Barbara Strasser

Resistance Training in the Treatment of the Metabolic Syndrome A Systematic Review and Meta-Analysis of the Effect of Resistance Training on Metabolic Clustering in Patients with Abnormal Glucose Metabolism

Over the last decade, investigators have given increased attention to the effects of resistance training (RT) on several metabolic syndrome variables. The metabolic consequences of reduced muscle mass, as a result of normal aging or decreased physical activity, lead to a high prevalence of metabolic disorders. The purpose of this review is: (i) to perform a meta-analysis of randomized controlled trials (RCTs) regarding the effect of RT on obesity-related impaired glucose tolerance and type 2 diabetes mellitus; and (ii) to investigate the existence of a dose-response relationship between intensity, duration and frequency of RT and the metabolic clustering. Thirteen RCTs were identified through a systematic literature search in MEDLINE ranging from January 1990 to September 2007. We included all RCTs comparing RT with a control group in patients with abnormal glucose regulation. For data analysis, we performed random effects meta-analyses to determine weighted mean differences (WMD) with 95% confidence intervals (CIs) for each endpoint. All data were analysed with the software package Review Manager 4.2.10 of the Cochrane Collaboration. In the 13 RCTs included in our analysis, RT reduced glycosylated haemoglobin (HbA1c) by 0.48% (95% CI -0.76, -0.21; p = 0.0005), fat mass by 2.33 kg (95% CI -4.71, 0.04; p = 0.05) and systolic blood pressure by 6.19 mmHg (95%CI 1.00, 11.38; p = 0.02). There was no statistically significant effect of RT on total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and diastolic blood pressure. Based on our meta-analysis, RT has a clinically and statistically significant effect on metabolic syndrome risk factors such as obesity, HbA1c levels and systolic blood pressure, and therefore should be recommended in the management of type 2 diabetes and metabolic disorders.

Resistance training, visceral obesity and inflammatory response: a review of the evidence

Intra‐abdominal obesity is an important risk factor for low‐grade inflammation, which is associated with increased risk for diabetes mellitus and cardiovascular disease. For the most part, recommendations to treat or prevent overweight and obesity via physical activity have focused on aerobic endurance training as it is clear that aerobic training is associated with much greater energy expenditure during the exercise session than resistance training. However, due to the metabolic consequences of reduced muscle mass, it is understood that normal ageing and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Whether resistance training alters visceral fat and the levels of several pro‐inflammatory cytokines produced in adipose tissue has not been addressed in earlier reviews. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to a better metabolic control. Considering the benefits of resistance training on visceral fat and inflammatory response, an important question is: how much resistance training is needed to confer such benefits? Therefore, the purpose of this review was to address the importance of resistance training on abdominal obesity, visceral fat and inflammatory response.

Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults

PurposeRecent data suggest that chronic low-grade inflammation, a characteristic of obesity, is associated with altered tryptophan (Trp) and tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The present study assessed the effect of an extreme short-term diet on Trp breakdown and inflammatory biomarkers in overweight adults.MethodsThirty-eight overweight participants (16 women, 22 men; average body mass index: 29xa0kg/m2, mean age 52.8xa0years) were randomized into two diet groups: a very low kcal diet group (VLCD; Ø 600xa0kcal/day, nxa0=xa021) and a low kcal diet group (LCD; Ø 1,200xa0kcal/day, nxa0=xa017). Assays included the measurement of Trp, kynurenine (Kyn), and their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin, plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as biochemical and inflammatory markers at baseline and after 2xa0weeks of treatment.ResultsWeight loss diet lowered leptin levels in both groups by 46xa0%, although not reaching significance. Trp and Kyn decreased significantly by 21 and 16xa0% for VLCD and by 15 and 17xa0% for the LCD group, respectively. A significant reduction in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were not significantly altered during the study period. Leptin was significantly correlated with Trp breakdown before and after the intervention (Pxa0<xa00.02).ConclusionsSince disturbed metabolism of Trp affects biosynthesis of serotonin and might be associated with increased susceptibility for mood disturbances and carbohydrate craving, strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms.

Mood, food, and cognition: role of tryptophan and serotonin.

Purpose of reviewFood is not only necessary as a metabolic fuel for the body, it becomes more and more evident that there exists an association between food and brain functions like mood and cognition. Tryptophan represents a key element for brain functioning, because of its role as a precursor for production of neurotransmitter serotonin (5-hydroxytryptamine). In clinical conditions, which involve chronic immune system activation or under cytokine therapy, lower tryptophan levels because of high catabolism of tryptophan as indicated by the kynurenine to tryptophan ratio are common and often associate with depressive mood. Recent findingsStudies in the in vitro model of mitogen-stimulated peripheral blood mononuclear cells revealed that several phytocompounds, mainly antioxidants like polyphenols and vitamins, can interfere with inflammatory signaling cascades including tryptophan breakdown. If extrapolated to the in vivo situation, such compounds could increase blood and brain tryptophan availability for serotonin production. Although there is some in vivo evidence for the effect of such compounds, outcomes are hardly predictable and most likely depend on the individuals immunological state. SummaryNot only a diet rich in tryptophan but also a diet rich in antioxidants can have a positive impact on mood and cognition. This could be of special relevance for individuals who present with low grade inflammation conditions.

Effects of resistance training on respiratory function in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

PurposeOver the last decade, the potential use of resistance training (RT) for patients with chronic obstructive pulmonary disease (COPD) has gained increasing attention. Many COPD patients experience muscle dysfunction and reduced muscle mass, primarily as a result of chronic immobilization. These symptoms have been associated with reduced exercise tolerance and complaints of fatigue and dyspnea (even after minimal exertion). This paper presents findings from a systematic review that sought to: (1) present a meta-analysis of randomized controlled trials (RCT) investigating the effects of RT on respiratory function measures in patients with COPD and (2) investigate the existence of a dose–response relationship between intensity, duration and frequency of RT and assessed outcomes.MethodsA systematic literature search of MEDLINE electronic database (January 1980 to December 2009) produced a body of research on the effects of RT with a control group in patients with COPD. Data analysis involved a random effects meta-analysis, in order to determine weighted mean differences with 95 confidence intervals (95% CI) for each endpoint. All data were analyzed with the software package Review Manager V 4.2.10 (of the Cochrane Collaboration); 14 RCTs were included in the meta-analysis.ResultsFindings demonstrated that RT did not substantially increase forced expiratory volume in 1xa0s. In addition, the weighted mean difference was 2.71% of predicted (95% CI, −1.86 to 7.27; pu2009=u20090.25) or by absolute 0.08xa0L (95% CI, −0.03 to 0.19; pu2009=u20090.14). It appeared that maximum minute ventilation increased by 3.77xa0L/min (95% CI, −0.51 to 8.04; pu2009=u20090.08).ConclusionsBased on findings from the meta-analysis, RT produces a clinically and statistically significant effect on respiratory function (such as forced vital capacity) and is therefore recommended in the management of COPD.

Kynurenine pathway metabolism and immune activation: Peripheral measurements in psychiatric and co-morbid conditions.

Immune activation is inextricably linked with dysregulation of the tryptophan metabolism, shifting catabolic routes towards oxidative breakdown along the kynurenine axis. Several enzymes are able to metabolize tryptophan, but activity of inducible indoleamine 2,3-dioxygenase (IDO-1) plays a major role under pro-inflammatory, interferon-γ (IFN-γ) dominated settings. Accelerated breakdown of tryptophan into kynurenine, dysregulation of further downstream metabolism and impaired enzymatic activities due to the absence of oxidation sensitive cofactors are associated with a broad variety of primary disorders and co-morbidities. Deprivation of the essential amino acid tryptophan suppresses growth of pathogens or tumor cells but also restricts T cell proliferation, which favors immunosuppression. In addition, diminished levels of tryptophan lead to lower synthesis of neurotransmitter serotonin, this being probably the most important biochemical cause of psychiatric co-morbidities associated with a broad variety of chronic inflammatory disorders. Also other frequent co-occurring symptoms and conditions such as anemia or cachexia may be at least partially caused by the lowered levels of the essential growth factor tryptophan. Tissue and cell specific expression of kynurenine downstream processing enzymes and their defective regulation may contribute to symptom diversification. Several kynurenine downstream metabolites show potent bioactivities, thus leading to the defects in a variety of affected target pathways. Measuring peripheral tryptophan breakdown, which is usually done by estimating the kynurenine to tryptophan ratio, in parallel to determination of other immune activation markers to confirm the involvement of IDO-1 activity in deregulated breakdown, is a reliable tool to monitor status and progression of a variety of disorders and has great potential to be applied to monitor treatments and to predict e.g. the necessity of psychiatric interventions before aggravation of symptoms, thus in helping to personalize therapeutic strategies. This article is part of the Special Issue entitled The Kynurenine Pathway in Health and Disease.

Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes.

Exhaustive exercise can cause a transient depression of immune function. Data indicate significant effects of immune activation cascades on the biochemistry of monoamines and amino acids such as tryptophan. Tryptophan can be metabolized through different pathways, a major route being the kynurenine pathway, which is often systemically up-regulated when the immune response is activated. The present study was undertaken to examine the effect of exhaustive aerobic exercise on biomarkers of immune activation and tryptophan metabolism in trained athletes. After a standardized breakfast 2 h prior to exercise, 33 trained athletes (17 women, 16 men) performed an incremental cycle ergometer exercise test at 60 rpm until exhaustion. After a 20 min rest phase, the participants performed a 20 min maximal time-trial on a cycle ergometer (RBM Cyclus 2, Germany). During the test, cyclists were strongly encouraged to choose a maximal pedalling rate that could be maintained for the respective test duration. Serum concentrations of amino acids tryptophan, kynurenine, phenylalanine, and tyrosine were determined by HPLC and immune system biomarker neopterin by ELISA at rest and immediately post exercise. Intense exercise was associated with a strong increase in neopterin concentrations (p<0.001), indicating increased immune activation following intense exercise. Exhaustive exercise significantly reduced tryptophan concentrations by 12% (p<0.001) and increased kynurenine levels by 6% (p = 0.022). Also phenylalanine to tyrosine ratios were lower after exercise as compared with baseline (p<0.001). The kynurenine to tryptophan ratio correlated with neopterin (r = 0.560, p<0.01). Thus, increased tryptophan catabolism by indoleamine 2,3-dioxygenase appears likely. Peak oxygen uptake correlated with baseline tryptophan and kynurenine concentrations (r = 0.562 and r = 0.511, respectively, both p<0.01). Findings demonstrate that exhaustive aerobic exercise is associated with increased immune activation and alterations in monoamine metabolism in trained athletes which may play a role in the regulation of mood and cognitive processes.

Association between muscular strength and inflammatory markers among elderly persons with cardiac disease: results from the KORA-Age study.

Little is known about the association between muscle strength and inflammation in diseased individuals and particularly in cardiac patients. Thus, our purpose was to examine the association of muscular strength with the inflammatory status in older adults with and without cardiac disease. The cross-sectional analysis was based on 1079 adults aged 65–94xa0years, who participated in the KORA-Age study. Participants underwent an interview and extensive physical examinations including anthropometric measurements, registration of diseases and drug intake, determination of health-related behaviors, collection of blood samples for measurements of interleukin-6 and hs-CRP and muscle strength measurement using hand-grip dynamometry. Cardiac patients (nxa0=xa0323) had higher levels of IL-6 and poorer muscle strength compared with older adults without cardiac disease. Among persons with cardiac diseases, muscle strength in the lower tertile compared to the upper tertile was significantly associated with increased odds of having elevated IL-6 levels (OR 3.53, 95xa0% CI 1.18–10.50, pxa0=xa00.024) after controlling for age, gender, body fat, alcohol intake, smoking status, diseases, medications and physical activity, whereas the association between muscle strength and hs-CRP remained borderline significant (OR 2.80, 95xa0% CI 0.85–9.24, pxa0=xa00.092). The same trends, with slightly lower odds ratios, were also observed in older adults without cardiac disease. Lower levels of muscular strength are associated with higher concentrations of IL-6 and hs-CRP in elderly individuals with and without cardiac disease suggesting a significant contribution of the muscular system in reducing low-grade inflammation that accompanies cardiac disease and aging.

Tryptophan Metabolism in Allergic Disorders.

Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-γ (IFN-γ). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may play a relevant role in the pathophysiology of allergic disorders.

Gender differences in the association between grip strength and mortality in older adults: results from the KORA-age study.

BackgroundReduced muscular strength in the old age is strongly related to activity impairment and mortality. However, studies evaluating the gender-specific association between muscularity and mortality among older adults are lacking. Thus, the objective of the present study was to examine gender differences in the association between muscular strength and mortality in a prospective population-based cohort study.MethodsData used in this study derived from the Cooperative Health Research in the Region of Augsburg (KORA)-Age Study. The present analysis includes 1,066 individuals (mean age 76u2009±u200911 SD years) followed up over 3xa0years. Handgrip strength was measured using the Jamar Dynamometer. A Cox proportional hazard model was used to determine adjusted hazard ratios of mortality with 95% confidence intervals (95% CI) for handgrip strength. Potential confounders (i.e. age, nutritional status, number of prescribed drugs, diseases and level of physical activity) were pre-selected according to evidence-based information.ResultsDuring the follow-up period, 56 men (11%) and 39 women (7%) died. Age-adjusted mortality rates per 1,000 person years (95% CI) were 77 (59–106), 24 (13–41) and 14 (7–30) for men and 57 (39–81), 14 (7–27) and 1 (0–19) for women for the first, second and third sex-specific tertile of muscular strength, respectively. Low handgrip strength was significantly associated with all-cause mortality among older men and women from the general population after controlling for significant confounders. Hazard ratios (95% CI) comparing the first and second tertile to the third tertle were 3.33 (1.53–7.22) and 1.42 (0.61-3.28), respectively. Respective hazard ratios (95% CI) for mortality were higher in women than in men ((5.23 (0.67–40.91) and 2.17 (0.27–17.68) versus 2.36 (0.97–5.75) and 0.97 (0.36–2.57)).ConclusionsGrip strength is inversely associated with mortality risk in older adults, and this association is independent of age, nutritional status, number of prescribed drugs, number of chronic diseases and level of physical activity. The association between muscular strength and all-cause mortality tended to be stronger in women. It seems to be particularly important for the weakest to enhance their levels of muscular strength in order to reduce the risk of dying early.