS All body mass and composition variables were lower immediately after weight loss than at baseline (all P < 0.05). More fat than lean mass was lost with weight loss, which resulted in body-composition changes favoring a lower percentage of body fat and a higher lean-to-fat mass ratio (P < 0.001). Considerable interindividual variability in weight regain was noted (CV = 1.07). In women who regained ≥2 kg body weight, a decreasing trend in the lean-to-fat mass ratio was observed, which indicated greater fat mass accretion than lean mass accretion (P < 0.001). Specifically, for every 1 kg fat lost during the weight-loss intervention, 0.26 kg lean tissue was lost; for every 1 kg fat regained over the following year, only 0.12 kg lean tissue was regained. CONCLUSIONS Although not all postmenopausal women who intentionally lose weight will regain it within 1 y, the data suggest that fat mass is regained to a greater degree than is lean mass in those who do experience some weight regain. The health ramifications of our findings remain to be seen.

Contribution of Cardiorespiratory Fitness to the Obesity Paradox

Until recently, cardiorespiratory fitness (CRF) has been overlooked as a potential modifier of the inverse association between obesity and mortality (the so-called obesity paradox), observed in patients with known or suspected cardiovascular (CV) disease. Evidence from five observational cohort studies of 30,104 patients (87% male) with CV disease indicates that CRF significantly alters the obesity paradox. There is general agreement across studies that the obesity paradox persists among patients with low CRF, regardless of whether adiposity is assessed by body mass index, waist circumference, or percentage body fat. However, among patients with high CRF, risk of all-cause mortality is lowest for the overweight category in some, but not all, studies, suggesting that higher levels of fitness may modify the relationship between body fatness and survival in patients manifesting an obesity paradox. Further study is needed to better characterize the joint contribution of CRF and obesity on mortality in diverse populations.

Long-Term Physical Activity and Inflammatory Biomarkers in Older Adults

PURPOSE The purpose of this study was to determine the effects of a 12-month physical activity (PA) intervention on inflammatory biomarkers in elderly men and women. METHODS Four hundred and twenty-four elderly (age = 70-89 yr), nondisabled, community-dwelling men and women at risk for physical disability were enrolled in a multicenter, single-blind, randomized controlled trial. Participants were randomized to participate in either a 12-month moderate-intensity PA intervention or a successful aging health education intervention. Biomarkers of inflammation (interleukin (IL)-6sR, IL-1sRII, soluble tumor necrosis factor receptors 1 and 2 (sTNFRI, sTNFRII), IL-8, IL-15, adiponectin, IL-1ra, IL-2sRα, and TNFα) were measured at baseline, at 6 months, and at 12 months. RESULTS A baseline blood sample was successfully collected from 368 participants. After adjustment for gender, clinic site, diabetes status, and baseline outcome measure, IL-8 was the only inflammatory biomarker affected by the PA intervention (P = 0.03). The adjusted mean IL-8 at month 12 was 9.9% (0.87 pg·mL) lower in the PA compared with the successful aging group. Secondary interaction analyses between baseline biomarker status and treatment showed one significant interaction (P = 0.02) such that the PA intervention reduced IL-15 concentrations in participants with a baseline IL-15 above the median value of 1.67 pg·mL. However, these associations were no longer significant after consideration for multiple comparisons. CONCLUSIONS Overall, this study does not provide definitive evidence for an effect of regular exercise for altering systemic concentrations of the measured inflammatory biomarkers in older adults.

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality. Methods 2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials. Results Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m2, follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I2 = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00). Conclusions In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.

Exposure to isoflavone-containing soy products and endothelial function: A Bayesian meta-analysis of randomized controlled trials

BACKGROUND AND AIMS To determine whether and to what degree exposure to isoflavone-containing soy products affects EF. Endothelial dysfunction has been identified as an independent coronary heart disease risk factor and a strong predictor of long-term cardiovascular morbidity and mortality. Data on the effects of exposure to isoflavone-containing soy products on EF are conflicting. METHODS AND RESULTS A comprehensive literature search was conducted using the PUBMED database (National Library of Medicine, Bethesda, MD) inclusively through August 21, 2009 on RCTs using the keywords: soy, isoflavone, phytoestrogen, EF, flow mediated vasodilation, and FMD. A Bayesian meta-analysis was conducted to provide a comprehensive account of the effect of isoflavone-containing soy products on EF, as measured by FMD. A total of 17 RCTs were selected as having sufficient data for study inclusion. The overall mean absolute change in FMD (95% Bayesian CI) for isoflavone-containing soy product interventions was 1.15% (-0.52, 2.75). When the effects of separate interventions were considered, the treatment effect for isolated isoflavones was 1.98% (0.07, 3.97) compared to 0.72% (-1.39, 2.90) for isoflavone-containing soy protein. The models were not improved when considering study-specific effects such as cuff measurement location, prescribed dietary modification, and impaired baseline FMD. CONCLUSIONS Cumulative evidence from the RCTs included in this meta-analysis indicates that exposure to soy isoflavones can modestly, but significantly, improve EF as measured by FMD. Therefore, exposure to isoflavone supplements may beneficially influence vascular health.

Fat Mass Loss Predicts Gain in Physical Function With Intentional Weight Loss in Older Adults

BACKGROUND Clinical recommendation of weight loss (WL) in older adults remains controversial, partially due to concerns regarding lean mass loss and potential loss of physical function. The purpose of this study is to determine the independent associations between changes in fat and lean mass and changes in physical function in older, overweight, and obese adults undergoing intentional WL. METHODS Data from three randomized-controlled trials of intentional WL in older adults with similar functional outcomes (short physical performance battery and Pepper assessment tool for disability) were combined. Analyses of covariance models were used to investigate relationships between changes in weight, fat, and lean mass (acquired using dual-energy x-ray absorptiometry) and changes in physical function. RESULTS Overall loss of body weight was -7.8 ± 6.1 kg (-5.6 ± 4.1 kg and -2.7 ± 2.4 kg of fat and lean mass, respectively). In all studies combined, after adjustment for age, sex, and height, overall WL was associated with significant improvements in self-reported mobility disability (p < .01) and walking speed (p < .01). Models including change in both fat and lean mass as independent variables found only the change in fat mass to significantly predict change in mobility disability (β[fat] = 0.04; p < .01) and walking speed (β[fat] = -0.01; p < .01). CONCLUSIONS Results from this study demonstrate that loss of body weight, following intentional WL, is associated with significant improvement in self-reported mobility disability and walking speed in overweight and obese older adults. Importantly, fat mass loss was found to be a more significant predictor of change in physical function than lean mass loss.

Soy consumption, adhesion molecules, and pro-inflammatory cytokines: a brief review of the literature.

Given the interest in the vascular effects of both soyfoods and soy isoflavones, the purpose of this short review is to evaluate clinical trials that have examined the effects of isoflavone-rich soy products on the novel cardiovascular risk factors, cellular adhesion molecules, and pro-inflammatory cytokines. A total of 14 randomized clinical studies were assessed. From the data evaluated, evidence suggests that neither soyfoods nor soy isoflavones affect IL-6 or TNF-alpha expression. In contrast, the effects of soy on cellular adhesion molecules are mixed. Study design characteristics possibly contributing to the inconsistent data are discussed and recommendations for future research in this area are presented.

Effect of an 18-month physical activity and weight loss intervention on body composition in overweight and obese older adults

Our primary objective was to determine the long‐term effects of physical activity (PA) and weight loss (WL) on body composition in overweight/obese older adults. Secondarily, the association between change in body mass and composition on change in several cardiometabolic risk factors and mobility was evaluated.