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Differential Effects of Very-Low-Volume Exercise Modalities on Telomere Length, Inflammation, and Cardiometabolic Health in Obese Metabolic Syndrome Patients: A Subanalysis from Two Randomized Controlled Trials.
Reljic, D, Koller, A, Herrmann, HJ, Ekici, AB, Neurath, MF, Zopf, Y
Antioxidants (Basel, Switzerland). 2023;(10)
Abstract
Oxidative stress (OS) and inflammation are features of metabolic syndrome (MetS) that can contribute to the shortening of telomere length (TL), a marker of cellular ageing. Research indicates that exercise can positively influence MetS-associated conditions and TL. However, the effects of low-volume exercise types on TL are still unknown. We investigated the impact of very-low-volume high-intensity interval training (LV-HIIT), one-set resistance training (1-RT), and whole-body electromyostimulation (WB-EMS) on TL, inflammation, and cardiometabolic indices in 167 MetS patients. Data were derived from two randomized controlled trials where patients were allocated to an exercise group (2 sessions/week, for 12 weeks) or a control group. All groups received standard-care nutritional weight loss counselling. TL was determined as the T/S ratio (telomere to single-copy gene amount). All groups significantly reduced body weight (p < 0.05), but the T/S-ratio (p < 0.001) only increased with LV-HIIT. OS-related inflammatory markers (C-reactive protein, interleukin-6, and lipopolysaccharide-binding protein) only decreased (p < 0.05) following LV-HIIT. The MetS severity z-score improved with LV-HIIT (p < 0.001) and 1-RT (p = 0.014) but not with WB-EMS. In conclusion, very-low-volume exercise modalities have differential effects on telomeres, inflammation, and cardiometabolic health. Only LV-HIIT but not strength-based low-volume exercise increased TL in MetS patients, presumably due to superior effects on OS-related inflammatory markers.
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Impact of insulin and insulin resistance on brain dopamine signalling and reward processing - An underexplored mechanism in the pathophysiology of depression?
Gruber, J, Hanssen, R, Qubad, M, Bouzouina, A, Schack, V, Sochor, H, Schiweck, C, Aichholzer, M, Matura, S, Slattery, DA, et al
Neuroscience and biobehavioral reviews. 2023;:105179
Abstract
Type 2 diabetes and major depressive disorder (MDD) are the leading causes of disability worldwide and have a high comorbidity rate with fatal outcomes. Despite the long-established association between these conditions, the underlying molecular mechanisms remain unknown. Since the discovery of insulin receptors in the brain and the brain's reward system, evidence has accumulated indicating that insulin modulates dopaminergic (DA) signalling and reward behaviour. Here, we review the evidence from rodent and human studies, that insulin resistance directly alters central DA pathways, which may result in motivational deficits and depressive symptoms. Specifically, we first elaborate on the differential effects of insulin on DA signalling in the ventral tegmental area (VTA) - the primary DA source region in the midbrain - and the striatum as well as its effects on behaviour. We then focus on the alterations induced by insulin deficiency and resistance. Finally, we review the impact of insulin resistance in DA pathways in promoting depressive symptoms and anhedonia on a molecular and epidemiological level and discuss its relevance for stratified treatment strategies.
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Feasibility, Safety, and Preliminary Efficacy of Very Low-Volume Interval Training in Advanced Cancer Patients.
Reljic, D, Herrmann, HJ, Jakobs, B, Dieterich, W, Mougiakakos, D, Neurath, MF, Zopf, Y
Medicine and science in sports and exercise. 2022;(11):1817-1830
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Abstract
PURPOSE High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (CRF) and health-related outcomes in various chronic diseases, including cancer. However, data on feasibility and efficacy of HIIT in advanced cancer patients are still sparse, presumably because of safety concerns, like suspected immunosuppression after vigorous exercise. This randomized, sham-intervention controlled study aimed to investigate feasibility, safety, and preliminary efficacy of very low-volume HIIT (LOW-HIIT) in advanced cancer patients. METHODS Twenty-seven patients (55.4 ± 13.2 yr) with different advanced cancers (Union for International Cancer Control [UICC] III/IV) were randomly allocated to LOW-HIIT ( n = 13), consisting of 5 × 1 min cycle ergometer intervals (14 min per session total duration) at 80% to 95% HR peak (two sessions per week for 12 wk), or a sham intervention ( n = 14) performing light physical mobilization exercises (SHAM). Primary outcomes were attrition and attendance rates, with values of ≤25% and ≥80%, respectively, considered acceptable. Secondary outcomes were safety, protocol fidelity, physiological (including CRF measures) and patient-reported outcomes (including fatigue and quality of life). RESULTS One of 13 patients (8%) receiving LOW-HIIT dropped out. Mean attendance rate was ~93%. The prescribed minimum exercise intensity was consistently reached by all patients. Low-volume HIIT was well tolerated and not associated with any serious adverse event nor with increased infection susceptibility. There were no biochemical signs of acute immunosuppression after LOW-HIIT. Contrarily, differentiation and degranulation of natural killer cells was acutely increased postexercise. Low-volume HIIT improved CRF measures including peak oxygen uptake, self-reported fatigue, physical, and social functioning. No significant changes occurred in the SHAM group. CONCLUSIONS Low-volume HIIT can be regarded as feasible and safe in advanced cancer patients. Our preliminary data indicate favorable acute effects on NK-cells and beneficial chronic adaptations in CRF, fatigue, and aspects of quality of life.
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Protein Supplementation Does Not Maximize Adaptations to Low-Volume High-Intensity Interval Training in Sedentary, Healthy Adults: A Placebo-Controlled Double-Blind Randomized Study.
Reljic, D, Zieseniss, N, Herrmann, HJ, Neurath, MF, Zopf, Y
Nutrients. 2022;(19)
Abstract
There is ample evidence that specific nutritional strategies can enhance adaptions to resistance and endurance training. However, it is still unclear whether post-session protein supplementation may increase the effects of low-volume high-intensity interval training (LOW-HIIT). We examined the impact of LOW-HIIT combined with protein vs. placebo supplementation on cardiometabolic health indices in sedentary healthy individuals. Forty-seven participants (31.1 ± 8.0 yrs) performed cycle ergometer LOW-HIIT (5−10x1 min at 80−95% maximum heart rate) for eight weeks and randomly received double-blinded 40 g of whey protein (PRO-HIIT, N = 24) or an isocaloric placebo (maltodextrin, PLA-HIIT, N = 23) after each session. The maximum oxygen uptake (VO2max, primary outcome) and several secondary cardiometabolic outcomes were determined pre-/post-intervention. VO2max increased in PRO-HIIT (+2.8 mL/kg/min, p = 0.003) and PLA-HIIT (+3.5 mL/kg/min, p < 0.001). Systolic and diastolic blood pressure decreased in PRO-HIIT (−7/3 mmHg, p < 0.05) and PLA-HIIT (−8/5 mmHg, p < 0.001). Gamma glutamyl transferase (−2 U/L, p = 0.003) decreased in PRO-HIIT and alanine aminotransferase (−3 U/L, p = 0.014) in PLA-HIIT. There were no significant between-group differences in any of the outcome changes. In conclusion, LOW-HIIT improved VO2max and other cardiometabolic markers irrespective of the supplementation condition. Post-session protein supplementation does not seem to provide any additional benefit to LOW-HIIT in improving cardiometabolic health in sedentary healthy individuals.
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"HIIT the Inflammation": Comparative Effects of Low-Volume Interval Training and Resistance Exercises on Inflammatory Indices in Obese Metabolic Syndrome Patients Undergoing Caloric Restriction.
Reljic, D, Dieterich, W, Herrmann, HJ, Neurath, MF, Zopf, Y
Nutrients. 2022;(10)
Abstract
Exercise is a cornerstone in metabolic syndrome (MetS) treatment. However, the effects of low-volume exercise modalities on MetS-associated low-grade inflammation are unclear. A total of 106 MetS patients (53.7 ± 11.4 years) were randomized to low-volume high-intensity interval training (LOW-HIIT, 14 min/session), single-set resistance training (1-RT, ~15 min/session), whole-body electromyostimulation (WB-EMS, 20 min/session), three-set resistance training (3-RT, ~50 min/session), each performed 2 ×/week for 12 weeks, or a control group (CON). All groups received nutritional counseling for weight loss. Inflammatory and cardiometabolic indices were analyzed pre- and post-intervention. All groups significantly reduced body weight by an average of 3.6%. Only LOW-HIIT reduced C-reactive protein (CRP) (−1.6 mg/L, p = 0.001) and interleukin-6 (−1.1 pg/mL, p = 0.020). High-sensitivity CRP and lipopolysaccharide-binding protein decreased following LOW-HIIT (−1.4 mg/L, p = 0.001 and −2.1 ng/mL, p = 0.004) and 3-RT (−0.6 mg/L, p = 0.044 and −2.0 ng/mL, p < 0.001). MetS severity score improved with LOW-HIIT (−1.8 units, p < 0.001), 1-RT (−1.6 units, p = 0.005), and 3-RT (−2.3 units, p < 0.001). Despite similar effects on body weight, low-volume exercise modalities have different impact on inflammatory and cardiometabolic outcomes in MetS patients. LOW-HIIT has superior efficacy for improving inflammation compared to 1-RT and WB-EMS. Resistance-based exercise appears to require a higher volume to promote beneficial impact on inflammation.
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An algorithm for differentiating food antigen-related gastrointestinal symptoms.
Rostami, K, Bold, J, Ismail Ali, J, Parr, A, Dieterich, W, Zopf, Y, Htoo, A, Rostami-Nejad, M, Danciu, M
Gastroenterology and hepatology from bed to bench. 2021;14(1):8-16
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Irritable bowel syndrome (IBS) is a collection of gastrointestinal symptoms. Due to multiple etiologies, the pathogenesis of IBS is poorly understood. The aim of this audit was to assess the outcomes achieved using a lactose and gluten-free diet clinical intervention in patients traditionally diagnosed with IBS. This study was an audit of outcomes from the records of 149 patients presenting with IBS symptoms at secondary and tertiary Gastroenterology outpatients in two UK hospitals. This audit has demonstrated that more than 70% of patients presenting with IBS symptoms improved by following a diet eliminating lactose and gluten containing grains (improvement for >30% in their symptoms). The success of the elimination diet did not seem to be correlated with the body mass index (BMI). The best outcome was recorded in patients with normal BMI and also in the overweight group. Patients with higher BMI >30 or low below 18 also responded well to nutrition therapy. In conclusion, multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
Abstract
AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
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Iron Beats Electricity: Resistance Training but Not Whole-Body Electromyostimulation Improves Cardiometabolic Health in Obese Metabolic Syndrome Patients during Caloric Restriction-A Randomized-Controlled Study.
Reljic, D, Herrmann, HJ, Neurath, MF, Zopf, Y
Nutrients. 2021;(5)
Abstract
Caloric restriction (CR) and exercise are cornerstones in the treatment of obesity and cardiometabolic disorders. Recently, whole body electromyostimulation (WB-EMS) has emerged as a more time-efficient alternative to traditional resistance training (RT). However, the effects of WB-EMS compared to RT on cardiometabolic health in obese metabolic syndrome (MetS) patients performed during CR are still unclear. In total, 118 obese MetS patients (52.7 ± 11.8 years, BMI: 38.1 ± 6.9 kg/m2) undergoing CR over 12 weeks (aim: -500 kcal deficit/day) were randomly allocated to either WB-EMS, single-set RT (1-RT), 3-set RT (3-RT) or an inactive control group (CON). Primary outcome was MetS severity (MetS z-score). Secondary outcomes were body composition, muscle strength and quality of life (QoL). All groups significantly reduced body weight (~3%) and fat mass (~2.6 kg) but only 1-RT and 3-RT preserved skeletal muscle mass (SMM). All exercise groups increased muscle strength in major muscle groups (20-103%). However, only the two RT-groups improved MetS z-score (1-RT: -1.34, p = 0.003; 3-RT: -2.06, p < 0.001) and QoL (1-RT: +6%, p = 0.027; 3-RT: +12%, p < 0.001), while WB-EMS and CON had no impact on these outcomes. We conclude that traditional RT has superior effects on cardiometabolic health, SMM and QoL in obese MetS patients undergoing CR than WB-EMS.
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Food Intolerance of Unknown Origin: Caused by Mucosal Inflammation? A Pilot Study.
Dieterich, W, Tietz, E, Kohl, M, Konturek, PC, Rath, T, Neurath, MF, Zopf, Y
Clinical and translational gastroenterology. 2021;(2):e00312
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Abstract
INTRODUCTION The prevalence of patients with food intolerance (FI) has increased significantly. Immunoglobulin (Ig)E-mediated food allergies (FAs) are detected by determining IgE antibodies and skin prick test. Carbohydrate malabsorptions are clarified with breath tests. However, these diagnostic measures cannot capture all intolerances and have limitations in case of gut-mediated FI. The aims of this pilot study were to evaluate different methods to determine intestinal mucosal IgE in patients with FA and to characterize the intestinal mucosa in patients with FI of unknown origin (FH). METHODS Patients with FA and FH were compared with healthy controls. To determine the IgE antibodies and the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ of the intestinal mucosal, a lavage was performed as part of an ileocolonoscopy and samples were taken using the cytobrush and biopsy forceps. In a subgroup, mucosal samples were also taken from the duodenum. RESULTS Data in homogenates of intestinal mucosal samples yielded the highest sensitivity for IgE antibody titers compared with lavage and cytobrush. Patients with FA presented increased intestinal TNF-α and low IFN-γ values. This was in contrast to FH patients, who showed low intestinal IgE antibodies and TNF-α levels, but increased IFN-γ values. DISCUSSION The determination of IgE antibodies to diagnose intestinal IgE-mediated FA is most reliable in intestinal mucosal samples. Increased TNF-α and low IFN-γ levels in patients with FA characterize an allergic reaction. Decreased TNF-α and increased IFN-γ levels in patients with FH indicate an inflammation-related intolerance reaction (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A520).
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Effects of very low volume high intensity versus moderate intensity interval training in obese metabolic syndrome patients: a randomized controlled study.
Reljic, D, Frenk, F, Herrmann, HJ, Neurath, MF, Zopf, Y
Scientific reports. 2021;(1):2836
Abstract
Physical activity is a cornerstone in the treatment of obesity and metabolic syndrome (MetS). Given the leading physical activity barrier of time commitment and safety concerns about vigorous exercise in high-risk groups, this study aimed to investigate the effects of two extremely time-efficient training protocols (< 30 min time effort per week), either performed as high- (HIIT) or moderate-intensity interval training (MIIT) over 12 weeks, in obese MetS patients. In total, 117 patients (49.8 ± 13.6 years, BMI: 38.2 ± 6.2 kg/m2) were randomized to HIIT (n = 40), MIIT (n = 37) or an inactive control group (n = 40). All groups received nutritional counseling to support weight loss. Maximal oxygen uptake (VO2max), MetS severity (MetS z-score), body composition and quality of life (QoL) were assessed pre-and post-intervention. All groups significantly reduced body weight (~ 3%) but only the exercise groups improved VO2max, MetS z-score and QoL. VO2max (HIIT: + 3.1 mL/kg/min, p < 0.001; MIIT + 1.2 mL/kg/min, p < 0.05) and MetS z-score (HIIT: - 1.8 units, p < 0.001; MIIT - 1.2 units, p < 0.01) improved in an exercise intensity-dependent manner. In conclusion, extremely low-volume interval training, even when done at moderate intensity, is sufficiently effective to improve cardiometabolic health in obese MetS patients. These findings underpin the crucial role of exercise in the treatment of obesity and MetS.
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A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.
Schuppan, D, Mäki, M, Lundin, KEA, Isola, J, Friesing-Sosnik, T, Taavela, J, Popp, A, Koskenpato, J, Langhorst, J, Hovde, Ø, et al
The New England journal of medicine. 2021;(1):35-45
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Abstract
BACKGROUND In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. METHODS In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). RESULTS Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. CONCLUSIONS In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.).